Adjuvant systemic therapy lowers the incidence of recurrence by 25% to 30%. It is important to understand that the proportional reduction in risk of relapse is relatively constant regardless of absolute risk (113). The EBCTCG meta-analysis showed that the risk reduction of recurrence and breast cancer–specific mortality from polychemotherapy occurs in all women, but the most benefit occurs in women under the age of 50 (Table 40.6). A meta-analysis from the EBCTCG assessing the effect of polychemotherapy and tamoxifen on estrogen receptor–poor breast cancer found that women under the age of 50 or between the ages of 50 and 69 had statistically significant decreases in 10-year risks of recurrence and mortality, with more benefit in women under the age of 50, confirming the results of the earlier study in patients with estrogen receptor–poor breast cancer (114). Tamoxifen did not add any benefit in patients with estrogen receptor–poor tumors. Adjuvant cytotoxic chemotherapy appears to affect the natural history of patients with either axillary node–negative or node–positive breast cancer. All high-risk patients with node-negative disease are considered candidates for adjuvant cytotoxic therapy.
In postmenopausal, estrogen receptor–positive women, chemotherapy is about one-half as effective as tamoxifen in the adjuvant setting (115). For most postmenopausal women with hormone-responsive disease (estrogen-and progesterone-responsive positivity), including node-positive patients, hormonal therapy alone may be adequate treatment. High-risk patients with hormone-resistant disease benefit from cytotoxic systemic therapy. Caution should be exercised when using chemotherapeutic agents. Patients in whom the risk of recurrence is low are likely to derive little overall benefit from the use of adjuvant systemic therapy, whereas those with a
Table 40.6 Effect of Systemic Therapy on Recurrence and Survival from Breast Cancer
From Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomized trials. Lancet 1998;352:930, with permission.
high risk of recurrence are likely to receive the greatest benefit. Comorbidities must always be considered on an individual basis.
The current recommendations for adjuvant systemic therapy in breast cancer are summarized as follows: 1.
Premenopausal women with lymph node involvement should be treated with adjuvant combination chemotherapy. Tamoxifen should be added for patients with estrogen receptor–positive tumors following cytotoxic therapy.
2.
Premenopausal women without evidence of lymph node involvement but with large (>1 cm) size, aneuploid, or estrogen receptor–negative tumors should be treated with combination chemotherapy. Tamoxifen should be given to patients with estrogen receptor– positive tumors.
3.
Postmenopausal patients with negative lymph nodes who are hormone receptor–positive should receive adjuvant aromatase inhibitor therapy as primary therapy. Those with positive lymph nodes should receive multidrug cytotoxic therapy, or a combination thereof if there are no medical contraindications.
4.
Postmenopausal women with lymph node metastases who are hormone receptor– negative may be treated with adjuvant chemotherapy.
5.
Adjuvant systemic therapy is not recommended for patients with favorable tumors smaller than 1 cm. Hormonal therapy may be considered if the patient’s tumor is estrogen receptor–positive.
6.
Trastuzumab is recommended as adjuvant treatment in addition to chemotherapy for patients with Her-2/neu positive breast cancer, especially those with positive nodes, young women, and women with large tumors.