Anthracycline Regimen Superior in High Risk Early Stage Breast Cancer

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately, 246,660 new cases of invasive breast cancer will be diagnosed in 2016 and 40,450 women will die of the disease. The superiority of Anthracycline based chemotherapy regimens for the treatment of breast cancer was demonstrated in the mid 1980’s. The Early Breast Cancer Trialists Collaborative Group (EBCTCG) overview analysis published in the Lancet in 1998 concluded that there was a 12% proportional reduction in the risk of recurrence and 11% proportional reduction in mortality with Anthracycline containing regimens versus non-Anthracycline containing chemotherapy regimens. There is however a small risk of cardiotoxicity even with cumulative doses of Doxorubicin of less than 550 mg/m2. Jones and colleagues in 2009 published the results of US Oncology Research Trial 9735 which compared TC with AC and concluded that TC is superior to AC chemotherapy regimen and would be a reasonable option for both younger and older patients requiring chemotherapy, who are hormone receptor positive or negative with either node negative disease or have 1-3 positive lymph nodes.

The ABC (Anthracyclines in early Breast Cancer) adjuvant phase III trials (USOR 06-090, NSABP B-46I/USOR 07132, NSABP B-49) done in sequence, were developed by USOR and NSABP to determine if a regimen of TC for 6 cycles was non-inferior to combination regimens of Doxorubicin/Cyclophosphamide with Docetaxel or Paclitaxel (TaxAC), in patients with resected, high risk, HER2-negative breast cancer. The final analysis set from these collective trials known as ABC included 4130 patients, of whom 2078 patients were randomized to TC and 2052 patients to TaxAC. The treatment groups were well balanced. Sixty nine percent (69%) were hormone receptor positive, 41% were node negative and 51% had high grade tumors. The Primary Endpoint was invasive Disease Free Survival (iDFS) and the median follow up was 3.2 years.

At the time of pre-planned analysis with 399 invasive Disease Free Survival events, the 4 year DFS was significantly higher with TaxAC (90.7%) compared to 88.2% with TC (P=0.04). TaxAC provided little or no added benefit in hormone receptor positive and node negative patients. There was some benefit for patients with hormone receptor positive disease with 1-3 positive lymph nodes and those with hormone receptor negative disease with negative nodes. The most benefit was seen with TaxAC in patients with hormone receptor positive disease with 4 or more positive lymph nodes and in those with hormone receptor negative disease with positive nodes. The 4 year Overall Survival was comparable in both treatment groups although longer follow up is needed.

It can be concluded based on these findings that in early stage breast cancer, Anthracycline containing regimens are superior to non-Anthracycline regimens in patients with triple negative breast cancer and for those hormone receptor positive patients with 4 or more positive lymph nodes. There may be some benefit in select group of hormone receptor positive patients with 1-3 positive lymph nodes and in some patients with node negative, hormone receptor negative disease. Non-Anthracycline regimen such as TC is appropriate in node negative, hormone receptor positive patients. Interim joint analysis of the ABC (anthracyclines in early breast cancer) phase III trials (USOR 06-090, NSABP B-46I/USOR 07132, NSABP B-49 [NRG Oncology]) comparing docetaxel + cyclophosphamide (TC) v anthracycline/taxane-based chemotherapy regimens (TaxAC) in women with high-risk, HER2-negative breast cancer. Blum JL, Flynn PJ, Yothers G, et al. J Clin Oncol 34, 2016 (suppl; abstr 1000)