Anthracycline chemotherapy outcomes according to breast cancer subtype

This study investigated the use of anthracycline-based chemotherapy according to different breast cancer subtypes.

Breast cancer is classified into different subtypes depending on the presence or absence of certain receptors (proteins found on the surface of the cancer cells). Some breast cancers grow in response to female sex hormones (such as estrogen or progesterone), and are referred to as hormone receptor-positive (HR+) breast cancers. Human epidermal growth factor receptor 2 (HER2) is another receptor found on the surface of some breast cancer cells which stimulates tumor growth and spread. Cancer cells negative for both hormone receptors and HER2 are often referred to as triple-negative breast cancer. Breast cancer subtypes not only influence treatment options, but also directly affect disease prognosis. 

Chemotherapy is commonly used in the treatment of all breast cancer sub-types. A triple drug combination referred to as CMF (Cyclophosphamide, Methotrexate and 5-fluorouracil) is often employed. Anthracyclines (such as epirubicin or doxorubicin) are often added to standard chemotherapy in an attempt to improve treatment outcomes, despite the risk of additional toxic side effects. However, the effects of anthracycline chemotherapy according to breast cancer sub-type have not yet been thoroughly investigated.

705 women diagnosed with breast cancer of any stage were randomized to receive either CMF alone, epirubicin followed by CMF, or CMF followed by epirubicin. Women were followed for an average of 5 years following treatments.

Among the 156 triple-negative (HR-/HER2-) breast cancer patients, 85% of the 116 women receiving epirubicin plus CMF remained disease free 5-years following treatment, compared to only 55% of the 40 women receiving CMF alone. 5-year overall survival rates were 91% among women receiving epirubicin plus CMF, compared to 71% among women receiving CMF alone.

Among the 473 hormone receptor-positive (HR+) breast cancer patients, 85% of the 371 women receiving epirubicin plus CMF remained disease free 5-years following treatment, compared to only 80% of the 102 women receiving CMF alone. 5-year overall survival rates were 95% among women receiving epirubicin plus CMF, compared to 93% among women receiving CMF alone.

Among the 76 hormone receptor-negative HER2-positive (HR-/HER2+) breast cancer patients, the addition of epirubicin to CMF did not seem to significantly affect treatment outcome, with 5-year overall survival rates ranging from 83% to 87%.

Women with triple unfavorable tumors, referring to tumors that are both hormone receptor-negative (HR-), and express high amounts of Ki-67 (a protein associated with cell proliferation), showed the greatest benefit from the addition of epirubicin to treatments. Among the 200 women with triple unfavorable tumors, 82% of the 148 women receiving epirubicin plus CMF remained disease free 5-years following treatment, compared to only 58% of the 52 patients who received CMF alone. 5-year overall survival rates were 90% among women receiving epirubicin plus CMF, compared to 72% among women receiving CMF alone.

This study concluded that the addition of epirubicin to standard chemotherapy significantly improves both overall, and disease-free, survival. The greatest benefits with the addition of epirubicin were seen among triple unfavorable, triple negative and hormone receptor-positive breast cancer patients.