The Evolving Adjuvant Treatment Landscape in Patients with Early Breast Cancer

Breast cancer is the most common cancer in women in the USA and second only to lung cancer in mortality. It is estimated that there will be 231,840 new cases of invasive breast cancer and 40,290 deaths from the disease in 2015. While the incidence of breast cancer has increased steadily in the United States through the 1980s, it has now stabilized at about 125 cases per 100,000 per year. Breast cancer survival has significantly improved over the years, reflecting advances in effective local and systemic therapy. Moreover, adjuvant systemic therapy reduces the risk of distant recurrence presumably by treating micro-metastatic disease that may not be clinically evident at the time of definitive local therapy. While the benefit from endocrine and HER-2 directed therapy is predicted by the expression of their respective receptors, predicting response to chemotherapy remains a challenge. Several multi parameter gene expression assays have now been developed, which provide further prognostic information and more importantly predict benefit from adjuvant chemotherapy. These assays will help tailor therapy towards patients who will derive greatest benefit from chemotherapy.

chemotherapy for breast cancer

Endocrine therapy reduces the risk of breast cancer recurrence in hormone receptor positive disease, when used with or without chemotherapy. In 1982, 2-year adjuvant tamoxifen treatment was shown to reduce the risk of recurrence and improve survival, with subsequent studies revealing that five-year tamoxifen therapy was more effective than shorter durations. Five-year tamoxifen decreased recurrence by about 40% and breast cancer mortality by 30%, interestingly the effect of tamoxifen was present not only during therapy (1-5 years) but also after tamoxifen was discontinued(carryover effect). Tamoxifen risk reductions were substantial and consistent for women in each age range (including post-menopausal woman). First generation Aromatase inhibitors were too toxic in pivotal clinical trials and further development of third generation Aromatase inhibitors showed better toxicity profile and subsequently were found to improve DFS and OS when compared to tamoxifen in postmenopausal women. Hormone receptor positive disease is known to have recurrence even beyond 5 years of diagnosis; therefore clinical trials with longer endocrine therapy were developed. Extended adjuvant therapy for up to 10 years was shown to be more effective than 5 years of therapy, including sequential tamoxifen followed by an aromatase inhibitor, or tamoxifen for up to 10 years. Finally, in premenopausal women at high risk for recurrence, ovarian suppression plus an aromatase inhibitor was shown to be more effective than tamoxifen.

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