Breast Cancer Management Assays

Carcinoma of the breast, the most common type of breast cancer, begins as a neoplastic proliferation of epithelial cells which line the ducts or lobules of breast.

Epidemiology

• Prevalence
  • In U.S., 180,510 new cases and 40,460 deaths each year (American Cancer Society, 2007 est.)
• Age
  • Prevalence increases with age 
• Sex
  • Most common cancer in females; also occurs in males, but rare (2,030/year in U.S.)

Risk Factors

• 10% linked to genetics – BRCA-1, BRCA-2, p53 mutations
• Early menarche
• Late menopause
• Childbirth after age 30
• Menopausal estrogen and progesterone use
• Chest radiation before age 30
• Moderate alcohol intake
• Family history of breast cancer
• An interactive tool has been designed by scientists at the National Cancer Institute (NCI) and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to estimate a woman's risk of developing invasive breast cancer (Gail Model)

Click here to access tool

Pathophysiology

• Tumors are mostly epithelial cell in origin and only rarely sarcomatous or lymphoma
• Tumors exist also in noninvasive forms:
  • Ductal carcinoma in situ (DCIS)
  • Lobular carcinoma in situ (LCIS)

Clinical Presentation

• Breast mass
• Nipple discharge
• Breast asymmetry

Diagnosis

• Early diagnosis is crucial for curative resection
  • Genetic status of tumor is crucial in therapeutic decisions which include histologic and nuclear grade, estrogen-receptor (ER) and progesterone-receptor (PR) status, measures of proliferative capacity and HER-2/neu gene amplification and HER-2/neu overexpression
• Breast tumor tissue should be tested for receptors that may be useful in guiding therapeutic decisions
• American Society of Oncology Guidelines
  • HER-2/neu positivity is associated with worse prognosis in node-positive patients, but provides target for trastuzumab (Herceptin) therapy
  • Estrogen/progesterone positivity associated with improved prognosis with anti-estrogen therapy
  • p53 positivity may be associated with worse prognosis; insufficient data to recommend use in management of breast cancer
  • Aneuploid and high S-phase tumors associated with worse prognosis in node-negative cancers; low S-phase and diploid DNA content associated with better prognosis
  • High Ki-67 associated with aggressive tumor behavior; insufficient data to recommend use in management of breast cancer
  • Oncotype testing:
    • In ER(+) node negative patients treated with Tamoxifen, test gives low and high risk recurrence scores to help assess risk
    • Treatment management trials are occurring to evaluate if therapeutic decisions can be based on high/low recurrence scores

Disease Monitoring

• Yearly mammography
• Cancer antigen markers testing
  • CA 15-3 – management of Stage II and III breast cancer patients in conjunction with diagnostic imaging, history, physical
  • CA 27.29 – monitoring treatment response in patients previously treated for Stage II or III breast cancer in conjunction with diagnostic imaging, history, physical
  • Carcinogenicembryonic antigen – can be used in conjunction with imaging, history, physical for metastatic disorders

Disease Screening

• Screening (mammogram, clinical breast exam, breast self-exam)
• Breast cytology screening is not yet recommended but may be useful in high-risk patients (eg, ductal lavage)
• No tumor markers recommended

Indications for Ordering

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

• Click on number for test-specific information in the ARUP Laboratory Test Directory