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, 233,000 new cases of invasive breast cancer will be diagnosed in 2014 and 40,000 women will die of the disease. The HER or erbB family of receptors consist of HER1, HER2, HER3 and HER4. Approximately 15%-20% of invasive breast cancers overexpress HER2/neu oncogene, which is a negative predictor of outcomes, without systemic therapy. Patients with early stage breast cancer often receive adjuvant chemotherapy and this is even more so true for HER positive and triple negative (ER, PR and HER negative) breast cancer patients, who are at an increased risk to develop recurrent disease. Even though majority of the patients start their adjuvant chemotherapy within 4-6 weeks following surgery, the impact of delay in the initiation of adjuvant therapy, on outcomes, has remained unclear. Preclinical models have suggested that there is phase of increased angiogenesis and accelerated growth of micrometastases, as well as development of drug resistant clones, following removal of the primary tumor. Previously published data from a large meta-analysis had suggested that a four week delay in the initiation of adjuvant chemotherapy resulted in a 6% increase in the risk of death and an 8% increase in the risk of relapse. Based on this background information, the authors in this study evaluated the impact of time to initiation of adjuvant chemotherapy, on survival, in patients with various stages and subtypes of early stage breast cancer. In this single institution study, 6,827 women diagnosed with stages I to III breast cancer between 1997 and 2011, were categorized into one of three groups – 30 days or less, 31 to 60 days and 61 days or more, according to the time from definitive surgery to adjuvant chemotherapy. Survival outcomes were then estimated in these three groups. The median follow up was 59.3 months and majority of the patients (84.5%) had stage I or II breast cancer and 15.5% of the patients had stage III disease. The authors noted that outcomes were inferior among patients with stage II and stage III disease when chemotherapy was initiated 61 days or more after surgery, with a 76% increase in the risk of death among patients with stage III disease. This disadvantage was however not noted in patients with stage I disease. Survival estimates based on the tumor sub types revealed that patients with triple negative breast cancer tumors and those with HER-2 positive (Human Epidermal growth factor Receptor- 2) tumors, treated 61 days or more after surgery with HERCEPTIN® (Trastuzumab) based chemotherapy, had the worse survival, compared with those who initiated adjuvant treatment within the first 30 days after surgery. Patients with hormone receptor positive tumors were however not impacted. The authors concluded that delaying the initiation of adjuvant chemotherapy in patients with high risk disease such as those with Stages II and III breast cancer and those with triple negative breast cancer and HER-2 positive tumors, can negatively impact survival outcomes. de Melo Gagliato D, Gonzalez-Angulo AM, Lei X, et al. J Clin Oncol 2014;32:735-744
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