BreastCancer

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					BREAST CANCER


 Shahid Waheed, M.D.
• RISK FACTORS IN SCREENING FOR
 BREAST CANCER
Epidemiology
• Breast cancer most invasive cancer in the
  United States
• Second leading cause of cancer death
  behind lung cancer
• In 1997 approximately 186,000 new cases
  of breast cancer diagnosed in United States
  and 46,000 patients died from the disease
Epidemiology
• Breast cancer incidence has increased in North
  America and northern Europe with intermediate
  rates in southern Europe and South America.
• Among Japanese women who have migrated to
  the United States the incidence of breast cancer
  remains low for the immigrants themselves but
  rises sharply in second and third generation
  offspring to approximate the risk for white women
  in the U.S.
Epidemiology
• The incident rates of breast cancer are
  higher in white women than black women
  over the age of 45.
• Rates are similar between the ages of 40-44
  and higher in black women under age 40.
Mortality Trends
• Between 1989 and 1992, mortality among
  whites declined by 5.5% but actually
  increased by 2.6% in the African American
  community.
• Statistics continue to show a small decline
  in mortality.
Socioeconomic Status

• The incidence of breast cancer is greater in
  women of higher socioeconomic
  background.
Disease Site

• The left breast is involved more frequently
  than the right and the most common
  locations of the disease are the upper outer
  quadrant and the retroareolar region.
Survival
• Survival of Women with Breast Cancer
 According to Stage
 • Stage I: survival rate at 80-90%
 • Stage II: survival rate at 70%
 • Stage III: survival rate at 40%
 • Stage IV: survival rate at 10%
Etiology and Risk Factors
Genetic Alterations Causing
Increased Susceptibility

• The cloning of BRCA1 and BRCA2 in 1994
  and 1995 provided the genetic background
  for familial breast cancer.
• BRCA1 and BRCA2 are thought to account
  for 80% of all hereditary breast cancers and
  5-6% of all breast cancers.
BRCA1
• BRCA1 has 5,592 nucleotides and is
  located on chromosome 17.
• A specific mutation occurs in 1% of
  Ashkenazi Jews, 185 del AG, ten-fold
  higher than in the general population post-
  op. It accounts for 16% of all breast cancer
  and 39% of all ovarian cancer.
BRCA1
• Struewing, et. Al. The New England Journal of
  Medicine, (1997) showed a risk of 56% by age 70
  compared to 13% without known genetic
  susceptibility and a 16% chance for getting
  ovarian cancer compared to 1.6% in non-carriers.
• Survival from BRCA1-associated cancer is no
  different than is seen in sporadic breast cancer
  patients.
BRCA2
• The BRCA2 gene has 11,385 nucleotides
  and is located on chromosome 13. It is
  associated with female breast cancer, male
  breast cancer, and to a lesser extent, ovarian
  cancer and pancreatic cancer.
• Also associated with prostate and colon
  cancer.
• More frequently seen in Iceland.
BRCA3

• Not yet cloned.
• May be on chromosome 8
• None of the women had ovarian cancer
Li-Fraumeni Syndrome

• Description of four families in 1969
• P53 mutations are detectable in 50% of
  patients and are a major contributor to the
  occurrence of breast cancer.
Cowden’s Disease

• Breast carcinoma, high arched palate, CNS
  problems, thyroid cancer
• Rare disease localized to chromosome 10
• Approximately 200 reported cases
Ataxia Telangiectasia
• A relative risk for AT heterozygotes – 3.9
• Gene on chromosome 11
  • 1% of general population may be heterzygotes
    for AT.
  • Could account for 8% of breast carcinoma
    below age 40 and 2% of cases between 40-60.
  • Not a good predictor of familial breast cancer
    but may be important for general population
Reproductive Variables
• Early menarche and late menopause
  increases risk.
• Hysterectomy, bilateral, decreases breast
  cancer risk in pre-menopausal women.
• There is an inverse relationship between the
  number of months of breast feeding and
  breast cancer risk.
Reproductive Variables (con’t)

• Increased risk would be age at first birth. After
  first pregnancy prolectin level decreases.
• High parity may provide additional protection.
• Abortion does not seem to increase risk for breast
  cancer.
• Oral contraception – most published studies show
  no association.
Reproductive Variables (con’t)
• Estrogen replacement treatment – the degree of
  risk associated with taking estrogen replacement
  therapy remains unclear
• Weight – obesity appears to be linked positively
  with the development of breast cancer
• Family history – overall relative risk of breast
  cancer in a woman with a positive family history
  in a first-degree relative – mother, daughter, or
  sister – is 1.7%
Proliferative Breast Disease
• The diagnosis of certain conditions after breast
  biopsy is also associated with an increased risk for
  the subsequent development of invasive breast
  cancer.
   • Moderate, or florid, ductal hyperplasia and sclerosing
     adenosis increases the risk of breast cancer by 1.5 to 2
     times.
   • Atypical ductal or lobular hyperplasia increases the risk
     moderately 4-5 times.
   • Lobular carcinoma in situ markedly increases the risk
     8-11 times.
Personal Cancer History

• A personal history of breast cancer is a
  significant risk factor for the subsequent
  development for a second new breast
  cancer.
Radiation

• Radiation increases risk for breast cancer
  • Hodgkin’s Disease. Patients who received
    Mantiel radiation for Hodgkin’s disease have a
    dramatically increased risk for developing
    breast cancer 10-25 years later.
Diet

• There is compelling evidence showing that
  populations that consume a high-fat diet
  have an increased risk of breast cancer.
Alcohol Consumption

• Several studies show a dosal response
  relationship between alcohol consumption
  and breast cancer.
Screening and Diagnostic Tests
in Breast Cancer
• Screening efforts are based on the widely
  accepted notion that women detected with
  earlier stages of breast cancer have longer
  survival and higher cure rates.
   • Breast self-examination
   • Clinical breast examination
Screening and Diagnostic Tests
in Breast Cancer
• Usual characteristics of benign lesions are
  not always reliable.
   • Example
     • About 60% of cancers are somewhat movable
     • 40% have regular borders by palpation
     • 40% can feel soft or cystic
Mammography
• Mammography was first used to identify
  breast lesions in the 1930’s but was used as
  a practical tool in the 1960’s.
• Initial randomized and control trial
  assessing the efficacy of screening with
  mammography for breast cancer was
  conducted by the Health Insurance Plan of
  New York during the mid to late 1960’s.
Mammography
• The study group of 30,000 patients was followed
  by periodic screening using both physical
  examination and mammography while an equal
  number in the control group received routine
  medical care.
   • In women 50 years and older a 30% reduction in
     mortality was noted after 6 years compared to the
     control group
   • In an 18-year follow-up reported benefit was seen in
     women age 20-49.
   • The difference in mortality achieved significance 9
     years after the completion of the study.
Mammography
Mammography
• National Cancer Advisory Board, National
 Institute of Health, recommends
 mammography screening every 1-2 years
 for women ages 40-49 if they are at average
 risk for cancer. Their review of many
 studies show regular mammography
 screening reduces death from breast cancer
 by about 17%.
Mammography
• The U.S. Preventive Services Task Force
  recommends annual or biannual mammography
  after age 50. However, the American Cancer
  Society, the American College of Radiology and
  American College of Obstetrics and Gynecology
  recommend mammogram every 1-2 years between
  age 40-50, then annually after age 50.
• American Cancer Society advises baseline
  mammogram between ages 35 and 40.
Mammography
• Mammography in Elderly Women
  • No universally accepted policy directed toward
    screening in patients over age 70
  • A suggestion that there is a 13% improvement
    in mortality if mammographic screening is done
    between the ages of 70 and 74
Other Imaging Methods
• MRI

• Digital mammography

• Several other methods in process of
  development
Chemo Prevention of Breast
Cancer
• NSABP Trial P-1
  • In September, 1998, NSABP published results
    of the P-1 trial to reveal whether or not
    Tamoxifen was useful in decreasing the risk of
    breast cancer in a group of high-risk women.
  • The studies revealed that Tamoxifen reduced
    the risk of invasive breast cancer by 49%
    overall.
Evaluation of a Cystic Mass
• Initial Evaluation
  • When a dominant breast mass is present and
    history and physical exam suggests cyst, the
    mass can be aspirated with a fine needle and
    ultrasound used to determine whether the lesion
    is solid or cystic.
  • Biopsy is indicated if the cyst fluid is bloody or
    if the mass does not resolve completely after
    aspiration.
Evaluation of a Solid Mass
• A mammography can be used to assess the
  radiological characteristic of the mass.
• Fine needle aspiration is a simple, easy to perform,
  method for obtaining material for cytologic
  examination.
• An excisional biopsy in which the entire breast
  mass is removed definitely establishes diagnosis.
   • If mass is extremely large, an incisional biopsy may be
     more appropriate.
Evaluation of Non-palpable
Mammographic Abnormalities
• Several methods can be used to evaluate
  mammographically-detected abnormalities.
  • Ultrasound guided FNA (fine needle aspiration)
    or core biopsy
  • Stereotatic core biopsy
  • Needle localization breast biopsy
TNM STAGING
Pathology of Invasive Carcinoma
• Ductal Carcinoma
  • Most cases of invasive carcinomas of the breast are
    ductal in origin
  • Different histological subtypes of ductal carcinoma are:
     •   Tubular
     •   Medullary
     •   Mucinous
     •   Papillary
  • These have been associated with a favorable outcome.
Pathology of Invasive Carcinoma
• Lobular Carcinoma
  • Approximately 5-10% of invasive breast
    cancers are lobular in origin.
  • The histology as been associated with
    synchronous and metachronous contralateral
    primary tumors in as many as 30% of cases.
Pathology of Invasive Carcinoma

• Lymphomas
    Primary breast lymphomas are very rare,
    accounting for about 2.5% of all breast
    malignancies.
Pathology of Invasive Carcinoma
• Soft Tissue Sarcomas
  • All soft tissue sarcomas of the breast are also
    uncommon. They account for less than 1% of
    all breast malignancies.
  • The most common histological types of soft
    tissue sarcomas of the breast, excluding
    angiosarcoma, are malignant fibrous
    histiocytoma, liposarcoma, and fibrosarcoma.
Treatment Options for Breast
Carcinoma
• Treatment options for breast carcinoma
  depends upon:
   • the size of tumor
   • prognostic factors including estrogen receptor,
    progesterone receptor
  • HER-2 oncoprotein positive or negative
  • lymph node status
  • other risk factors
Treatment Options for Breast
Carcinoma

• Stage I and II disease can be treated with
  lumpectomy plus radiation plus or minus
  chemotherapy depending upon the size of
  the tumor and node status.
Treatment Options for Breast
Carcinoma

• Mastectomy plus or minus chemotherapy or
 hormonal therapy depending on the size of
 the tumor, risk factors, and nodal status
Systemic Therapy Options for Post-
Surgical Breast Cancer Patients

•   Observation
•   Endocrine therapy
•   Chemotherapy
•   Other treatment
•   Combined therapy
• Multi-Modality Approach to
 Locally Advanced Breast Cancer
• TREATMENT APPROACH TO
 METASTATIC BREAST CANCER

				
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