Improving Outcomes in Early-Stage Breast Cancer - TotalMedEd by linxiaoqin

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A Supplement to




                                                                    A UBM Medica Publication®




                            OCTOBER 2010            VOL 24 • NO 11 • SUPPLEMENT NO 4




                                      Improving Outcomes in
                                     Early-Stage Breast Cancer
                                                 Expert Reviewers
                                                 Stefan Glück, md, phd
                                             Sylvester Professor of Medicine
                                           Division of Hematology/Oncology
                                                 Department of Medicine
                                         Sylvester Comprehensive Cancer Center
                                                   University of Miami
                                                     Miami, Florida

                                           Terry Mamounas, md, mph, facs
                                                 Professor of Surgery
                                            Northeastern Ohio Universities
                                                 College of Medicine
                                                  Medical Director
                                                Aultman Cancer Center
                                                    Canton, Ohio


                                                   Medical Writer
                                                  Jennifer Klem, phd




                                                               1.0
                                                   1.0 Category 1 credit
                                                   1.5 Category 1 credits




                              For ONCOLOGY on the Web, visit www.cancernetwork.com
               Improving Outcomes in
              Early-Stage Breast Cancer

                                 Expert Reviewers


      Stefan Glück, MD, PhD                       Terry Mamounas, MD, MPH, FACS
     Sylvester Professor of Medicine                      Professor of Surgery
    Division of Hematology/Oncology                  Northeastern Ohio Universities
         Department of Medicine                           College of Medicine
Sylvester Comprehensive Cancer Center                       Medical Director
           University of Miami                          Aultman Cancer Center
              Miami, Florida                                  Canton, Ohio

                                   Medical Writer

                                Jennifer Klem, PhD
                         Klem Medical Communications, LLC
                                  Coppell, Texas




         Supported by an educational grant from Genentech, Inc. and Pfizer Inc.
PROGRAM OVERVIEW                                             •	 Conduct	an	informed	and	interactive	clinical	consulta-
Program Title                                                   tion for each patient with ESBC, including discussion
                                                                of multiple alternative treatment options, and provide
The Criteria for Improving Outcomes in Early-Stage              opportunities for the patient to request prognosis
Breast Cancer: Guidelines, Individualized Treatment,            information and second opinions
and Enhanced Communication.
                                                             •	 Implement	a	checklist-based	system	for	transferring	
Statement of Need                                               case-specific data to primary care physicians and
                                                                patients to improve long-term survivorship care of
Breast cancer is the most prevalent type of cancer              ESBC patients
among women in the United States. It is the second
leading cause of cancer-related deaths in this popula-       •	 Summarize	recent	clinical	findings	of	hormone	therapy	
tion, despite the fact that the majority of women with          and chemotherapy regimens for ESBC, interpret how
newly diagnosed breast cancer have early-stage                  they may benefit patients with hormone-sensitive
breast cancer (ESBC), which has a favorable prog-               breast cancer, and select appropriate patients to enroll
nosis. Nonetheless, specific practice patterns in the           in active clinical trials for treatment of ESBC
treatment of ESBC prevent optimal clinical outcome           Accreditation and Designation
for some patients. Established national guidelines for
the surgical and adjuvant treatment of ESBC are fre-         Physicians
quently not followed, with particular patient subpopula-     This activity has been planned and implemented in ac-
tions disproportionately affected by these disparities       cordance with the Essential Areas and policies of the
in care. Furthermore, a plethora of evidence indicates       Accreditation Council for Continuing Medical Education
not only that doctor-patient communication is crucial        (ACCME) through the joint sponsorship of the University
to patient satisfaction and outcomes, but also that this     of Kentucky College of Medicine and The Center for
type of communication is often inadequate in meeting         Medical Knowledge. The University of Kentucky Col-
the needs of the patient. Finally, in recent years a new     lege of Medicine is accredited by the ACCME to provide
set of unmet needs has been acknowledged – that of           continuing medical education for physicians.
the breast cancer survivor, specifically with respect to
smoothing the transition to management by a primary          The University of Kentucky College of Medicine des-
care provider.                                               ignates this educational activity for a maximum of 1.0
                                                             AMA PRA Category 1 Credits™. Physicians should
This monograph will present current guidelines with          only claim credit commensurate with the extent of their
discussion focused on circumstances and reasons              participation in the activity.
for nonadherence as well as proposed strategies for
increasing the use of guideline-recommended care for         The University of Kentucky College of Medicine presents
these patients. Additionally, the importance of and strat-   this activity for educational purposes only. Participants
egies for improvement of doctor-patient communication,       are expected to utilize their own expertise and judgment
the needs of breast cancer survivors, and the value of       while engaged in the practice of medicine. The content
staying up-to-date of current and emerging data in the       of the presentations is provided solely by presenters
field of ESBC will be explored.                              who have been selected for presentations because of
                                                             recognized expertise in their field.
Target Audience
                                                             Physicians Assistants
This is a 1-hour activity accredited for oncologists,        AAPA accepts AMA PRA Category 1 Credits™ from
physician assistants, nurse practitioners, nurses, and       organizations accredited by the ACCME.
pharmacists.
                                                             Nurse Practitioners
Learning Objectives
                                                             AANP accepts AMA PRA Category 1 Credits™ from
Upon completion of this activity, participants should        organizations accredited by the ACCME.
be able to:                                                  Nurses
•	 Implement	 current	 evidence-based	 guidelines	 for	      TCL Institute, LLC is a provider approved by the California
   breast-conserving surgery, lymph node dissection,         Board of Registered Nursing, Provider Number 15225, for
   radiation therapy, and radical mastectomy into your       1.2 contact hours. RNs outside of California must verify
   practice, specifically taking into consideration the      with their licensing agency for approval of this course.
   preferred first-line course and need for individualized
   treatment of patients with ESBC                           Pharmacists
•	 Design	and	employ	individualized	surgical,	adjuvant,	               The University of Kentucky College of
   and endocrine therapy regimens for patients with                    Pharmacy is accredited by the Accredi-
   postmenopausal, hormone receptor–positive ESBC,                     tation Council for Pharmacy Education
   and incorporate ongoing discussions with patients                   (ACPE) as a provider of continuing phar-
   regarding the importance of compliance throughout                   macy education.
   the prescribed course of treatment



                                                                SUPPLEMENT • OCTOBER 2010 • ONCOLOGY                   3
PROGRAM OVERVIEW (continued)                                   1.   Complete the activity in its entirety
Pharmacists (continued)                                        2.   After the activity, go to www.CECentral.com/getcredit
                                                               3.   Enter activity code XEN10095
This knowledge-based activity has been assigned ACPE
#022-999-10-071-H04-P and will award up to 1.0 contact         4.   Select the type of credit you wish to claim
hour (0.1 CEU) of continuing pharmacy education credit         5.   Log in or register for a free account
in states that recognize ACPE providers.                       6.   Complete the evaluation
Statements of credit will indicate hours and CEUs based on     7.   Get credit. A printable certificate will be available.
participation and will be issued online at the conclusion of
                                                               Nurses ONLY
the activity. Successful completion includes completing the
activity, its accompanying evaluation and posttest (score      Nurses only should log onto http://www.TotalMedEd.com/
70% or higher) and requesting credit online at conclusion      links/9044GMonograph/index.html and complete the on-
of the activity.The College complies with the Accreditation    line evaluation to receive credit. A printable certificate will
Standards for Continuing Pharmacy Education.                   be available upon completion of the activity evaluation.
Disclosures                                                    Disclosure of Unlabeled or Investigational Drugs
All planners, speakers, authors, reviewers, and staff          This educational activity may contain discussion of
members involved with content development for con-             published and/or investigational uses of agents that are
tinuing education activities sponsored by the University       not indicated by the FDA. The opinions expressed in the
of Kentucky Colleges of Medicine and Pharmacy are              educational activity are those of the faculty. Please refer
expected to disclose any real or perceived conflict of         to the official prescribing information for each product for
interest related to the content of the activity. Detailed      discussion of approved indications, contraindications, and
disclosures will be included in participant materials or       warnings. Further, attendees/participants should appraise
given prior to the start of the activity.                      the information presented critically and are encouraged to
Accordingly:                                                   consult appropriate resources for any product or device
                                                               mentioned in this program.
Dr. Stefan Glück reported that he is a consultant to, a
speaker for, and receives research support from Genen-         Disclaimer
tech, Inc.; Hoffman-La Roche Inc.; Genomic Health, Inc.;       The content and views presented in this educational activ-
sanofi-aventis U.S. LLC; Novartis Corporation; Pfizer          ity are those of the authors and do not necessarily reflect
Inc.; GlaxoSmithKline; and Abraxis BioScience, LLC.            those of the University of Kentucky Colleges of Medicine
Dr. Terry Mamounas reported that he is a consultant to         and Pharmacy; the Center for Medical Knowledge; Genen-
and speaker for sanofi-aventis U.S. LLC and Genomic            tech, Inc.; or Pfizer Inc. This material is prepared based
Health, Inc. He also reported that he is a consultant          upon a review of multiple sources of information, but it
to Genentech, Inc.; Novartis Corporation; and Bayer            is not exhaustive of the subject matter. Therefore, health
Corporation.                                                   care professionals and other individuals should review
                                                               and consider other publications and materials on the
The University of Kentucky Colleges of Medicine and            subject matter before relying solely upon the information
Pharmacy staff and The Center for Medical Knowledge            contained within this educational activity.
staff that were involved in the development of this activ-
ity have no financial relationship with any commercial         This activity has been planned and produced by the
interests that are relevant to this activity.                  University of Kentucky Colleges of Medicine and Phar-
                                                               macy and The Center for Medical Knowledge strictly as a
To resolve identified conflicts of interest, the educational   nonpromotional continuing medical education activity.The
content was fully peer-reviewed by a physician who has         University of Kentucky is an equal opportunity university.
nothing to disclose. The resulting certified activity was
found to provide educational content that is current,          Support Statement
evidence-based, and commercially balanced.
                                                               This activity is supported by an educational grant from
Instruction on How to Receive Credit                           Genentech, Inc. and Pfizer Inc.
In order to receive credit, participants must review the
CME information (accreditation, learning objectives,
faculty disclosures, etc) and complete the activity in its
entirety.                                                      Cosponsored by the University of Kentucky Colleges
                                                               of Medicine and Pharmacy and The Center for Medical
Physicians, Physician Assistants,
                                                               Knowledge.
Nurse Practitioners, and Pharmacists
The method of participation for physicians, physician
assistants, nurse practitioners, and pharmacist is as
follows:




4          ONCOLOGY • VOLUME 24 • NUMBER 4 • SUPPLEMENT
expert reviewers
stefan glück, md, phd                      Improving Outcomes in
                                           Early-Stage Breast Cancer
Sylvester Professor of Medicine
Division of Hematology/Oncology
Department of Medicine
Sylvester Comprehensive
Cancer Center
University of Miami
Miami, Florida                                                                ABSTRACT
                                                  Early-stage breast cancer is a prevalent malignancy that continues
terry mamounas, md, mph,                      to cause a significant number of cancer-related deaths each year. Cur-
facs
                                              rent evidence points to suboptimal care in patients with early-stage
Professor of Surgery
Northeastern Ohio Universities                breast cancer, especially with regard to physician use of guideline-
College of Medicine                           recommended care. Such appropriate treatment regimens as breast-
Medical Director                              conserving therapy and adjuvant therapy (including radiation therapy,
Aultman Cancer Center                         chemotherapy, and hormonal therapy) are underutilized in this patient
Canton, Ohio                                  population. Critical steps toward optimizing the appropriate treatment of
                                              early-stage breast cancer and providing the most significant benefits for
medical writer                                patients include increasing awareness of potential barriers and develop-
jennifer klem, phd                            ing strategies to overcome them. Improved communication, increased
Klem Medical Communications, llc              proactive behavior in terms of emerging data, and promotion of clinical
Coppell, Texas                                trial participation may additionally improve outcomes in this patient
                                              population. This review incorporates pertinent oncology literature
                                              in a comprehensive overview of early-stage breast cancer treatment,


I
    t is estimated that more than             including a review of existing guidelines, race and age disparities, and
    207,000 women will be diagnosed           communication strategies for oncologists. The focus is on appropriate,
    with breast cancer in 2010;[1] the        evidence-based treatment of this patient population.
majority of these women will have
early-stage disease.[2] Breast cancer
survival has increased dramatically
since 1975, from a 5-year survival         important. Each treatment modality         undergone axillary lymph node dis-
rate of 75.5% for all patients com-        used in the management of ESBC             section (ALND).[12] Thus, treatment
bined to a rate of 90.6% in 2002.          has numerous associated morbidities:       of ESBC should be based on a careful
[3] This improvement in survival is        some unique to a particular modal-         risk/benefit analysis. This monograph
also manifested in decreased breast        ity and some overlapping with other        will explore ways to improve the out-
cancer mortality rates across all age      modalities. For instance, radiation        comes of women with ESBC.
groups, although the largest magni-        therapy can increase the risk of cardiac
tude of benefit appears in patients        dysfunction, lung dysfunction, and         Treatment for ESBC:
over 70 years old.[4] While survival       secondary cancers.[6] Chemotherapy         Guidelines and Adherence
is highly favorable overall for patients   and other systemic therapies may put
with early-stage disease, it decreases     patients at risk for both permanent side   Need for Any Type of Adjuvant
dramatically within this category by       effects (infertility, cardiac dysfunc-     Therapy
stage, from a 5-year relative survival     tion) and transient side effects (cog-        According to breast cancer treat-
of 100% for stage I disease to only        nitive impairment, nausea, fatigue,        ment guidelines developed by the
67% for stage IIIA disease.[5]             hair loss).[7-10] Hormonal therapy         National Comprehensive Cancer
    Although survival is the most          can lead to bone loss, hot flashes, and    Network (NCCN), adjuvant therapy—
crucial outcome for patients with          arthralgia.[11] Even surgical proce-       which may include chemotherapy,
early-stage breast cancer (ESBC),          dures can have long-term implica-          hormonal therapy, targeted therapy,
because many patients have excellent       tions for a patient’s health, as in the    and/or radiation therapy—should be
long-term outcomes, minimizing mor-        case of lymphedema and decreased           used for women over 70 years old
bidity from treatment is also highly       arm function in patients who have          who have lymph node involvement or


                                                                   SUPPLEMENT • OCTOBER 2010 • ONCOLOGY                       5
 tumors greater than 1 cm in diameter.          adjuvant therapy, were less likely to      majority of women with stage I and II
 [13] However, compliance with these            know that adjuvant therapy improved        breast cancer, and that it is preferable
 guidelines is poor; a recent study of          survival. Moreover, they had greater       because it provides survival that is
 354 patients from 6 surgical oncology          mistrust of the medical system and less    equivalent to total mastectomy and ax-
 practices in the northeastern United           self-efficacy.                             illary dissection while preserving the
 States with stage 0, stage I, or stage            While this study identified some        breast.[18] Similarly, the 2010 NCCN
 IIA/node-negative disease reported             potential patient-centered explana-        guidelines state that BCT consisting
 that 40% did not receive guideline-            tions for underutilization of adjuvant     of lumpectomy, ALND, and whole-
 recommended care, which included               therapy, another study conducted by        breast irradiation is equivalent to
 surgery, radiation therapy, and hor-           Bickell and colleagues focused on          mastectomy with axillary dissection as
 monal therapy.[14] While this lack of          the surgeon’s perspective. This study      primary breast treatment for the major-
 compliance can represent either under-         surveyed breast cancer surgeons            ity of women with stage I and II breast
 or overutilization of therapy, evidence        who treated 119 women who did              cancers.[13] This statement is based
 suggests that adjuvant therapy is more         not receive guideline-recommended          on numerous studies demonstrating
 often underutilized. Investigators from        adjuvant therapy.[17] Investigators        that BCT produces equivalent survival
 Mount Sinai School of Medicine ex-             reported a nearly equal distribution       to that of mastectomy (Table 1). BCT
 amined the treatment of 723 women              among the top three reasons for un-        has increased over time, but stage II
 with ESBC treated surgically at four           derutilization: (1) the perceived risks,   patients lag behind stage I patients in
 Mount Sinai hospitals and found that           as judged by the surgeon, exceeded         utilization rates.[19]
 between 18% and 33% of those pa-               the expected benefits, (2) the patient         The National Cancer Institute
 tients who could have benefited from           refused treatment despite surgeon          (NCI) recently reported data sug-
 adjuvant therapy did not receive it (the       recommendation, and (3) the patient        gesting that BCS is underutilized,
 omitted therapies included radiation           did not receive surgeon-recommended        with 35% of patients with stage I
 therapy after breast-conserving sur-           care for an unknown reason (termed         or II disease receiving mastectomy.
 gery [BCS], adjuvant chemotherapy,             system failures). The authors provided     [25] Predictors for underutilization
 and hormonal therapy).[15]                     evidence that these system failures        of BCS that have been identified by
    In a study of 258 women with                were likely often due to suboptimal        a number of investigators are listed
 ESBC who underwent surgery but did             interactions between a patient’s sur-      in Table 2.[26-30] These predictors
 not receive guideline-recommended              geon and her medical oncologist, as        are varied, with some being associ-
 adjuvant therapy (radiation therapy,           when patients were referred to an          ated with patient/tumor characteristics
 chemotherapy, or hormonal therapy,             oncology clinic rather than a specific     (lower socioeconomic status, larger
 where appropriate), the same group of          oncologist’s office.                       tumor size), some associated with
 investigators surveyed these patients                                                     characteristics of the surgeon (male
 regarding their care, knowledge, medi-         Breast-Conserving Therapy                  gender, surgical training outside the
 cal mistrust, and physician communi-           (BCS With Radiation Therapy)               United States), and others associated
 cation in an attempt to define reasons            In 1990, the National Institutes        with a variety of factors (lower BCS
 for this underutilization of care.[16]         of Health (NIH) released guidelines        reimbursement, residence outside a
 They reported that untreated women,            stating that breast-conserving therapy     metropolitan area).
 compared to those who received                 (BCT) is appropriate treatment for the         Despite research showing that radi-
                                                                                           ation therapy following BCS reduces
                                                                                           local recurrence rates and increases
Table 1                                                                                    survival,[31] the NCI has reported that
Clinical Trials Showing Equivalent Overall Survival Between                                radiation therapy is omitted from BCT
Breast-Conserving Therapy and Mastectomy in Patients With                                  in one-third of women receiving BCS.
Early-Stage Breast Cancer                                                                  [25] Predictors for omission of radia-
                                                                                           tion therapy include older age, tumor
Author,                                          OS Results:
Year                    N        Length of OS    BCT vs Mastectomy       P Value           size greater than 2 cm, negative nodes,
                                                                                           treatment by surgical oncologist, and
Arriagada,                179    15 yr           RR: 1.41                  .19
1996[20]
                                                                                           residence in the western United States.
                                                                                           [26,29,32] It should be mentioned that
van Dongen,               868    10 yr           65% vs 66%                .11
2000[21]
                                                                                           omission of radiation therapy may not
                                                                                           be considered underutilization for pa-
Fisher,                 1851     20 yr           RR: 0.97                  .74             tients older than 70 with hormone re-
2002[22]
                                                                                           ceptor (HR)-positive disease who are
Veronesi,                 701    20 yr           41.7% vs 41.2%          1.0               being treated with hormonal therapy;
2002[23]
                                                                                           recent data have demonstrated that
Poggi,                    237    18.4 yr         54% vs 58%                .67             outcomes in this patient population
2003[24]                                                                                   did not improve with the addition of
OS = overall survival; RR = relative risk.                                                 radiation therapy to BCS.[33]


6             ONCOLOGY • VOLUME 24 • NUMBER 4 • SUPPLEMENT
Lymph Node Dissection                       Table 2
    Two different national guide-
                                            Characteristics Associated With Decreased Rates of
lines—from the NCCN and the
                                            Breast-Conserving Surgery (BCS)
American Society of Clinical Oncol-
ogy (ASCO)—support the use of               Patient/Tumor Characteristic                                Author, Year
sentinel lymph node biopsy (SLNB)           Age ≥ 70 yr                                                 Siesling, 2007[26];
for patients with clinically node-                                                                      Hershman, 2009[27];
negative breast cancer.[13,34] A                                                                        Smith, 2009[28]
small randomized study of patients          Lower socioeconomic status                                  Hershman, 2009[27];
with negative sentinel lymph nodes                                                                      Smith, 2009[28]
provided early support for this ap-         Lower education level                                       Smith, 2009[28]
proach; the study found that SLNB           Tumor size 2–5 cm                                           Siesling, 2007[26];
was associated with equivalent breast                                                                   Morrow, 2001[29]
cancer–related events (P = .52) and         Tumors with an extensive intraductal component              Morrow, 2001[29]
a trend toward increased survival
                                            Positive nodes                                              Siesling, 2007[26];
(P = .15) compared with ALND.[35]                                                                       Smith, 2009[28]
Sentinel lymph node biopsy has sev-
                                            Surgeon Characteristic                                      Author, Year
eral advantages over ALND, including
decreases in lymphedema, sensory            Male gender                                                 Hershman, 2009[27];
loss, drain usage, length of hospital                                                                   Mandelblatt, 2001[30]
stay, and time to resumption of nor-        Surgical training outside US                                Hershman, 2009[27]
mal daily activities; and increases in      Educated prior to 1975                                      Hershman, 2009[27]
patient-recorded quality-of-life (QOL)      Lack of belief in patient participation in treatment        Mandelblatt, 2001[30]
and arm function scores.[12] The            decisions
NCCN guidelines also support SLNB
                                            Other Characteristic                                        Author, Year
for clinically positive lymph nodes
if they are found to be negative by         Lower BCS reimbursement                                     Mandelblatt, 2001[30]
fine needle aspiration or core biopsy       Geographical region, outside northeastern US                Morrow, 2001[29];
prior to surgery.[13] Acceptance of                                                                     Smith, 2009[28]
SLNB is high, and SLNB alone for            Population density, outside metropolitan area               Smith, 2009[28]
patients with negative sentinel nodes       Practices with low volume of breast cancer cases            Mandelblatt, 2001[30]
is currently the accepted standard of
care.[12]
    Recent data from two indepen-           1 cm; the guidelines also state that                While it is true that adjuvant
dent studies presented at the 2010          chemotherapy should be considered               chemotherapy improves the overall
ASCO annual meeting confirmed               for women with lymph node–nega-                 survival of patients with ESBC, not all
that, compared to SLNB, ALND did            tive, HR-negative tumors between 0.6            patients in this population benefit from
not improve outcome in patients with        and 1.0 cm in size.[13] Each of the             it. Adjuvant chemotherapy can come
clinically node-negative disease, re-       NCCN’s seven preferred combination              at a high cost with respect to financial
gardless of whether the disease was         adjuvant chemotherapy regimens con-             resources and acute and chronic side
sentinel node–negative or sentinel          tain an anthracycline (doxorubicin), a          effects. Therefore, it is desirable to
node–positive.[36,37] However, re-          taxane (docetaxel), or both.[13] The            limit adjuvant chemotherapy to only
sults from the study examining node-        Early Breast Cancer Trialists’ Collab-          those patients most likely to derive
negative disease must be interpreted        orative Group has performed several             benefit. Within the past decade, ge-
with caution, as it did not reach its ac-   meta-analyses showing that combina-             nomic profiling tools designed to help
crual goal and was thus underpowered.       tion chemotherapy reduces the risk of           identify such patients have become
                                            death from breast cancer in women               available. The most widely used of
Chemotherapy                                with ESBC, and three of their publica-          these tools in the United States is the
   The 2000 NIH consensus state-            tions have reported that this survival          21-gene recurrence score assay, which
ment recommends chemotherapy for            advantage is present largely regardless         has been developed for patients with
women with node-positive tumors or          of HR status or nodal status.[39-41]            HR-positive, human epidermal growth
with node-negative tumors larger than           Despite the overwhelming evi-               factor receptor 2 (HER2)-negative,
1 cm, regardless of HR status.[38]          dence that adjuvant chemotherapy has            node-negative disease.[44] Using
Largely similar are the 2010 NCCN           a survival advantage in patients with           the reverse-transcriptase polymerase
breast cancer guidelines, which sup-        ESBC, some studies have shown that it           chain reaction profiles of 16 tumor-
port the use of adjuvant chemotherapy       is underutilized in ESBC populations,           associated genes and 5 housekeep-
for women with lymph node–positive          regardless of these disease character-          ing genes, a recurrence score can
disease or with lymph node–nega-            istics: node-negative, node-positive,           be calculated that classifies patients
tive, HR-negative tumors larger than        HR-negative, HR-positive.[14,42,43]             into 3 categories: low, intermediate,


                                                                        SUPPLEMENT • OCTOBER 2010 • ONCOLOGY                       7
 and high risk for recurrence when                 taking AIs have an increased risk of          examined exemestane (Aromasin) as
 treated with tamoxifen. Patients with             arthralgia, myalgia, and bone loss.           up-front therapy vs sequential therapy
 a low recurrence score are unlikely to            [56] The life-threatening nature of the       of tamoxifen followed by exemestane.
 benefit from chemotherapy and, thus,              increased risk of tamoxifen-specific          [49] Jones and colleagues reported
 may reasonably avoid an expensive,                toxicities creates a safety profile for       that, after a median follow-up of
 potentially toxic treatment.[45]                  tamoxifen that is less favorable than         5 years, both regimens produced
     It is currently unclear whether               that of the AIs.                              similar DFS, overall survival (OS),
 patients with an intermediate recur-                  A number of randomized clinical           and recurrence rates, showing that ex-
 rence score derive substantial benefit            trials have reported positive results         emestane used as up-front or sequen-
 from chemotherapy,[45] but TAI-                   with the three commercially available         tial therapy provides similar results
 LORx (Trial Assessing Individual-                 AIs. Three different approaches to hor-       to tamoxifen in women with ESBC.
 ized Options for Treatment for Breast             monal therapy have been examined:                 The third up-front therapy trial,
 Cancer), an international randomized              (1) up-front therapy, in which an AI is       BIG (Breast International Group)
 trial, seeks to address this issue.[46]           compared to tamoxifen, (2) sequential         1-98, was designed to compare 5-year
 This trial will complete accrual later            therapy, in which the AI is given 2 to        treatment with letrozole (Femara) to
 in 2010.                                          3 years after completion of tamoxifen         tamoxifen.[50] The initial design was
                                                   treatment, and (3) extended adjuvant          one of up-front therapy, with patients
 Hormonal Therapy                                  therapy, in which an AI is given              to receive either letrozole or tamoxi-
    Tamoxifen was the first hormonal               5 years after completion of tamoxifen         fen. But because positive results
 agent to demonstrate a survival ad-               treatment.                                    were being published with sequential
 vantage in the adjuvant setting.[47]                  The first clinical trial to report fa-    therapy, the trial was amended to
 More recently, the third-generation               vorable results with up-front therapy         include two additional arms: 2 years
 aromatase inhibitors (AIs) were in-               was the ATAC (Arimidex, Tamoxi-               of tamoxifen followed by 3 years of
 vestigated as potential therapies to              fen, Alone and in Combination) trial,         letrozole and 2 years of letrozole fol-
 improve outcomes in postmenopausal                which demonstrated that anastrozole           lowed by 3 years of tamoxifen.
 women with ESBC.[48-55] As a class,               (Arimidex) produced superior disease-             Up-front therapy results showed
 the AIs have a safety profile that is dis-        free survival (DFS) compared with             that patients receiving letrozole
 tinct from that of tamoxifen. Whereas             tamoxifen.[48] The TEAM (Tamoxi-              showed a significant 19% improve-
 patients taking tamoxifen have an                 fen Exemestane Adjuvant Multi-                ment in DFS (hazard ratio, 0.81;
 increased risk of endometrial cancer              national) trial was an international          P = .003) and a reduced risk of dis-
 and thromboembolic disease, patients              study of nearly 10,000 patients that          tant recurrence (hazard ratio, 0.73;
                                                                                                 P = .001) compared with those receiv-
                                                                                                 ing tamoxifen. When examining the
Table 3
                                                                                                 sequential therapy arms of the BIG
Barriers to Adherence to Oral Hormonal Therapies—and                                             1-98 trial, both had similar DFS rates
Strategies to Overcome These                                                                     after 5 years, with 87.6% for letrozole
Barriers to Adherence                 Strategies to Overcome Barriers                            followed by tamoxifen and 86.2%
Lack of tangible benefit              Discuss studies showing the benefit of adjuvant            for tamoxifen followed by letrozole,
                                      endocrine therapy                                          and neither was superior to letrozole
Lack of understanding of the                                                                     monotherapy.[51] Switching from le-
importance of adherence                                                                          trozole to tamoxifen after 2 to 3 years
Length of treatment
                                                                                                 had no impact on patient outcomes,
                                                                                                 with the letrozole monotherapy arm
Side effects of medication            Review potential side effects and develop                  and the letrozole → tamoxifen arm
                                      management strategies, as needed                           both having similar DFS and OS rates
Busy schedule (not enough             Encourage mail-order prescription refills                  at 5 years.[51] This indicates that pa-
time to refill prescriptions)                                                                    tients who are intolerant of letrozole
Cost                                  Discuss strategies to decrease costs and save time
                                                                                                 or who have developed bone loss in
                                      (mail-order refills, discount drug programs)               the first 2 to 3 years should be able to
Patient dissatisfaction with          Augment patient-provider communication by having
                                                                                                 switch to tamoxifen without compro-
treating physician                    the nurse solicit questions that may be intimidating       mising outcome.
                                      or embarrassing                                                The IES (Intergroup Exemestane
General barriers                      Identify potential barriers; provide written information   Study) trial, which took a sequential
                                      about the therapy; provide patient with professional       approach to therapy by randomly
                                      contact information; schedule regular follow-up;           assigning patients to receive either
                                      provide a list of relevant organizations and support       5 years of tamoxifen or to 2 to 3 years
                                      groups; explore specific needs/characteristics of
                                      the patient
                                                                                                 of tamoxifen followed by 2 to 3 years
                                                                                                 of exemestane, showed that patients
Data from Miaskowski et al,[62] Moore,[63] and Kirk and Hudis.[64]                               who switched from tamoxifen to


8            ONCOLOGY • VOLUME 24 • NUMBER 4 • SUPPLEMENT
exemestane after 2 to 3 years had
                                           Table 4
improved DFS compared with those
                                           Survivorship Issues Specific to Patients With Breast Cancer
who received 5 years of tamoxifen.
[52] The next two sequential therapy       Need for continuing medical evaluation
trials—ARNO (Arimidex-Nolvadex)            Local complications of therapy (eg, lymphedema, pain, numbness)
95 and The Austrian Breast and             Late complications of chemotherapy (eg, secondary leukemia, cardiac impairment,
Colorectal Cancer Study Group Trial        osteoporosis)
8—were similar to the IES trial in         Gynecologic and reproductive issues (eg, infertility, amenorrhea, increased risk of
design but examined the use of an-         endometrial cancer)
astrozole instead of exemestane.[53]       Management of menopausal symptoms
Because they were nearly identical in
design and inclusion criteria, the two     Discussion of hormone-replacement therapy
trials were analyzed together. Results     Psychosocial issues (eg, anxiety, mood disorders, sexual dysfunction)
showed a significant improvement in        Changes in lifestyle (eg, weight gain, exercise)
event-free survival with anastrozole
                                           Adapted from Burstein and Winer.[98]
(hazard ratio, 0.60; P = .0009).
    MA.17, an extended therapy trial,
provided evidence that DFS was pro-        gesterone receptor–positive invasive           tics (eg, busy schedule that makes it
longed when patients received 5 years      breast cancers regardless of patient           challenging to refill prescriptions).[62-
of letrozole after 5 years of tamoxifen.   age, lymph node status, or plans for           64] These barriers can potentially be
[54] Mamounas and colleagues con-          adjuvant chemotherapy.[13] Despite             overcome by employing the strategies
ducted the National Surgical Adjuvant      these broad guidelines, adjuvant               in Table 3. For instance, with patients
Breast and Bowel Project (NSABP)           hormonal therapy is underutilized in           who do not appreciate the benefit of
B-33 trial to similarly test exemestane    women with HR-positive ESBC, with              adjuvant hormonal therapy, studies
as extended adjuvant therapy.[55]          approximately 30% of patients not re-          showing the benefit of adjuvant en-
In this trial, postmenopausal breast       ceiving hormonal therapy, regardless           docrine therapy should be discussed.
cancer patients who were disease-          of nodal status.[57]                           General strategies to increase adher-
free after 5 years of tamoxifen were           Several studies have shown that ad-        ence, such as scheduling regular
randomly assigned to receive either        herence to hormonal therapy by wom-            follow-up, may also be used.[62,63]
5 years of exemestane (25 mg daily)        en with ESBC is low. For instance,
or 5 years of placebo. Because of the      Chlebowski and Geller reported that            Trastuzumab Therapy
positive results from the MA.17 trial,     23% to 28% of women who were                      Four large randomized trials
the NSABP trial was terminated and         enrolled in adjuvant breast cancer             examining adjuvant trastuzumab
unblinded after approximately half of      clinical trials prematurely discontin-         (Herceptin) therapy nearly simultane-
the patients had been accrued. Despite     ued hormonal therapy (tamoxifen or             ously demonstrated that the addition of
this reduction in power, results showed    AIs) after at least 4 years of follow-up.      trastuzumab to adjuvant chemotherapy
a borderline significant improvement       [58] Charlson and colleagues reported          produced a dramatic DFS and overall
in 4-year DFS in patients receiving        a similar percentage (23%) of older            survival advantage in patients with
exemestane (91% vs 89%; relative           patients prematurely discontinuing             HER2-positive ESBC.[65-67] Reduc-
risk [RR], 0.68; P = .07) as well as       adjuvant hormonal therapy.[59]                 tion in the risk of DFS events ranged
a significant improvement in 4-year        Finally, in a study of almost 1,500            from 36% to 52% and reduction in
relapse-free survival (96% vs 94%;         insured, low-income women, 36% did             the risk of death with trastuzumab
RR, 0.44; P = .004).                       not even fill their prescription for hor-      ranged from 33% to 41%. As a re-
    The use of AIs rather than tamoxi-     monal therapy, and 20% of those who            sult, practice was quickly changed to
fen is supported primarily by their        did were nonpersistent (had a greater          include adjuvant trastuzumab for
more favorable safety profile and          than 90-day gap in prescription refills).      patients with HER2-positive, stage I
their ability to reduce the risk of re-    [60] Not surprisingly, nonadherence            or greater disease[13]; the US Food
currence, rather than by an ability to     to adjuvant hormonal therapy has a             and Drug Administration (FDA) ap-
improve OS. Moreover, this choice of       negative impact on survival.[61]               proved adjuvant use of trastuzumab
hormonal therapy is only available to          A number of barriers to adherence          in November 2006.[68] Physician
postmenopausal women; tamoxifen            to oral hormonal therapies have been           adherence to HER2 testing is high,
is the only option for premenopausal       identified (Table 3) and include issues        with a recent study reporting 98.1%
women because AIs do not sufficiently      specific to therapy (eg, side effects,
block ovarian production of estrogen.      cost, and length of treatment), patient
    As a result of the above stud-         attitudes (eg, patient dissatisfaction         Address all correspondence to:
ies of hormonal agents, the NCCN           with the treating physician, lack of           TCL Institute, LLC
                                                                                          104 Towerview Court
recommends that hormonal therapy           appreciation of benefit, and lack of           Cary, NC 27513
should be considered for patients          appreciation of the importance of              919-467-0006 x 233
with estrogen receptor– and/or pro-        adherence), and patient characteris-           cme@tclinstitute.com



                                                                       SUPPLEMENT • OCTOBER 2010 • ONCOLOGY                       9
 adherence in 322 patients for whom             Racial Disparities                              Racial disparities in the treatment
 HER2 testing was indicated (breast                 In the United States, the incidence     of ESBC are not only con ned to the
 cancers that are stage 1 or higher).           of breast cancer in Caucasians exceeds      African American population. In a
 [69] In this study, trastuzumab use            that in African Americans and other         cross-sectional study of 677 women
 was appropriately administered in 51           ethnicities[2]; however, breast cancer      with ESBC treated in New York,
 of 52 patients, with 1 patient having          mortality is higher in African Ameri-       Bickell and colleagues found that race
 no documentation of HER2 overex-               cans than in Caucasians (Figure 1).[2]      played a statistically signi cant role
 pression. However, of the 45 patients          Although a number of factors may            in the underutilization of appropriate
 with stage 2 or higher HER2-positive           contribute to this disparity in mortal-     adjuvant therapy, with Caucasians
 breast cancer, 13% did not receive             ity, including differences in breast can-   having the least underuse (16%),
 trastuzumab. The reasons for this              cer screening, tumor biology, genetic       followed by Hispanics (23%) and
 underutilization of trastuzumab were           predisposition, demographics, and           African Americans (34%).[43] His-
 not explored in this study. However,           comorbidities, substantial evidence         panics are more likely to be diagnosed
 because trastuzumab increases the risk         exists that treatment differences across    at later stages than Caucasians, even
 of cardiotoxicity,[70] cardiovascular          races account for at least some of the      after poverty level is accounted for.
 morbidity is one valid reason to avoid         observed disparity.[72]                     [76] Furthermore, Hispanic patients
 trastuzumab, particularly in patients              Several independent studies ex-         with ESBC had the lowest rates of
 with increased cardiovascular risk.            amined two large US databases (Sur-         de nitive local therapy of all races in
     In the pivotal adjuvant trastuzumab        veillance, Epidemiology, and End            an analysis of SEER data from over
 trials, the incidence of class III or IV       Results [SEER] and National Cancer          375,000 women.[77]
 congestive heart failure or death from         Database) to identify treatment dif-            Sometimes, treatment disparities
 cardiac causes in the trastuzumab arm          ferences between African American           may affect QOL more than survival,
 was 4.1% in the NSABP B-31 trial               and Caucasian women.[73-75] While           as in the case of Asian American
 and 2.9% in the North Central Cancer           no disparity in the rate of BCS was         women and their mastectomy rate.
 Treatment Group N9831 trial.[65]               observed,[73] African Americans             Asian Americans have higher rates
 Examination of cardiac dysfunction             were reported to be 24% less likely         of mastectomy than other races. Im-
 reported in the N9831 trial revealed           to receive radiation therapy follow-        portant factors that contribute to this
 that older age, lower baseline left            ing BCS and to have lower odds of           increased rate include fear, cultural
 ventricular ejection fraction, and             receiving definitive locoregional           beliefs, smaller breast size, and pa-
 antihypertensive medications are risk          therapy, adjuvant hormonal therapy,         tient attitudes toward preserving the
 factors for trastuzumab-associated             and adjuvant chemotherapy.[74,75]           breast.[78] A study of 93 patients who
 cardiac dysfunction.[71]                                                                                underwent either BCT
 Despite the risk of cardio-                                                                             or mastectomy revealed
 toxicity, it is widely ac-                                                                              a modest but signi cant
                                     100
 cepted that the bene ts of                                                                              improvement in QOL
 trastuzumab outweigh the                                                                                with BCT compared with
                                      90
 risks for most patients.                                                                                mastectomy.[79]
                                           80
 Disparities in the                                                                                      Age Disparities
 Care of Patient                           70                                                               It is well established
 Subsets                                                                                                 that older women with
                                      60                                                                 breast cancer are treated
    In the above section,                                                                                less aggressively and
                                 Percent




 different areas of treat-            50                                                                 with less adherence to
 ment nonadherence were                                                                                  treatment guidelines than
 discussed in the context of          40                                                                 are younger women. For
 the general ESBC popu-                                                                                  instance, SEER data
 lation. However, non-                30                                                                 showed that increasing
 adherence is not evenly                                                                  All Races
                                                                                                         age was significantly
 distributed across the               20                                                                 associated with decreas-
                                                                                          Black
 US patient population;                                                                                  ing BCS rates, with 48%
                                      10                                                  White
 rather, certain subgroups                                                                               of patients older than
 receive less guideline-                                                                                 50 years receiving BCS,
                                       0
 recommended care than                   r o   r     r     r     r     r     r     r     r       r   a r but only 35% of patients
                                       Ze 1 yea 2 yea 3 yea 4 yea 5 yea 6 yea 7 yea 8 yea 9 yea 0 ye
 other subgroups. The               me                                                           1       older than 80 years re-
                                 Ti
 following discussion will                                   Survival Interval                           ceiving the same treat-
 focus on US treatment                                                                                   ment.[24] Similarly,
 disparities with respect to   Figure 1: Racial disparities in breast cancer survival. From numerous studies have
 race and age.                 National Cancer Institute.[2]                                             concluded that older age


10          ONCOLOGY • VOLUME 24 • NUMBER 4 • SUPPLEMENT
(aged ≥ 70-80 years) is a predictor of
less frequent utilization of radiation                                         1.0




                                            Ratio of annual recurrence rates
therapy following BCS than is seen
with younger patients.[26,29,32]                                               0.8
                                                                                                                                            < 40 years
SEER data also showed that older                                                                                                            40-49 years
women (aged ≥ 80 years) were less                                              0.6                                                          50-59 years
likely to undergo lymph node dissec-                                                                                                        60-69 years
tion as part of their BCT than younger                                         0.4                                                          < 69 years
women.[80] Finally, elderly patients
(aged ≥ 70 years) with nodal involve-                                          0.2
ment or HR-negative tumors were
less likely to receive adjuvant che-
                                                                               0.0
motherapy than younger controls.[81]
                                                                                     Recurrence rate             Mortality rate
    While it is clear that older patients
with ESBC are treated differently than        Figure 2: Effect of age on the efficacy of combination chemotherapy in patients
their younger cohorts, the question is        with early-stage breast cancer. Reprinted from Early Breast Cancer Trialists’
whether this is appropriate. There is a       Collaborative Group.[41] With permission from Elsevier.
paucity of national guidelines on the
topic of treating older patients with          be treated differently with respect to                        more intense chemotherapy produced
breast cancer, primarily because so            lymph node assessment.                                        superior outcomes.[88] Patients on
few elderly patients enroll in clinical            Finally, the NCCN guidelines de-                          capecitabine had an almost two-fold
trials, making conclusions about their         cline to make de nitive chemotherapy                          increase in the risk of death compared
responses to treatment challenging.            recommendations for patients older                            with the patients on combination che-
For instance, the NCCN does not make           than 70 years due to insuf cient data.                        motherapy (P = .02). Older patients
speci c recommendations regarding              [13] In fact, a meta-analysis conducted                       are most often inappropriately under-
the use of BCS in elderly patients             by the EBCTCG found that the ef-                              treated, primarily because of bias on
and suggests that radiation therapy              cacy of combination chemotherapy                            the part of one or more parties—phy-
is not always necessary for women              in patients with ESBC declines with                           sicians, patients, or family members.
aged 70 years or older.[13] Yood and           age (Figure 2).[41]                                           It is possible that less aggressive
colleagues, however, demonstrated                  Older patients with breast cancer                         management of breast cancer in older
that older women receiving BCT with            have an increased likelihood of having                        patients is only infrequently the result
radiation therapy had similar mortality        more favorable biologic tumor char-                           of medical complications. Thus, older
rates to those receiving mastectomy,           acteristics than younger patients,[84]                        patients should be treated according to
whereas those receiving BCS alone              which can translate into older patients                       guidelines whenever possible, as long
(without radiation therapy) were twice         with ESBC being treated less aggres-                          as such treatment does not exacerbate
as likely to die as those receiving            sively. Similarly, comorbidities (eg,                         existing comorbidities and does not
mastectomy.[82] However, the NCCN              hypertension, heart-related conditions,                       cause signi cant side effects.
recommendation that radiation ther-            arthritis, and gastrointestinal prob-
apy may be omitted in women aged               lems) increase with age,[85] making it                        Doctor-Patient Communication
70 years or older who have HR-posi-            more challenging to provide adjuvant
tive, node-negative T1 tumors[13] is           therapy to this patient population. In                            The importance of doctor-patient
supported by recent data presented at          fact, comorbidities, including heart                          communication is often ignored in the
ASCO 2010; these data showed that              failure and diabetes, are not only                            literature and in practice, but it has an
patients aged 70 years or older with           associated with the underuse of ad-                           enormous impact on patient care. For
HR-positive disease who were treated           juvant therapy;[38] they also have a                          instance, a retrospective study of near-
with BCS with tamoxifen had approxi-           signi cant negative effect on survival.                       ly 10,000 elderly women with breast
mately the same survival whether or            [86,87] However, it is not an accepted                        cancer showed that consulting with a
not radiation therapy was added.[33]           fact that older patients with ESBC                            medical oncologist prior to surgery
    The NCCN guidelines also state             derive less benefit from adjuvant                             increased the likelihood of receiving
that both ALND and SLNB are op-                therapy than younger patients, with                           guidelines-recommended care.[89]
tional in elderly patients due to the ab-      the possible exception of combition                           Another study of patients with breast
sence of de nitive data demonstrating          chemotherapy. When comparing                                  cancer, speci cally node-negative,
superior survival with the use of these        adjuvant combination chemotherapy                             HR-positive disease, demonstrated
procedures;[13] however, recent data           to single-agent capecitabine (Xeloda)                         that patients with more favorable
show that older patients (aged 55 years        in women aged 65 years or older,                              ratings of provider communication
or older) with small tumors are not less       Muss and colleagues determined that,                          were more likely to receive adjuvant
likely to have positive sentinel lymph         although moderate-to-severe toxici-                           chemotherapy.[90]
nodes than a younger cohort,[83] sug-          ties were elevated in the combination                             However, the challenges involved
gesting that older patients should not         chemotherapy arm (64% vs 33%), the                            in establishing effective doctor-pa-


                                                                                               SUPPLEMENT • OCTOBER 2010 • ONCOLOGY                  11
 tient communication are substantial.            Keating and colleagues reported that           tions, and encouraging patient partici-
 Results of a survey of over 1,100               78% of over 2,000 patients surveyed            pation in decision making.[94-96]
 women with ESBC and their surgeons              had experienced at least one of the
 demonstrated that patients and their            following problems with their physi-           Breast Cancer Survivorship
 surgeons disagreed about whether both           cian, which caused them to consider
 BCS and mastectomy were discussed               changing physicians: (1) not giving               Cancer survivorship is a relatively
 as treatment options, with patients in          understandable answers to questions,           new area of research and care that ac-
 one-third of the cases reporting that           (2) not taking enough time to answer           knowledges that the needs of patients
 both options had not been discussed             questions, and (3) not giving enough           with cancer diagnoses do not stop
 while their surgeons asserted that they         medical information.[93]                       after active treatment is terminated.
 had.[91] Another study illustrated                  Although physicians are often not          [97] According to the Institute of
 the dissatisfaction sometimes expe-             adequately trained in communication            Medicine (IOM), cancer survivorship
 rienced by patients: in this survey of          skills, several groups have studied            care is a distinct phase of care that has
 over 600 patients with breast cancer,           strategies for improving doctor-patient        been neglected in such diverse areas
 30% rated their physicians 5 or less            communication. These include in-               as advocacy, education, clinical prac-
 on a scale from 1 (poor) to 10 (good)           creasing affective, or emotional, par-         tice, and research. In the 2006 seminal
 with respect to the completeness of             ticipation with the patient, attending         report on survivorship, From Cancer
 information they received about their           to both verbal and nonverbal patient           Patient to Cancer Survivor: Lost in
 disease and treatment.[92] Moreover,            cues, encouraging patients to ask ques-        Transition, the IOM proposed four
                                                                                                essential components of patient-cen-
Table 5                                                                                         tered survivorship care: (1) preven-
Phase III Trials Currently Recruiting Patients With Early-Stage                                 tion of recurrent and new cancers and
Breast Cancer                                                                                   other late effects; (2) surveillance for
                                                                                                cancer spread, recurrence, or second
1.   Radiation therapy trials
                                                                                                cancers, and assessment of medical
     • Intraoperative vs postoperative radiation therapy (ClinicalTrials.gov identifier:        and psychosocial late effects; (3) in-
       NCT00983684)
                                                                                                tervention for consequences of cancer
     • Intensity-modulated radiation therapy vs partial organ radiation therapy
       (ClinicalTrials.gov identifier: NCT01185132)
                                                                                                and its treatment; and (4) coordination
     • Three intensity-modulated radiation therapy schedules following BCS
                                                                                                between specialists and primary care
       (ClinicalTrials.gov identifiers: NCT00818051; NCT00337064; NCT00909909)                  providers (PCPs) to ensure that all of
     • Conventional radiation therapy vs tomotherapy (ClinicalTrials.gov identifier:            the survivors’ health needs are met.
       NCT00459628)                                                                             Burstein and Winer have also identi-
     • Whole breast irradiation vs partial breast irradiation (ClinicalTrials.gov identifier:   fied a number of specific breast cancer
       NCT00892814)                                                                             survivorship issues (Table 4),[98]
2.   Hormonal therapy trials                                                                    many of which can be categorized
     • Intermittent vs continuous use of letrozole (ClinicalTrials.gov identifier:              under one of the four IOM essential
       NCT00553410)                                                                             components of survivorship care
     • Letrozole after tamoxifen (ClinicalTrials.gov identifier: NCT01064635)                   mentioned above; however, novel
     • Anastrozole with and without fulvestrant (Faslodex) (ClinicalTrials.gov identifier:      areas of need identified by these au-
       NCT00570323)                                                                             thors include psychosocial issues (eg,
3.   HER2-directed therapy trials                                                               anxiety, mood disorders, and sexual
                                                                                                dysfunction) and changes in lifestyle
     • Neratinib (anti-HER2 tyrosine kinase inhibitor) vs placebo (ClinicalTrials.gov
       identifier: NCT00878709)                                                                 (eg, weight gain and the need for
     • Lapatinib (Tykerb) vs trastuzumab (ClinicalTrials.gov identifier: NCT01137994)           increased exercise).
     • Lapatinib with trastuzumab (ClinicalTrials.gov identifier: NCT00470704)                     Central to providing comprehen-
     • Trastuzumab with and without bevacizumab (Avastin) (ClinicalTrials.gov                   sive survivorship care are cancer
       identifier: NCT00625898)                                                                 treatment summaries and survivor-
4.   Trials focusing on other therapies
                                                                                                ship care plans.[99] Although prepar-
                                                                                                ing a concise summary of previous
     • Denosumab (Prolia; anti–receptor activator of nuclear factor κB ligand                   treatment may appear to be a trivial
       [RANKL] antibody) as adjuvant treatment in high-risk early breast cancer
       (ClinicalTrials.gov identifier: NCT01077154)                                             and uncomplicated matter, the fre-
     • Bevacizumab with combination chemotherapy (ClinicalTrials.gov identifier:                quent separation of the various breast
       NCT00679029)                                                                             cancer treatments in time, space, and
     • Ixabepilone (Ixempra) vs paclitaxel for triple-negative disease (ClinicalTrials.gov      health care systems makes the likeli-
       identifier: NCT00789581)                                                                 hood of mistakes and oversight high.
     • Adjuvant sequential vs combination chemotherapy (ClinicalTrials.gov identifier:          Thus, such a summary should be
       NCT00670878)                                                                             prepared to facilitate communication
     • Bisphosphonates as adjuvant therapy (ClinicalTrials.gov identifiers:                     among providers. Survivorship care
       NCT00332709; NCT00196872)
                                                                                                plans are also created to facilitate
c


12           ONCOLOGY • VOLUME 24 • NUMBER 4 • SUPPLEMENT
the coordination of care with other        ularly relevant to patients with ESBC       mendations, with respect to BCT,
physicians (eg, internal medicine          because the vast majority of them will      hormonal therapy, and chemotherapy.
specialists, PCPs, gynecologists) who      spend many years as cancer survivors        Moreover, particular subpopulations
can provide successful ongoing care        as a result of their favorable progno-      of patients are disproportionately
for breast cancer patients. These plans    ses. In addition, they receive a wide       affected by these disparities in care.
must address not only immediate            range of different therapies, includ-       Other areas of physician behavior that
posttreatment and long-term effects        ing surgical resection/reconstruction,      can create barriers to appropriate pa-
of cancer treatment, but also the ongo-    hormonal therapy, chemotherapy,             tient management include unsatisfac-
ing psychosocial burden of a cancer        and radiation therapy, so they may be       tory doctor-patient communication, a
diagnosis, and the potential for late      dealing with a multitude of chronic         lack of proactive behavior regarding
sequelae of treatment. Survivorship        or late effects of therapy. Thus, this      emerging data, including the promo-
care plans, which are a relatively new     population of patients stands to derive     tion of clinical trial participation, and
concept, have yet to be widely used        great benefit from improvements in          inadequate care of patients after they
in practice.                               survivorship care.                          have reached the survivorship stage,
    The need for improved survivor-                                                    which can be decades-long for many
ship care is great, as attested by pa-     Ongoing Clinical Trials and                 patients with ESBC. Finally, because
tients and physicians alike. A 2007        Emerging Data                               these patients often receive oral agents
survey of PCPs revealed that confi-                                                    (eg, tamoxifen, AIs) as part of their
dence in caring for cancer survivors          Staying abreast of emerging data         treatment, patient adherence is also
is not high; only 49% of respondents       and ongoing clinical trials is crucial      an obstacle to optimal care. As these
were comfortable having responsibil-       to providing optimal care to patients       issues are brought to the forefront of
ity for surveillance of breast cancer      with ESBC. Practice-changing results        physicians’ awareness and strategies
recurrence and even fewer (41%)            are frequently unveiled at annual           are developed to minimize problems
were confident that they were follow-      oncology conferences, such as those         in each area, patients with ESBC will
ing standard surveillance guidelines       of ASCO, the European Society               reap the benefits through improve-
for breast cancer recurrence.[100]         of Medical Oncology, and the San            ments in clinical outcomes.
The same survey reported that 57%          Antonio Breast Cancer Symposium.
of PCPs rated the current transfer         Even physicians who cannot attend
of care from oncologists as fair or        these conferences can learn what was          References
poor. From the patients’ perspec-          presented by attending seminars that
tive, this problem may be even more        report conference highlights, perusing          1. American Cancer Society. Cancer Facts &
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                                                                                       Figures/cancer-facts-and-figures-2010. Accessed
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their PCP.[101] While most survivors       Awareness of these trials is important      Epidemiology and End Results breast cancer
(more than 70%) were positive re-          not only in order to anticipate what        fact sheet. Available at http://seer.cancer.gov/
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                                                                                       Accessed August 4, 2010.
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survivorship: breast cancer patients       women are diagnosed with early-stage            6. Buchholz TA. Radiation therapy for early-
reported difficulties transitioning to     disease, which has a favorable prog-        stage breast cancer after breast-conserving sur-
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                                                                    SUPPLEMENT • OCTOBER 2010 • ONCOLOGY                                13
 systematic review. Fertil Steril. 2010;94:138-43.         25. National Cancer Institute. Cancer trends       tamoxifen and of cytotoxic therapy on mortality
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14             ONCOLOGY • VOLUME 24 • NUMBER 4 • SUPPLEMENT
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                                                                                    SUPPLEMENT • OCTOBER 2010 • ONCOLOGY                                  15
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