Breast Cancer (3)

Diagnosis


Testing is required to differentiate benign lesions from cancer. Because early detection and treatment of breast cancer improves prognosis, this differentiation must be conclusive before evaluation is terminated.

If advanced cancer is suspected based on physical examination, biopsy should be done first; otherwise, the approach is as for breast lumps. A prebiopsy bilateral mammogram may help delineate other areas that should be biopsied and provides a baseline for future reference. However, mammogram results should not alter the decision to perform a biopsy. Biopsy can be needle or incisional biopsy or, if the tumor is small, excisional biopsy. Any skin with the biopsy specimen should be examined because it may show cancer cells in dermal lymphatic vessels. Routinely, stereotactic biopsy (needle biopsy during mammography) or ultrasound-guided biopsy is being used to improve accuracy.

Evaluation after cancer diagnosis: Part of a positive biopsy specimen should be analyzed for estrogen and progesterone receptors and for HER2 protein. WBCs should be tested for BRCA1 and BRCA2 genes when family history includes multiple cases of early-onset breast cancer, when ovarian cancer develops in patients with a family history of breast or ovarian cancer, when breast and ovarian cancer occur in the same patient, when patients have Ashkenazi Jewish heritage, or when family history includes a single case of male breast cancer.

Chest x-ray, CBC, and liver function tests should be done to check for metastatic disease. Generally, measuring serum carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, CA 27-29, or a combination is not recommended because results have no effect on treatment or outcome. Bone scanning should be done if patients have tumors > 2 cm, musculoskeletal pain, lymphadenopathy, or elevated serum alkaline phosphatase or Ca levels. Abdominal CT is done if patients have abnormal liver function results, hepatomegaly, or locally advanced cancer with or without axillary lymph node involvement.

Grading and staging follow the TNM classification (see Table 2: Breast Disorders: Staging and Survival of Breast Cancer). Staging is refined during surgery, when regional lymph nodes can be evaluated.

Screening: Screening includes mammography, clinical breast examination (CBE) by health care practitioners, and monthly breast self-examination (BSE).

Mammography, done annually, reduces mortality rate by 25 to 35% in women ≥ 50 yr. However, there is considerable disagreement about screening for women 40 to 50 yr; recommendations include annual mammography (American Cancer Society), mammography every 1 to 2 yr (National Cancer Institute), and no periodic mammography (American College of Physicians).

CBE is usually part of routine annual care for women > 35; it can detect 7 to 10% of cancers that cannot be seen on a mammogram. In the US, CBE augments rather than replaces screening mammography. However, in some countries where mammography is considered too expensive, CBE is the sole screen; reports on its effectiveness in this role vary.

BSE has not been shown to reduce mortality rate but is widely practiced. Because a negative BSE may tempt some women to forego mammography or CBE, the need for these procedures is reinforced when BSE is taught.

Prognosis


Long-term prognosis depends on extent of lymph node involvement, number of axillary lymph nodes involved, size of primary tumor, tumor grade, stage, presence of estrogen and progesterone receptors, patient age, and presence of HER2 protein.

Nodal status correlates with disease-free and overall survival better than other prognostic factors. For node-negative patients, 10-yr disease-free survival rate is > 70%, and overall survival rate is > 80%. For node-positive patients, rates are about 25% and 40%, respectively.

Larger tumors are more likely to be node-positive and also confer a worse prognosis independent of nodal status. Patients with poorly differentiated tumors have a worse prognosis.

Patients with ER+ tumors have a somewhat better prognosis and are more likely to benefit from hormone therapy. Patients with progesterone receptors on a tumor may also have a better prognosis.

When the HER2 gene is amplified, HER2 is overexpressed, increasing cell growth and reproduction and often resulting in more aggressive tumor cells. Overexpression of HER2 may be associated with high histologic grade, ER– tumors, greater proliferation, larger tumor size, and thus a poor prognosis.

For any given stage, patients with the BRCA1 gene appear to have a worse prognosis than those with sporadic tumors, perhaps because they have a higher proportion of high-grade, hormone receptor-negative cancers. Patients with the BRCA2 gene probably have the same prognosis as those without the genes if the tumors have similar characteristics. With either gene, risk of a 2nd cancer in remaining breast tissue is increased (to perhaps as high as 40%).