Docstoc

Systemic therapy in Breast cancer

Document Sample
Systemic therapy in Breast cancer Powered By Docstoc
					64   ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




·π«∑“ß°“√√—°…“¡–‡√Á߇μâ“π¡√–¬–·√°¥â«¬
Systemic therapy




¡–‡√Áß«‘∑¬“ ¡“§¡·Ààߪ√–‡∑»‰∑¬
§≥–Õπÿ°√√¡°“√ºŸâ®—¥∑”
1. 𓬷æ∑¬å«‘‡™’¬√                ÿ ‘   ‘ ‘
                             »√’¡ππ∑√åπ¡μ
2. ·æ∑¬åÀ≠‘ß “«‘μ√’          ‡¡“Ãï°ÿ≈‰æ‚√®πå
3. ·æ∑¬åÀ≠‘ß∏‘쑬“              ‘ ‘
                              ‘√ ßÀå
4. ·æ∑¬åÀ≠‘ß®“√ÿ«√√≥         ‡Õ°«—≈≈¿
5. ·æ∑¬åÀ≠‘߇Õ◊ÈÕ¡·¢          ÿ¢ª√–‡ √‘∞
                                                            ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 65




·π«∑“߇«™ªØ‘∫—μ‘ „π°“√√—°…“‚√§¡–‡√Á߇μâ“π¡
                                  Ë                                                             Ë
          ¡–‡√Á߇μâ“π¡‡ªìπ¡–‡√Áß∑’æ∫∫àÕ¬‡ªìπÕ—π¥—∫ Õß„πÀ≠‘߉∑¬·≈–‡ªì𠓇Àμÿ°“√쓬®“°‚√§¡–‡√Áß∑’æ∫∫àÕ¬‡ªìπÕ—π¥—∫
 “¡√Õß®“°¡–‡√Áßμ—∫·≈–¡–‡√Áߪե ¥â«¬«‘∑¬“°“√·≈–§«“¡√Ÿâ„π ¡—¬ªí®®ÿ∫—π ºŸâªÉ«¬¡–‡√Á߇μâ“π¡„π√–¬–·√° “¡“√∂√—°…“
„ÀâÀ“¬¢“¥‰¥â„π®”π«π∑’Ë¡“°¢÷Èπ  à«πºŸâªÉ«¬¡–‡√Á߇μâ“π¡„π√–¬–·æ√à°√–®“¬ ·¡â®–‰¡à “¡“√∂√—°…“„ÀâÀ“¬¢“¥‰¥â ·μà°“√
√—°…“¥â«¬ŒÕ√å‚¡π·≈–¬“‡§¡’∫”∫—¥°Á„Àâº≈¥’¡“°  “¡“√∂∫√√‡∑“Õ“°“√®“°‚√§≈߉¥â „πºŸâªÉ«¬ à«π„À≠à ™à«¬„Àâ¡’ §ÿ≥¿“æ
™’«μ∑’¥’ ·≈–¡’™«μ√Õ¥Õ¬Ÿ‰¥âπ“π°«à“°≈ÿ¡∑’√°…“μ“¡Õ“°“√ ªí®®ÿ∫π¡’¬“„À¡à‡¢â“¡“„Àâ‡≈◊Õ°„™âÀ≈“¬™π‘¥ ®”π«π¡“°¡’√“§“·æß
   ‘ Ë          ’‘       à           à Ë—                   —
                                                    Ë          â                        Ë ÷
¡–‡√Áß«‘∑¬“ ¡“§¡œ ®÷߉¥â‡ πÕ·π«∑“ß°“√√—°…“ ‡æ◊Õ„À⇰‘¥§«“¡§ÿ¡§à“„π°“√√—°…“ Ÿß ÿ¥‡∑à“∑’æß°√–∑”‰¥â‰«â„π·π«∑“ßπ’È
„π°“√„™âŒÕ√å‚¡π·≈–¬“‡§¡’∫”∫—¥·æ∑¬åºŸâ√—°…“§«√¡’§«“¡√Ÿâ‡°’ˬ«°—∫º≈¢â“߇§’¬ß¢Õ߬“·μà≈–™π‘¥μ≈Õ¥®π°“√¥Ÿ·≈‡¡◊ËÕ¡’
º≈¢â“߇§’¬ß‡°‘¥¢÷Èπ °“√√—°…“¡–‡√Á߇æ◊ËÕ„À⇰‘¥ª√–‚¬™πå Ÿß ÿ¥·°àºŸâªÉ«¬ §«√‰¥â√—∫°“√¥Ÿ·≈®“°ºŸâ‡™’ˬ«™“≠·μà≈–
                                                  —              ‘               ‘
 “¢“√à«¡°—π ‰¥â·°à  “¢“»—≈¬»“ μ√å  “¢“√—ß ’√°…“  “¢“欓∏‘«∑¬“  “¢“√—ß«‘π®©—¬·≈– “¢“Õ“¬ÿ√»“ μ√å¡–‡√Áß

«—μ∂ÿª√– ß§å
         ‡æ◊ËÕ„Àâ·æ∑¬å„™â‡ªìπ·π«∑“ß„π°“√√—°…“ºŸâªÉ«¬¡–‡√Á߇μâ“π¡‰¥âÕ¬à“߇À¡“– ¡ ¡’§ÿ≥¿“æ·≈–¡’ª√– ‘∑∏‘º≈ ≈¥
§«“¡ ‘Èπ‡ª≈◊Õß∑√—欓°√ °“√ªØ‘∫—μ‘μ“¡·π«∑“ß°“√√—°…“π’ȧ«√‡ªìπ‰ª‚¥¬§«“¡ ¡—§√„®¢Õß·æ∑¬åºŸâ√—°…“ ·≈–‰¡à®”‡ªìπ
μâÕ߬÷¥·π«∑“߇«™ªØ‘∫—μ‘π’ȇªìπ·π«∑“ß∑’Ë쓬엫·π«∑“߇¥’¬« ·æ∑¬åºŸâ¥Ÿ·≈Õ“®æ‘®“√≥“‡≈◊Õ°«‘∏’ √—°…“Õ◊Ëπ Ê ‰¥âμ“¡§«“¡
‡À¡“– ¡„π§π‰¢â·μà≈–√“¬
§ÿ≥¿“æ¢ÕßÀ≈—°∞“π (Quality or strength of evidence)
                                 Ë                                                                  Ë
       √–¥—∫ A À¡“¬∂÷ßÀ≈—°∞“π∑’‰¥â®“° systematic review ¢Õß randomized controlled clinical trials ∑’¥”‡π‘π°“√Õ¬à“ß
‡À¡“– ¡À√◊ÕÀ≈—°∞“π∑’ˉ¥â®“° randomized controlled clinical trials
         √–¥—∫ B À¡“¬∂÷ßÀ≈—°∞“π∑’ˉ¥â®“° systematic review ¢Õß controlled clinical studies À√◊ÕÀ≈—°∞“π∑’ˉ¥â®“°
controlled clinical studies ‡™àπ non-randomized controlled trials, cohort studies, case-control studies, cross sectional
studies ∑’Ë¥”‡π‘π°“√Õ¬à“߇À¡“– ¡ À√◊Õ®“° randomized controlled clinical trials ∑’Ë¥”‡π‘π°“√‰¡à‡À¡“– ¡
         √–¥—∫ C À¡“¬∂÷ßÀ≈—°∞“π∑’ˉ¥â®“° systematic review ¢Õß descriptive studies
       √–¥—∫ D À¡“¬∂÷ßÀ≈—°∞“π∑’ˉ¥â®“°§«“¡‡ÀÁπÀ√◊Õ©—π∑“¡μ‘ (consensus) ¢ÕߺŸâ‡™’ˬ«™“≠ ‡π◊ËÕß®“°‰¡à¡’À≈—°∞“π
®“°º≈ ß“π°“√«‘®—¬∑“ߧ≈‘π‘°‡°’ˬ«°—∫‡√◊ËÕßπ—ÈπÊ

√–¥—∫§”·π–π” (Grade of recommendation)
         1A §«“¡¡—Ëπ„®¢Õߧ”·π–π”Õ¬Ÿà„π√–¥—∫ Ÿß §”·π–π”¥—ß°≈à“« “¡“√∂𔉪„™â‰¥â°—∫ºŸâªÉ«¬ à«π¡“°„π·∑∫∑ÿ°
 ∂“π°“√≥å
         1B §«“¡¡—Ëπ„®¢Õߧ”·π–π”Õ¬Ÿà„π√–¥—∫ Ÿß §”·π–π”¥—ß°≈à“«§«√®–𔉪„™â°—∫ºŸâªÉ«¬ à«π¡“°‰¥â
         1C §«“¡¡—Ëπ„®¢Õߧ”·π–π”Õ¬Ÿà„π√–¥—∫ª“π°≈“ß §”·π–π”¥—ß°≈à“«πà“®–𔉪„™â°—∫ºŸâªÉ«¬ à«π„À≠à‰¥â
         1D §«“¡¡—Ëπ„®¢Õߧ”·π–π”Õ¬Ÿà„π√–¥—∫μË” À“°‰¡à®”‡ªìπ ‰¡à§«√𔧔·π–π”¥—ß°≈à“«‰ª„™â
         0A §«“¡¡—Ëπ„®¢Õߧ”·π–π”Õ¬Ÿà„π√–¥—∫ª“π°≈“ß ºŸâª√–°Õ∫«‘™“™’懫™°√√¡®–ªØ‘∫—μ‘μ“¡§”·π–π”¥—ß°≈à“«
À√◊Õ‰¡à ¢÷ÈπÕ¬Ÿà°—∫ªí®®—¬Õ◊ËπÊ
         0B §«“¡¡—Ëπ„®¢Õߧ”·π–π”Õ¬Ÿà„π√–¥—∫ª“π°≈“ß À“°‰¡à®”‡ªìπ‰¡à§«√𔧔·π–π”¥—ß°≈à“«‰ª„™â
66     ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




         0C §«“¡¡—Ëπ„®¢Õߧ”·π–π”Õ¬Ÿà„π√–¥—∫μË” À“°‰¡à®”‡ªìπ‰¡à§«√𔧔·π–π”¥—ß°≈à“«‰ª„™â
         0D §«“¡¡—Ëπ„®¢Õߧ”·π–π”Õ¬Ÿà„π√–¥—∫μË” À“°‰¡à®”‡ªìπ‰¡à§«√𔧔·π–π”¥—ß°≈à“«‰ª„™â

·π«∑“ß°“√√—°…“‡ √‘¡¢Õß¡–‡√Á߇μâ“π¡√–¬–·√°¥â«¬¬“ŒÕ√å‚¡π·≈– /
À√◊Õ¬“‡§¡’∫”∫—¥ (Adjuvant systemic therapy)
           ®ÿ¥ª√– ß§å¢Õß°“√√—°…“‡ √‘¡¢Õß¡–‡√Á߇μâ“π¡√–¬–·√° §◊Õ°“√√—°…“‡æ◊ËÕ‡æ‘Ë¡Õ—μ√“°“√À“¬¢“¥ ‡æ‘Ë¡√–¬–‡«≈“
°“√ª≈Õ¥‚√§ ·≈–√–¬–‡«≈“¢Õß°“√¡’™’«‘μÕ¬Ÿà °“√√—°…“‡ √‘¡¢Õß¡–‡√Á߇μâ“π¡√–¬–·√° §◊Õ°“√√—°…“„π°√≥’∑’˺ŸâªÉ«¬‰¥â
                                 ’ â                                      Ë
√—∫°“√ºà“μ—¥‡√’¬∫√âÕ¬·≈â« ·≈–‰¡à¡°Õπ¡–‡√Á߇À≈◊Õμ°§â“ß °“√„™â¬“μà“ß Ê ‡æ◊Õ√—°…“‡ √‘¡®÷ß®”‡ªìπμâÕßæ‘®“√≥“∂÷ß ª√–‚¬™πå
∑’˺ŸâªÉ«¬®–‰¥â√—∫„πÕπ“§μ ‡ª√’¬∫‡∑’¬∫°—∫º≈¢â“߇§’¬ß¢Õ߬“∑’Ë®–‡°‘¥¢÷Èπ ªí®®ÿ∫—π·π«‚πâ¡¢Õß°“√√—°…“‡ √‘¡¢Õß¡–‡√Áß
‡μâ“π¡®–æ¬“¬“¡‡≈◊Õ°°“√√—°…“®”‡æ“–μ“¡≈—°…≥–¢Õ߇π◊ÈÕßÕ°·≈–°“√μÕ∫ πÕßμàÕ°“√√—°…“„πºŸâªÉ«¬·μà≈–§π¡“°¢÷Èπ
®ÿ¥ª√– ß§å‡æ◊ËÕÀ≈’°‡≈’ˬߺ≈¢â“߇§’¬ß∑—Èß„π√–¬– —Èπ·≈–√–¬–¬“« ∑’Ë ”§—≠¡“°„πªí®®ÿ∫—π§◊Õ°“√æ‘®“√≥“§«“¡ “¡“√∂„π
°“√μÕ∫ πÕßμàÕ°“√√—°…“∑“ߌÕ√å‚¡π„πºŸâªÉ«¬·μà≈–§π (√à«¡°—∫¬“‡§¡’∫”∫—¥) ¥—ßμ“√“ß∑’Ë 1
μ“√“ß∑’Ë 1 °“√ª√–‡¡‘𧫓¡ “¡“√∂„π°“√μÕ∫ πÕßμàÕ°“√√—°…“∑“ߌÕ√å‚¡π„πºŸâªÉ«¬·μà≈–√“¬ (assessment
of endocrine responsiveness)
°≈ÿࡺŸâªÉ«¬·∫àßμ“¡°“√               §”®”°—¥§«“¡                            §”Õ∏‘∫“¬‡æ‘Ë¡‡μ‘¡
μÕ∫ πÕß∑“ߌÕ√å‚¡π
Endocrine responsive                 ºŸâªÉ«¬∑’Ë¡’ ER ·≈– PgR positive       ºŸâªÉ«¬°≈ÿà¡π’ȇªìπºŸâªÉ«¬∑’Ë®–‰¥âª√–‚¬™πå Ÿß ÿ¥
                                     ®“°°“√√—°…“∑“ߌÕ√å‚¡π                  ·≈– “¡“√∂∑’Ë ® –æ‘ ® “√≥“°“√√— ° …“∑“ß
                                                                            ŒÕ√å‚¡π‡æ’¬ßÕ¬à“߇¥’¬«‡ªìπ°“√√—°…“‡ √‘¡‰¥â
Endocrine response uncertain         À¡“¬∂÷ߺŸâªÉ«¬∑’Ë¡’≈—°…≥–‡¢â“‰¥â°—∫ ºŸâ ªÉ « ¬°≈ÿà ¡ π’È ‰ ¥â ª √–‚¬™πå ® “°°“√√— ° …“∑“ß
                                     °≈ÿà¡„¥°≈ÿà¡Àπ÷ËßμàÕ‰ªπ’È              ŒÕ√å‚¡π®√‘ß·μàÕ“®‰¥â‰¡à‡μÁ¡∑’Ë ¥—ßπ—Èπ°“√√—°…“
                                     1.ER + ·μà PgR -                       ‡ √‘ ¡ À≈— ß ºà “ μ— ¥ ¢ÕߺŸâ ªÉ « ¬„π°≈ÿà ¡ π’È Õ “®®–
                                     2.low level of hormone                 æ‘®“√≥“∑—Èß°“√√—°…“∑“߇§¡’∫”∫—¥·≈–°“√
                                         receptor (<10% of cell positive) √—°…“∑“ߌÕ√å‚¡π
                                     3.ºŸâªÉ«¬∑’Ë¡’ HER2 positive
                                     4.ºŸâªÉ«¬∑’Ë¡’°“√°√–®“¬‰ª¬—ß
                                         μàÕ¡πÈ”‡À≈◊Õß®”π«π¡“°
                                         >/= 4 μàÕ¡

Endocrine non-responsive                ºŸâªÉ«¬∑’Ë¡’ ER ·≈– PgR negative        ºŸâªÉ«¬°≈ÿà¡π’ȉ¡à‰¥â√—∫ª√–‚¬™π宓°°“√√—°…“
                                                                                ∑“ߌÕ√å‚¡π §«√„™â‡§¡’∫”∫—¥‡æ’¬ßÕ¬à“߇¥’¬«
                                                                                „π°“√√—°…“‡ √‘¡

                               Ë
*À¡“¬‡Àμÿ : ≈—°…≥–¢Õß¡–‡√Áß∑’‡ªìπ Hormone receptor positive §◊ÕμâÕ߬âÕ¡μ‘¥≈—°…≥– nuclear staining ·≈–¡“°°«à“√âÕ¬≈–
10 ¢Õ߇´≈≈å¡–‡√Áß∑—ÈßÀ¡¥¢÷Èπ‰ª
                                                          ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 67




®“°π—Èπ·∫àߺŸâªÉ«¬‡ªìπ “¡°≈ÿà¡μ“¡§«“¡‡ ’ˬ߄π°“√°≈—∫‡ªìπ´È” ¥—ßμ“√“ß∑’Ë 2
μ“√“ß∑’Ë 2 §”®”°—¥§«“¡¢Õߧ«“¡‡ ’ˬ߄π°“√°≈—∫‡ªìπ´È”
Risk category
Low risk        ºŸâªÉ«¬∑’ˉ¡à¡’°“√°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß ·≈–¡’§ÿ≥ ¡∫—쑧√∫∑ÿ°Õ¬à“ßμàÕ‰ªπ’È
                      1. pT </= 2 cm ·≈–
                      2. Histology grade 1 tumor ·≈–
                      3. ‰¡à¡’ peritumoral vascular invasion ·≈–
                      4. HER 2 negative ·≈–
                      5. Õ“¬ÿ >/= 35 ªï
Intermediate risk 1. ºŸâªÉ«¬∑’ˉ¡à¡’°“√°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß ·μà¡’≈—°…≥–Õ¬à“ß„¥Õ¬à“ßÀπ÷ËßμàÕ‰ªπ’È
                        1. pT > 2 cm À√◊Õ
                        2. Histology grade 2 -3 À√◊Õ
                        3. ¡’ peritumoral vascular invasion À√◊Õ
                        4. HER 2 positive À√◊Õ
                        5. Õ“¬ÿ < 35 ªï
                  2. ºŸâªÉ«¬∑’Ë¡’°“√°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß 1 - 3 μàÕ¡ ·≈– HER 2 negative
High risk         ºŸâªÉ«¬∑’Ë¡’°“√°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß 1 - 3 μàÕ¡ ·μà¡’ HER 2 positive À√◊Õ
                  ºŸâªÉ«¬∑’Ë¡’°“√°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß¡“°°«à“À√◊Õ‡∑à“°—∫ 4 μàÕ¡
À¡“¬‡Àμÿ : ºŸâªÉ«¬∑’ˇªì𧫓¡‡ ’ˬߪ“π°≈“ß (intermediate risk) ª√–°Õ∫‰ª¥â«¬∑—ÈߺŸâªÉ«¬∑’Ë¡’·≈–‰¡à¡’°“√°√–®“¬‰ª¬—ß
μàÕ¡πÈ”‡À≈◊Õß  ∂“π¿“æ°“√· ¥ßÕÕ°¢Õ߬’π HER2 μâÕß∑”„πÀâÕߪؑ∫—μ‘°“√∑’˺à“π°“√√—∫√Õߧÿ≥¿“æ ‚¥¬„™â𑬓¡
¡“μ√∞“π¢Õß∑—Èß IHC ·≈– FISH test
        ®“°π—Èπ„Àâπ”∑—Èߧ«“¡ “¡“√∂„π°“√μÕ∫ πÕßμàÕ°“√√—°…“∑“ߌÕ√å‚¡π·≈–§«“¡‡ ’ˬߢÕߺŸâªÉ«¬„π°“√°≈—∫‡ªìπ
´È”¡“æ‘®“√≥“«‘∏’°“√√—°…“‡ √‘¡À≈—ߺà“μ—¥ √“¬≈–‡Õ’¬¥¥—ßμ“√“ß∑’Ë 3
         μ“√“ß∑’Ë 3 ∑“߇≈◊Õ°„π°“√æ‘®“√≥“°“√√—°…“‡ √‘¡À≈—ߺà“μ—¥
Risk category       Endocrine responsive    Endocrine response uncertain            Endocrine non-responsive
Low risk            ET                      ET                                      Not applicable
                        a
                    Nil                     Nila
Intermediate risk ET alone or               CT then ETb                             CTd
                    CT then ETb             ET alonec
High risk           CT then ETb             CT then ETb                             CT
            a
              ‡ªìπ∑“߇≈◊Õ°Àπ÷Ëß„π°“√√—°…“„πºŸâªÉ«¬∑’Ë¡’¢âÕÀâ“¡„π°“√√—°…“∑“ߌÕ√å‚¡πÕ¬à“ß„¥Õ¬à“ßÀπ÷Ëß ‡™àπ ¡’ª√–«—μ‘°“√
Õÿ¥μ—π¢ÕßÀ≈Õ¥‡≈◊Õ¥ ¡Õß À≈Õ¥‡≈◊Õ¥À—«„®‡ªìπμâπ
            b
              ¡’¢âÕ¡Ÿ≈·πà™—¥«à“°“√„Àâ°“√√—°…“∑“ߌÕ√å‚¡π¥â«¬ tamoxifen §«√„ÀâÀ≈—ß®“°∑’Ë√—°…“∑“߇§¡’∫”∫—¥‡ √Á®·≈â«
            c
              °“√„À⇩擖°“√√—°…“∑“ߌÕ√å‚¡πÕ“®æ‘®“√≥“„πºŸâªÉ«¬∑’Ë ¿“æ√à“ß°“¬‰¡à‡À¡“– ¡À√◊Õ‡ ’ˬߠŸßμàÕ°“√‡°‘¥º≈
¢â“߇§’¬ß‡π◊ËÕß®“°¬“‡§¡’∫”∫—¥ À√◊Õ„πºŸâªÉ«¬∑’Ë¡’≈—°…≥–· ¥ß™—¥‡®π«à“‰¥âª√–‚¬™πå‡μÁ¡∑’Ë®“°°“√√—°…“¥â«¬ŒÕ√å‚¡π ‡™àπ
ºŸâªÉ«¬∑’Ë¡’ strong ER positive À√◊Õ„πºŸâªÉ«¬∑’Ë ER negative ·μà PgR positive
            d
              §«√æ‘®“√≥“‡¡◊ËÕ¢π“¥¢Õß°âÕπ¡–‡√Áß > 1 ´¡.
68    ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




Abbreviations : CT = chemotherapy, ET = endocrine therapy, Nil = no further treatment
À¡“¬‡Àμÿ : °“√√—°…“„πÕ—π¥—∫·√°‡ªìπ°“√√—°…“∑’Ë·π–π”„Àâæ‘®“√≥“°àÕπ  à«π°“√√—°…“„πÕ—π¥—∫∑’Ë Õ߇ªìπ∑“߇≈◊Õ°„π
°√≥’∑’ˉ¡à “¡“√∂„Àâ°“√√—°…“∑’Ë·π–𔇪ìπÕ—π¥—∫·√°‰¥â
        √“¬≈–‡Õ’¬¥„π°“√„Àâ°“√√—°…“‡ √‘¡À≈—ߺà“μ—¥∑—È߇§¡’·≈–ŒÕ√å‚¡πμ“¡§«“¡‡ ’Ë¬ß §«“¡ “¡“√∂„π°“√μÕ∫ πÕß
∑“ߌÕ√å‚¡π ·≈– ∂“π–¿“æ¢Õߪ√–®”‡¥◊Õπ ¥—ßμ“√“ß∑’Ë 4, 5 ·≈– 6
         μ“√“ß∑’Ë 4 √“¬≈–‡Õ’¬¥°“√√—°…“‡ √‘¡„πºŸâªÉ«¬ endocrine responsive
Risk group                                         Endocrine responsive
                                Pre-menopausal                          Postmenopausal
                                          a
Low risk                        Tam or Nil                              Tam or Nila
                                                                        AIb
Intermediate risk               CT then Tamc or                         Tam or AI or
                                Tam +/- OFS or                          CT then Tamc or CT then AIc
                                OFSd
High risk                       CT then Tam                             CT then Tam or CT then AI
        a,b
          ‡ªìπ∑“߇≈◊Õ°Àπ÷Ëß„π°“√√—°…“„πºŸâªÉ«¬∑’Ë¡’¢âÕÀâ“¡„π°“√√—°…“∑“ߌÕ√å‚¡π¥â«¬ tamoxifen
        c
         °“√„™â‡§¡’∫”∫—¥‡ √‘¡„πºŸâªÉ«¬°≈ÿà¡π’ÈÕ“®æ‘®“√≥“μ“¡§«“¡ “¡“√∂„π°“√μÕ∫ πÕßμàÕ°“√√—°…“∑“ߌÕ√å‚¡π
        „πºŸâªÉ«¬∑’˧«“¡‡ ’ˬ߉¡à¡“°·≈–μÕ∫ πÕߥ’¡“°μàÕ°“√√—°…“∑“ߌÕ√å‚¡π ‡™àπ ¡’ high level of expression of
        hormonal receptor Õ“®æ‘®“√≥“‡©æ“–°“√√—°…“∑“ߌÕ√å‚¡π‡æ’¬ßÕ¬à“߇¥’¬«‰¥â
        d
         °“√„™â OFS ¥â«¬ GnRH analog ¡’ª√– ‘∑∏‘¿“æ‡∑’¬∫‡∑à“°—∫¬“‡§¡’∫”∫—¥·≈–Õ“®æ‘®“√≥“„πºŸâªÉ«¬∑’ˉ¡à “¡“√∂
        „Àâ°“√√—°…“∑“ߌÕ√å‚¡π¥â«¬ tamoxifen ‰¥âÀ√◊ÕºŸâªÉ«¬‰¡àμâÕß°“√ „πª√–‡∑»‰∑¬«‘∏’∑’Ë·π–π”„π°“√∑” OFS §◊Õ
        °“√∑”°“√ºà“μ—¥√—߉¢àÕÕ°∑—Èß Õߢâ“ßÀ√◊Õ„™â√—ß ’√—°…“
        Abbreviation : Tam = tamoxifen, OFS = ovarian function suppression, CT = chemotherapy, AI = aromatase
        inhibitor
À¡“¬‡Àμÿ : °“√√—°…“„πÕ—π¥—∫·√°‡ªìπ°“√√—°…“∑’Ë·π–π”„Àâæ‘®“√≥“°àÕπ  à«π°“√√—°…“„πÕ—π¥—∫∑’Ë Õ߇ªìπ∑“߇≈◊Õ°„π
°√≥’∑’ˉ¡à “¡“√∂„Àâ°“√√—°…“∑’Ë·π–𔇪ìπÕ—π¥—∫·√°‰¥â
         μ“√“ß∑’Ë 5 √“¬≈–‡Õ’¬¥°“√√—°…“‡ √‘¡„πºŸâªÉ«¬ endocrine response uncertain
Risk group                              Endocrine response uncertain
                            Pre-menopausal                          Postmenopausal
                                       a
Low risk                    Tam or Nil                              Tam or AI or Nilb
Intermediate risk           CTc then Tamd                           CT then AI or CT then Tam
                            Tam +/- OFS                             TAM or AI alone
                               c          d
High risk                   CT then Tam                             CT then AI or CT then Tam
                                                 (¥Ÿμ“√“ß∑’Ë 4)
        a,b
          ‡ªìπ∑“߇≈◊Õ°Àπ÷Ëß„π°“√√—°…“„πºŸâªÉ«¬∑’Ë¡’¢âÕÀâ“¡„π°“√√—°…“∑“ߌÕ√å‚¡π¥â«¬ tamoxifen À√◊Õ¬“°≈ÿà¡ AI
        c
         °“√„™â‡§¡’∫”∫—¥‡ √‘¡„πºŸâªÉ«¬°≈ÿà¡π’ÈÕ“®æ‘®“√≥“μ“¡§«“¡ “¡“√∂„π°“√μÕ∫ πÕßμàÕ°“√√—°…“∑“ߌÕ√å‚¡π
        „π°≈ÿࡺŸâªÉ«¬∑’ˉ¡à·πà„®„π°“√μÕ∫ πÕß∑“ߌÕ√å‚¡π °“√„™â‡§¡’∫”∫—¥∂◊Õ«à“‡ªìπ°“√√—°…“∑’ˇÀ¡“– ¡
        d
         tamoxifen §«√„ÀâÀ≈—ß®“°√—°…“‡ √‘¡¥â«¬‡§¡’∫”∫—¥®∫ ‘Èπ·≈â«
                                                         ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 69




         μ“√“ß∑’Ë 6 √“¬≈–‡Õ’¬¥°“√√—°…“‡ √‘¡„πºŸâªÉ«¬ endocrine non-responsive
Risk group                                                 Endocrine non-responsive
                                                  both pre-menopausal and post-menopausal
Low risk                                                        Not applicable
Intermediate risk                                                    CTa
High risk                                                            CT
a
  §«√æ‘®“√≥“‡¡◊ËÕ¢π“¥¢Õß°âÕπ¡–‡√Áß > 1 ´¡.

        1. °“√√—°…“‡ √‘¡¥â«¬«‘∏’°“√∑“ߌÕ√å‚¡π (adjuvant hormonal therapy)
        °“√‡≈◊Õ°„™âŒÕ√å‚¡π„π°“√√—°…“‡ √‘¡ ”À√—∫¡–‡√Á߇μâ“π¡π—Èπ ºŸâªÉ«¬μâÕß¡’°“√· ¥ßÕÕ°¢Õßμ—«√—∫∑“ߌÕ√å‚¡π∫π
º‘«‡´≈≈剥ⷰà estrogen receptor (ER) ·≈– / À√◊Õ progesterone receptor (PgR) ‡ªìπº≈∫«°  ”À√—∫ºŸâªÉ«¬∑’ˉ¡à∑√“∫º≈
                                      Ë â É                            à                        ’Ë
ER ·≈– PgR Õ“®æ‘®“√≥“„ÀâŒÕ√å‚¡π‡¡◊ÕºŸª«¬¡’Õ“¬ÿ¡“°°«à“ 50 ªï À√◊ÕÕ¬Ÿ„π«—¬À¡¥ª√–®”‡¥◊Õπ °√≥’∑®–„™â Aromatase
inhibitor (AI) §«√μâÕß¡’ hormone receptors ‡ªìπº≈∫«°‡∑à“π—Èπ
        °“√√—°…“‡ √‘¡¥â«¬ŒÕ√å‚¡π tamoxifen ‡ªìπ¬“∑’Ë„™â¡“¬“«π“π·≈–¡’¢âÕ¡Ÿ≈¡“°  à«π Ovarian function suppression
‚¥¬°“√©“¬√—ß ’√—°…“À√◊Õ°“√ºà“μ—¥√—߉¢àÀ√◊Õ„™â¬“„π°≈ÿà¡ GnRH À√◊Õ LHRH agonist („πª√–‡∑»‰∑¬·π–π”„ÀℙⰓ√
ºà“μ—¥√—߉¢àÀ√◊Õ°“√©“¬√—ß ’∑’Ë√—߉¢à∑—Èß Õߢâ“ß) ‡ªìπ«‘∏’°“√√—°…“¥â«¬ŒÕ√å‚¡π∑’Ëπ”¡“„™â„πºŸâªÉ«¬«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ
ªí®®ÿ∫—π¡’¢âÕ¡Ÿ≈¡“°¢÷Èπ ‡°’ˬ«°—∫ Aromatase inhibitors (AI) „π°“√√—°…“‡ √‘¡¥â«¬ŒÕ√å‚¡π„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬–·√°
„π«—¬À¡¥ª√–®”‡¥◊Õπ
            1.1 Tamoxifen
                  1.1.1 ºŸâªÉ«¬∑’Ë¡’ hormone receptor ‡ªìπº≈∫«°À√◊Õ‰¡à∑√“∫º≈ hormone receptor æ∫«à“°“√„Àâ
tamoxifen ‡ªìπ°“√√—°…“‡ √‘¡π“π 5 ªï  “¡“√∂≈¥ Õ—μ√“°“√°≈—∫‡ªìπ´È”¢Õß‚√§·≈–Õ—μ√“쓬‰¥â 41% ·≈– 34%
μ“¡≈”¥—∫(2) ®“° overview analysis ≈à“ ÿ¥æ∫«à“ tamoxifen  “¡“√∂≈¥Õ—μ√“‡ ’ˬߢÕß°“√°≈—∫¡“¢Õß‚√§∑’Ë 15 ªï ‚¥¬¡’
absolute reduction 11.8% ·≈–≈¥Õ—μ√“‡ ’ˬߢÕß°“√쓬¢Õß‚√§∑’Ë 15 ªï ‚¥¬¡’ absolute reduction 9.2%(44) ª√–‚¬™πå
∑’ˉ¥â√—∫®“°°“√„™â tamoxifen ‰¡à¢÷ÈπÕ¬Ÿà°—∫Õ“¬ÿÀ√◊Õ ∂“π¿“æ°“√°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß ®÷ß·π–π”„Àâ „™â‡ªìπ°“√
√—°…“‡ √‘¡ „πºŸâªÉ«¬∑’Ë¡’ hormone receptor ‡ªìπº≈∫«° ‚¥¬ “¡“√∂„™â ‰¥â∑—ÈߺŸâªÉ«¬°àÕπ·≈–À≈—ßÀ¡¥ª√–®”‡¥◊Õπ
                  √–¥—∫§”·π–π”:              √–¥—∫ 1
                  §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
                1.1.2 ºŸâªÉ«¬«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ·≈– hormone receptor ‡ªìπº≈≈∫ æ∫«à“°“√„Àâ tamoxifen
‰¡à¡’ª√–‚¬™πå ®“°°“√ »÷°…“·∫∫ randomized controlled trials „πºŸâªÉ«¬ high risk ·≈– node negative ´÷Ëß√—°…“¥â«¬
chemotherapy + tamoxifen æ∫«à“°≈ÿà¡∑’ˉ¥â tamoxifen ¡’ 5-year disease-free survival μË”°«à“°≈ÿà¡∑’ˉ¡à‰¥â tamoxifen
(83% vs 86%)(3) ®÷߉¡à·π–π”„Àâ„™â„πºŸâªÉ«¬°≈ÿà¡π’È
                √–¥—∫§”·π–π”:              √–¥—∫ 1
                §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
                 1.1.3 ºŸª«¬«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ·≈– hormone receptor ‡ªìπº≈∫«° æ∫«à“°“√„Àâ tamoxifen
                             â É
π“π 5 ªï„πºŸâªÉ«¬∑—Èß node negative À√◊Õ node positive  “¡“√∂‡æ‘Ë¡Õ—μ√“°“√Õ¬Ÿà√Õ¥∑’Ë 10 ªï ‡∑à“°—∫ 5.6% ·≈– 10.9%
μ“¡≈”¥—∫(2) ®÷ß·π–π”„Àâ„™â tamoxifen ‡ªìπ°“√√—°…“‡ √‘¡„πºŸâªÉ«¬°≈ÿà¡π’È
                 √–¥—∫§”·π–π”:              √–¥—∫ 1
                 §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
70    ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




                 1.1.4 ¢π“¥¬“ tamoxifen ·≈–√–¬–‡«≈“∑’Ë„™â
¢π“¥¢Õ߬“ tamoxifen ∑’·π–π”„Àâ„™â§Õ¢π“¥ 20 mg μàÕ«—π(4) ®“°º≈°“√»÷°…“ ¢Õß Early Breast Cancer Trialistsû
                         Ë              ◊
Collaborative Group (EBCTCG) ‚¥¬«‘∏’ meta-analysis ·≈– National Surgical Adjuvant Breast and Bowel Project
(NSABP) B-14 æ∫«à“√–¬–‡«≈“∑’ˇÀ¡“– ¡„π°“√√—°…“¥â«¬ tamoxifen §◊Õ 5 ªï(5,6)
                 √–¥—∫§”·π–π”:               √–¥—∫ 1
                 §ÿ≥¿“æÀ≈—°∞“π:              √–¥—∫ A
                 1.1.5 °“√„ÀâŒÕ√å‚¡π√à«¡°—∫‡§¡’∫”∫—¥
                 ºŸâªÉ«¬¡–‡√Á߇μâ“π¡∑’Ë¡’ hormone receptors ‡ªìπ∫«° À≈—ß®“°∑’ˉ¥â√—∫ adjuvant chemotherapy ·≈â«
§«√„Àâ tamoxifen √—°…“‡ √‘¡¥â«¬(7,8)
                 √–¥—∫§”·π–π”:               √–¥—∫ 1
                 §ÿ≥¿“æÀ≈—°∞“π:              √–¥—∫ A
         1.2. Ovarian ablation
                Ovarian ablation ‡ªìπ°“√√—°…“¥â«¬ŒÕ√å‚¡πÕ’°«‘∏’Àπ’Ëß‚¥¬°“√À¬ÿ¥°“√∑”ß“π¢Õß√—߉¢à ‡æ◊ËÕ≈¥√–¥—∫
estrogen „π√à“ß°“¬¥â«¬°“√ºà“μ—¥√—߉¢àÕÕ°À√◊Õ©“¬√—ß ’∑’Ë√—߉¢à À√◊Õ‚¥¬°“√√—°…“¥â«¬¬“ gonadrotropin-releasing
hormone (GnRH) À√◊Õ luteinizing hormone releasing hormone (LHRH) «‘∏’À≈—ßπ’È ‡√’¬°«à“ medical ovarian ablation
                     Ovarian ablation ‰¥â∂Ÿ°π”¡“„™â‡ªìπ°“√√—°…“‡ √‘¡„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ À√◊Õ
ºŸâªÉ«¬∑’Ë¡’ Õ“¬ÿπâÕ¬°«à“ 50 ªï ‡π◊ËÕß®“°°“√»÷°…“ randomized controlled trials „πºŸâªÉ«¬À≠‘ßÕ“¬ÿ > 50 ªï æ∫«à“°“√∑”
ovarian ablation ‰¡à¡’º≈∑”„Àâ recurrence free survival ·≈– overall survival ‡æ‘Ë¡¢÷Èπ(9) ¢≥–∑’Ë°“√∑” ovarian ablation
„πºŸâªÉ«¬ «—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ  “¡“√∂≈¥Õ—μ√“°“√쓬‰¥â 6.3% À≈—ß®“°μ‘¥μ“¡ºŸâªÉ«¬π“π 15 ªï(9) ºŸâªÉ«¬«—¬°àÕπ
À¡¥ª√–®” ‡¥◊Õπ∑’ˉ¥â√—∫¬“‡§¡’∫”∫—¥√à«¡¥â«¬Õ“®¡’º≈∑“ßÕâÕ¡‰ª¬—∫¬—Èß°“√∑”ß“π¢Õß√—߉¢à ·π«∑“ß°“√„™â ovarian
ablation „π ºŸâªÉ«¬¡–‡√Á߇μâ“π¡¡’¥—ßπ’È
                   1.2.1. ºŸâªÉ«¬«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ∑’Ë hormone receptors ‡ªìπº≈∫«°·≈–‰¡à‰¥â√—∫¬“‡§¡’∫”∫—¥
√à«¡¥â«¬ °“√∑” ovarian ablation  “¡“√∂≈¥Õ—μ√“°“√°≈—∫¡“¢Õß‚√§ 12.2% ∑’Ë 10 ªï ·≈– 13.3% ∑’Ë 15 ªï ·≈–Õ—μ√“
쓬≈¥≈ß 8.3% ∑’Ë 10 ªï ·≈– 10.4 % ∑’Ë 15 ªï(10) ®“° overview analysis ªï§.». 2000 æ∫«à“¡’ absolute reduction ¢Õß
Õ—μ√“‡ ’ˬߢÕß°“√°≈—∫¡“¢Õß‚√§·≈–°“√쓬∑’Ë 15 ªï ‡ªìπ 4.3% ·≈– 3.2% μ“¡≈”¥—∫(44) πÕ°®“°π—Èπ¬—ß¡’°“√»÷°…“
‡ª√’¬∫‡∑’¬∫º≈°“√√—°…“‡ √‘¡√–À«à“ß°“√„À⬓‡§¡’∫”∫—¥¥â«¬ cyclophosphamide / methotrexate / 5-FU (CMF)
°—∫ ovarian ablation „πºŸâªÉ«¬«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ∑’Ë¡’ hormone receptors ‡ªìπº≈∫«° æ∫«à“ºŸâªÉ«¬∑—Èß Õß°≈ÿà¡¡’
Õ— μ √“°“√Õ¬Ÿà √ Õ¥‰¡à · μ°μà “ ß°— π (11) °“√»÷ ° …“„πºŸâ ªÉ « ¬«— ¬ °à Õ πÀ¡¥ª√–®”‡¥◊ Õ π ·≈–°”≈— ß ®–À¡¥ª√–®”‡¥◊ Õ π
(perimenopausal) ‚¥¬°“√„Àâ°“√√—°…“‡ √‘¡¥â«¬¬“‡§¡’∫”∫—¥ (CMF regimen) ‡ª√’¬∫‡∑’¬∫°—∫ ovarian ablation √à«¡°—∫
°“√„À⬓ tamoxifen °Áæ∫«à“ Õ—μ√“°“√Õ¬Ÿà√Õ¥∑—Èß disease-free ·≈– overall survival ¢ÕߺŸâªÉ«¬∑—Èß Õß°≈ÿࡉ¡à·μ°μà“ß°—π
‡™àπ°—π(12)
¥—ßπ—Èπ ®÷ß·π–π”„Àâ„™â ovarian ablation Õ¬à“߇¥’¬« À√◊Õ√à«¡°—∫¬“ tamoxifen „πºŸâªÉ«¬«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ∑’Ë¡’
hormone receptors ‡ªìπº≈∫«° ·≈–ºŸâªÉ«¬ªØ‘‡ ∏°“√√—°…“‡ √‘¡¥â«¬¬“‡§¡’∫”∫—¥
                 √–¥—∫§”·π–π”:              √–¥—∫ 1
                 §ÿ≥¿“æÀ≈—°∞“π:             √–¥—∫ A
                                                              ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 71




                   1.2.2. ºŸª«¬«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ·≈–‰¥â√∫¬“‡§¡’∫”∫—¥√à«¡¥â«¬®“°°“√»÷°…“‡ª√’¬∫‡∑’¬∫
                             â É                                 —
ºŸâªÉ«¬ Õß°≈ÿà¡∑’ˉ¥â√—∫‡§¡’∫”∫—¥ CMFP + surgical oophorectomy æ∫«à“°≈ÿà¡∑’ˉ¥â oophorectomy √à«¡¥â«¬ ‰¡à‰¥â¡’
Õ—μ√“°“√Õ¬Ÿà√Õ¥‡æ‘Ë¡¢÷Èπ(13) ®÷߉¡à·π–π”„Àâ„™â ovarian ablation „πºŸâªÉ«¬°≈ÿà¡π’È
                   √–¥—∫§”·π–π”:           √–¥—∫ 1
                   §ÿ≥¿“æÀ≈—°∞“π:          √–¥—∫ A
         1.3 Aromatase inhibitors
                         — â          à                                       â É                        Ë ’
                 „πªí®®ÿ∫π¡’¢Õ¡Ÿ≈·∫∫ ÿ¡„π°“√„™â AI ‡ªìπ°“√√—°…“‡ √‘¡„πºŸª«¬¡–‡√Á߇μâ“π¡«—¬À¡¥ª√–®”‡¥◊Õπ∑’¡º≈
                                                   (14,15,36)       (37,38)            (39)  (40)      (41,42)
hormone receptor ‡ªìπ∫«°Õ¬Ÿà 5 °“√»÷°…“ §◊Õ ATAC              , IES        , ABCSG/ARNO , ITA , MA17
               (43)
·≈– BIG-1-98 ‚¥¬ “¡“√∂·∫àß°“√»÷°…“¥—ß°≈à“«ÕÕ°μ“¡√Ÿª·∫∫¢Õß°“√„™â AI ‰¥â “¡√Ÿª·∫∫¥—ßμàÕ‰ªπ’È
                    1. Upfront AI §◊Õ°“√„™â AI ‡ªìπ°“√√—°…“‡ √‘¡μ—Èß·μàμâπ∑¥·∑π tamoxifen ¡’ Õß°“√»÷°…“ ”§—≠§◊Õ
ATAC trial ·≈– BIG-1-98 trial ATAC trial ‡ªìπ°“√»÷°…“·√°·≈–¡’°“√μ‘¥μ“¡º≈‡ªìπ√–¬–‡«≈“¬“«π“π∑’Ë ÿ¥ ‡ªìπ°“√
»÷°…“‡ª√’¬∫‡∑’¬∫√–À«à“ß°“√„™â anastrozole ‡ªìπ‡«≈“ 5 ªï °—∫ Tamoxifen 5 ªï ‡ªìπ°“√√—°…“‡ √‘¡„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡
                      Ë ’                                                       Ë
«—¬À¡¥ª√–®”‡¥◊Õπ∑’¡º≈ hormone receptor ‡ªìπ∫«° ®“°°“√μ‘¥μ“¡‚¥¬‡©≈’¬π“π 68 ‡¥◊Õπ æ∫«à“ °≈ÿ¡∑’‰¥â anastrozoleà Ë
¡’ disease- free survival (DFS) ·≈– time to recurrence ¥’°«à“°≈ÿà¡∑’ˉ¥â tamoxifen μ≈Õ¥®πÕÿ∫—μ‘°“√≥å¢Õß°“√‡°‘¥
¡–‡√Á߇μâ“π¡¢â“ßμ√ߢⓡ≈¥≈ßÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ ·μàÕ—μ√“°“√√Õ¥™’«‘μ‰¡à·μ°μà“ß°—π  à«π BIG 1-98 ‡ªìπ
°“√»÷°…“·∫∫ ÿࡇª√’¬∫‡∑’¬∫√–À«à“ß°“√„™â tamoxifen ‡ªìπ‡«≈“ 5 ªï°—∫°“√„™â letrozole 5 ªï À√◊Õ tamoxifen 2 ªï ·≈â«
μ“¡¥â«¬ letrozole 3 ªï À√◊Õ letrozole 2 ªï ·≈â«μ“¡¥â«¬ tamoxifen 3 ªï ¡’°“√√“¬ß“πº≈°“√√—°…“‚¥¬‡©≈’ˬ 25.8
‡¥◊Õπ‡ª√’¬∫‡∑’¬∫√–À«à“ß°≈ÿà¡∑’ˉ¥â letrozole μ—Èß·μà‡√‘Ë¡μâπ°—∫°≈ÿà¡∑’ˉ¥â tamoxifen μ—Èß·μà‡√‘Ë¡μâπ (primary core analysis)
æ∫«à“°≈ÿà¡∑’ˉ¥â letrozole μ—Èß·μàμâπ ¡’ DFS ¥’°«à“°≈ÿà¡∑’ˉ¥â tamoxifen Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘·μà„π‡ßà¢Õß°“√√Õ¥™’«‘μ
‰¡à·μ°μà“ß°—π (43) (36)
                  2. Switching AI §◊Õ„™â AI À≈—ß®“°∑’˺ŸâªÉ«¬‰¥â√—∫°“√√—°…“‡ √‘¡¥â«¬ tamoxfen ·≈⫇ªìπ‡«≈“ 2-3 ªï
      à È ’          Ë                                         Ë ’ Ÿâ É                Ëÿ
„π°≈ÿ¡π’¡°“√»÷°…“∑’ ”§—≠ 4 °“√»÷°…“ IES trial ‡ªìπ°“√»÷°…“∑’¡ºª«¬„π°“√»÷°…“¡“°∑’ ¥·≈–μ‘¥μ“¡º≈¬“«π“π∑’ ¥        Ëÿ
„™â exemestane ‡ªìπ switching AI  à«π ABCSG/ARNO ·≈– ITA ‡ªìπ°“√»÷°…“∑’Ë¡’ºŸâªÉ«¬„π°“√»÷°…“πâÕ¬°«à“·≈–„™â
anastrozole ‡ªìπ switching AI ‚¥¬¡’°“√μ‘¥μ“¡‚¥¬‡©≈’ˬ 37.4 ‡¥◊Õπ„π IES trial 28 ‡¥◊Õπ „π ABCSG/ARNO trial ·≈–
36 ‡¥◊Õπ„π ITA trial æ∫«à“ °“√„™â sequential À√◊Õ switching AI ¡’ DFS ¥’°«à“ Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘„π∑ÿ°°“√»÷°…“
                   ‘ È                      Ë                           à â É                              Ë
„π·ßà¢Õß°“√√Õ¥™’«μπ—π„π°“√»÷°…“ IES trial ∑’√“¬ß“π≈à“ ÿ¥æ∫«à“„π°≈ÿ¡ºŸª«¬∑’Ë ER positive ·≈– unknown °“√‡ª≈’¬π¡“„™â
exemestane ¡’Õ—μ√“√Õ¥™’«‘μ∑’Ë·μ°μà“ß°—πÕ¬à“ß¡’π—¬ ”§—≠  à«π°“√»÷°…“·∫∫ switching ∑’Ë„™â anastrozole À≈—ß®“°„™â
tamoxifen 2-3 ªï ¡’°“√»÷°…“·∫∫ meta-analysis √«¡°“√»÷°…“ ABCSG/ARNO ·≈– ITA trial ∑”„Àâ®”π«πºŸâªÉ«¬
‡æ‘Ë¡¢÷Èπ‡ªìπ 4000 §π æ∫«à“°“√„™â switching AI ≈¥Õ—μ√“쓬‰¥âÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘쑇™àπ‡¥’¬«°—π (44)
                  3. Extended adjuvant therapy §◊Õ„™â tamoxifen „π√–¬–‡«≈“¡“μ√∞“π§◊Õ 5 ªï®π§√∫°àÕπ À≈—ß®“°
π—Èπ„Àâ°“√√—°…“μàե⫬ AI Õ’°‡ªìπ‡«≈“ 5 ªï „π°≈ÿà¡π’È¡’°“√»÷°…“ ”§—≠§◊Õ MA-17 trial ´÷Ë߇ªìπ°“√»÷°…“·∫∫ ÿࡇª√’¬∫
‡∑’¬∫√–À«à“ß°“√„™â tamoxifen ‡ªìπ‡«≈“ 5 ªï°—∫°“√„™â tamoxifen 5 ªï ·≈â«μ“¡¥â«¬ letrozole 5 ªï ®“°°“√μ‘¥μ“¡
º≈°“√√—°…“‚¥¬‡©≈’ˬ 2.5 ªï æ∫«à“°≈ÿà¡∑’ˉ¥â tamoxifen 5 ªï·≈â«μ“¡¥â«¬ letrozole 5 ªï ¡’ DFS ¥’°«à“°≈ÿà¡∑’ˉ¥â tamoxifen
5 ªïÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘·μà„π‡ßà¢Õß°“√√Õ¥™’«‘μ‰¡à·μ°μà“ß°—π ·μஓ° subgroup analysis æ∫«à“°≈ÿà¡∑’Ë‚√§
°√–®“¬‰ªμàÕ¡πÈ”‡À≈◊Õß¡’°“√√Õ¥™’«‘μ‡æ‘Ë¡¡“°¢÷ÈπÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ (41,42)
                    ¡“§¡¡–‡√Áß·Ààß À√—∞Õ‡¡√‘°“ (ASCO) ‰¥âÕÕ°¢âÕ·π–𔇰’ˬ«°—∫°“√„™â AI ‡ªìπ°“√√—°…“‡ √‘¡„π
ºŸâªÉ«¬¡–‡√Á߇μâ“π¡«—¬À¡¥ª√–®”‡¥◊Õπ∑’Ë¡’º≈ hormone receptor ‡ªìπ∫«°´÷Ë߉¥â√“¬ß“π„πª≈“¬ªï 2004 ¢âÕ·π–π”§◊Õ
°“√√—°…“‡ √‘¡∑’Ë¥’∑’Ë ÿ¥„πªí®®ÿ∫—π„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡«—¬À¡¥ª√–®”‡¥◊Õπ∑’Ë¡’º≈ hormone receptor ‡ªìπ∫«°§«√¡’°“√„™â
AI √à«¡¥â«¬‡π◊ËÕß®“°™à«¬≈¥°“√°≈—∫¡“¢Õß‚√§·≈–‡√‘Ë¡¡’¢âÕ¡Ÿ≈ π—∫ πÿπ‡√◊ËÕß°“√‡æ‘Ë¡Õ—μ√“√Õ¥™’«‘μ‡æ‘Ë¡¢÷Èπ  “¡“√∂„™â AI
72    ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




‡ªìπμ—«‡√‘Ë¡μâπ·∑π∑’Ë tamoxifen ‰¥â„π°√≥’∑’Ë¡’¢âÕÀâ“¡„π°“√„™â tamoxifen À√◊Õ∑πμàÕ tamoxifen ‰¡à‰¥â À√◊ÕÕ“®„™â AI
„π≈—°…≥– switching À√◊Õ extended adjuvant therapy(16)
                   §”®”°—¥§«“¡¢ÕߺŸâªÉ«¬¡–‡√Á߇μâ“π¡«—¬À¡¥ª√–®”‡¥◊Õπ§◊Õ 1. Õ“¬ÿ > 60 ªï 2. Õ“¬ÿ < 60 ªï·≈–√–¥Ÿ
À¡¥‰ª‡Õßμ“¡∏√√¡™“μ‘ 1 ªï¢÷Èπ‰ª‚¥¬ºŸâªÉ«¬μâÕ߉¡à‰¥â√—∫‡§¡’∫”∫—¥, tamoxifen À√◊Õ GnRH analogue ·≈–√–¥—∫¢Õß FSH,
estradiol Õ¬Ÿà„π‡°≥±å«—¬À¡¥ª√–®”‡¥◊Õπ 3. ¡’ª√–«—μ‘ºà“μ—¥√—߉¢à∑—Èß Õߢâ“ß
                 1.3.1 ·π–π”„Àâ„™â AI ‡©æ“–„π«—¬À¡¥ª√–®”‡¥◊Õπ ∑’Ë¡’º≈ hormone receptor ‡ªìπ∫«°‡∑à“π—Èπ
                                     È     Ë                                Ë ’ â
‚¥¬Õ“®æ‘®“√≥“„™â 1. ·∑π tamoxifen μ—ß·μà‡√‘¡·√°‡ªìπ‡«≈“ 5 ªï ‚¥¬‡©æ“–„π√“¬∑’¡¢ÕÀâ“¡À√◊Õ∑πμàÕ tamoxifen
‰¡à‰¥â À√◊Õ 2.Õ“®„™â tamoxifen °àÕπ 2-3 ªï ·≈â«μ“¡¥â«¬ AI 2-3 ªï®π§√∫ 5 ªï À√◊Õ 3. „™â tamoxifen ‡ªìπ‡«≈“
5 ªï·≈â«μ“¡¥â«¬ AI μàÕÕ’° 5 ªï ‚¥¬‡©æ“–„π°≈ÿࡇ ’ˬߠŸß∑’Ë‚√§®–°≈—∫¡“‰¥â·°à°≈ÿà¡∑’Ë¡’°“√·æ√à°√–®“¬‰ª
μàÕ¡πÈ”‡À≈◊Õß
                 √–¥—∫§”·π–π”:           √–¥—∫ 1
                 §ÿ≥¿“æÀ≈—°∞“π:          √–¥—∫ A

         2. Adjuvant chemotherapy
            °“√„™â¬“‡§¡’∫”∫—¥„π°“√√—°…“‡ √‘¡À≈—ß°“√ºà“μ—¥ (adjuvant chemotherapy) „πºŸâªÉ«¬¡–‡√Á߇μâ“π¡ √–¬–·√°
                          Ë               ‘                                          ÷È
æ∫«à“¡’ª√–‚¬™πå„π°“√‡æ‘¡Õ—μ√“°“√√Õ¥™’«μ ·≈–≈¥Õ—μ√“°“√쓬®“°¡–‡√Á߇μâ“π¡ ‚¥¬‰¡à¢π°—∫ √–¬–¢Õß‚√§«à“ ®–‡ªìπ√–¬–
node negative À√◊Õ node positive «—¬¢ÕߺŸâªÉ«¬«à“®–‡ªìπ«—¬°àÕπÀ√◊ÕÀ≈—ßÀ¡¥ª√–®”‡¥◊Õπ ·≈– ∂“π¿“æ ¢Õß hormone
receptors „π°âÕπ¡–‡√Áß«à“‡ªìπº≈∫«°À√◊Õº≈≈∫ ¢âÕ¡Ÿ≈¥—ß°≈à“«‰¥â¡“®“° meta-analysis ‚¥¬ Early Breast Cancer Trialistsû
Collaborative Group (EBCTCG) „πªï §.». 2000(17) ´÷Ëß «‘‡§√“–Àå¢âÕ¡Ÿ≈ ∑’Ë√«∫√«¡®“°°“√»÷°…“∑—ÈßÀ¡¥ 47
°“√»÷°…“∑’ˇª√’¬∫‡∑’¬∫·∫∫ ÿà¡μ—«Õ¬à“ß√–À«à“ß°“√„Àâ combination chemotherapy ·≈–°“√‰¡à„Àâ chemotherapy æ∫«à“
adjuvant chemotherapy  “¡“√∂≈¥§«“¡‡ ’ˬߢÕß°“√‡°‘¥‡ªìπ´È”¢Õß¡–‡√Áß (reduction in annual odds of recurrence)
= 23.5% ·≈–≈¥§«“¡‡ ’ˬߢÕß°“√쓬®“°¡–‡√Áß (reduction in annual odds of death) = 15% ºŸâÀ≠‘ßÕ“¬ÿπâÕ¬°«à“
50 ªï ®–‰¥âª√–‚¬™πå¡“°°«à“ºŸâÀ≠‘ßÕ“¬ÿ 50-69 ªï ‚¥¬¡’ absolute improvement ∑’Ë 15 ªï ¢Õß relapse-free survival 12%
„πºŸâÀ≠‘ß∑’ËÕ“¬ÿπâÕ¬°«à“ 50 ªï ·≈– 4% „πºŸâÀ≠‘ß∑’ËÕ“¬ÿ 50-69 ªï ·≈–¡’ absolute improvement ∑’Ë 15 ªï ¢Õß overall
survival ‡ªìπ 10% ·≈– 3% „π°≈ÿà¡¥—ß°≈à“« μ“¡≈”¥—∫(44) πÕ°®“° meta-analysis ¢â“ßμâπ ¬—ß¡’¢âÕ¡Ÿ≈®“° randomized
controlled trials Õ’° 4 °“√»÷°…“ (18,19,20,21) ´÷Ëß π—∫ πÿπ«à“°“√„Àâ adjuvant chemotherapy ‡æ‘Ë¡Õ—μ√“°“√¡’™’«‘μ√Õ¥
∑—Èß disease-free survival ·≈– overall survival „πºŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬–·√°
          2.1. ·π–π”°“√„Àâ adjuvant chemotherapy „π à«π„À≠à¢ÕߺŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬–·√°¿“¬À≈—ß°“√
ºà“μ—¥ ‚¥¬‡©æ“–„πºŸâªÉ«¬∑’ˇªìπ endocrine non-responsive ∑’Ë¡’¢π“¥ > 1 cm ‰¡à«à“®–‡ªìπ intermediate À√◊Õ high
risk ·≈–„πºŸâªÉ«¬ endocrine response uncertain ∑’ˇªìπ high risk  à«π„π endocrine response uncertain ∑’ˇªìπ‡æ’¬ß
intermediate risk °“√„™â adjuvant chemotherapy §«√æ‘®“√≥“μ“¡§«“¡‡À¡“– ¡‚¥¬§”π÷ß∂÷ߪ√–‚¬™πå·≈–º≈
¢â“߇§’¬ß∑’ËÕ“®‡°‘¥¢÷Èπ  à«πºŸâªÉ«¬∑’ˇªìπ endocrine responsive disease §«√„™â‡§¡’∫”∫—¥„πºŸâªÉ«¬ high risk  à«πºŸâ
ªÉ«¬ intermediate risk Õ“®æ‘®“√≥“‡≈◊Õ°„™â‡ªìπ√“¬Ê‰ª
                  √–¥—∫§”·π–π”:               √–¥—∫ 1
                  §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
                   ”À√—∫ºŸâªÉ«¬∑’Ë¡’Õ“¬ÿ¡“°°«à“ 70 ªï ¢âÕ¡Ÿ≈¢Õß°“√√—°…“¥â«¬ adjuvant chemotherapy ¡’®”°—¥∑’Ë®– √ÿª
‰¥â«“ °“√√—°…“¥—ß°≈à“«¡’ª√–‚¬™πå„π°“√‡æ‘¡Õ—μ√“°“√¡’™«μ√Õ¥ (overall survival)(17) ºŸª«¬°≈ÿ¡π’π“®–‰¥â√∫ª√–‚¬™π宓°
    à                                      Ë           ’‘                          â É   à È à      —
°“√‰¥â√—∫ adjuvant chemotherapy §≈⓬§≈÷ß°—∫„πºŸâªÉ«¬∑’Ë¡’Õ“¬ÿπâÕ¬°«à“ 70 ªï Õ¬à“߉√°Áμ“¡ μâÕߧ”π÷ß∂÷ߺ≈¢â“߇§’¬ß
                                                            ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 73




®“°°“√√—°…“¥â«¬¬“‡§¡’∫”∫—¥∑’„Àâ„π¢π“¥¡“μ√∞“π∑’·π–π”(20) √«¡∑—ß¿“«–À√◊Õ‚√§Õ◊π Ê πÕ°®“°¡–‡√Áß∑’Õ“®‡ªìπ  “‡Àμÿ
                                Ë                  Ë           È             Ë                 Ë
¢Õß°“√‡ ’¬™’«‘μ„πºŸâªÉ«¬„π«—¬π’È√à«¡¥â«¬„π°“√æ‘®“√≥“°“√·π–π”°“√√—°…“¥â«¬ adjuvant chemotherapy
                 √–¥—∫§”·π–π”:               √–¥—∫ 1
                 §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ C

™π‘¥ √–¬–‡«≈“ ·≈–¢π“¥¢Õ߬“‡§¡’∫”∫—¥ (regimen, duration and dosage of adjuvant chemotherapy)
                  ¢âÕ¡Ÿ≈®“° meta-analysis ‚¥¬ EBCTCG(17) æ∫«à“°“√„À⬓‡§¡’∫”∫—¥‚¥¬„™â¬“μ—Èß·μà 2 ™π‘¥¢÷Èπ‰ª
                   È                                               Ë             ’‘          â É
‡ªìπ®”π«π 4-6 §√—ß À√◊Õ‡ªìπ√–¬–‡«≈“ 3-6 ‡¥◊Õπ‡æ’¬ßæÕ„π·ßà°“√‡æ‘¡Õ—μ√“°“√¡’™«μ√Õ¥¢ÕߺŸª«¬¡–‡√Á߇μâ“π¡√–¬–·√°
                         Ë                 à                                                       Ë           ’‘
°“√‡≈◊Õ° „™â¬“‡§¡’∫”∫—¥∑’ª√–°Õ∫¥â«¬¬“°≈ÿ¡ anthracyclines ‰¥â·°à doxorubicin, epirubicin  “¡“√∂‡æ‘¡Õ—μ√“°“√¡’™«μ√Õ¥
Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫°“√„™â¬“‡§¡’∫”∫—¥∑’ˉ¡à¡’¬“°≈ÿà¡ anthracyclines Õ¬Ÿà¥â«¬ ‚¥¬ anthracycline-
containing regimens  “¡“√∂≈¥§«“¡‡ ’ˬߢÕß°“√‡°‘¥‡ªìπ´È” ¢Õß¡–‡√Áß (reduction in annual odds of recurrence) =
11% ·≈–≈¥§«“¡‡ ’ˬߢÕß°“√쓬®“°¡–‡√Áß (reduction in annual odds of death) = 16% ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫
nonanthracycline-containing regimens(17) ·≈–‰¥âª√–‚¬™πå∑—ÈߺŸâªÉ«¬∑’ËÕ“¬ÿπâÕ¬·≈–Õ“¬ÿ¡“°°«à“ 50 ªï
                          Ë                              ËŸ                  È                          Ë
                   °“√‡æ‘¡¢π“¥¢Õ߬“‡§¡’∫”∫—¥„π¢π“¥∑’ ß°«à“¢π“¥¡“μ√∞“π∑—ß cyclophosphamide („π¢π“¥∑’¡“°°«à“
                     (26,27)                                           2       (28)
600 mg/m2/cycle)                                       Ë
                             À√◊Õ doxorubicin („π¢π“¥∑’¡“°°«à“ 60 mg/m /cycle) √à«¡°—∫°“√„™â granulocyte-colony
sitmulating factor (G-CSF) æ∫«à“‰¡à™à«¬‡æ‘Ë¡∑—Èß disease-free survival ·≈– overall survival
          2.2 ‰¡à·π–π”„Àℙ⬓‡§¡’∫”∫—¥„π¢π“¥∑’Ë Ÿß°«à“¢π“¥¡“μ√∞“π„π°“√„Àâ adjuvant chemotherapy
              √–¥—∫§”·π–π”:          √–¥—∫ 1
              §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
                   °“√„À⬓‡§¡’∫”∫—¥„π¢π“¥ Ÿß√à«¡°—∫°“√„™â bone marrow transplantation À√◊Õ stem cell support
„π adjuvant setting „πºŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬–·√°∑’Ë¡’§«“¡‡ ’ˬߠŸß„π°“√‡°‘¥‡ªìπ´È”¢Õß¡–‡√Áß ‰¥â·°à ºŸâªÉ«¬∑’Ë¡’°“√
°√–®“¬¢Õß¡–‡√Á߉ª∑’Ë axillary nodes μ—Èß·μà 10 nodes ¢÷Èπ‰ª ®“°°“√»÷°…“¢Õß randomized controlled trials 3
°“√»÷ ° …“(29,30,31) æ∫«à“‰¡à™à«¬‡æ‘Ë¡∑—Èß disease-free survival ·≈– overall survival ¡’‡æ’¬ßÀπ÷Ëß°“√»÷°…“( 32)
´÷Ë߇ªìπ randomized controlled trial ∑’Ë»÷°…“„πºŸâªÉ«¬∑’Ë¡’°“√°√–®“¬¢Õß¡–‡√Á߉ª∑’Ë axillary nodes μ—Èß·μà 4 nodes ¢÷Èπ‰ª
            ’                 È                                               â É Ë —
æ∫«à“ ‰¡à¡§«“¡·μ°μà“ߢÕß∑—ß relapse-free survival ·≈– overall survival „πºŸª«¬∑’‰¥â√∫¬“‡§¡’∫”∫—¥„π¢π“¥¡“μ√∞“π
·≈–„π¢π“¥ Ÿß√à«¡°—∫°“√„™â stem cell rescue ·μà„π planned subgroup analyses „π°“√»÷°…“π’È æ∫«à“ °“√„™â
high-dose chemotherapy with stem cell rescue ¡’·π«‚πâ¡∑’Ë®–™à«¬‡æ‘Ë¡ relapse-free survival „πºŸâªÉ«¬∑’Ë¡’°“√°√–®“¬
¢Õß¡–‡√Á߉ª∑’Ë axillary nodes μ—Èß·μà 10 nodes ¢÷Èπ‰ª (p = 0.05)
          2.3 ‰¡à·π–π”„Àℙ⬓‡§¡’∫”∫—¥„π¢π“¥ Ÿß√à«¡°—∫°“√„™â bone marrow transplantation À√◊Õ stem
cell support „π°“√„Àâ adjuvant chemotherapy
                 √–¥—∫§”·π–π”:           √–¥—∫ 1
                 §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
                   °“√„™â¬“‡§¡’∫”∫—¥„π°≈ÿà¡ taxanes ‰¥â·°à paclitaxel, docetaxel ´÷Ë߇ªì𬓇§¡’∫”∫—¥∑’ˉ¥âº≈¥’„π°“√
√—°…“¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬  ”À√—∫„π adjuvant setting „πªí®®ÿ∫—π¡’¢âÕ¡Ÿ≈®“°°“√»÷°…“¢Õß randomized
controlled trials 8 °“√»÷°…“∑’Ë»÷°…“∂÷ß°“√„Àâ adjuvant taxanes ‡ªìπ°“√√—°…“‡ √‘¡„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡∑’Ë¡’°“√°√–®“¬
‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß ¥—ßπ’È
74     ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




         1. °“√»÷°…“¢Õß°≈ÿà¡ Cancer And Leukemia Group B (CALGB 9344)(28) ∑’Ë√“¬ß“π¢âÕ¡Ÿ≈À≈—ß ÿ¥«à“ °“√„Àâ
adjuvant paclitaxel x 4 cycles À≈—ß®“°∑’Ë„Àâ AC regimen x 4 cycles ‡¡◊ËÕ‡∑’¬∫°—∫°“√„Àâ adjuvant AC regimen x 4 cycles
¡’º≈™à«¬‡æ‘Ë¡ absolute benefit ¢Õß disease-free survival ·≈– overall survival ∑’Ë 5 ªï ‡∑à“°—∫ 5% ·≈– 3% μ“¡≈”¥—∫
‚¥¬¡’ 5-year disease-free survival ‡ªìπ 70% vs. 65% ·≈– 5-year overall survival ‡ªìπ 80% vs. 77% ·≈–
           ’Ë —                           à          à â É Ë                                           —
ª√–‚¬™πå∑‰¥â√∫®“°°“√„Àâ paclitaxel ¡’Õ¬Ÿ‡©æ“–„π°≈ÿ¡ºŸª«¬∑’¡’ hormone receptors ‡ªìπº≈≈∫ ·≈–‰¡à‰¥â√∫¬“ tamoxifen
√à«¡¥â«¬
         2. °“√»÷°…“¢Õß°≈ÿà¡ National Surgical Adjuvant Breast and Bowel Project (NSABP B-28) ∑’Ë√“¬ß“π ¢âÕ¡Ÿ≈
     (33)
                  Ë ’       Ë Ë ‘     â É                                         â É   à Ë —
≈à“ ÿ¥ À≈—ß®“°∑’¡√–¬–‡©≈’¬∑’μ¥μ“¡ºŸª«¬ (median follow-up) ∂÷ß 67 ‡¥◊Õπ æ∫«à“ºŸª«¬°≈ÿ¡∑’‰¥â√∫ adjuvant paclitaxel
x 4 cycles ¿“¬À≈—ß®“°∑’ˉ¥â√—∫ AC regimen x 4 cycles ‡¡◊ËÕ‡∑’¬∫°—∫°“√„Àâ adjuvant AC regimen x 4 cycles ¡’ 5-year
disease-free survival ∑’Ë¥’°«à“ (76% vs. 72%) ·μଗ߉¡à¡’§«“¡·μ°μà“ßÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘„π·ßà¢Õß overall
survival (85% vs. 85%) ª√–‚¬™πå∑’ˉ¥â‡°‘¥∑—Èß„π°≈ÿà¡∑’Ë¡’ ER ‡ªìπº≈∫«° ·≈– ‡ªìπº≈≈∫
          3. °“√»÷°…“¢Õß°≈ÿà¡ Breast Cancer International Research Group (BCIRG 001)(34) ∑’ˇª√’¬∫‡∑’¬∫ √–À«à“ß
°“√„Àâ docetaxel / doxorubicin / cyclophosphomide (TAC) x 6 cycles °—∫ 5-FU / doxorubicin / cyclophosphamide
(FAC) x 6 cycles À≈—ß®“°∑’Ë¡’√–¬–‡©≈’ˬ∑’Ëμ‘¥μ“¡ºŸâªÉ«¬ (median follow-up) 55 ‡¥◊Õπ æ∫«à“°≈ÿà¡∑’ˉ¥â√—∫ TAC ¡’ 5-year
disease-free survival (75% vs. 68%) ·≈– overall survival (87% vs. 81%) ∑’Ë¥’°«à“Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ º≈
™à«¬‡æ‘Ë¡ absolute benefit ¢Õß disease-free survival ·≈– overall survival ∑’Ë 5 ªï ‡∑à“°—∫ 7% ·≈– 6% μ“¡≈”¥—∫ ·≈–
ª√–‚¬™πå∑’ˉ¥â‡°‘¥∑—Èß„π°≈ÿà¡∑’Ë¡’ ER ‡ªìπº≈∫«° ·≈– ‡ªìπº≈≈∫ ‚¥¬‡©æ“–„πºŸâªÉ«¬∑’Ë¡’ node positive 1-3 nodes æ∫«à“¡’
disease-free ·≈– overall survival ∑’Ë¥’°«à“ ·μà‰¡à¡’§«“¡·μ°μà“ß°—πÕ¬à“ß™—¥‡®π„πºŸâªÉ«¬∑’Ë¡’ node positive > 4 nodes
πÕ°®“°π’È TAC regimen ¬—ß¡’º≈¢â“߇§’¬ß¡“°°«à“ FAC „π¥â“π febrile neutropenia ´÷Ëß Ÿß∂÷ß 24.7% ·¡â«à“®–¡’°“√„™â
prophylactic antibiotic „π°≈ÿà¡∑’ˉ¥â TAC regimen
         4. °“√»÷°…“¢Õß PACS01(47) ∑’‡ª√’¬∫‡∑’¬∫ √–À«à“ß°“√„Àâ 5-FU / Epirubicin 100 mg/m2 / cyclo-phosphmide
                                         Ë
(FEC100) x 6 cycles °—∫ FEC100 x 3 cycles ·≈â«μ“¡¥â«¬ docetaxel x 3 cycles À≈—ß®“°∑’Ë¡’√–¬–‡©≈’ˬ∑’Ëμ‘¥μ“¡ºŸâªÉ«¬
(median follow-up) 59.7 ‡¥◊Õπ æ∫«à“°≈ÿà¡∑’ˉ¥â√—∫ FEC100 x 3 cycles ·≈â«μ“¡¥â«¬ docetaxel x 3 cycles ¡’ 5-year
disease-free survival (78.3% vs. 73.2%) ·≈– overall survival (90.7% vs. 86.7%) ∑’Ë¥’°«à“Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘
º≈™à«¬‡æ‘Ë¡ absolute benefit ¢Õß disease-free survival ·≈– overall survival ∑’Ë 5 ªï ‡∑à“°—∫ 5% ·≈– 4% μ“¡≈”¥—∫
·≈–ª√–‚¬™πå∑’ˉ¥â‡°‘¥‡©æ“–„πºŸâÀ≠‘ßÕ“¬ÿμ—Èß·μà 50 ªï¢÷Èπ‰ª ·≈–„πºŸâªÉ«¬∑’Ë¡’ node positive 1-3 nodes ‚¥¬æ∫«à“¡’
disease-free survival ∑’Ë¥’°«à“ ·μà‰¡à¡’§«“¡·μ°μà“ß°—πÕ¬à“ß™—¥‡®π„πºŸâÀ≠‘ßÕ“¬ÿπâÕ¬°«à“ 50 ªï·≈– „πºŸâªÉ«¬∑’Ë¡’ node
positive > 4 nodes
           5. °“√»÷°…“¢Õß°≈ÿà¡ Cancer And Leukemia Group B (CALGB 9741)(35) ‡ªìπ°“√»÷°…“ ∂÷ß°“√„À⬓‡§¡’
∫”∫—¥„π≈—°…≥–∑’ˇæ‘Ë¡ dose density ‚¥¬„À⬓„π√–¬–Àà“ß∑’Ë —Èπ°«à“ §◊Õ ∑ÿ° 2  —ª¥“Àå √à«¡°—∫°“√„™â granulocyte-colony
stimulating factor (G-CSF) „πºŸâªÉ«¬¡–‡√Á߇μâ“π¡∑’Ë¡’°“√°√–®“¬‰ª¬—ß μàÕ¡πÈ”‡À≈◊Õß ‡ª√’¬∫‡∑’¬∫°—∫°“√„À⬓„π√–¬–
Àà“ß¡“μ√∞“π §◊Õ ∑ÿ° 3  —ª¥“Àå ®“°°“√»÷°…“¥—ß°≈à“«æ∫«à“ ∑’Ë√–¬– ‡©≈’ˬ¢Õß°“√μ‘¥μ“¡ºŸâªÉ«¬ (median follow-up) ∑’Ë 3
ªï ºŸâªÉ«¬„π°≈ÿà¡∑’ˉ¥â√—∫¬“‡§¡’∫”∫—¥∑ÿ° 2  —ª¥“Àå ¡’ 4-year disease-free survival (82% vs. 75%) ·≈– overall survival
                       Ë ’   â É      à Ë —
(92% vs. 90%) ∑’¥°«à“ºŸª«¬„π°≈ÿ¡∑’‰¥â√∫¬“‡§¡’∫”∫—¥∑ÿ° 3  —ª¥“Àå (risk ratio = 0.74 ·≈– 0.69 μ“¡≈”¥—∫) √“¬ß“π
≈à“ ÿ¥®“°°“√μ‘¥μ“¡º≈ 6.5 ªï æ∫«à“ dose-dense treatment ¡’ DFS ‡æ‘Ë¡¢÷Èπ (HR = 0.75; p=0.012) ·≈–¡’ OS ‡æ‘Ë¡¢÷Èπ
·μ৫“¡·μ°μà“ßπâÕ¬≈ß¡“°‡¡◊ËÕ‡∑’¬∫°—∫√“¬ß“π§√—Èß·√° (HR=0.85; p=0.049) (56) ·≈–°“√„™â¬“ Ÿμ√π’ÈμâÕß §”π÷ß∂÷ß
§à“„™â®à“¬∑’ˇæ‘Ë¡¢÷ÈπÕ¬à“ß¡“°®“°°“√„™â G-CSF √à«¡¥â«¬„π°“√∑’Ë®–·π–π”°“√√—°…“„πºŸâªÉ«¬·μà≈–√“¬
                                                         ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 75




         6. °“√»÷°…“¢Õß°≈ÿà¡ US Oncology (48) ∑’ˇª√’¬∫‡∑’¬∫√–À«à“ß°“√„Àâ docetaxel / cyclophosphomide (TC) x 4
cycles °—∫ doxorubicin / cyclophosphamide (AC) x 4 cycles „πºŸâªÉ«¬ 1016 √“¬ À≈—ß®“°∑’Ë¡’√–¬–‡©≈’ˬ∑’Ëμ‘¥μ“¡ºŸâªÉ«¬
(median follow-up) 66 ‡¥◊Õπ æ∫«à“°≈ÿà¡∑’ˉ¥â√—∫ TC ¡’ 5-year disease-free survival ¥’°«à“ AC (86% vs. 80%;
HR= 0.67; p=0.015) ·μà overall survival ‰¡à·μ°μà“ß°—π (90% vs. 87%; HR= 0.76; p=0.13)
         7. °“√»÷°…“ E2197(49) ∑’‡ª√’¬∫‡∑’¬∫√–À«à“ß°“√„Àâ doxorubicin/docetaxel (AT) x 4 cycles °—∫ doxorubicin /
                                  Ë
cyclophosphamide (AC) x 4 cycles À≈—ß®“°∑’Ë¡’√–¬–‡©≈’ˬ∑’Ëμ‘¥μ“¡ºŸâªÉ«¬ (median follow-up) 53 ‡¥◊Õπ æ∫«à“°≈ÿà¡∑’Ë
‰¥â√—∫ AT À√◊Õ AC ¡’ 4-year disease-free survival (87% vs. 87%) ·≈– overall survival ‰¡à·μ°μà“ß°—π
         8. °“√»÷°…“ BIG 2-98(50) ∑”°“√»÷°…“„πºŸª«¬¡–‡√Á߇μâ“π¡∑’¡°“√°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß ‡ª√’¬∫‡∑’¬∫
                                                    â É              Ë ’
°“√√—°…“ 4 °≈ÿà¡ ‚¥¬ “¡“√∂·∫àßÕÕ°‰¥â‡ªìπ Õß°≈ÿà¡„À≠à§◊Õ°≈ÿà¡∑’Ë¡’·≈–‰¡à¡’ docetaxel ·≈–¬—ß “¡“√∂·∫àß°≈ÿ࡬àÕ¬¢Õß
°“√„Àâ docetaxel ‡ªìπ·∫∫„Àâæ√âÕ¡°—∫ anthracyclines ·≈–·∫∫ sequential À≈—ß®“°μ‘¥μ“¡ºŸâªÉ«¬ 62 ‡¥◊Õπ æ∫«à“
‚¥¬√«¡°≈ÿà¡∑’ˉ¥â¬“ docetaxel ¡’Õ—μ√“√Õ¥™’«‘μ‚¥¬ª√“»®“°‚√§∑’Ë¥’°«à“·μà‰¡à∂÷ß√–¥—∫¡’π—¬ ”§—≠∑“ß ∂‘μ‘ ·μà‡¡◊ËÕ
‡ª√’¬∫‡∑’¬∫‡©æ“–°“√„Àâ docetaxel ·∫∫ sequential (A x 3 then T x 3 then CMF x 3) ®–¡’ DFS ¥’°«à“°≈ÿà¡∑’ˉ¥â‡©æ“–
anthracyclines (A x 4 then CMF x 4) Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ HR = 0.79 ·≈–°“√„Àâ docetaxel ·∫∫ sequential
¥’°«à“°“√„Àâ·∫∫ combination Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘쑇™àπ‡¥’¬«°—π ·μàÕ¬à“߉√°Áμ“¡°“√„™â docetaxel ‡ √‘¡‰¡à°àÕ„À⇰‘¥
§«“¡·μ°μà“ß∑“ߥâ“π overall survival ‰¡à«à“®–‡ª√’¬∫‡∑’¬∫·∫∫„¥°Áμ“¡
          °“√»÷°…“‚¥¬°≈ÿà¡ CALGB ·≈– US intergroup(51) ∑’Ë∑”°“√√«∫√«¡°“√»÷°…“ 3 °“√»÷°…“„À≠à∑’Ë∑”„π™à«ß‡«≈“
20 ªï∑’˺à“π¡“¢Õß°“√√—°…“¥â«¬‡§¡’‡ √‘¡À≈—ߺà“μ—¥ °“√»÷°…“ CALGB 8541 ‡ª√’¬∫‡∑’¬∫°“√„™â dose doxorubicin
„π√–¥—∫ low, intermediate, high °“√»÷°…“ CALGB 9344 ‡ª√’¬∫‡∑’¬∫√–À«à“ß°≈ÿà¡∑’Ë„™â·≈–‰¡à‰¥â„™â¬“ taxanes °“√»÷°…“
CALGB 9741 ‡ª√’¬∫‡∑’¬∫√–À«à“ß°“√„™â¬“ taxanes ·∫∫∏√√¡¥“∑ÿ° “¡ —ª¥“Àå°—∫·∫∫ dose dense ∑ÿ° Õß —ª¥“Àå
‡¡◊ËÕæ‘®“√≥“ subgroup μ“¡°“√· ¥ßÕÕ°À√◊Õ‰¡à· ¥ßÕÕ°¢Õß ER æ∫«à“°“√„™â doxorubicin ∑’Ë Ÿß°«à“¢π“¥¡“μ√∞“π
À√◊Õ°“√‡æ‘Ë¡°“√„™â taxanes ‡¢â“‰ª„π·ßà°“√√—°…“‡ √‘¡ À√◊Õ°“√„™â·∫∫ dose dense ®–„Àâª√–‚¬™πå∑’ˇæ‘Ë¡¢÷Èπ„π·ßà DFS
Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘쑇©æ“–„πºŸâªÉ«¬∑’Ë¡’ ER negative ‡∑à“π—Èπ ·μà„πºŸâªÉ«¬∑’Ë¡’°“√· ¥ßÕÕ°¢Õß ER ‰¡àæ∫«à“®–‰¥â
ª√–‚¬™πå‡æ‘Ë¡¢÷Èπ
           „π·ßà°“√‡ª√’¬∫‡∑’¬∫ª√– ‘∑∏‘¿“æ¢Õ߬“ Õßμ—«„π°≈ÿà¡ taxanes §◊Õ paclitaxel ·≈– docetaxel ¡’°“√»÷°…“
       (52)
E1199 ∑”°“√»÷°…“„πºŸâªÉ«¬∑’Ë¡’°“√°√–®“¬¢Õß‚√§‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß À≈—ß®“°∑’ˉ¥â√—∫ AC x 4 cycles ºŸâªÉ«¬®–∂Ÿ°
 ÿà¡„À≥â√—∫Àπ÷Ëß„π 4 Õ¬à“ßμàÕ‰ªπ’ȧ◊Õ paclitaxel 175 mg/m2 q 3 week ®”π«π 4 cycles À√◊Õ paclitaxel 80 mg/m2
weekly x 12 weeks À√◊Õ docetaxel 100 mg/m2 q 3 week ®”π«π 4 cycles À√◊Õ docetaxel 30 mg/m2 weekly x 12
weeks À≈—ß®“°μ‘¥μ“¡°“√√—°…“‡ªìπ‡«≈“ 4 ªï ‰¡àæ∫«à“¡’§«“¡·μ°μà“ß°—π∑—Èß„π·ßà DFS ·≈– OS „π∑ÿ°°≈ÿà¡°“√√—°…“
                 2.4.1 ‰¡à “¡“√∂·π–π”„Àâ „™â taxane ‡ªìπ¡“μ√∞“π„π°“√„Àâ adjuvant chemotherapy „πºŸâ
                   Ë ’                                                        â É Ë
ªÉ«¬¡–‡√Á߇μâ“π¡ ∑’¡°“√°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß∑ÿ°√“¬ ·μàÕ“®æ‘®“√≥“„πºŸª«¬∑’‡ªìπ endocrine non-responsive
high risk ·≈– endocrine response uncertain ‚¥¬‡©æ“–Õ¬à“߬‘ËߺŸâªÉ«¬∑’ˬâÕ¡μ‘¥ HER 2
                          √–¥—∫§”·π–π”:          √–¥—∫ 0
                          §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
              2.4.2 ‰¡à·π–π”„Àâ„™â taxane ‡ªìπ adjuvant chemotherapy „πºŸâªÉ«¬¡–‡√Á߇μâ“π¡∑’ˉ¡à¡’°“√
°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß ‡π◊ËÕß®“°¬—߉¡à¡’¢âÕ¡Ÿ≈ π—∫ πÿπ
                       √–¥—∫§”·π–π”:            √–¥—∫ 1
                       §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
76   ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




             2.4.3 ‰¡à “¡“√∂·π–π”°“√„Àâ adjuvant chemotherapy „π≈—°…≥–∑’ˇæ‘Ë¡ dose density ‡ªìπ
¡“μ√∞“π„π°“√ √—°…“ºŸâªÉ«¬¡–‡√Á߇μâ“π¡∑’Ë¡’°“√°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß
                      √–¥—∫§”·π–π”:            √–¥—∫ 0
                      §ÿ≥¿“æÀ≈—°∞“π:           √–¥—∫ A

       2.5 ¬“‡§¡’∫”∫—¥∑’Ë∂◊Õ‡ªìπ¡“μ√∞“π¢Õß adjuvant chemotherapy „πºŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬– ·√°
           2.5.1 cyclophosphamide/methotrexate/5-fluorouracil x 6 cycles (CMF, preferably oralregimen)(22)
                  cyclophophamide           100 mg/m2/day PO day 1-14 q 28 days
                  methotrexate              40 mg/m2 IV day 1 and day 8 q 28 days
                  5-fluorouracil            600 mg/m2 IV day 1 and day 8 q 28 days
            2.5.2 doxorubicin / cyclophophamide x 4 cycles (AC)(23)
                  doxorubicin                 60 mg/m2 IV day 1 q 21 days
                  cyclophosphamide            600 mg/m2 IV day 1 q 21 days
            2.5.3 cyclophosphamide / doxorubicin / 5-fluorouracil x 6 cycles (CAF)(24)
                  cyclophosphamide               500 mg/m2 IV day 1 q 21 days
                  doxorubicin                    50 mg/m2 IV day 1 q 21 days
                  5-fluorouracil                 500 mg/m2 IV day 1 q 21 days
            2.5.4 cyclophosphamide / epirubicin / 5-fluorouracil x 6 cycles (CEF)(25)
                  cyclophosphamide               75 mg/m2/day PO day 1-14 q 28 days
                  epirubicin                     60 mg/m2 IV day 1 and day 8 q 28 days
                  5-fluorouracil                 500 mg/m2 IV day 1 and day 8 q 28 days
            2.5.5 5-fluorouracil / epirubicin / cyclophosphamide / x 6 cycles (FEC100)(45)
                  5-fluorouracil                 500 mg/m2 IV day 1 q 21 days
                  epirubicin                     100 mg/m2 IV day 1 q 21 days
                  cyclophosphamide               500 mg/m2 IV day 1 q 21 days
            2.5.6 doxorubicin / cyclophophamide x 4 cycles (AC) followed by paclitaxel x 4 cycles(28)
                  doxorubicin                    60 mg/m2 IV day 1 q 21 days
                  cyclophosphamide               600 mg/m2 IV day 1 q 21 days
                  Then paclitaxel                175 mg/m2 IV day 1 q 21 days
            2.5.7 doxorubicin / cyclophophamide x 4 cycles (AC) followed by paclitaxel weekly x 12 weeks
                  doxorubicin                    60 mg/m2 IV day 1 q 21 days
                  cyclophosphamide               600 mg/m2 IV day 1 q 21 days
                  Then paclitaxel                80 mg/m2 IV day 1 weekly q 12 weeks
            2.5.8 doxorubicin / cyclophophamide x 4 cycles (AC) followed by docetaxel x 4 cycles(28)
                  doxorubicin                    60 mg/m2 IV day 1 q 21 days
                  cyclophosphamide               600 mg/m2 IV day 1 q 21 days
                  Then docetaxel                 100 mg/m2 IV day 1 q 21 days
                                                            ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 77




               2.5.9 doxorubicin / cyclophophamide x 4 cycles (AC) followed by docetaxel weekly x 12 weeks(28)
                      doxorubicin                    60 mg/m2 IV day 1 q 21 days
                      cyclophosphamide               600 mg/m2 IV day 1 q 21 days
                      Then docetaxel                 30 mg/m2 IV day 1 weekly x 12 weeks
               2.5.10 docetaxel / doxorubicin / cyclophosphamide / x 6 cycles (TAC)(34)
                      docetaxel                      75 mg/m2 IV day 1 q 21 days
                      doxorubicin                    50 mg/m2 IV day 1 q 21 days
                      cyclophosphamide               500 mg/m2 IV day 1 q 21 days
               i.     5-fluorouracil / epirubicin / cyclophosphamide x 3 cycles (FEC100) followed by docetaxel
                      x 3 cycles (46)
                      5-fluorouracil                 500 mg/m2 IV day 1 q 21 days
                      epirubicin                     100 mg/m2 IV day 1 q 21 days
                      cyclophosphamide               500 mg/m2 IV day 1 q 21 days
                      Then Docetaxel                 100 mg/m2 IV day 1 q 21 days

√–¥—∫§”·π–π”:              √–¥—∫ 1
§ÿ≥¿“æ¢ÕßÀ≈—°∞“π:          √–¥—∫ A

       3. Adjuvant Trastuzumab
           „πªí®®ÿ∫—π¡’°“√»÷°…“„À≠à 4 °“√»÷°…“‡ª√’¬∫‡∑’¬∫°“√„™â trastuzumab ‡ªìπ°“√√—°…“‡ √‘¡„πºŸâªÉ«¬¡–‡√Áß
√–¬–‡√‘Ë¡μâπ∑’Ë¡’ HER2 ‡ªìπº≈∫«° ·≈–∑ÿ°°“√»÷°…“¡’√“¬ß“π‡∫◊ÈÕßμâπ·≈â««à“°“√„™â trastuzumab π—Èπ¡’ª√–‚¬™πå®√‘ß
„π¥â“π≈¥°“√‡ªìπ´È”  à«π°“√≈¥Õ—μ√“°“√‡ ’¬™’«‘μ¡’ 3 °“√»÷°…“∑’Ë√“¬ß“πº≈«à“°“√„™â trastuzumab ¡’ª√–‚¬™πå
™à«¬≈¥Õ—μ√“‡ ’¬™’«‘쉥âÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘  à«πÕ’°Àπ÷Ëß°“√»÷°…“¬—߉¡à¡’√“¬ß“π √“¬≈–‡Õ’¬¥¡’¥—ßμàÕ‰ªπ’È
            1. °“√√«¡¢âÕ¡Ÿ≈¢Õß 2 °“√»÷°…“‡¢â“¥â«¬°—π ‰¥â·°à NSABP B-31 ·≈– NCCTG N9831(53) ®“°°“√μ‘¥μ“¡
º≈°“√√—°…“‚¥¬‡©≈’ˬ 2 ªï æ∫«à“°≈ÿà¡∑’ˉ¥â‡§¡’∫”∫—¥·≈– trastuzumab ‡ªìπ‡«≈“ 1 ªï ¡’ 4-year disease-free survival
¥’°«à“°≈ÿà¡∑’ˉ¥â‡§¡’∫”∫—¥Õ¬à“߇¥’¬«Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ (85% °—∫ 67% μ“¡≈”¥—∫) ·≈–‰¥âª√–‚¬™πå„π·ßà≈¥Õ—μ√“
°“√‡ ’¬™’«‘μÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘쑇™àπ‡¥’¬«°—π (91% °—∫ 87%) ·≈–ª√–‚¬™πå∑’ˉ¥â‰¡à¢÷Èπ°—∫Õ“¬ÿ°“√· ¥ßÕÕ°¢Õß
hormonal receptor ·≈–°“√°√–®“¬À√◊Õ‰¡à°√–®“¬‰ª¬—ßμàÕ¡πÈ”‡À≈◊Õß
              2. °“√»÷°…“¢Õß HERA(54, 57) √“¬ß“π≈à“ ÿ¥®“°°“√μ‘¥μ“¡º≈°“√√—°…“‚¥¬‡©≈’ˬ 2 ªï æ∫«à“°≈ÿà¡∑’ˉ¥â‡§¡’
∫”∫— ¥ ·≈â « μ“¡¥â « ¬ trastuzumab ‡ªì 𠇫≈“ 1 ªï ¡’ 3-year disease-free survival ¥’ ° «à “ °≈ÿà ¡ ∑’Ë ‰ ¥â ‡ §¡’ ∫”∫— ¥
‡æ’¬ßÕ¬à“߇¥’¬« Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ (80.6% °—∫ 74.3% μ“¡≈”¥—∫) ·≈–¡’ 3-year overall survival ¥’°«à“
°≈ÿà¡∑’ˉ¥â√—∫‡§¡’∫”∫—¥‡æ’¬ßÕ¬à“߇¥’¬«Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ (92.4% °—∫ 89.7% μ“¡≈”¥—∫)
           3. °“√»÷°…“ BCIRG 006(55) æ∫«à“°≈ÿ¡∑’‰¥â trastuzumab ‡ªìπ°“√√—°…“‡ √‘¡ ‰¡à«“®–„™â√«¡°—∫ Ÿμ√¬“∑’¡À√◊Õ‰¡à¡’
                                                  à Ë                                   à       à         Ë ’
anthracyclines ‡ªì π  à « πª√–°Õ∫ √“¬ß“πÀ≈— ß μ‘ ¥ μ“¡º≈°“√√— ° …“ 23 ‡¥◊ Õ π æ∫«à “ °≈ÿà ¡ ∑’Ë ‰ ¥â trastuzumab
¡’ DFS ∑’Ë¥’°«à“°≈ÿà¡∑’ˉ¡à‰¥â√—∫¬“Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ ·μଗ߉¡à¡’√“¬ß“πº≈„π¥â“π overall survival
           ‚¥¬ √ÿª°“√„™â trastuzumab ‡ªìπ°“√√—°…“‡ √‘¡„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬–·√°∑’Ë¡’ HER2 positive æ∫«à“
¬—ߧ߄ÀâÕ—μ√“√Õ¥™’«‘μ‚¥¬ª√“»®“°‚√§∑’Ë¥’°«à“°≈ÿà¡∑’ˉ¡à‰¥â√—∫¬“Õ¬à“ß¡’π—¬ ”§—≠ ·≈–¡’¢âÕ¡Ÿ≈™—¥‡®π¢÷Èπ„π·ßà°“√≈¥
78    ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




Õ—μ√“°“√‡ ’¬™’«‘μ«à“¥’¢÷ÈπÕ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘Õ¬à“ßπâÕ¬ Õß°“√»÷°…“ ·μàÕ¬à“߉√°Áμ“¡¬—ß¡’∫“ß®ÿ¥∑’ˬ—߉¡à¡’§”μÕ∫
  Ë —                    Ë                                                                             à
∑’™¥‡®π‡™àπ√–¬–‡«≈“∑’‡À¡“– ¡„π°“√„Àâ trastuzumab √–À«à“ß 1 À√◊Õ 2 ªï °“√„À⬓ trastuzumab √à«¡°—∫¬“°≈ÿ¡ taxanes
À√◊Õ„™âÀ≈—ß®“°√—°…“¥â«¬‡§¡’∫”∫—¥®∫ ‘Èπ·≈â« ·≈–°“√√—°…“¥â«¬ trastuzumab ¡’º≈¢â“߇§’¬ßμàÕÀ—«„®‡æ‘Ë¡¡“°¢÷Èπ ®÷ßμâÕß¡’
§«“¡æ√âÕ¡

                                                                â É                   Ë     Ë
        3.1 ‰¡à “¡“√∂·π–π”„Àâ„™â trastuzumab „π°“√√—°…“‡ √‘¡„πºŸª«¬¡–‡√Á߇μâ“π¡√–¬–‡√‘¡μâπ∑’¡’ HER
2 ‡ªìπº≈∫«° ‡π◊ËÕß®“°√–¬–‡«≈“„π°“√μ‘¥μ“¡°“√√—°…“¬—߉¡àπ“πæÕ
        √–¥—∫§”·π–π”:               √–¥—∫ 0
        §ÿ≥¿“æÀ≈—°∞“π:              √–¥—∫ A

References
   1. Goldhirsch A, Glick J, Gelber R, et al. Meeting Highlights: International Expert Consensus on the Primary
      Treatment of Early Breast Cancer 2005. Ann Oncol 2005 (September 7).
   2. Early Breast Cancer Trialistsû Collaborative Group. Tamoxifen for early breast cancer: an overview of the
      randomised trials. Lancet 2005; 365: 1687-1717.
   3. Hutchins L, Green S, Ravdin P, et al. CMF versus CAF +/- tamoxifen in high-risk node negative breast
      cancer patients and a natural history follow-up study in low-risk node-negative patients: update of tamoxifen
      results. Breast Cancer Res Treat 1999; 57(1): 25.
   4. Bratherton C, Brown C, Buchanan R et al. A comparison of two doses tamoxifen (Nolvadex) in postmenopausal
      women with advanced breast cancer: 10mg bd versus 20mg bd. Br J Cancer 1984; 50: 199-205.
   5. Fisher B, Dignam J, Bryant J, et al.: Five versus more than five years of tamoxifen therapy for breast cancer
      patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 1996; 88(21):
      1529-1542.
   6. Swain SM. Tamoxifen: the long and short of it. J Natl Cancer Inst 1996; 88(21): 1510-1512.
   7. National Institutes of Health Consensus Development Panel. National Institutes of Health Consensus
      Development Conference Statement: Adjuvant therapy for breast cancer, November 1-3, 2000. J Natl
      Cancer Inst 2001; 93: 979-89.
   8. Matti S. Aapro. Adjuvant therapy of primary breast cancer: A review of key findings from the 7th international
      conference, St Gallen, February 2001. The Oncologist 2001; 6: 376-385.
   9. Early Breast Cancer Trialistsû Collaborative Group. Ovarian ablation in early breast cancer: overview of the
      randomised trials. Lancet 1996; 348(9036): 1189-1196.
  10. Pritchard K. Best type of endocrine treatments. The Breast 2001; 10(Suppl 1): S9.
  11. Scottish Cancer Trials Breast Group and ICRF Breast Unit, Guyûs Hospital, London. Adjuvant ovarian ablation
      versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish
      trial. Lancet 1993; 341(8856): 1293-1298.
  12. Boccardo F, Rubagotti A, Amorosa D, et al. Cyclophosphamide, methotrexate, and fluorouraciol versus tamoxifen
      plus ovarian suppression as adjuvant treatment of estrogen receptor-positive pre-/perimenopausal breast
      cancer patients: results of the Italian Breast Cancer Adjuvant Study Group 02 randomized trial. J Clin Oncol
      2000; 18(14): 2718-2727.
                                                         ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 79




13. Ludwig Breast Cancer Study Group: Chemotherapy with or without oophorectomy in high-risk premenopausal
    patients with operable breast cancer. J Clin Oncol 1985; 3(8): 1059-1067.
14. The ATAC Trialistsû Group. Arimidex, tamoxifen alone or in combination: Anastrozole alone or in combination
    with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast
    cancer: first results of the ATAC randomized trial. Lancet 2002; 359(9324): 2131-2139.
15. Baum M, Buzdar A, Cuzick J, et al. anastrozole alone or in combination with tamoxifen versus tamoxifen alone
    for adjuvant treatment of postmenopausal women with early-stage breast cancer. Results of the ATAC (Arimidex,
    Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 2003;98:1802-1810.
16. Winer EP, Hudis C, Burstein HJ, et al. American Society of Clinical Oncology Technology Assessment on the
    use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive
    breast cancer: status report 2004. J Clin Oncol 2005;23:1-11.
17. Early Breast Cancer Trialistsû Collaborative Group. Polychemotherapy for early breast cancer: an overview of
    the randomised trials. Lancet 2005; 365: 1687-1717.
18. Fisher B, Redmond C, Legault-Poisson S, et al. Postoperative chemotherapy and tamoxifen compared with
    tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors
    responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin
    Oncol 1990; 8(6):1005-1018.
19. Mansour EG, Gray R, Shatila AH, et al. Survival advantage of adjuvant chemotherapy in high-risk
    node-negative breast cancer: ten-year analysis-an intergroup study. J Clin Oncol 1998; 16(11):3486-3492.
20. Fisher B, Dignam J, Mamounas EP, et al. Sequential methotrexate and fluorouracil for the treatment of
    node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from
    National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP
    B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and
    fluorouracil. J Clin Oncol 1996; 14(7): 1982-1992.
21. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen
    receptor-positive breast cancer. J Natl Cancer Inst 1997; 89(22): 1673-1682.
22. Bonadonna G, Valagussa P, Moliterni A, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in
    node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 1995; 332(14): 901-906.
23. Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without
    interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and flourouracil in
    positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results of the NSABP B-15.
    J Clin Oncol 1990; 8(9): 1483-1496.
24. Hutchins L, Green S, Ravdin P, et al. CMF versus CAF with and without tamoxifen in high-risk node-negative
    breast cancer patients and a natural history follow-up study in low-risk node-negative patients: first results of
    intergroup trial INT 0102. Proc ASCO 1998; 17: 1a(abstr 2).
25. Levine MN, Bramwell VH, et al. for the National Cancer Institute of Canada Clinical Trials Group: Randomized
    trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with
    cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer.
    J Clin Oncol 1998; 16(8): 2651-2658.
80   ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




 26. Fisher B, Anderson S, Wickerham DL, et al. Increased intensification and total dose of cyclophosphamide in
     a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National
     Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol 1997; 15(5): 1858-1869.
 27. Fisher B, Anderson S, DeCillis A, et al. Further evaluation of intensified and increased total dose of
     cyclophosphamide for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast
     and Bowel Project B-25. J Clin Oncol 1999; 17(11): 3374-3388.
 28. Henderson IC, Berry D, Demetri G, et al. Improved outcomes from adding sequential paclitaxel but not from
     escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary
     breast cancer. J Clin Oncol 2003; 21(6): 976-983.
 29. Peters W, Rosner G, Vredenburgh, et al. A prospective, randomized comparison of two doses of combination
     alkylating agents (AA) as consolidation after CAF in high-risk primary breast cancer involving ten or more
     axillary lymph nodes: preliminary results of CALGB 9082 /SWOG 9114/NCIC MA-13. Proc ASCO 1999;
     18: 1a(abstr 2).
 30. Bergh J, Wiklund T, Elikstein B, et al. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with
     marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised
     trial. Lancet 2000; 356(9239): 1384-1391.
 31. Tallman M, Gray R, Robert N, et al. Conventional adjuvant chemotherapy with or without high-dose
     chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J Med 2003;
     349(1): 17-26.
 32. Rodenhuis S, Bontenbal M, Beex L, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for
     high-risk breast cancer. N Engl J Med 2003; 349(1): 7-16.
 33. Mamounas E, Bryant J, Lembersky B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant
     chemotherapy for node-positive breast cancer: Results from NSABP B-28. J Clin Oncol 2005;23:3686-96.
 34. Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med
     2005;352:2302-13.
 35. Citron M, Berry D, Cirrincione C, et al. Randomized trial of does-dense versus conventionally scheduled and
     sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive
     primary breast cancer: first report of intergroup trial C9741 / Cancer and Leukemia Group B trial 9741. J Clin
     Oncol 2003; 21(8): 1431-1439.
 36. Howell A, Cuzick J, Baum M et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial
     after completion of 5 years. adjuvant treatment for breast cancer. Lancet 2005;365:60-62.
 37. Coombes RC, Hall E, Gibson L, et al. A randomized trial of exemestane after two to three years of tamoxifen
     therapy in postmenopausal women with primary breast cancer. N Eng J Med 2004;350:1081-92
 38. Coombes RC, Parisdaen M, Jassem C, et al. First mature analysis of the Intergroup Exemestane Study. Proc
     Am Soc Clin Onc 2006.
 39. Jakesz R, Kaufmann M, Gnant M, et al. Benefits of switching postmenopausal women with hormone-sensitive
     early breast cancer to anastrozole after 2 years adjuvant tamoxifen: comined results from 3,123 women
     enrolled in the ABCSG Trial8 and the ARNO95 Trial. Breast Cancer Res Treat 2004:88 (Suppl 1):S7
                                                         ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 81




40. Boccardo F, Rubagotti A, Puntoni M, et al. Switching to anastrozole versus continued tamoxifen treatment of
    early breast cancer: Preliminary results of the Italian Tamoxifen Anastrozole trial. J Clin Oncol 2005;23:5138-47
41. Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years
    of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003;349:1793-1802
42. Goss PE, Ingle JN, Martino S, et al. Updated analysis of the NCIC CTG MA. 17 randomized placebo
    controlled trial of letrozole after five years of tamoxifen in postmenopausal women with early stage breast
    cancer. Proc Am Soc Clin Oncol 2004;23:87 (abstr 84)
43. Thurlimann B, Keshaviah A, Mouridsen HT et al. BIG 1-98: randomized double-blind phase III study to
    evaluate letrozole (L) vs. tamoxifen (T) as adjuvant endocrine therapy for postmenopausal women with
    receptorpositive breast cancer. J Clin Oncol 2005;23:6S.
44. Jonat W, Gnant M, Boccardo F et al. Switching from adjuvant tamoxifen to anastrozole in postmenopausal
    women with hormone-responsive early breast cancer: a meta-analysis of the ARNO 95 trial, ABCSG Trial 8,
    and the ITA trial.
45. Early Breast Cancer Trialistsû Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy
    for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials.
    Lancet 2005;365:1687-1717
46. The French Adjuvant Study Group. Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for
    node-positive breast cancer patients with poor prognostic factors: 5-years follow-up results of French
    Adjuvant Study Group 05 randomized trial. J Clin Oncol 2001;19:602-11.
47. Rocheû H, Fumoleau P, Spielmann M, et al. Five years analysis of the PACS 01 trial: 6 cycles of FEC100 vs
    3 cycles of FEC100 followed by 3 cycles of docetaxel for the adjuvant treatment of node positive breast
    cancer. Breast Cancer Res Treat 2004;88 (Suppl 1):S16 (abstr 27)
48. Jones SE, Holmes FA, OûShaughnessy JA, et al. Final analysis: TC (docetaxel/cyclophosphamide, 4 cycles)
    has a superior disease-free survival compared to standard AC (doxorubicin/cyclophosphamide) in 1016
    women with early breast cancer. In SABCS 2005; abstr 40.
49. Goldstein LJ, OûNeill A, Sparano J, et al. E2197: Phase III AT (doxorubicin/docetaxel) vs. AC (doxorubicin/
    cyclophosphamide) in the adjuvant treatment of node positive and high risk node negative breast cancer.
    J Clin Oncol 2005;23:7s (abstr 512)
50. Crown J, Francis P, Di Leo A, et al. Docetaxel given concurrently or sequentially to anthracyclines based
    adjuvant therapy for patients with node-positive breast cancer. A comparison with non-taxane combination
    chemotherapy. First result of the BIG 2-98 trial at 5 years median follow-up. Proc Am Soc Clin Oncol 2006;
    abstr 519.
51. Berry et al. Effects of chemotherapy on ER negative, node positive breast cancer; 20 year experience of
    CALGB and US Breast Intergroup. SABCS 2004. Abstr 29.
52. Sparano J, Martino S, Jones V, et al. Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel
    of docetaxel given every 3 weeks of weekly in patients with axillary node positive or high risk node negative
    breast cancer: results of North American Breast cancer Intergroup Trial E1199. SABCS 2005; abstr 48.
53. Romond E, Perez E, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2 positive
    breast cancer. N Eng J Med 2005; 353: 1673-84.
82   ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




 54. Piccart-Gebhart M, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER 2
     positive breast cancer. N Eng J Med 2005; 353: 1659-72.
 55. Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide
     followed by docetaxel with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab
     with docetaxel, carboplatin and trastuzumab in HER-2 positive early breast cancer patients: BCIRG 006
     study. SABCS 2005 (abstr 1).
 56. Hudis C, Berry D, Cirrinecione C, et al. Five-year follow-up of INT C9741: dose-dense (DD) chemotherapy
     (CRx) is safe and effective. SABCS 2005; abstr 41
 57. Smith IE. HERA trial update. Proc Am Soc Clin Oncol 2006. Late-breaking scientific session.
                                                          ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 83




Neoadjuvant chemotherapy
         Noeadjuvant chemotherapy À√◊Õ preoperative chemotherapy ‡ªìπ«‘∏’°“√√—°…“‚¥¬°“√„À⬓‡§¡’∫”∫—¥°àÕπ°“√
„Àâ°“√√—°…“‡©æ“–∑’˥⫬°“√ºà“μ—¥À√◊Õ°“√„™â√—ß ’√—°…“ „π√–¬–‡√‘Ë¡·√°‰¥â¡’°“√„™â neoadjuvant chemotherapy „π°“√
√—°…“¡–‡√Á߇μâ“π¡∑’Ë≈ÿ°≈“¡‡©æ“–∑’Ë (locally advanced breast cancer) ´÷Ë߉¡à “¡“√∂ºà“μ—¥‡Õ“°âÕπ¡–‡√ÁßÕÕ°‰¥â (1)
‡æ◊ËÕ∑”„Àâ°âÕπ¡–‡√Áß¡’¢π“¥‡≈Á°≈ß®π “¡“√∂ºà“μ—¥‡Õ“°âÕπ¡–‡√ÁßÕÕ°‰¥â ®“°°“√∑’Ëæ∫«à“¡–‡√Á߇μâ“π¡¡’°“√μÕ∫ πÕߥ’
μàÕ¬“‡§¡’∫”∫—¥ ‰¥â𔉪 Ÿà°“√√—°…“¥â«¬ neoadjuvant chemotherapy „π°âÕπ¡–‡√Áß∑’Ë “¡“√∂√—°…“‰¥â¥â«¬°“√ºà“μ—¥
(operable breast cancer) ‡æ◊Ëՙ૬„π°“√√—°…“¥â«¬°“√ºà“μ—¥·∫∫ breast conservation ‰¥â(2) °“√„Àâ neoadjuvant
chemotherapy ¬—ß¡’¢âÕ¥’Õ◊Ëπ Ê ¥—ßπ’È
         -  “¡“√∂ª√–‡¡‘π°“√μÕ∫ πÕߢÕß‚√§μàÕ°“√√—°…“‰¥â„π√–¬–‡«≈“∑’Ë —Èπ°«à“°“√„Àâ adjuvant chemotherapy
         -  “¡“√∂ª√–‡¡‘πÀ“ molecular markers ∑’Ë®–™à«¬„π°“√欓°√≥å°“√μÕ∫ πÕßÀ√◊Õ°“√¥◊ÈÕ¬“¢Õß‚√§¡–‡√Áß
         - ∫Õ°°“√欓°√≥å¢Õß‚√§„π√–¬–¬“« ‚¥¬¥Ÿ®“°°“√μÕ∫ πÕßμàÕ neoadjuvant chemotherapy æ∫«à“°“√
μ√«®∑“ß欓∏‘«‘∑¬“∑’ˉ¡àæ∫‡´≈≈å¡–‡√Áß„πμàÕ¡πÈ”‡À≈◊Õß∑’Ëμ—¥ÕÕ°¡“ ®– —¡æ—π∏å°—∫°“√欓°√≥å‚√§∑’Ë¥’°«à“„π°√≥’∑’Ëæ∫
‡´≈≈å¡–‡√Áß„πμàÕ¡πÈ”‡À≈◊Õß(3)
        1.1. ·π–π”°“√„Àâ neoadjuvant chemotherapy  ”À√—∫ºŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬–≈ÿ°≈“¡‡©æ“–∑’Ë (locally
advanced breast cancer) ‰¥â·°à ¡–‡√Áß∑’ËÕ¬Ÿà„π√–¬– T4 À√◊Õ N2, N3 À√◊Õ T3 ∫“ß√“¬∑’ËμâÕß°“√√—°…“¥â«¬°“√
ºà“μ—¥·∫∫ breast conservation À√◊Õ¬—ߺà“μ—¥‰¡à‰¥â
        √–¥—∫§”·π–π”:            √–¥—∫ 1
        §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ B
         ‰¥â¡’°“√»÷°…“·∫∫ randomized controlled trials À≈“¬°“√»÷°…“„πºŸâªÉ«¬∑’ˇªìπ operable breast cancer
‚¥¬‡ª√’¬∫‡∑’¬∫°“√√—°…“‚¥¬°“√„Àâ neoadjuvant chemotherapy μ“¡¥â«¬°“√ºà“μ—¥ °—∫°“√√—°…“¥â«¬°“√ºà“μ—¥°àÕπ„Àâ
¬“‡§¡’∫”∫—¥‡ √‘¡ (adjuvant chemotherapy)(2,4-7) ‰¥âº≈∑’ˇÀ¡◊Õπ°—π«à“ ‰¡à¡’§«“¡·μ°μà“ß°—π„π¥â“π disease-free
survival ·≈– overall survival μ—«Õ¬à“ßÀπ÷Ë߉¥â·°à °“√»÷°…“¢Õß°≈ÿà¡ National Surgical Adjuvant Breast Project (NSABP)
trial B18 »÷°…“ºŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬–∑’Ë 1-3 ®”π«π 1,523 √“¬ ‚¥¬°“√„Àâ cyclophosphamide √à«¡°—∫ doxorubicin
x 4 cycles ‚¥¬„À⇪ìπ·∫∫ neoadjuvant ·≈–·∫∫ adjuvant(2) æ∫«à“ ‰¡à¡’§«“¡·μ°μà“ß„π¥â“π disease-free survival ·≈–
overall survival ‡¡◊ËÕ¡’√–¬–°“√μ‘¥μ“¡ºŸâªÉ«¬‡©≈’ˬ∑’Ë 5 ªï
        1.2 ·π–π”°“√„Àâ neoadjuvant chemotherapy „πºŸâªÉ«¬¡–‡√Á߇μâ“π¡∑’Ë “¡“√∂ºà“μ—¥‰¥â (operable breast
cancer) ·≈–μâÕß°“√√—°…“¥â«¬°“√ºà“μ—¥·∫∫ breast conservation ºŸâªÉ«¬°≈ÿà¡π’ÈμâÕß¡’¢âÕ∫àß™’È«à“§«√‰¥â√—∫°“√
√—°…“‡ √‘¡¥â«¬¬“‡§¡’∫”∫—¥À≈—ß°“√ºà“μ—¥ (adjuvant chemotherapy)(8)
        √–¥—∫§”·π–π”:           √–¥—∫ 1
        §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
™π‘¥ √–¬–‡«≈“ ·≈–¢π“¥¢Õ߬“‡§¡’∫”∫—¥ (regimen, duration and dosage of neoadjuvant chemotherapy)
            ’                     Ë
        ‰¥â¡°“√»÷°…“∂÷ß™π‘¥¢Õ߬“∑’„™â„π°“√√—°…“·∫∫ neoadjuvant chemotherapy  à«π„À≠à‡ªìπ anthracycline-based
regimen °“√»÷°…“„π°“√„À⬓‡§¡’∫”∫—¥‡ √‘¡À≈—ß°“√ºà“μ—¥¡–‡√Á߇μâ“π¡ æ∫«à“ ¬“°≈ÿà¡ anthracycline containing
regimen ¡’ª√– ‘∑∏‘¿“æ·≈–‰¥âº≈¥’°«à“¬“°≈ÿà¡∑’ˉ¡à¡’ anthracycline(9) æ∫«à“Õ—μ√“°“√μÕ∫ πÕߢÕß¡–‡√Á߇μâ“π¡μàÕ
neoadjuvant chemotherapy ∑’ˇªì𬓰≈ÿà¡ anthracycline-based regimen Õ¬Ÿà„π™à«ß√–À«à“ß 60-70% ·≈–¡’°“√
μÕ∫ πÕßÕ¬à“ß ¡∫Ÿ√≥凡◊ËÕμ√«®∑“ß欓∏‘«‘∑¬“ (pathologic complete response) ª√–¡“≥ 10-15%(10-12)
84    ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




          1.3 ·π–π”„Àâ„™â anthracycline containing regimen (doxorubicin or epirubicin) ‡ªìπ Ÿμ√¬“¡“μ√∞“π„π
                                          Ë                   Ÿ      Ë
°“√„Àâ·∫∫ neoadjuvant chemotherapy ‚¥¬∑—«‰ª “¡“√∂‡≈◊Õ°„™â μ√¬“∑’‡ªìπ¡“μ√∞“π¢Õß adjuvant chemotherapy
„πºŸâªÉ«¬¡–‡√Áß√–¬–·√° ‚¥¬°“√„Àâ neoadjuvant chemotherapy ®–„Àâª√–¡“≥ 3-6 §√—Èß À√◊Õ®π¡’°“√μÕ∫ πÕß
∑’Ë¡“°∑’Ë ÿ¥∑’Ë “¡“√∂®–∑”°“√ºà“μ—¥‰¥â
                √–¥—∫§”·π–π”:            √–¥—∫ 1
                §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:        √–¥—∫ A
                                                                      Ë
               ¡’°“√»÷°…“·∫∫ randomized controlled trials 2 °“√»÷°…“∑’‡ª√’¬∫‡∑’¬∫°“√„Àâ neoadjuvant chemotherapy
¥â«¬ epirubicin-based regimen „π≈—°…≥–∑’ˇæ‘Ë¡ dose density ‚¥¬„À⬓„π√–¬–Àà“ß∑’Ë —Èπ°«à“ §◊Õ ∑ÿ° 2  —ª¥“Àå √à«¡°—∫
°“√„™â granulocyte-colony stimulating factor (G-CSF) À√◊Õ granulocyte macrophage-colony stimulating factor
(GM-CSF) °—∫°“√„À⬓„π√–¬–Àà“ß¡“μ√∞“π §◊Õ ∑ÿ° 3-4  —ª¥“Àå
                „πºŸâªÉ«¬ locally advanced breast cancer(13,14) æ∫«à“ °“√‡æ‘Ë¡ dose density ¢Õ߬“‡§¡’∫”∫—¥„π
  â É    à          à Ë
ºŸª«¬°≈ÿ¡π’È ‰¡à‰¥â™«¬‡æ‘¡Õ—μ√“°“√μÕ∫ πÕߢÕß‚√§ ·≈–‰¡àæ∫§«“¡·μ°μà“ß°—π„π¥â“π disease-free survival ·≈– overall
survival ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫°“√„À⬓„π¢π“¥·≈–√–¬–¡“μ√∞“π
           1.4 ‰¡à “¡“√∂·π–π”°“√„Àâ neoadjuvant chemotherapy „π≈—°…≥–∑’ˇæ‘Ë¡ dose density ‡ªìπ¡“μ√∞“π
„π°“√√—°…“ºŸâªÉ«¬∑’ˇªìπ locally advanced breast cancer
                √–¥—∫§”·π–π”:               √–¥—∫ 1
                §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:           √–¥—∫ A
               °“√„™â¬“‡§¡’∫”∫—¥„π°≈ÿà¡ taxanes ‰¥â·°à paclitaxel, docetaxel ´÷Ë߇ªì𬓇§¡’∫”∫—¥∑’ˉ¥âº≈¥’„π°“√√—°…“
¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬ ·≈–¡’¢âÕ¡Ÿ≈¡“°¢÷Èπ„π°“√„™â„π°“√√—°…“‡ √‘¡„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡∑’Ë°“√°√–®“¬‰ª¬—ß
                  ’
μàÕ¡πÈ”‡À≈◊Õß ‰¥â¡°“√»÷°…“·∫∫ phase III randomized controlled trials ‚¥¬°“√„™â taxanes „π°“√√—°…“·∫∫ neoadjuvant
chemotherapy ∑—Èß„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡ ‚¥¬‡ª√’¬∫‡∑’¬∫°—∫°“√„™â¬“¡“μ√∞“π∑’ˉ¡à¡’ taxanes °“√»÷°…“ à«π„À≠à
®–√«¡∑—ÈߺŸâªÉ«¬„π°≈ÿà¡∑’ˇªìπ¡–‡√Áß∑’ˉ¡à “¡“√∂ºà“μ—¥‰¥âμ—Èß·μà·√° (locally advanced breast cancer) ·≈–°≈ÿà¡∑’ˇªìπ
¡–‡√Áß∑’Ë “¡“√∂ºà“μ—¥‰¥â (operable breast cancer) °“√»÷°…“μà“ß Ê ¡’¥—ßπ’È
                   1. °“√»÷°…“¢Õß°≈ÿ¡ National Surgical Adjuvant Breast and Bowel Project (NSABP B-27)(15) ‡ªìπ°“√
                                      à
»÷°…“‡ª√’¬∫‡∑’¬∫ neoadjuvant anthracycline regimen °—∫ anthracycline-taxane regimen ∑’Ë¡’®”π«πºŸâªÉ«¬¡“°∑’Ë ÿ¥ ‚¥¬
¡’ºŸâªÉ«¬∑—Èß ‘Èπ 2411 §π∑’Ë¡’¡–‡√Á߇μâ“π¡√–¬– T1c-T3N0 À√◊Õ T1-T3N1 ‰¥â√—∫°“√ ÿà¡°“√√—°…“‡ªìπ 3 °≈ÿà¡ ‰¥â·°à °≈ÿà¡∑’Ë
1 ‰¥â√—∫ neoadjuvant AC regimen x 4 cycles μ“¡¥â«¬°“√ºà“μ—¥, °≈ÿà¡∑’Ë 2 ‰¥â√—∫ neoadjuvant AC x 4 cycles μàե⫬
docetaxel x 4 cycles μ“¡¥â«¬°“√ºà“μ—¥ ·≈–°≈ÿà¡∑’Ë 3 ‰¥â√—∫ neoadjuvant AC x 4 cycles μ“¡¥â«¬°“√ºà“μ—¥·≈– adjuvant
docetaxel x 4 cycles æ∫«à“ºŸâªÉ«¬„π°≈ÿà¡∑’Ë 2 ∑’ˉ¥â√—∫ neoadjuvant docetaxel ¡’Õ—μ√“°“√μÕ∫ πÕß∑’Ë¡“°°«à“°≈ÿà¡∑’ˉ¡à
‰¥â√—∫ (°≈ÿà¡∑’Ë 1 √«¡°—∫°≈ÿà¡∑’Ë 3) ∑—Èß„π¥â“π clinical response rate (cRR, 91% vs 85%), clinical complete response
rate (cCR, 64% vs 40%) ·≈– pathological complete response in breast rate (pCR, 26% vs 14%) Õ¬à“ß¡’π—¬
                                                                                                    à Ë
 ”§—≠∑“ß ∂‘μ‘ (p < 0.001) ‰¡àæ∫«à“¡’§«“¡·μ°μà“ß°—π„π°“√ºà“μ—¥·∫∫ breast conservation √–À«à“ß°≈ÿ¡∑’‰¥â neoadjuvant
docetaxel ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫°≈ÿà¡∑’ˉ¥â neoadjuvant AC (63% vs 62%) ·≈–‰¡à¡’§«“¡·μ°μà“ß„π¥â“π disease-free
survival ·≈– overall survival √–À«à“ß°≈ÿà¡∑’ˉ¥â neoadjuvant docetaxel °—∫°≈ÿà¡∑’ˉ¥â√—∫ neoadjuvant AC Õ¬à“߉√°Áμ“¡
„π°≈ÿࡺŸâªÉ«¬∑’ˉ¥â√—∫ neoadjuvant AC ·≈–¡’ partial response (cPR) °“√‰¥â√—∫ neoadjuvant docetaxel À≈—ß®“°‰¥â√—∫ AC
¡’º≈™à«¬‡æ‘Ë¡ disease-free survival Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘쑇¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫°≈ÿà¡∑’ˉ¥â√—∫ neoadjuvant AC
·μà‡æ’¬ßÕ¬à“߇¥’¬« (HR = 0.71, p = 0.007)
                                                           ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 85




                2. °“√»÷°…“¢Õß Aberdeen trial(16) ¡’ºŸâªÉ«¬ 162 §π∑—Èß∑’Ë¡’¡–‡√Á߇μâ“π¡¢π“¥ T > 3 cm ·≈– T3-T4N2
‰¥â√—∫°“√√—°…“¥â«¬ neoadjuvant CVAP (cyclophosphamide, vincristine, doxorubicin, prednisone) x 4 cycles
ºŸâªÉ«¬∑’Ë¡’°“√μÕ∫ πÕßμàÕ CVAP ‰¥â√—∫°“√ ÿà¡·∫à߇ªìπ 2 °≈ÿà¡ ‚¥¬°≈ÿà¡∑’Ë 1 ‰¥â√—∫¬“ CVAP μàÕÕ’° 4 cycles  à«π°≈ÿà¡∑’Ë 2
‰¥â√—∫¬“ docetaxel x 4 cycles ºŸâªÉ«¬∑’ˉ¡à¡’°“√μÕ∫ πÕßμàÕ CVAP ‰¥â√—∫°“√‡ª≈’Ë¬π¬“‡ªìπ docetaxel x 4 cycles æ∫«à“
Õ—μ√“°“√μÕ∫ πÕß‚¥¬√«¡À≈—ß®“°‰¥â√—∫ CVAP x 4 cycles = 66% (CR 14%, PR 52%) ºŸâªÉ«¬∑’Ë¡’°“√μÕ∫ πÕß
μàÕ CVAP ·≈–‰¥â¬“ docetaxel æ∫«à“ ¡’Õ—μ√“°“√μÕ∫ πÕß∑’Ë Ÿß°«à“ (85% vs 64%, p = 0.03), pathological complete
response rate (pCR) ∑’Ë Ÿß°«à“ (31% vs 15%, p = 0.06), 5-year disease-free survival ·≈– 5-year overall survival
∑’Ë Ÿß°«à“ (90% vs 72%, p = 0.04 ·≈– 97% vs 78%, p = 0.04 μ“¡≈”¥—∫) ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫°≈ÿà¡∑’ˉ¥â√—∫ CVAP
μàÕÕ’° 4 cycles πÕ°®“°π’È ºŸâªÉ«¬°≈ÿà¡∑’ˉ¡àμÕ∫ πÕßμàÕ CVAP ¬—ß¡’°“√μÕ∫ πÕß∑’Ë¥’μàÕ docetaxel (overall response
rate = 47%, CR11%, PR 36%)
               3. °“√»÷°…“¢Õß°≈ÿà¡ Anglo-Celtic Cooperative Oncology Group (ACCOG)(17) »÷°…“„πºŸâªÉ«¬ 363 §π
  Ë ’
∑’¡¡–‡√Á߇μâ“π¡¢π“¥ T > 3 cm ·≈– locally advanced cancer / inflammatory cancer ‚¥¬ ‡ª√’¬∫‡∑’¬∫°“√„Àâ neoadjuvant
AC x 6 cycles °—∫ AD (doxorubicin, docetaxel) x 6 cycles æ∫«à“∑’Ë√–¬–°“√μ‘¥μ“¡ºŸâªÉ«¬∑’Ë 32 ‡¥◊Õπ ‰¡à¡’§«“¡
·μ°μà“ß„π¥â“π overall response rate (61% vs 70%, p = 0.06) clinical complete response rate (cCR, 17% vs 20%,
p = 0.42) pathological complete response rate in breast (pCR, 24% vs 21%, p = 0.61) Õ—μ√“°“√ºà“μ—¥·∫∫ breast
conservation (20% vs 20%) ·≈–Õ—μ√“°“√°≈—∫‡ªìπ´È” (relapse rate, 31% vs 25%) „π°≈ÿà¡∑’ˉ¥â√—∫ AC °—∫°≈ÿà¡∑’ˉ¥â√—∫
AD μ“¡≈”¥—∫
                4. °“√»÷°…“¢Õß MD Anderson Cancer Center)(18) ∑’Ë»÷°…“„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡„π√–¬–∑’Ë II-IIIA (38%
node positive) 174 §π ‚¥¬‡ª√’¬∫‡∑’¬∫√–À«à“ß°“√„Àâ neoadjuvant FAC x 4 cycles °—∫ neoadjuvant paclitaxel „π¢π“¥
250 mg/m2 x 4 cycles μ“¡¥â«¬°“√ºà“μ—¥·≈– adjuvant FAC x 4 cyclesæ∫«à“ ºŸâªÉ«¬∑—Èß Õß°≈ÿà¡∑’Õ—μ√“°“√μÕ∫ πÕß
∑’Ë„°≈⇧’¬ß°—π ‚¥¬°≈ÿà¡∑’ˉ¥â FAC ¡’ overall response rate 79% (CR 24%) ‡∑’¬∫°—∫°≈ÿà¡∑’ˉ¥â paclitaxel ¡’ overall
response rate 80% (CR 26%) °≈ÿà¡∑’ˉ¥â FAC ¡’ pathological complete response rate ∑’Ë Ÿß°«à“°≈ÿà¡∑’ˉ¥â paclitaxel
(16% vs 8%) 2-year disease-free survival §≈⓬§≈÷ß°—π„π∑—Èß Õß°≈ÿà¡ (FAC 89%, paclitaxel 94%)
        1.5 ∫∑∫“∑¢Õß Taxane „π neoadjuvant chemotherapy
                1.5.1 ‰¡à·π–π”„Àâ „™â taxane ‡ªìπ¡“μ√∞“π„π°“√„Àâ neoadjuvant chemotherapy „πºŸâªÉ«¬
¡–‡√Á߇μâ“π¡∑ÿ°√“¬ ·μàÕ“®æ‘®“√≥“„πºŸâªÉ«¬∑’Ë¡’ locally advanced breast cancer ·≈–‰¡àμÕ∫ πÕßÀ√◊ÕμÕ∫
          ’ à                                                                     Ë Ÿâ É  —
 πÕ߉¡à¥μÕ neoadjuvant anthracycline-based regimen ‚¥¬·π–π”„Àâ„™â taxane À≈—ß®“°∑’ºª«¬‰¥â√∫ anthracycline
                √–¥—∫§”·π–π”:            √–¥—∫ 1
                §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
                 1.5.2 ‰¡à·π–π”„Àâ„™â taxane „π≈—°…≥–¢Õß concomitant °—∫ anthracycline „π°√≥’∑’Ëæ‘®“√≥“
„™â taxane ‡ªìπ neoadjuvant chemotherapy „πºŸâªÉ«¬∑’ˇªìπ locally advanced breast cancer
                 √–¥—∫§”·π–π”:           √–¥—∫ 1
                 §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
                „πªí®®ÿ∫—π¡’°“√„™â trastuzumab „π°“√√—°…“ºŸâªÉ«¬¡–‡√Á߇μâ“π¡„π√–¬–·æ√à°√–®“¬∑’Ë¡’ HER-2/neu
‡ªìπº≈∫«° ‰¥â¡’°“√»÷°…“‚¥¬°“√„Àâ neoadjuvant chemotherapy √à«¡°—∫ trastuzumab „π≈—°…≥–¢Õß phase II ´÷Ëßæ∫
86    ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




«à“¡’ pathologic complete response (pCR) Õ¬Ÿà„π√–À«à“ß 12%-45%(19,20) ¡’°“√»÷°…“∑’ˇªìπ phase III ‚¥¬°≈ÿà¡ MD
Anderson Cancer Center(21) ‡ª√’¬∫‡∑’¬∫°“√„Àâ neoadjuvant chemotherapy Õ¬à“߇¥’¬«´÷Ëߪ√–°Õ∫¥â«¬ paclitaxel x 4
cycles μ“¡¥â«¬ FEC x 4 cycles °—∫°“√„Àâ neoadjuvant trastuzumab ∑ÿ° Ìª¥“À凪ìπ‡«≈“ 24  —ª¥“Àå √à«¡°—∫
chemotherapy  Ÿμ√¥—ß°≈à“«„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬–∑’Ë II ·≈– IIIA ∑’Ë¡’ HER-2/neu ‡ªìπº≈∫«° æ∫«à“ μâÕߪî¥
°“√»÷°…“°àÕπ§√∫°”Àπ¥À≈—ß®“°∑’Ë¡’ºŸâªÉ«¬„π°“√«‘®—¬ 42 §π®“°∑’Ë«“ß·ºπ‡¥‘¡ 164 §π ‡π◊ËÕß®“°°≈ÿà¡∑’ˉ¥â trastuzumab
√à«¡¥â«¬‰¥âº≈¥’°«à“Õ¬à“ß™—¥‡®π„π¥â“π¢Õß pCR ∂÷ß 65% ‡¡◊ËÕ‡∑’¬∫°—∫ 26% „π°≈ÿà¡∑’ˉ¥â√—∫ chemotherapy Õ¬à“߇¥’¬«
(p = 0.016) ∑—Èßπ’ȉ¡àæ∫§«“¡·μ°μà“ß°—π„π¥â“π breast conserving surgery ·≈–º≈¢â“߇§’¬ß¥â“π°≈â“¡‡π◊ÈÕÀ—«„®
„π¢≥–∑’Ë¡’ºŸâªÉ«¬®”π«ππâÕ¬°«à“∑’Ë°”Àπ¥ Õ¬à“߉√°Áμ“¡ ¬—߉¡à¡’¢âÕ¡Ÿ≈«à“°“√„Àâ neoadjuvant trastuzumab ®–¡’º≈
™à«¬‡æ‘Ë¡Õ—μ√“°“√¡’™’«‘μ√Õ¥
       1.6 ‰¡à·π–π”„Àâ„™â neoadjuvant trastuzumab „π°“√√—°…“ºŸâªÉ«¬¡–‡√Á߇μâ“π¡∑—Èß∑’˺à“μ—¥‰¥â À√◊Õ locally
advanced breast cancer
                √–¥—∫§”·π–π”:          √–¥—∫ 1
                §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ B
                  °“√√—°…“¡–‡√Á߇μâ“π¡¥â«¬ŒÕ√å‚¡π¡’ª√–‚¬™πå„πºŸâªÉ«¬∑’Ëμ√«®æ∫ hormone receptors ‰¥â·°à estrogen
receptor (ER) ·≈– / À√◊Õ progesterone receptor (PgR) ‡ªìπº≈∫«°„π‡´≈≈å¡–‡√Áß ®“°°“√»÷°…“¢Õß neoadjuvant
                                                         â É Ë
chemotherapy À≈“¬°“√»÷°…“„π°“√√—°…“¡–‡√Á߇μâ“π¡ æ∫«à“ ºŸª«¬∑’¡’ ER ‡ªìπº≈∫«°¡’°“√μÕ∫ πÕß‚¥¬‡©æ“– pathologic
complete response (pCR) ∑’ËμË”°«à“°≈ÿà¡∑’Ë¡’ ER ‡ªìπº≈≈∫(15,22) °“√»÷°…“¥â«¬°“√„™â¬“ŒÕ√å‚¡π„π°“√√—°…“·∫∫
neoadjuvant „πºŸâªÉ«¬∑’Ë¡’ ER ‡ªìπº≈∫«° æ∫«à“Õ—μ√“°“√μÕ∫ πÕß·∫∫ pCR §àÕπ¢â“ßμË” ‚¥¬Õ¬Ÿà„π™à«ß√–À«à“ß 0-2%
 ”À√—∫ tamoxifen(23-25) ·≈– 2-5%  ”À√—∫¬“„π°≈ÿà¡ aromatase inhibitors(24-26) °“√»÷°…“·∫∫ randomized phase III
‡ª√’¬∫‡∑’¬∫°“√„™â neoadjuvant endocrine therapy ¥â«¬ tamoxifen versus aromatase inhibitors ( anastrozole, letrozole,
exemestane) „πºŸâªÉ«¬«—¬À¡¥ª√–®”‡¥◊Õπ∑’Ë¡’ ER ‡ªìπº≈∫«° æ∫«à“ ¬“„π°≈ÿà¡ aromatase inhibitors „Àâº≈°“√μÕ∫
 πÕß∑’Ë¥’°«à“ ·≈– “¡“√∂√—°…“¥â«¬°“√ºà“μ—¥·∫∫ breast conservation ‰¥â¡“°°«à“ tamoxifen(25,27-28)
       1.7 ‰¡à·π–π”„Àâ „™â¬“ŒÕ√å‚¡π‡ªìπ neoadjuvant therapy  ”À√—∫ºŸâªÉ«¬¡–‡√Á߇μâ“π¡‚¥¬∑—Ë«‰ª ·μàÕ“®
æ‘®“√≥“„Àℙ⠉¥â„πºŸâªÉ«¬ ŸßÕ“¬ÿ ( > 70 ªï) ∑’Ë¡’ ¿“æ√à“ß°“¬‰¡à·¢Áß·√ß À√◊Õ¡’‚√§Õ◊Ëπ√à«¡¥â«¬∑’Ë∑”„Àâ ‰¡à‡À¡“–
 ¡μàÕ°“√√—°…“¥â«¬ neoadjuvant chemotherapy ·≈–ºŸâªÉ«¬μâÕß¡’º≈ ER ·≈–/À√◊Õ PgR ‡ªìπº≈∫«°
                 √–¥—∫§”·π–π”:            √–¥—∫ 1
                 §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ B
                                                        ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 87




References
 1. De Lena M, Zucali R, Viganotti G, et al. Combined chemotherapy-radiotherapy approach in locally advanced
    (T3b-T4) breast cancer. Cancer Chemother Pharmacol 1978;1:53-59.
 2. Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with
    operable breast cancer. J Clin Oncol 1998;16:2672-2685.
 3. Kuerer HM, Newman LA, Smith TM, et al. Clinical course of breast cancer patients with complete pathologic
    primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin
    Oncol 1999;17:460-469.
 4. Scholl SM, Fourquet A, Asselain B, et al. Neoadjuvant versus adjuvant chemotherapy in premenopausal
    patients with tumours considered too large for breast conserving surgery : preliminary results of a randomized
    trial : S6. Eur J Cancer 1994;30:645-652.
 5. Mauriac L, MacGrogan G, Avril A, et al. Neoadjuvant chemotherapy for operable breast carcinoma larger than
    3 cm : a unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe
    Sein (IBBGS). Ann Oncol 1999;10:47-52.
 6. van der Hage JA, van de Velde CJ, Julien JP,et al. Preoperative chemotherapy in primary operable breast
    cancer. Result from the European Organization for Research and Treatment of Cancer trial 10902. J Clin
    Oncol 2001;19:4224-4237.
 7. Mauri D, Pavlidis N, Loannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: A meta-
    analysis. J Natl Cancer Inst 2005;97:188-194.
 8. Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an International Expert Panel on the
    use of neoadjuvant (primary) systemic treatment of operable breast cancer: An update. J Clin Oncol
    2006;24:1940-1949.
 9. Early Breast Cancer Trialistsû Collaborative Group (EBCTCG). Effect of chemotherapy and hormonal therapy
    for early breast cancer for recurrence and 15-year survival: an overview of the randomized trials. Lancet
    2005;365:1687-1717.
10. Smith IE, Walsh G, Jones A, et al. High complete remission rates with primary neoadjuvant infusional
    chemotherapy for large early breast cancer. J Clin Oncol 1995;13:424-429.
11. Coconi G, di Blasio B, Bisagni G, et al. Neoadjuvant chemotherapy or chemotherapy and endocrine therapy in
    locally advanced breast carcinoma. Am J Clin Oncol 1990;13:226-232.
12. Schwartz GF, Cantor RI, Biermann WA. Neoadjuvant chemotherapy before definitive treatment for stage III
    carcinoma of the breast. Arch Surg 1987;122:1430-1434.
13. Therasse P, Mauriac L, Welnicka-Jaskiewicz M, et al. Final results of a randomized phase III trial comparing
    cyclophosphamide, epirubicin and fluorouracil with a dose-intensified epirubicin and cyclophosphamide +
    filgrastim as neoadjuvant treatment in locally advanced breast cancer: An EORTC-NCIC-SIKK multicenter
    study. J Clin Oncol 2003;21:843-850,
14. Baldini E, Gardin G, Giannessi PG, et al. Accelerated versus standard cyclophosphamide, epirubicin and
    5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil: a randomized phase III trial in locally
    advanced breast cancer. Ann Oncol 2003;14:227-232.
88   ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




15. Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative
    doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and
    Bowel Project protocol B-27. J Clin Oncol 2006;24:2019-2027.
16. Smith IC, Heys SD, Hutcheon AW, et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced
    response with docetaxel. J Clin Oncol 2002;20:1456-1466.
17. Evans TRJ, Yellowless A, Foster E et al. Phase III randomized trial of doxorubicin and docetaxel versus
    doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an Anglo-Celtic
    Cooperative Oncology Group study. J Clin Oncol 2005;23:2988-2995.
18. Buzdar AU, Singletary SE, Theriault RL, et al. Prospective evaluation of paclitaxel versus combination
    chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with
    operable breast cancer. J Clin Oncol 1999;17:3412-3417.
19. Burstein HJ, Harris LN, Gelman R, et al. Preoperative therapy with trastuzumab and paclitaxel followed by
    sequential adjuvant doxorubicin / cyclophosphamide for HER2 overexpressing stage II and III breast cancer:
    a pilot study. J Clin Oncol 2003;21:46-53.
20. Wenzel C, Hussian D, Bartsch R, et al. Preoperative therapy with epidoxorubicin and docetaxel plus trastuzumab
    in patients with primary breast cancer: a pilot study. J Cancer Res Clin Oncol 2004;130:400-404.
21. Buzdar AU, Ibrahim NK, Francis D, et al. Significant higher pathologic complete remission rate after neoadjuvant
    therapy with trastuzumab, paclitaxel and epirubicin chemotherapy: result of a randomized trial in human
    epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 2005;23:3676-3685.
22. Gianni L, Baselga L, Eiermann W, et al. Feasibility and tolerability of sequential doxorubicin / paclitaxel
    followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative
    therapy. Clin Cancer Res 2005;11:8715-8721.
23. Mauriac L, Debled M, Durand M, et al. Neoadjuvant tamoxifen for hormone-sensitive non-metastatic breast
    carcinomas in early postmenopausal women. Ann Oncol 2002;13:293-298.
24. Eiermann W, Paepke S, Appfelstaedt J, et al. Preoperative treatment of postmenopausal breast cancer
    patients with letrozole: a randomized double-blind multicenter study. Ann Oncol 2001;12:1527-1532.
25. Ellis MJ, Coop A, Singh B, et al. Letrozole is more effective neoadjuvant endocrine chemotherapy than tamoxifen
    in erbB-1 and / or erbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase
    III randomized trial. J Clin Oncol 2001;19:3808-3816.
26. Semiglazov VF, Ivanov VG, Ziltzova EK, et al. The relative efficacy of neoadjuvant endocrine therapy versus
    chemotherapy in postmenopausal women with ER positive breast cancer. Proc Am Soc Clin Oncol 2004;23:519a.
27. Smith IE, Dowsett M, Ebbs SR, et al. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole,
    tamoxifen or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen or Combined with
    Tamoxifen (IMPACT) multicenter, double-blind randomized trial. J Clin Oncol 2005;23:5108-5116.
28. Semiglazov VF, Kletsel AE, Semiglazov VV, et al. Exemestane versus tamoxifen as neoadjuvant endocrine
    therapy for postmenopausal women with ER positive breast cancer (T2N1-2, T3N0-1, T4N0M0). Proc Am
    Soc Clin Oncol 2005;24:530a.
                                                            ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 89




·π«∑“ß°“√√—°…“¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬
        °“√√—°…“¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬ ‰¡à “¡“√∂√—°…“„ÀâÀ“¬¢“¥‰¥â„πªí®®ÿ∫—π ®ÿ¥ª√– ß§å¢Õß°“√√—°…“ ‡æ◊ËÕ
              Ë                  ÿ       ‘
√—°…“ Õ“°“√∑’‡°‘¥®“°¡–‡√Áß ∑”„Àâ§≥¿“æ™’«μ¢ÕߺŸª«¬¥’¢π·≈–¡’™«μ¬◊𬓫¢÷π ¥—ßπ—π„π°“√√—°…“®÷ßμâÕßæ‘®“√≥“ √–À«à“ß
                                                â É   ÷È   ’‘        È      È
ª√–‚¬™πå∑’ˉ¥â√—∫°—∫º≈¢â“߇§’¬ßμ≈Õ¥®π§à“„™â®à“¬¢Õß°“√√—°…“
          ·π«∑“ß°“√√—°…“¡’ 3 «‘∏’§◊Õ °“√„ÀâŒÕ√å‚¡π °“√„À⬓‡§¡’∫”∫—¥ ·≈– °“√„Àâ trastuzumab ‰¡à¡’°“√»÷°…“·∫∫
 ÿà¡μ—«Õ¬à“ß∑’ˇª√’¬∫‡∑’¬∫√–À«à“ß°“√„ÀâŒÕ√å‚¡πÀ√◊Õ‡§¡’∫”∫—¥ °—∫°≈ÿà¡∑’Ë√—°…“‡æ’¬ßμ“¡Õ“°“√ ·μà¡’¢âÕ¡Ÿ≈«à“ºŸâªÉ«¬∑’Ë¡’°“√
μÕ∫ πÕß μàÕ°“√√—°…“¥â«¬¬“‡§¡’∫”∫—¥ ®–¡’™’«‘μ¬◊𬓫°«à“ºŸâªÉ«¬∑’ˉ¡àμÕ∫ πÕßμàÕ°“√√—°…“ (1)
I. °“√√—°…“¥â«¬ŒÕ√å‚¡π
         1. §«√„™âŒÕ√å‚¡π„π°“√√—°…“„π°√≥’∑’Ë
            1.1 ¡’º≈ Estrogen receptor (ER) ·≈– / À√◊Õ Progesterone receptor (PR) ‡ªìπº≈∫«° ·≈–¡–‡√Á߬—ß
                 ‰¡à·æ√à°√–®“¬‰ªÕ«—¬«–¿“¬„π ´÷ËßÕ“®∑”„À⺟âªÉ«¬∂÷ß·°à™’«‘μ„π‡«≈“Õ—π√«¥‡√Á«
                 ‡™àπ extensive liver metastasis À√◊Õ pulmonary lymphangitic spread À√◊Õ brain metastasis ‡ªìπμâπ
            1.2 °√≥’∑’ˉ¡à∑√“∫º≈ ER ·≈– PR ®–æ‘®“√≥“„ÀâŒÕ√å‚¡π‡¡◊ËÕ
                 1.2.1 √–¬–ª≈Õ¥‚√§ ( disease-free interval ) π“π‡°‘π 2 ªï
                 1.2.2 μ”·Àπà ß ¢Õß°“√·æ√à ° √–®“¬‰¡à ∑”„Àâ ºŸâ ªÉ « ¬‡ ’ ¬ ™’ «‘ μ ‚¥¬√«¥‡√Á « ‡™à π μà Õ ¡πÈ” ‡À≈◊ Õ ß
                          ‡π◊ÈÕ‡¬◊ËÕ º‘«Àπ—ß °√–¥Ÿ° ‡¬◊ËÕÀÿ⡪ե ‡ªìπμâπ
                 1.2.3 Õ“¬ÿ¡“°°«à“ 50 ªï À√◊Õ «—¬À¡¥ª√–®”‡¥◊Õπ
                 1.2.4 ‡§¬μÕ∫ πÕßμàÕ°“√√—°…“¥â«¬ŒÕ√å‚¡π¡“°àÕπ
            √–¥—∫§”·π–π”:                      √–¥—∫ 1
            §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:                  √–¥—∫ A
        °“√μÕ∫ πÕßμàÕŒÕ√å‚¡π®–¢÷ÈπÕ¬Ÿà°—∫º≈¢Õß ER ·≈–/À√◊ÕPgR(2) ‚¥¬ºŸâªÉ«¬∑’Ë¡’∑—Èß ER ·≈– PR ‡ªìπº≈∫«°
¡’‚Õ°“ μÕ∫ πÕßμàÕŒÕ√å‚¡πª√–¡“≥ 50%-70%„π°√≥’∑’Ë ER À√◊Õ PR ‡ªìπº≈∫«°¡’°“√μÕ∫ πÕß 33% (·μà„π°√≥’∑’Ë
ER ·≈– PR ‡ªìπº≈≈∫ ¡’°“√μÕ∫ πÕß‡æ’¬ß 5%-10%
        °“√μÕ∫ πÕßμàÕŒÕ√å‚¡π∑—Èß„π«—¬‡®√‘≠æ—π∏ÿå·≈–«—¬À¡¥ª√–®”‡¥◊ÕπÕ¬Ÿà„π‡°≥±å„°≈⇧’¬ß°—π
         2. °“√„™âŒÕ√å‚¡π√—°…“ §«√„Àâ§√—Èß≈–™π‘¥μàÕ°—π ‰¡à§«√„ÀâÀ≈“¬™π‘¥æ√âÕ¡°—π
            √–¥—∫§”·π–π”:                 √–¥—∫ 1
            §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:             √–¥—∫ A
           ¡’¢Õ¡Ÿ≈∫àß™’«“°“√„ÀâŒÕ√å‚¡πÀ≈“¬μ—«æ√âÕ¡°—π‰¡à‰¥â∑”„Àâ¡™«μ¬◊𬓫¢÷π‡¡◊Õ‡∑’¬∫°—∫°“√„ÀâŒÕ√å‚¡πμ—«‡¥’¬«(3-14)
              â        Èà                                         ’ ’‘      È Ë
ºŸâªÉ«¬∑’ËμÕ∫ πÕßμàÕŒÕ√å‚¡πμ—«Àπ÷Ëß ·≈â«μàÕ¡“¡’°“√¥◊ÈÕ¬“‡°‘¥¢÷ÈπÕ“®μÕ∫ πÕßμàÕŒÕ√å‚¡πμ—«Õ◊Ëπ(15)
         3. ‰¡à·π–π”„Àâ„™âŒÕ√å‚¡πæ√âÕ¡°—∫‡§¡’∫”∫—¥„π°“√√—°…“¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬
            √–¥—∫§”·π–π”:               √–¥—∫ 1
            §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:           √–¥—∫ A
       ®“°¢âÕ¡Ÿ≈°“√»÷°…“·∫∫ Randomized trials ·≈– overview analysis æ∫«à“°“√„™âŒÕ√å‚¡πæ√âÕ¡°—∫‡§¡’∫”∫—¥ Õ“®
¡’°“√μÕ∫ πÕß∑’ˇæ‘Ë¡¢÷Èπ ·μà‰¡à∑”„À⺟âªÉ«¬¡’™’«‘μ¬◊𬓫¢÷Èπ‡¡◊ËÕ‡∑’¬∫°—∫°“√„™âŒÕ√å‚¡π‡æ’¬ßÕ¬à“߇¥’¬«(3,4,16-21)
90    ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




       4. „π°“√„™âŒÕ√å‚¡π·μà≈–™π‘¥®–‡ª≈’ˬπ·ª≈ß™π‘¥„À¡àμàÕ‡¡◊ËÕ‚√§≈ÿ°≈“¡¢÷Èπ‡∑à“π—Èπ „π°√≥’∑’Ë‚√§¬—ߧß
¢π“¥‡¥‘¡ (stable disease)  “¡“√∂„™âŒÕ√å‚¡πμ—«‡¥‘¡μàÕ‰ª‰¥â
          √–¥—∫§”·π–π”:                 √–¥—∫ 1
          §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:             √–¥—∫ A
        ¡’°“√»÷°…“æ∫«à“™à«ß™’«‘μ¢ÕߺŸâªÉ«¬∑’Ë√—°…“¥â«¬ŒÕ√å‚¡π·μà‚√§¬—ߧ߇¥‘¡®–‡∑à“°—∫¢ÕߺŸâªÉ«¬∑’Ë¡’°“√μÕ∫ πÕß
∫“ß à«π À√◊Õ ¡∫Ÿ√≥å ( partial À√◊Õ complete response )(22,23)
         5. ™π‘¥¢ÕߌÕ√å‚¡π∑’Ë„™â : ¢÷ÈπÕ¬Ÿà°—∫«à“ºŸâªÉ«¬‡ªìπ«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ À√◊Õ «—¬À≈—ßÀ¡¥ª√–®”‡¥◊Õπ
            5.1 ºŸâªÉ«¬«—¬°àÕπÀ¡¥ª√–®”‡¥◊Õπ : ‰¥â·°àºŸâªÉ«¬∑’ˬ—ß¡’ª√–®”‡¥◊ÕπÕ¬ŸàÀ√◊Õª√–®”‡¥◊ÕπÀ¡¥‰ªμ“¡
                 ∏√√¡™“쑉¡à‡°‘π 1 ªï
                 5.1.1 ŒÕ√å‚¡πμ—«·√°∑’˧«√„™â ; Tamoxifen À√◊Õ ovarian ablation
            √–¥—∫§”·π–π”:                    √–¥—∫ 1
            §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:                √–¥—∫ A
          „π ¡—¬°àÕπ·π–π”„Àâ∑” ovarian ablation (bilateral oophorectomy) ‡ªìπ°“√√—°…“À≈—° æ∫«à“¡’°“√μÕ∫ πÕß
Õ¬Ÿà„π™à«ß 15%-56%·≈–¡’°“√μÕ∫ πÕß‚¥¬‡©≈’ˬ 9-15 ‡¥◊Õπ (24) °“√∑” bilateral oophorectomy Õ“®„™â«‘∏’ºà“μ—¥
©“¬· ß À√◊ Õ „Àâ ¬ “°≈ÿà ¡ LHRH agonist ‡™à π leuprolide À√◊ Õ goserelin (25) „π√–¬–À≈— ß π‘ ¬ ¡„Àâ Tamoxifen
‡ªìπ°“√√—°…“À≈—°¡“°¢÷Èπ ‡π◊ËÕß®“°¡’√“¬ß“π«à“¡’ª√– ‘∑∏‘¿“æ‡∑à“°—∫°“√∑” bilateral oophorectomy (26,27)
          ®–æ‘®“√≥“„™â Tamoxifen „π°√≥’∑’˺ŸâªÉ«¬‰¡à‡§¬‰¥â Tamoxifen ¡“°àÕπÀ√◊Õ‡§¬‰¥â Tamoxifen ‡ªìπ°“√√—°…“
‡ √‘¡¿“¬À≈—ߺà“μ—¥·≈â«À¬ÿ¥‰ª·≈â«π“π‡°‘π 1 ªï¢÷Èπ‰ª
               5.1.2 ŒÕ√å‚¡πμ—«∑’Ë Õß∑’˧«√„™â °√≥’∑’Ë‚√§≈ÿ°≈“¡¡“°¢÷ÈπÀ≈—ß®“°∑’Ë¡’°“√μÕ∫ πÕßμàÕ
ŒÕ√å‚¡πμ—«·√°√–¬–Àπ÷Ëß §◊Õ Ovarian ablation À√◊Õ Tamoxifen
          √–¥—∫§”·π–π”:                 √–¥—∫ 1
          §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:             √–¥—∫ B
         °√≥’∑’˺ŸâªÉ«¬‡§¬„™â Tamoxifen ‡ªìπμ—«·√° Õ“®æ‘®“√≥“„™â ovarian ablation À√◊Õ∂⓺ŸâªÉ«¬‡§¬„™â Ovarian
ablation ‡ªìπμ—«·√°°Áæ‘®“√≥“ „Àâ Tamoxifen ‡ªìπμ—«∑’Ë Õß (28,29)
                 5.1.3 ŒÕ√å ‚ ¡πμ— « ∑’Ë   “¡∑’Ë § «√„™â ° √≥’ ∑’Ë ‚ √§≈ÿ ° ≈“¡¡“°¢÷È π À≈— ß ®“°∑’Ë ¡’ ° “√μÕ∫ πÕßμà Õ
ŒÕ√å‚¡πμ—«∑’Ë Õß√–¬–Àπ÷Ëߧ◊Õ progestin ( megestrol acetate À√◊Õ medroxyprogesterone acetate ) À√◊Õ selective
aromatase inhibitors (AI)
           √–¥—∫§”·π–π”:                    √–¥—∫ 1
           §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:                √–¥—∫ B
        „π°√≥’∑’Ë¥◊ÈÕμàÕŒÕ√å‚¡πμ—«∑’Ë ÕßÀ≈—ß®“°μÕ∫ πÕß√–¬–Àπ÷Ëß Õ“®æ‘®“√≥“„Àâ Progestin À√◊Õ Õ“®æ‘®“√≥“ „Àâ AI
‰¥â„π√“¬∑’Ë∑” Oophorectomy ·≈â«(30)
          5.2 ºŸâªÉ«¬«—¬À≈—ßÀ¡¥ª√–®”‡¥◊Õπ : ‰¥â·°à 1. ºŸâªÉ«¬Õ“¬ÿ > 60ªï À√◊Õ 2. ºŸâªÉ«¬Õ“¬ÿ < 60ªï ·≈–ª√–®”
‡¥◊ÕπÀ¡¥‰ªμ“¡∏√√¡™“μ‘¡“°°«à“ 1 ªï ‚¥¬ºŸâªÉ«¬μâÕ߉¡à‰¥â√—∫‡§¡’∫”∫—¥ GnRH analogue À√◊Õ tamoxifen ·≈–√–¥—∫¢Õß
FSH ·≈– estradiol Õ¬Ÿà„π‡°≥±å«—¬À¡¥ª√–®”‡¥◊Õπ À√◊Õ 3. ‡§¬ºà“μ—¥√—߉¢àÕÕ°∑—Èß Õߢâ“ß
             5.2.1 ŒÕ√å‚¡πμ—«·√°∑’˧«√„™â§◊Õ Tamoxifen À√◊Õ selective aromatase Inhibitor
          √–¥—∫§”·π–π”:                  √–¥—∫ 1
          §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:              √–¥—∫ A
                                                           ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 91




         Tamoxifen ‰¥â√—∫°“√¬Õ¡√—∫«à“ §«√„™â‡ªìπŒÕ√å‚¡πμ—«·√°„πºŸâªÉ«¬¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬ „πºŸâªÉ«¬
«—¬À¡¥ª√–®”‡¥◊Õπ (31-33) ´÷Ëß¡’°“√μÕ∫ πÕß 50% ·≈–¡’√–¬–‡«≈“¢Õß°“√μÕ∫ πÕß 12-15 ‡¥◊Õπ
         ¡’√“¬ß“π¢Õß Toremifene «à“¡’ª√– ‘∑∏‘¿“æ·≈–º≈¢â“߇§’¬ß‡∑à“°—∫ Tamoxifen (34)
         ¡’√“¬ß“π°“√»÷°…“¢Õß selective AI ( ‡™àπ anastrozole, letrozole À√◊Õ exemestane ) ‡ª√’¬∫‡∑’¬∫°—∫ Tamoxifen
‚¥¬„™â‡ªìπŒÕ√å‚¡πμ—«·√°„π°“√√—°…“¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬ æ∫«à“ selective AI ¡’ª√– ‘∑∏‘¿“æ ‡∑à“°—∫À√◊Õ¥’°«à“
Tamoxifen ‡™àπ„π·ßà response rate, time to progression ·μà‰¡à¡’§«“¡·μ°μà“ß°—π„π·ßà¢Õß overall survival (35-37)
         Õ¬à“߉√°Áμ“¡·π–π”„Àâ„™â Tamoxifen ‡ªìπŒÕ√å‚¡πμ—«·√° ·≈–Õ“®æ‘®“√≥“„™â selective AI „π°√≥’∑’˺ŸâªÉ«¬
¡’¢âÕÀâ“¡„π°“√„™â Tamoxifen ‡™àπ ¡’ªí≠À“ thromboembolism (deep vein thrombosis)
                 5.2.2 ŒÕ√å‚¡πμ—«∑’Ë Õß∑’˧«√„™â °√≥’∑’Ë‚√§≈ÿ°≈“¡¡“°¢÷ÈπÀ≈—ß®“°∑’Ë¡’°“√μÕ∫ πÕßμàÕ
                                   Ë
ŒÕ√å‚¡πμ—«·√° (tamoxifen) √–¬–Àπ÷ß §◊Õ selective aromatase Inhibitor (‡™àπ anastrozole, letrozole À√◊Õ exemestane)
À√◊Õ progestin (megestrol acetate À√◊Õ medroxyprogesterone acetate)
                 √–¥—∫§”·π–π”:            √–¥—∫ 1
                 §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
         „πÕ¥’μ·π–π”„Àâ„™â Progestin „π°√≥’∑’Ë¥◊ÈÕμàÕ tamoxifen ·≈â« ·μà¡’°“√»÷°…“‡ª√’¬∫‡∑’¬∫√–À«à“ß selective
aromatase Inhibitor (‡™àπ anastrozole, letrozole À√◊Õ exemestane) °—∫ Progestin „πºŸâªÉ«¬∑’Ë‚√§≈ÿ°≈“¡À≈—ß„Àâ tamoxifen
æ∫«à“ selective AI ¡’ª√– ‘∑∏‘¿“æ„π·ßà°“√μÕ∫ πÕßÀ√◊Õº≈μàÕ™à«ß™’«‘μ¥’°«à“À√◊Õ‡∑à“°—∫ Progestin ·μà¡’º≈¢â“߇§’¬ß
πâÕ¬°«à“‚¥¬‡©æ“–‡√◊ËÕßπÈ”Àπ—°μ—«∑’ˇæ‘Ë¡¢÷Èπ (38-40)
          „πªí®®ÿ∫—π·π–π”„Àâ„™â selective Al ‡ªìπŒÕ√å‚¡πμ—«∑’Ë ÕßÀ≈—ß®“°∑’Ë‚√§≈ÿ°≈“¡À≈—߉¥â tamoxifen ·μàÕ“®æ‘®“√≥“
„™â progestin ‰¥â„π°√≥’∑’˺ŸâªÉ«¬ºÕ¡À√◊Õ¡’Õ“°“√‡∫◊ËÕÕ“À“√√à«¡¥â«¬‡æ√“– progestin ∑”„À⺟âªÉ«¬Õ¬“°Õ“À“√·≈–πÈ”Àπ—°
‡æ‘Ë¡¢÷Èπ
         „π°√≥’∑’Ë„™â selective AI ‡ªìπŒÕ√å‚¡πμ—«·√° Õ“®æ‘®“√≥“„™â tamoxifen ‡ªìπŒÕ√å‚¡πμ—«∑’Ë Õß
                 5.2.3 ŒÕ√å ‚ ¡πμ— « ∑’Ë   “¡∑’Ë § «√„™â ° √≥’ ∑’Ë ‚ √§≈ÿ ° ≈“¡¡“°¢÷È π À≈— ß ®“°∑’Ë ¡’ ° “√μÕ∫ πÕßμà Õ
ŒÕ√å‚¡πμ—«∑’Ë Õß√–¬–Àπ÷Ëߧ◊Õ progestin ( megestrol acetate À√◊Õ medroxyprogesterone acetate) À√◊Õ selective
aromatase Inhibitor ( ‡™àπ anastrozole, letrozole À√◊Õ exemestane )
                 √–¥—∫§”·π–π”:               √–¥—∫ 1
                 §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ B
                                                                                                                   (41)
         ¡’√“¬ß“π°“√„™â AI „πºŸâªÉ«¬∑’Ë‚√§≈ÿ°≈“¡À≈—ß„Àâ tamoxifen ·≈– progestin ·≈â«æ∫«à“¡’°“√μÕ∫ πÕß
„π°√≥’∑’ˇ§¬‰¥â AI ‡ªìπŒÕ√å‚¡πμ—«∑’Ë Õß·≈â«‚√§≈ÿ°≈“¡ ·π–π”„Àâ„™â progestin ‡ªìπμ—«μàÕ‰ª
         6 ¢π“¥¢ÕߌÕ√å‚¡π·μà≈–™π‘¥∑’Ë·π–π”„Àâ„™â:
            Antiestrogen:
            Tamoxifen                                20 mg/day per oral
            Toremifene                               60 mg/day per oral
            LHRH agonist:
            Leuprolide                               3.75 mg subcutaneous q 4 weeks
            Goserelin                                3.6 mg subcutaneous at anterior abdominal wall q 4 wks
92    ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




           Selective aromatase inhibitors:
           Anastrozole                                1 mg/day per oral
           Letrozole                                  2.5 mg/day per oral
           Exemestane                                 25 mg/day per oral
           Progestin:
           Megestrol acetate                          160 mg/day per oral
           Medroxyprogesterone acetate                1000 mg/day per oral

II. °“√„™â¬“‡§¡’∫”∫—¥„π¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬
        1. ¢âÕ∫àß™’È :   1.1 ºŸâªÉ«¬∑’Ë¡’º≈ ER ·≈– PR ‡ªìπº≈≈∫
                         1.2 ºŸâªÉ«¬∑’Ë‚√§≈ÿ°≈“¡À√◊Õ¥◊ÈÕμàÕŒÕ√å‚¡π
                         1.3 ºŸâªÉ«¬∑’Ë‚√§·æ√à°√–®“¬Õ¬à“ß√«¥‡√Á«·≈–Õ“®¡’Õ—πμ√“¬∂÷ß™’«‘μ ‡™àπ °√–®“¬‰ªμ—∫,ªÕ¥
                             (lymphangitic spread) À√◊Õ ¡Õ߇ªìπμâπ
                  √–¥—∫§”·π–π”:              √–¥—∫ 1
                  §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
          ¬—߉¡à¡’°“√»÷°…“·∫∫ ÿࡇª√’¬∫‡∑’¬∫ °≈ÿà¡∑’Ë„À⇧¡’∫”∫—¥°—∫°≈ÿà¡∑’Ë√—°…“μ“¡Õ“°“√ ·μà¡’°“√»÷°…“·∫∫
meta-analysis ·≈– population-based cohort ∑’Ë∫àß«à“‡§¡’∫”∫—¥™à«¬„Àâ™à«ß™’«‘μ‡æ‘Ë¡¢÷Èπª√–¡“≥ 6-9 ‡¥◊Õπ (42,43)
        2. ‰¡à·π–π”„Àℙ⬓‡§¡’∫”∫—¥√à«¡°—∫ŒÕ√å‚¡πæ√âÕ¡°—π ·μà„Àâ„™âμàÕ®“°°—π
                √–¥—∫§”·π–π”:            √–¥—∫ 1
                §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
           °“√„™â‡§¡’∫”∫—¥æ√âÕ¡°—∫ŒÕ√å‚¡π‰¡à‰¥â∑”„Àâ™à«ß™’«‘μ‡æ‘Ë¡¢÷Èπ‡¡◊ËÕ‡∑’¬∫°—∫‡§¡’∫”∫—¥‡æ’¬ßÕ¬à“߇¥’¬« (3,4,44-53)
        3. ™π‘¥¢Õ߇§¡’∫”∫—¥:
           3.1 °√≥’¢Õ߬“ Ÿμ√·√°: ·π–π”„Àâ „™â classical CMF À√◊Õ Anthracycline-containing regimen
‡™àπ FAC, AC, EC, À√◊Õ FEC ‡ªìπμâπ ¥—ßπ’È:
                                ’Ë Ÿâ É         —
                3.1.1 °√≥’∑ºª«¬‰¡à‡§¬‰¥â√∫°“√√—°…“‡ √‘¡À≈—ߺà“μ—¥¥â«¬¬“‡§¡’∫”∫—¥¡“°àÕπ:·π–π”„Àâ„™â
classical CMF À√◊Õ Anthracycline-containing regimen ‡™àπ FAC, AC, EC, À√◊Õ FEC ‡ªìπμâπ
                 3.1.2 °√≥’∑’˺ŸâªÉ«¬‡§¬‰¥â√—∫°“√√—°…“‡ √‘¡À≈—ߺà“μ—¥¥â«¬¬“‡§¡’∫”∫—¥¡“°àÕππ“π‡°‘π 2 ªï
·π–π”„Àℙ⬓‡§¡’∫”∫—¥™ÿ¥‡¥‘¡‰¥â‚¥¬‡©æ“– classical CMF „π°√≥’¢Õß Anthracycline-containing regimen ·π–π”
„Àℙ⬓‡§¡’∫”∫—¥™ÿ¥„À¡à·∑π
              3.1.3 °√≥’∑’˺ŸâªÉ«¬‡§¬‰¥â√—∫°“√√—°…“‡ √‘¡À≈—ߺà“μ—¥¥â«¬¬“‡§¡’∫”∫—¥¡“°àÕππ“ππâÕ¬°«à“
2 ªï ·π–π”„Àℙ⬓‡§¡’∫”∫—¥™ÿ¥„À¡à·∑π
              √–¥—∫§”·π–π”:           √–¥—∫ 1
              §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
           ¡’°“√»÷°…“·∫∫ meta-analysis æ∫«à“°“√„™â¬“‡§¡’∫”∫—¥À≈“¬μ—«æ√âÕ¡°—π®–‰¥âª√– ‘∑∏‘¿“楒°«à“°“√„™â¬“
‡§¡’∫”∫—¥‡æ’¬ßμ—«‡¥’¬«‚¥¬¡’ relative hazard ratio (HR) ¢Õß™à«ß™’«‘쇪ìπ 0.70 (95% confidence intervals (CIs) 0.59-
0.84)(4) „π°√≥’¢Õß CMF°“√„™â classical CMF („™â cyclophosphamide ·∫∫°‘π) ‡¡◊ËÕ‡∑’¬∫°—∫°“√„™â modified CMF
(intravenous 3-week CMF) æ∫«à“°“√„™â classical CMF ¡’°“√μÕ∫ πÕß∑’Ë¥’°«à“ (48% °—∫ 29%; p 0.003) ·≈–¡’
                                                             ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 93




™à«ß™’«‘μ∑’Ë¥’°«à“ (17 °—∫ 12 ‡¥◊Õπ; p 0.016) °“√„™â modified CMF(55)
             Anthracycline-containing regimen ¡’°“√μÕ∫ πÕß∑’Ë¥’°«à“·≈–¡’™à«ß™’«‘μ∑’Ë¥’°«à“ CMF ‡≈Á°πâÕ¬‚¥¬¡’
relative HR 0.89 (95% CIs 0.82-0.97)(4) ·μà¡’º≈¢â“߇§’¬ß¡“°°«à“ CMF ¥â«¬ Õ¬à“߉√°Áμ“¡¢âÕ¡Ÿ≈¢Õß°“√»÷°…“‰¥â
√«¡∑—Èß classical CMF ·≈– modified CMF
             „πªí®®ÿ∫—π¡’¢âÕ¡Ÿ≈æ∫«à“°“√„™â Taxanes (docetaxel À√◊Õ paclitaxel) √à«¡°—∫ Anthracycline (doxorubicin
À√◊Õ epirubicin) ¡’°“√μÕ∫ πÕß∑’Ë¥’°«à“°“√„™â Anthracycline √à«¡°—∫ cyclophosphamide ·μଗ߉¡à¡’¢âÕ¡Ÿ≈™—¥‡®π«à“ ∑”„Àâ
™à«ß™’«‘μ¬◊𬓫¢÷Èπ (56-62) ®÷߬—߉¡à·π–π”„Àℙ⇪ì𬓙ÿ¥·√°„π¢≥–π’È
            3.2 °√≥’¢Õ߬“ Ÿμ√∑’Ë Õ߇¡◊ËÕ‚√§≈ÿ°≈“¡À≈—ß„À⬓™ÿ¥·√°:
                  3.2.1 °√≥’∑’ˇ§¬‰¥â Anthracycline-containing regimen ‡ªì𬓠Ÿμ√·√° ·π–π”„Àâ„™â Taxanes
                                                                                            Ë
(docetaxel À√◊Õ paclitaxel) (√–¥—∫§”·π–π”: √–¥—∫ 1, §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A) À√◊Õ ¬“μ—«Õ◊𠇙àπ Vinorelbine,
                                                                                                          Ë
capecitabine, gemcitabine À√◊Õ CMF ‡ªìπμâπ (√–¥—∫§”·π–π”: √–¥—∫ 1, §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ B) ‡ªì𬓠Ÿμ√∑’ Õß
                3.2.2 °√≥’ ∑’Ë „ ™â CMF ‡ªì 𠬓 Ÿ μ √·√° ·π–π”„Àâ „ ™â Anthracycline-containing regimen
‡ªì𬓠Ÿμ√∑’Ë Õß ·≈⫧àլ摮“√≥“„™â ¬“μ—«Õ◊Ëπ ¥—ß∑’Ë°≈à“«‰«â„π 3.2.1 μàÕ‰ª
                √–¥—∫§”·π–π”:           √–¥—∫ 1
                §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ B
            ‰¡à¡’¢âÕ¡Ÿ≈‡ª√’¬∫‡∑’¬∫√–À«à“ß°≈ÿà¡∑’Ë„À⬓‡§¡’∫”∫—¥°—∫°≈ÿà¡∑’Ë√—°…“μ“¡Õ“°“√ ·μà¡’¢âÕ¡Ÿ≈‡ª√’¬∫‡∑’¬∫√–À«à“ß
¬“„À¡à„π°≈ÿà¡ Taxane ·≈– Vinorelbine ‡∑’¬∫°—∫¬“‡°à“∑’ˇ§¬„™â„πÕ¥’μæ∫«à“ “¡“√∂∑”„Àâ¡’™’«‘μ¬◊𬓫¢÷Èπ (50,63-66)
¡’√“¬ß“π‡ª√’¬∫‡∑’¬∫√–À«à“ß°“√„™â docetaxel √à«¡°—∫ capecitabine °—∫ docetaxel ‡æ’¬ßμ—«‡¥’¬« „πºŸâªÉ«¬∑’ˇ§¬‰¥â√—∫
anthracycline ¡“°àÕπ æ∫«à“°“√„™â docetaxel √à«¡°—∫ capecitabine ∑”„Àâ¡’™à«ß™’«‘μ‡æ‘Ë¡¡“°¢÷Èπ (14.5 ‡¥◊Õπ °—∫ 11.5
‡¥◊Õπ; p=0.0126) ‡¡◊ËÕ‡∑’¬∫°—∫ docetaxel ‡æ’¬ßμ—«‡¥’¬«(54) ¡’√“¬ß“π‡ª√’¬∫‡∑’¬∫√–À«à“ß°“√„™â paclitaxel √à«¡°—∫
gemcitabine °—∫ pacllitaxel ‡æ’¬ßμ—«‡¥’¬« „πºŸâªÉ«¬∑’ˇ§¬‰¥â√—∫ anthracycline ¡“°àÕπ æ∫«à“°“√„™â paclitaxel √à«¡°—∫
gemcitabine ∑”„Àâ¡’ progression-free survival ·≈– overall survival ‡æ‘¡¡“°¢÷π ‡¡◊Õ‡∑’¬∫°—∫ paclitaxel ‡æ’¬ßμ—«‡¥’¬«(79,82)
                                                                      Ë       È Ë
¡’√“¬ß“π°“√„™â capecitabine, gemcitabine ·≈– Vinorelbine „πºŸâªÉ«¬∑’ˇ§¬‰¥â anthracycline ¡“°àÕπ ·≈â«æ∫«à“¡’°“√
μÕ∫ πÕß(80)
              3.3 °√≥’ ¢ Õ߬“ Ÿ μ √∑’Ë   “¡‡¡◊Ë Õ ‚√§≈ÿ ° ≈“¡À≈— ß „Àâ ¬ “ Ÿ μ √∑’Ë   Õß : ·π–π”„Àâ „ ™â Capecitabine
À√◊Õ Vinorelbine À√◊Õ Gemcitabine „π°√≥’∑’ˇ§¬‰¥â Taxane ‡ªì𬓠Ÿμ√∑’Ë Õß À√◊Õæ‘®“√≥“‡¢â“‚§√ß°“√»÷°…“
(clinical trial) À√◊Õ√—°…“μ“¡Õ“°“√·≈â«·μà°√≥’
                   √–¥—∫§”·π–π”:              √–¥—∫ 1
                   §ÿ≥¿“æ¢ÕßÀ≈—°∞“π:          √–¥—∫ B
            ¡’°“√»÷°…“·∫∫ Phase II ¢Õß Capecitabine „πºŸâªÉ«¬∑’Ë¥◊ÈÕμàÕ Anthracycline ·≈– Taxane æ∫«à“¡’°“√μÕ∫
            (67)
 πÕß 20%         πÕ°®“°π’È¡’°“√»÷°…“·∫∫ Phase II ¢Õß Vinorelbine ·≈– Gemcitabine „πºŸâªÉ«¬∑’Ë¥◊ÈÕμàÕ Taxane
·≈â«æ∫«à“¡’°“√μÕ∫ πÕ߇™àπ°—π(68,69)
94     ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




         4 √–¬–‡«≈“¢Õß°“√„À⬓‡§¡’∫”∫—¥: „π°√≥’∑’Ë¡’°“√μÕ∫ πÕßμàÕ¬“‡§¡’∫”∫—¥ Õ“®æ‘®“√≥“„À⬓‡§¡’
           ∫”∫—¥‰ª√–¬–Àπ÷Ëß ( 6-8 ™ÿ¥ ) ·≈â«À¬ÿ¥ À√◊Õ„Àâ ‰ª‡√◊ËÕ¬Ê ®π°«à“‚√§®–≈ÿ°≈“¡μàÕ‰ª
                ¢âÕ·π–π”:                √–¥—∫ 1
                §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
              ¡’°“√»÷°…“‡ª√’¬∫‡∑’¬∫√–À«à“ß°“√„À⇧¡’∫”∫—¥·∫∫ intermittent °—∫ continuous æ∫«à“º≈°“√»÷°…“
¬—߉¡à “¡“√∂¬◊π¬—π‰¥â™—¥‡®π«à“«‘∏’‰Àπ¥’°«à“°—π‡æ√“–¡’∑—ÈߢâÕ¡Ÿ≈∑’Ë«à“ °“√„Àâ·∫∫ continuous ‰¡à‰¥â∑”„Àâ ™à«ß™’«‘μ¬◊𬓫
¢÷Èπ ‡¡◊ËÕ‡∑’¬∫°—∫ intermittent(70-74) ·μàÕ“®¡’ progression-free survival ‡æ‘Ë¡¡“°¢÷Èπ(70,72,73) ∫“ß√“¬ß“πæ∫«à“°“√„Àâ·∫∫
continuous ¡’∑—Èß progression-free survival ·≈– overall survival ‡æ‘Ë¡¢÷Èπ ‡¡◊ËÕ‡∑’¬∫°—∫·∫∫ intermittent(75,76) Õ¬à“߉√
°Áμ“¡°“√„Àâ·∫∫ continuous ¡’º≈¢â“߇§’¬ß¡“°«à“·∫∫intermittent
       5. ∫∑∫“∑¢Õß high-dose chemotherapy ·≈– bone marrow transplantation À√◊Õ stem cell support :
‰¡à·π–π”„Àℙ⫑∏’°“√√—°…“¥—ß°≈à“«„π¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬„π¢≥–π’È
                 ¢âÕ·π–π”:              √–¥—∫ 1
                 §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
            ¡’¢Õ¡Ÿ≈„πªí®®ÿ∫πæ∫«à“°“√„™â high-dose chemotherapy ‰¡à∑”„À♫μ¬◊𬓫¢÷π ·μࡺ≈¢â“߇§’¬ß‡æ‘¡¢÷π(77,78)
               â           —                                            ’‘        È     ’             Ë È

         6. ¢π“¥·≈– Ÿμ√¢Õ߇§¡’∫”∫—¥∑’Ë·π–π”„Àâ„™â:
            . CMF regimen:    cyclophosphamide      100 mg/m2/day po d1-14
            (q 4 weeks)       Methotrexate          40 mg/m2 IV d1,8
                              5-FU                  600 mg/m2 IV d1,8
            . FAC regimen:    5-FU                  500 mg/m2 IV
            (q 3 weeks)       Doxorubicin           50 mg/m2 IV
            . AC regimen:     Doxorubicin           60 mg/m2 IV
            (q 3 weeks)       Cyclophosphamdie      600 mg/m2 IV
            . FEC regimen:    5-FU                  500 mg/m2 IV
            (q 3 weeks)       Epirubicin            50-90 mg/m2 IV
                              Cyclophosphamdie      500 mg/m2 IV
            . EC regimen:     Epirubicin            60-90 mg/m2 IV
            (q 3 weeks)       Cyclophosphamdie      600 mg/m2 IV
            Paclitaxel        175 mg/m2 IV over 3 hours q 3 weeks
            Docetaxel         70-100 mg/m2 IV over 1 hour q 3 weeks
            Gemcitabine       800-1250 mg/m2 IV over 30 minutes d1,8,15 q 4 weeks
            Vinorelbine       25-30 mg/m2 IV over 6-10 minutes d1,8 q 3 weeks
            Capecitabine      1250 mg/m2 PO bid pc d1-14 q 3 weeks
                                                          ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 95




III. °“√„™â Trastuzumab „π¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬: ·π–π”„Àℙ⠄π°√≥’∑’Ë °“√¬âÕ¡
HER-2 ‚¥¬«‘∏’ immunohistochemical stain (IHC) ‡ªìπ 3+ À√◊Õ 2+√à«¡°—∫ Fluorescence in situ hybridization (FISH)
‡ªìπº≈∫«° ‡∑à“π—Èπ ·≈–Õ“®æ‘®“√≥“„™â√à«¡°—∫ Taxane ‡ªì𬓠Ÿμ√·√°„π°√≥’∑’ˇ§¬‰¥â anthracycline ¡“°àÕπ
                  ¢âÕ·π–π”:               √–¥—∫ 1
                  §ÿ≥¿“æ¢ÕßÀ≈—°∞“π: √–¥—∫ A
            °“√„™â Trastuzumab §«√Õ¬Ÿà„π¥ÿ≈¬æ‘π‘®¢Õß·æ∑¬åºŸâ‡™’ˬ«™“≠∑“߇§¡’∫”∫—¥‡ªìπÀ≈—° ·≈–æ‘®“√≥“„™â
„πºŸâªÉ«¬‡ªìπ√“¬Ê‰ª
              ¡’√“¬ß“π°“√„™â Trastuzumab „π°“√√—°…“¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬ „πºŸâªÉ«¬∑’Ë¡’ HER-2 ‡ªìπº≈∫«°
∑—Èß„πºŸâªÉ«¬∑’ˉ¡à‡§¬‰¥â·≈–‡§¬‰¥â‡§¡’∫”∫—¥¡“°àÕπ æ∫«à“¡’°“√μÕ∫ πÕß 26% ·≈– 15% μ“¡≈”¥—∫ ¡’√“¬ß“π°“√„™â
Trastuzumab √à«¡°—∫‡§¡’∫”∫—¥ ‡ª√’¬∫‡∑’¬∫°—∫°“√„™â‡§¡’∫”∫—¥‡æ’¬ßÕ¬à“߇¥’¬« æ∫«à“°“√„™â Trastuzumab √à«¡°—∫‡§¡’
∫”∫—¥¡’°“√Õ¬Ÿà√Õ¥‚¥¬‡©≈’ˬ∑’Ë¥’°«à“°“√„™â‡§¡’∫”∫—¥‡æ’¬ßÕ¬à“߇¥’¬«Õ¬à“ß¡’π—¬ ”§—≠∑“ß ∂‘μ‘ Trastuzumab ®–‰¥âº≈¥’
‡©æ“–„πºŸâªÉ«¬∑’Ë¡’ HER-2 ‚¥¬°“√¬âÕ¡«‘∏’ IHC ‡ªìπ 3+ À√◊Õ 2+√à«¡°—∫ FISH ‡ªìπº≈∫«°‡∑à“π—Èπ(81) ¡’√“¬ß“π°“√„™â
Trastuzumab √à«¡°—∫ taxane (paclitaxel or docetaxel) ‡ª√’¬∫‡∑’¬∫°—∫°“√„™â taxane ‡æ’¬ßÕ¬à“߇¥’¬« æ∫«à“ Trastuzumab
√à«¡°—∫ taxane ¡’ª√– ‘∑∏‘¿“楒°«à“°“√„™â taxane ‡æ’¬ßÕ¬à“߇¥’¬«∑—Èß„π·ßà response rate, progression-free survival ·≈–
overall survival(83,84)
96   ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




      IV. ·π«∑“ß°“√√—°…“¡–‡√Á߇μâ“π¡√–¬–·æ√à°√–®“¬ ( ¥Ÿ·ºπ¿Ÿ¡‘∑’Ë 1-3)
·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 97
98   ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡
                                                           ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 99




References
 1. Greenberg PAC, Hortobagyi GN, Smith TL, et al. Long-term follow-up of patients with complete remission
    following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996;14:2197-2205.
 2. Osborne CR, Yochmowitz MG, Knignt WA IIII, McGuire W. The value of estrogen and progesterone receptors in
    the treatment of breast cancer. Cancer 1980;46 (12 suppl ): 2884-2888.
 3. Stockler M, Wilcken NRC, Ghersi D, Simes RJ. Systematic reviews of chemotherapy and endocrine therapy in
    metastatic breast cancer. Cancer Treat Rev 2000;26:151-168.
 4. Fossati R, Confalonieri C, Torri V, et al. Cytotoxic and hormonal treatment for metastatic breast cancer: a
    systematic review of published randomized trials involving 31,510 women. J Clin Oncol 1998;16:3439-3460.
 5. Powles TJ, Gordon C, Coombes RC. Clinical trial of multiple endocrine therapy for metastatic and loclly
    advanced breast cancer with tamoxifen-aminoglutethimide-danazol compared to tamoxifen used alone. Cancer
    Res 1982;42:3458s-3460s.
 6. Beltran M, Alonso MC, Ojeda MB, et al Alternating sequential endocrine therapy: tamoxifen and
    medroxyprogesterone acetate versus tamoxifen in postmenopausal advanced breast cancer patients. Ann Oncol
    1991;2:495-499.
 7. Gill PG, Gebski V, Snyder R, et al. Randomized comparison of the effects of tamoxifen, megestrol acetate, or
    tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer{see
    comments: Ann Oncol 1993;4:712-13} Ann Oncol 1993;4: 741-744.
 8. Boccardo F, Rubagotti A, Perrotta A, et al. Ovarian ablation versus goserelin with or without tamoxifen in
    pre-perimenopausal patients with advanced breast cancer:results of a multicentric Italian study. Ann Oncol
    1994;5:337-342.
 9. Jonat W, Kaufmann M, Blamey RW, et al. A randomised study to compare the effect of the luteinising hormone
    releasing hormone (LHRH) analogue goserelin with or without tamoxifen in pre-and perimenopausal patients
    with advanced breast cancer. Eur J Cancer 1995;31A:137-142.
10. Ingle JN, Twito DI, Schaid DJ, et al. Combination hormonal therapy with tamoxifen plus fluoxymesterone versus
    tamoxifen alone in postmenopausal women with metastatic breast cancer. An updated analysis. Cancer
    1991;67:886-891.
11. Ingle JN, Twito DI, Schaid DJ, et al. Randomized clinical trial of tamoxifen alone or combined with fluoxymesterone
    in postmenopausal women with metastatic breast cancer. J Clin Oncol 1988;6:825-831.
12. Bishop JF, Smith JG, Jeal PN, et al. The effect of danazol on tumour control and weight loss in patients on
    tamoxifen therapy for advanced breast cancer : a randomised double-blind placebo controlled trial. Eur j Cancer
    1993;29A:814-818.
13. Heinonen E, Alanko A, Grohn P, Rissanen P. Nandrolone decanoate added to tamoxifen in the treatment of
    advanced breast cancer. Breast Cancer Res Treat 1985;5:75-80.
14. De Lena M, Tommasi S, Schittulli F, Lorusso V, Paradiso A. Sequential alternate administration of tamoxifen and
    medroxyprogesterone acetate in advanced breast ancer: clinical -biological randomized study. Tumori
    1990;76:190-195.
100 ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




15. Kostraba N, Kiang D, Frenning D, et al. Multiple endocrine therapy (Rx) in the management of advanced breast
    cancer. Proc Am Assoc Cancer Res 1980;21;47.
16. Kiang DT , Gay J, Goldman A, Kennedy BJ. A randornized trial of chemotherapy and hormonal therapy in
    advanced breast cancer. New Engl J Med 1985;313:1241-1246.
17. Ahmann DL, Green SJ, Bisel HF, et al . An evaluation of early or delayed adjuvant chemotherapy in
    premenopausal patients with advanced breast cancer undergoing oophorectomy: a later analysis. Am J Clin
    Oncol 1982;5:355-358.
18. Rossof AH, Gelman F, Creech RH. Randomized evaluation of combination chemotherapy vs. observation alone
    following response or stabilization after oophorectomy for metastatic breast cancer in premenopausal women.
    Am J Clin Oncol 1982;5:253-259.
19. Bezwoda WR, Derman D, De Moor NG, Lange M, Levin J, Treatment of metastatic breast cancer in oestrogen
    receptor positive patients. A randomized trial comparing tamoxifen alone versus tamoxifen plus CMF. Cancer
    1982;50: 2747- 2750.
20. The Australian and New Zealand Breast Cancer Trials Group, Clinical Oncological Society of Australia. A
    randomized trial in postmenopausal patients with advanced breast cancer comparing endocrine and cytotoxic
    therapy given sequentially or in combination. J Clin Oncol 1986;4:186-193.
21. Falkson G Falkson HC, Glidewell O, Weinberg V, Leone L, Holland J. Improved remission rates and remission
    duration in young women with metastatic breast cancer following combined oophorectomy and chemotherapy: a
    study of Cancer and Leukemia Group B. Cancer 1979;43:2215-2222.
22. Paterson AH, Cyr M, Szafran O, et al. Response to treatment and its influence on survival in metastatic breast
    cancer. Am J Clin Oncol 1985;8:283-92.
23. Patel JK, Nemoto T, Vezeridis M, et al. Does more intense palliative treatment improve overall survival in
    metastatic breast cancer patients? Cancer 1986;57:567-70.
24. Mecklenburg RS, Lipsett MB. Disappearance of metastatic breast cancer after oophorectomy. N Engl J Med
    1973;289:845-6.
25. Bajetta E, Celio L, Zilembo N, et al. Ovarian function suppression in premenopausal advanced breast cancer.
    Tumori 1994;80:28-32.
26. Ingle JN, Krook JE, Green SJ, et al. Randomized trial of bilateral oophorectomy versus tamoxfen in premeno
    pausal women with metastatic breast cancer. J Clin Oncol 1986;4:178-85.
27. Paridaens R, Therasse P, Dirix L, et al. First line hormonal treatment for metastatic breast cancer with exemestane
    or tamoxifen in postmenopausal patients - A randomized phase III trial of the EORTC Breast Group. Proc Am
    Soc Clin Oncol 2004;23:6 (abstr 515)
28. Henderson IC, Canellos Gp. Cancer of the breast: the past decade (first of two parts). N Engl J Med
    1980;302:17-30.
29. Buzdar AU. Endocrine therapy in the treatment of metastatic breast cancer. Semin Oncol 2001;28:291-304.
30. Celio L, Martinetti A, Ferrari L, et al. Premenopausal breast cancer patients treated with a gonadotropin-
    releasing hormone analog alone or in combination with an aromatase inhibitor: A comparative endocrine study.
    Anticancer Res 1999;19:2261-2268.
31. Pearson OH, Manni A, Arafah BM. Antiestrogen treatment of breast cancer: an overview. Cancer Res
    1982;42:Suppl:3424s-9s.
                                                          ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 101




32. Beex L, Pieters G, Smals A, et al. Tamoxifen versus ethinyl estradiol in the treatment of postmenopausal women
    with advanced breast cancer. Cancer Treat Rep 1981;65:179-85.
33. Matelski H, Greene R, Huberman M, et al. Randomized trial of estrogen vs. Tamoxifen therapy for advanced
    breast cancer. Am J Clin Oncol 1985;8:128-33.
34. Hayes DF, Van Syl JA, Hacking A, et al. Randomized comparison of tamoxifen and two separate doses of
    toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol 1995;13:2556-2566.
35. Dirix L, Piccart J, Lohrisch C, et al. Efficacy of and tolerance to Exemestane (E) versus Tamoxifen (T) in 1st.
    line hormone therapy (HT) of postmenopausal metastatic breast cancer (MBC) patients (pts): A European
    Organisation for the Research and Treatment of Cancer (EORTC Breast Group) Phase II trial with Pharmacia
    and Upjohn. Proc Am Soc Clin Oncol 2001;20:29a (abstr 114)
36. Bonneterre J, Buzdar A, Nabholtz JM, et al. Anastrozole is superior to tamoxifen as first-line therapy in hormone
    receptor positive advanced breast carcinoma. Cancer 2001;92:2247-58.
37. Mouridsen H, Gershanovich M, Sun Y, et al. Phase III study of letrozole versus tamoxifen as first-line therapy of
    advanced breast cancer in postmenopausal women: Analysis of survival and update of efficacy from the
    international letrozole breast cancer group. J Clin Oncol 2003;21:2101-2109.
38. Buzdar A, Jonat W, Howell A, et al. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol
    acetate in postmenopausal women with advanced breast cancer: Results of overview and analysis of two phase
    III clinical trials-The Arimidex Study Group. J Clin Oncol 1996;14:2000-2011.
39. Dombernowsky P, Smith I, Falkson G, et al. Letrozole, a new oral aromatase inhibitor for advanced breast
    cancer: Double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared
    with megestrol acetate. J Clin Oncol 1998;16:453-461.
40. Kaufmann M, Bajetta E, Dirix LY, et al. Exemestane is superior to megestrol acetate after tamoxifen failure in
    postmenopausal women with advanced breast cancer: Results of a Phase III randomized double-blind trial-The
    Exemestane Study Group. J Clin Oncol 2000;18:1399-1411.
41. Goss PE, Strasser K. Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol
    2001;19:881-894.
42. AûHern R, Ebbs S, Baum M. Does chemotherapy improve survival in advanced breast cancer? A statistical
    overview. Br J Cancer 1988;57:615-8.
43. Cold S, Jensen N, Brincker H, et al. The influence of chemotherapy on survival after recurrence in breast cancer
    - A population-based study of patients treated in the 1950s,1960s and 1970s. Eur J Cancer 1993;29A:
    1146-52.
44. Boccardo F, Rubagotti A, Rosso R, Santi L. Chemotherapy with or without tamoxifen in postmenopausal patients
    with late breast cancer. A randomized study. J Steroid Biochem 1985;23:1123-1127.
45. Mouridsen HT, Rose C, Engelsmann E, Sylvester R, Rotmensz N. Combined cytotoxic and endocrine therapy in
    postmenopausal patients with advanced breast cancer. A randomized EORTC study of CMF vs CMF+ tamoxifen.
    J Steroid Biochem 1985;23:1141-1146.
46. Tominaga T, Abe O, Ohshima A, et al. Comparison of chemotherapy with or without medroxyprogesterone
    acetate for advanced or recurrent breast cancer. Eur J Cancer 1994;30A:959-964.
102 ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




47. Gundersen S, Kvinnsland S, Klepp O, Lund E, Hannisdal E, Host H. Chemotherapy with or without high-dose
    medroxyprogesterone acetate in ooestrogen-receptor-negative advanced breast cancer. Norwegian Breast
    Cancer Group . Eur J Cancr 1992;28:390-394.
48. Falkson G, Gelman R, Tormey D, et al. Treatment of metastatic breast cancer in premenopausal women using
    CAF with or without oophorectomy: An Eastern Cooperative Oncology Group study. J Clin Oncol 1987;5:881-9.
49. Cavalli F,Beer M, Martz G, et al. Concurrent or sequential use of cytotoxic chemotherapy and hormone
    treatment in advanced breast cancer: report of the Swiss Group for Clinical Cancer Research. Br Med J 1983;286:5-8.
50. Bergh J, Jonsson PE, Blimelius B, Nygren P. A systematic overview of chemotherapy effects in breast cancer.
    Acta Oncol 2001;40:253-281.
51. Falkson G, Holcroft C, Gelman RS, Tormey DC, Wolter JM, Cummings FJ. Ten-year follow-up study of
    premenopausal women with metastatic breast cancer: an Eastern Cooperative Oncology Group study . J Clin
    Oncol 1995;13:1453-1458.
52. Viladiu P, Alonso MC, Avella A, et al. Chemotherapy versus chemotherapy plus hormonotherapy in
    postmenopausal advanced breast cancer patients. A randomized trial. Cancer 1985;56:2745-2750.
53. Perry MC, Kardinal CG, Korzun AH, et al. Chemohormonal therapy in advanced carcimona of the breast: Cancer
    and Leukemia Group B protocol 8081.J Clin Oncol 1987;5:1534-1545
54. OûShaughnessy J, Miles D, Vukelja S, et al. Superior survival with capecitabine plus docetaxel combination
    therapy in anthracycline-pretreated patients with advanced breast cancer: Phase III trial results. J Clin Oncol
    2002;20:2812-23.
55. Engelsman E, Klijn J, Rubens R, et al. Classicalû CMF vs a 3-weekly intravenous CMF schedule in
    postmenopausal patients with advanced breast cancer. An EORTC breast cancer co-operative group phase III
    trial (10808). Eur J Cancr 1991;27:966-70.
56. Nabholtz JA, Falkson G, Campos D, et al. A Phase III trial comparing doxorubicin (A) and docetaxel (T) (AT)
    to doxorubicin and cyclophosphamide (AC) as first line chemotherapy for MBC. Proc Am Soc Clin Oncol
    1999;18:127a (abstr 485)
57. Nabholtz JA, Paterson A, Dirix L, et al. A Phase III randomized trial comparing docetaxel (T), doxorubicin (D)
    and cyclophosphamide (C) (TAC) to FAC as first line chemotherapy (CT) for patients (Pts) with metastatic
    breast cancer (MBC). Proc Am Soc Clin Oncol 2001;20:22a (abstr 83)
58. Carmichael J. UKCCCR trial of Epirubicin and Cyclophosphamide (EC) Vs Epirubicin and Taxol* (ET) in the
    first line treatment of women with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2001;20:22a
    (abstr 84)
59. Bonneterre J, Dieras V, Tubiana-Hulin M, et al. 6 cycles of Epirubicin/Docetaxel (ET) versus 6 cycles of 5FU
    Epirubicin/Cyclophosphamide (FEC) as first line metastatic breast cancer (MBC) treatment. Proc Am Soc Clin
    Oncol 2001;20:42a (abstr 163)
60. Biganzoli L, Cufer T, Bruning P, et al. Doxorubicin/Taxol versus Doxorubicin/ Cyclophosphamide as first line
    chemotherapy in metastatic breast cancer: A Phase III study. Proc Am Soc Clin Oncol 2000;19:73a
    (abstr 282)
                                                         ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡ 103




61. Pluzanska A, Pienkowski T, Jelic S, et al. Phase III multicenter trial comparing Taxol/Doxorubicin (AT) vs
    5-fluorouracil/doxorubicin and cyclophosphamide (FAC) as a first line treatment for patients with metastatic
    breast cancer. Breast Cancer Res Treat 1999;57:21a
62. Jassem J, Pienkowski T, Pluzanska A, et al. Doxorubicin and paclitaxel versus Fluorouracil, doxorubicin, and
    cyclophosphamide as first-line therapy for women with metastatic breast cancer: Final results of a randomized
    Phase III multicenter trial. J Clin Oncol 2001:19:1707-1715.
63. Jones S, Winer E, Vogel C, et al. Randomized comparison of vinorelbine and melphalan in anthracycline-
    refractory advanced breast cancer. J Clin Oncol 1995;13:2567-74.
64. Dieras V, Marty M, Tubiana N, et al. Phase II randomized study of paclitaxel vs mitomycin in advanced breast
    cancer. Semin Oncol 1995;22: 33-9.
65. Sjostrom J, Blomqvist C, Mouridsen H, et al. Docetaxel compared with sequential methotrexate and
    5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study
    with crossover on progression by the Scandinavian Breast Group. Eur J Cancer 1999;35:1194-201.
66. Nabholtz JM, Senn HJ, Bezwoda WR, et al. Prospective randomised trial of docetaxel vs mitomycin C plus
    vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing
    chemotherapy. J Clin Oncol 1999;17:1413-24.
67. Blum JL, Jones SE, Buzdar AU, et al. Multicenter phase II study of capecitabine in paclitaxel-refractory
    metastatic breast cancer. J Clin Oncol 1999;17:485-493.
68. Esteva FJ, Valero V, Pusztai L, et al. Chemotherapy of metastatic breast cancer: What to expect in 2001 and
    beyond. The Oncologist 2001;6:133-146.
69. Burstein HJ, Bunnell CA, Winer EP. New cytotoxic agents and schedules for advanced breast cancer. Semin
    Oncol 2001;28:344-358.
70. Muss H, Case L, Richard FI, et al: Interrupted versus continuous chemotherapy in patients with metastatic
    breast cancer. The Peidmont Oncology Association. N Eng J Med 1991;325:1342-1348.
71. Harris A, Cantwell B, Carmichael J, et al: Comparison of short-term and continuous chemotherapy (mitoxantrone)
    for advanced breast cancer. Lancet 1990;1:186-190.
72. Falkson G, Gelman R, Pandya K, et al: Eastern Cooperative Oncology Group randomized trials of observation
    versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction
    treatment, J Clin Oncol 1998;16;1669-1676.
73. Coates A, Gebski V, Stat M, et al: Improving quality of life during chemotherapy for advanced breast cancer.
    N Eng J Med 1987;317:1490-1495.
74. Cocconi G, Bisagni G, Bacchi M, et al. A comparison of continuation vs late intensification followed by
    discontinuation of chemotherapy in advanced breast cancer. A prospective randomized trial of the Italian
    Oncology Group for Clinical Research (G.O.I R.C.). Ann Oncol 1990;1:36-44.
75. Ejlertsen B, Pfeiffer P, Pedersen D, et al: Decreased efficacy of cyclophosphamide, epirubicin and
    5-fluorouracil in metastatic breast cancer when reducing treatment duration from 18 to 6 months. Eur J Cancer
    1993;29A: 527-531.
76. Dixon A , Jackson L, Chan S, et al: Continuous chemotherapy in responsive metastatic breast cancer: A role for
    tumour markers? Br J Cancer 1993;68:181-185.
104 ·π«∑“ß°“√μ√«®«‘π‘®©—¬·≈–√—°…“‚√§¡–‡√Á߇μâ“π¡




77. Stadtmauer EA, OûNeill A, Goldstein LJ, et al. Conventional-dose chemotherapy compared with high-dose
    chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer.
    Philadelphia Bone Marrow Transplant Group. N Eng J Med 2000;342:1069-1076.
78. Crump M, Gluck S, Stewart D, et al. A randomized trial of high-dose chemotherapy (HDC) with autologous
    peripheral blood stem cell support (ASCT) compared to standard therapy in women with metastatic breast
    cancer: A National Institute of Canada (NCIC) Clinical Trials Group study. Proc Am Soc Clin Oncol 2001;20:21a
    (abstr 82).
79. OûShaughnessy J, Nag S, Calderillo-Ruiz G, et al. Gemcitabine plus paclitaxel (GT) versus pacliltaxel (T) as
    first-line treatment for anthracycline pre-treated metastatic breast cancer (MBC): Interim results of a global
    phase III study. Proc Am Soc Clin Oncol 2003;22:7 (abstr 25).
80. OûShaughnessy J, Twelves, Aapro M. Treatment for Anthracycline-pretreated metastatic breast cancer. The
    Oncologist 2002;7 (suppl 6):4-12.
81. Horton J. Trastuzumab use in breast cancer. Cancer control 2002; 9: 499-507.
82. Albain KS, Nag S, Calderillo-Ruiz G, et al. Global phase III study of gemcitabine plus paclitaxel vs paclitaxel
    as frontline therapy for metastatic breast cancer: First report of overall survival. Proc Am Soc Clin Oncol
    2004;22:5 (abstr 510).
83. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for
    metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344:783-792.
84. Extra JM, Cognetti F, Chan S, et al. First-line trastuzumab (Herceptin) plus docetaxel versus docetaxel alone
    in women with HER2-positive metastatic breast cancer: results from a randomised phase II trial (M77001).
    Breast Cancer Res Treat 2003;82 (Suppl1):S34 (abstr 217).

				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:19
posted:6/25/2011
language:English
pages:41