High-grade breast cancers include both highly sensitive and highly resistant subsets to cytotoxic chemotherapy

We reported that breast cancers achieving pathological complete response (pCR) or progressive disease (PD) to neoadjuvant chemotherapy (NAC), which are considered exact opposites on the chemosensitivity spectrum, have certain clinicopathological features in common. To determine the highly sensitive and highly resistant subsets to cytotoxic chemotherapy, we evaluated predictive factors for pCR and PD to NAC, and assessed the similarities in these factors.

Subjects comprised 300 women with 304 stage II or III breast cancers treated with chemotherapy that was anthracycline-based, taxane, or both, followed by surgery between 2007 and 2008. We retrospectively evaluated pre-NAC clinicopathological features including chemotherapy regimen, clinical T stage, nuclear grade (NG), hormone receptor (HR) status, and human epidermal growth factor receptor-2 (HER2) status in pCR and PD, using univariate chi(2) testing and multivariate logistic regression analyses.

Of 304 tumors, 30 (10%) achieved pCR and 22 (7%) showed PD to NAC. Multivariate analysis demonstrated that anthracycline plus taxane chemotherapy (P = 0.006), NG3 (P = 0.006), HR-negativity (P = 0.013), and HER2-positivity (P = 0.010) were significant predictors of pCR, and T3-4 (P = 0.002) and NG3 (P = 0.010) were significant predictors of PD.

High-grade breast cancers include both highly sensitive and highly resistant subsets to cytotoxic chemotherapy. Three factors can help discriminate between these subsets. HR-negative and HER2-positive can be predictive of high chemosensitivity. Advanced primary tumor stage can be predictive of high chemoresistance.