Clinical Background
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). Refer to Breast Cancer Management topic at www.arupconsult.com for access to the Gail Model risk 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
See Also
Diagnosis
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
- Carcinogenic embryonic antigen - can be used in conjunction with imaging, history, physical for metastatic disorders
- Circulating tumor cell count - in metastatic tumors, monitor disease progression and response to therapy
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
| Tests |  |
Tests generally appear in the order most useful for common clinical situations
| Test name: Cytology, Fine Needle Aspirate |
| ARUP #: 8209706 |
| Methodology: Routine Cytopathologic Evaluation |
| Use:
Definitive tissue diagnosis
|
| Follow-up:
May want to do receptor analysis such as HER-2/neu, estrogen/progesterone receptor
|
| Test name: C-erb B-2 (HER-2/neu) Tissue Assay, Paraffin |
| ARUP #: 0049164 |
| Methodology: Immunohistochemistry |
| Use: Prognostic and predictive indicator |
| Limitations: |
| Follow-up: If 2+, order FISH testing to confirm gene amplification |
| Test name: DNA Content/Cell Cycle Analysis, Breast (Paraffin) |
| ARUP #: 0095735 |
| Methodology: Flow Cytometry |
| Use: Prognostic indicator for node-negative breast cancer Presence of aneuploid DNA content and high S-phase tends to correlate with worse prognosis |
| Limitations: Tumor-specific S-phase used when possible Average histogram S-phase used: - For diploid and some aneuploid tumors (where tumor and host S-phases cannot be separated) - When percentage of aneuploid cells in histogram low (<25%) |
| Follow-up: |
| Test name: p53 Tissue Assay, Paraffin |
| ARUP #: 0049250 |
| Methodology: Immunohistochemistry |
| Use: Prognostic marker Determine treatment method for lymph node negative breast cancer patients |
| Test name: Ki-67 Tissue Assay, Paraffin |
| ARUP #: 0049270 |
| Methodology: Immunohistochemistry |
| Use: Prognostic indicator for node-negative breast cancer High proliferation associated with more aggressive disease |
| Limitations: |
| Follow-up: |
| Test name: bcl-2 Tissue Assay, Paraffin |
| ARUP #: 0049260 |
| Methodology: Immunohistochemistry |
| Use: Prognostic marker in some studies Recently, less utilized prognostic marker |
| Test name: Cathepsin D, Paraffin |
| ARUP #: 0049220 |
| Methodology: Immunohistochemistry |
| Use: Prognostic marker for breast cancer in some studies Recently, less utilized prognostic marker |
| Test name: Circulating Tumor Cell Count (Cell Search™) |
| ARUP #: 0093399 |
| Methodology: Immunomagnetic separation/Immunofluorescence staining/Computer assisted analysis |
| Use: For use in metastatic tumors Use in conjunction with clinical data and imaging Monitor disease progression Monitor response to therapy when comparing baseline values to serially monitor response and assess prognosis Prognostic marker that provides information about progression free survival and overall survival |
| Test name: Estrogen/Progesterone Receptor Assay, Paraffin |
| ARUP #: 0049210 |
| Methodology: Immunohistochemistry |
| Use: Triage test for anti-estrogen therapy Test uses paraffin-embedded, formalin-fixed tissue |
| Limitations: |
| Follow-up: |
| Test name: HER-2/neu, Serum |
| ARUP #: 0098615 |
| Methodology: Enzyme-Linked Immunosorbent Assay |
| Use: Triage test for trastuzumab therapy in metastatic breast cancer when solid tissue unavailable |
| Limitations: Although positive results are reliable, this serum assay has many false-negatives (30%) |
| Follow-up: |
| Test name: HercepTest® Tissue Assay, Paraffin |
| ARUP #: 0049174 |
| Methodology: Immunohistochemistry |
| Use: Triage test for trastuzumab therapy (predictive indicator, FDA approved) |
| Limitations: FDA approved for formalin-fixed tissue only |
| Follow-up: If 2+, order FISH testing to confirm gene amplification |
| Test name: HER-2/neu by FISH (PathVysion™ HER-2) |
| ARUP #: 0049218 |
| Methodology: Fluorescence in situ Hybridization |
| Use: Triage test for trastuzumab therapy (predictive indicator, FDA approved) Use to confirm immunohistochemical positive results |
| Limitations: FDA approved for formalin-fixed tissue only |
| Follow-up: |
| Test name: Cytology, Breast Ductal Lavage |
| ARUP #: 8209730 |
| Methodology: Routine Cytopathologic Evaluation |
| Use: Cytomorphologic screening for breast cancer cells and precursor lesions Currently used as a risk assessment tool for women who are at high risk for breast cancer |
| Test name: Cytology, Breast Nipple Secretion |
| ARUP #: 8209700 |
| Methodology: Routine Cytopathologic Evaluation |
| Use: Cytomorphologic screening for breast cancer cells and precursor lesions Can potentially be used as a risk assessment tool for women |
| Limitations: Screening test with known false-negatives and false-positives |
| Test name: Cancer Antigen-Breast (CA 15-3) |
| ARUP #: 0080464 |
| Methodology: Electrochemiluminescent Immunoassay |
| Use:
Aid in the monitoring of stage II and III breast cancer patients Serial testing should be used in conjunction with other clinical methods for monitoring breast cancer |
| Limitations: Results obtained with different methods or kits cannot be used interchangeably Assay values should not be interpreted as absolute evidence of the presence or absence of malignant disease since patients with confirmed breast carcinoma frequently have CA 15-3 assay values in the same range as healthy individuals and elevations may be observed in patients with nonmalignant disease |
| Test name: Cancer Antigen 27.29 |
| ARUP #: 0080392 |
| Methodology: Chemiluminescent Immunoassay |
| Use:
Aid in monitoring patients previously treated for Stage II or III breast cancer Serial testing in patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence Use also as an aid in the management of breast cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment |
| Limitations: Results obtained with different methods or kits cannot be used interchangeably Assay values should not be interpreted as absolute evidence of the presence or absence of malignant disease since patients with confirmed breast carcinoma frequently have CA 27.29 levels within the reference interval and elevations may be observed in patients with nonmalignant disease |
| Follow-up: |
| Test name: Carcinoembryonic Antigen |
| ARUP #: 0080080 |
| Methodology: Eletrochemiluminescent Immunoassay |
| Use: Aid in the monitoring of stage II and III breast cancer patients Serial testing should be used in conjunction with other clinical methods for monitoring breast cancer |
| Test name: Immunohistochemistry Stain Offering |
| ARUP #: arup005 |
| Methodology: Immunohistochemistry |
| Use: For fixed tissue samples, diagnostic consultative services as well as immunohistochemical staining for Cathepsin D, c-erb (HER-2/neu), estrogen, Hercept Test™, Ki-67, p53, B72.3, Ber-Ep4, BRST II (GCDFP-15), CD95, CD117 (c-kit), CK-7, p16, Placental alkaline phosphatase (PLAP), PTEN and progesterone are available |
Additional Tests Available
| Test name: C-erb B-2 (HER-2/neu) with Reflex to HER-2/neu by FISH if 2+ |
| ARUP #: 0049166 |
| Methodology: Immunohistochemistry |
| Comments: |
| Test name: C-erb B-2 (HER-2/neu) with Reflex to HER-2/neu by FISH if 2+ or 3+ |
| ARUP #: 0049168 |
| Methodology: Immunohistochemistry |
| Comments: |
| Test name: HercepTest® with Reflex to HER-2/neu by FISH if 2+ |
| ARUP #: 0049178 |
| Methodology: Immunohistochemistry |
| Comments: |
| Test name: HercepTest® with Reflex to HER-2/neu by FISH if 2+ or 3+ |
| ARUP #: 0049172 |
| Methodology: Immunohistochemistry |
| Comments: |
Additional Information
BRCA-1 and BRCA-2 testing should be considered in patients with multiple female relatives with breast cancer.
References
Guidelines
General References
References from the ARUP Institute for Clinical and Experimental Pathology Research®
Medical Reviewers
Bentz, Joel S., M.D., M.S. Associate Professor, Pathology, University of Utah
Layfield, Lester , M.D. Fine-Needle Aspiration Services and Molecular Diagnostics at ARUP Laboratories; Professor and Division Head, Anatomic Pathology, University of Utah
Perkins, Sherrie L. , M.D., Ph.D. Medical Director, Hematopathology at ARUP Laboratories; Professor, Anatomic Pathology, University of Utah
Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah
Wittwer, Carl T., M.D., Ph.D. Medical Director, Flow Cytometry and New Technologies at ARUP Laboratories; Professor, Clinical Pathology, University of Utah
Comprehensive Review: May 2008
Last Update: September 2008
