Treatment: Breast Cancer

Five-year survival rate by stage is shown in Table 70-2. Treatment varies with stage of disease and expression of hormone receptors and HER2.

Ductal carcinoma in situ is noninvasive tumor present in the breast ducts. Treatment of choice is wide excision with breast radiation therapy. In one study, adjuvant tamoxifen further reduced the risk of recurrence.

Invasive breast cancer can be classified as operable, locally advanced, and metastatic. In operable breast cancer, the outcome of primary therapy is the same with modified radical mastectomy or lumpectomy followed by breast radiation therapy. Axillary dissection may be replaced with sentinel node biopsy to evaluate node involvement. The sentinel node is identified by injecting a dye in the tumor site at surgery; the first node in which dye appears is the sentinel node. Women with tumors <1 cm and negative axillary nodes require no additional therapy beyond their primary lumpectomy and breast radiation. Adjuvant combination chemotherapy for 6 months appears to benefit premenopausal women with positive lymph nodes, pre- and postmenopausal women with negative lymph nodes but with large tumors or poor prognostic features, and postmenopausal women with positive lymph nodes whose tumors do not express estrogen receptors. Estrogen receptor-positive tumors >1 cm with or without involvement of lymph nodes are treated with aromatase inhibitors. Women who began treatment with tamoxifen before aromatase inhibitors were approved should switch to an aromatase inhibitor after 5 years of tamoxifen and continue for another 5 years.

Adjuvant chemotherapy is added to hormonal therapy in estrogen receptor-positive, node-positive women and is used without hormonal therapy in estrogen receptor-negative node-positive women, whether they are pre- or postmenopausal. Various regimens have been used. The most effective regimen appears to be four cycles of doxorubicin, 60 mg/m², plus cyclophosphamide, 600 mg/m², IV on day 1 of each 3-week cycle followed by four cycles of paclitaxel, 175 mg/m², by 3-h infusion on day 1 of each 3-week cycle. In women with HER2+ tumors, trastuzumab augments the ability of chemotherapy to prevent recurrence. The activity of other combinations is being explored. In premenopausal women, ovarian ablation (e.g., with the luteinizing hormone-releasing hormone [LHRH] inhibitor goserelin) may be as effective as adjuvant chemotherapy.

Tamoxifen adjuvant therapy (20 mg/d for 5 years) or an aromatase inhibitor (anastrozole, letrozole, exemestane) is used for postmenopausal women with tumors expressing estrogen receptors whose nodes are positive or whose nodes are negative but with large tumors or poor prognostic features. Breast cancer will recur in about half of pts with localized disease. High-dose adjuvant therapy with marrow support does not appear to benefit even women with high risk of recurrence.

Pts with locally advanced breast cancer benefit from neoadjuvant combination chemotherapy (e.g., CAF: cyclophosphamide 500 mg/m², doxorubicin 50 mg/m², and 5-fluorouracil 500 mg/m² all given IV on days 1 and 8 of a monthly cycle for 6 cycles) followed by surgery plus breast radiation therapy.

Treatment for metastatic disease depends on estrogen receptor status and treatment philosophy. No therapy is known to cure pts with metastatic disease. Randomized trials do not show that the use of high-dose therapy with hematopoietic stem cell support improves survival. Median survival is about 22 months with conventional treatment: aromatase inhibitors for estrogen receptor-positive tumors and combination chemotherapy for receptor-negative tumors. Pts whose tumors express HER2/neu have higher response rates by adding trastuzumab (anti-HER2/neu) to chemotherapy. Trastuzumab emtansine is a drug conjugate that targets HER2-expressing cells and has antitumor activity. Some advocate sequential use of active single agents in the setting of metastatic disease. Active agents in anthracycline- and taxane-resistant disease include capecitabine, vinorelbine, gemcitabine, irinotecan, and platinum agents. Pts progressing on adjuvant tamoxifen may benefit from an aromatase inhibitor such as letrozole or anastrozole. Half of pts who respond to one endocrine therapy will respond to another. Bisphosphonates reduce skeletal complications and may promote antitumor effects of other therapy. Radiation therapy is useful for palliation of symptoms.