Search

Characterization of breast cancer phenotypes has improved our ability to predict breast cancer behavior. Triple-negative (TN) breast cancers have higher and earlier rates of distant events. It has been suggested that this behavior necessitates treating TNs faster than others, including use of neoadjuvant chemotherapy (NACT) if time to surgery is not rapid.A review of women diagnosed with non-inflammatory, invasive breast cancer was conducted using the National Cancer Database for patients not having NACT, diagnosed between 2010 and 2014. Changes in overall survival due to delay were measured by phenotype.Overall, 351,087 patients met the inclusion criteria, including 36,505 (10.4%) TNs, 77.9% hormone receptor-positive (HR+) and 11.7% human epidermal growth factor receptor 2 (HER2)-enriched (HER2+). Phenotype, among other factors, was predictive of treatment delays. Adjusted median days from diagnosis to surgery and chemotherapy were 29.9, 31.6 and 31.5 (p 0.001), and 72.7, 78.0 and 74.4 (p 0.001) for TNs, HR+ and HER2+ cancers, respectively. After diagnosis, OS declined for all patients per month of preoperative delay (hazard ratio 1.104; p 0.001). In models separating or combining surgery and chemotherapy, this survival decline did not vary by breast cancer phenotype (p 0.3).Delays cause small but measurable effects overall, but the effect on survival does not differ among breast cancer phenotypes. Our data suggest that urgency between diagnosis and surgery or chemotherapy is similar for breast cancers of different subtypes. Although NACT is sometimes advocated solely to avoid treatment delays, this study does not suggest a greater surgical urgency for TNs compared with other breast cancer phenotypes.

Purpose Glucocorticoid receptor (GR) overexpression is associated with poor prognosis ER-negative breast cancer. GR antagonism with mifepristone increases chemotherapy-induced breast cancer cell death, therefore we conducted a phase I clinical trial of mifepristone and nab-paclitaxel in advanced breast cancer. Methods A novel randomized phase I design was used to assess the effect of mifepristone on nab-paclitaxel pharmacokinetics and toxicity. Patients were randomized to placebo or mifepristone for the first cycle; mifepristone was given to all for subsequent cycles. Results Nine patients were enrolled. All were found to have a twofold or greater increase in serum cortisol after mifepristone administration, reflecting effective GR inhibition. Neutropenia occurred at both nab-paclitaxel dose levels studied (100 and 80 mg/m2), and was easily managed with dose reduction and/or growth factor administration. Pharmacokinetic data suggest an interaction between nab-paclitaxel and mifepristone in some patients. Two patients had complete responses (CR), three partial responses (PR), one stable disease (SD), and three progressive disease (PD). Immunohistochemical staining for GR found six of nine tumors were GR-positive. All six GR-positive tumors were triple-negative at the time of recurrence. Of these six patients, two had CRs, two PRs, one SD, and one PD. Conclusions GR appears to be a promising target in TNBC, and GR inhibition plus chemotherapy produces manageable toxicity. While neutropenia was observed in some, a nab-paclitaxel dose of 100 mg/m2 plus mifepristone 300 mg was found to be tolerable, and a randomized phase II trial of nab-paclitaxel with/without mifepristone is planned in GR-positive advanced TNBC. Electronic supplementary material The online version of this article (doi:10.1186/s40064-016-2457-1) contains supplementary material, which is available to authorized users.