p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes

We hypothesized that, among molecular subclasses of breast cancer, p53 status may have a differential predictive value for the efficacy of anthracyclines/alkylating agents-based regimen. We analysed the efficacy of a preoperative combination between 5-fluorouracil, anthracyclines and cyclophosphamide according to both p53 status and molecular classification. Oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) expression and p53 status were determined by immunohistochemistry in 293 samples from two different centres. A logistic regression model was used for multivariate analysis of predictors for pathological complete response (pCR). p53 immunostaining (54%) was associated with high grade (P=0.002) and ER negativity (P=0.04). p53 was detected in 59% of triple-negative tumours (ER-/PgR-/HER2-, n=120 patients). In the overall population, pCR (9.6%) was independently predicted by high tumour grade (P=0.002) and ER/PgR/HER2 triple negativity (P=0.0004), but not by p53 status (P=0.12). p53 immunostaining was associated with a trend for a higher rate of pCR in triple-negative tumours [relative risk (RR)=2.5, 95% confidence interval (CI)=0.8–7.5, P=0.09], but not in non-triple-negative tumours (RR=0.73, 95% CI=0.16–3.3, P=0.69). p53 status may have a different predictive value for efficacy of anthracycline/alkylating agents-based regimen in each molecular subclass, a result which may explain the different results reported in literature.