Predictors of Response to Trastuzumab Containing Neoadjuvant Chemotherapy in HER2 Positive Breast Cancers
Xin Li, Amal Kanbour-Shakir, David Dabbs, Rohit Bhargava. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: Trastuzumab-containing neoadjuvant chemotherapy (NACT) in patients with HER2-positive breast cancer is highly effective in reducing tumor volume and enables more patients to have breast conserving surgery. We have previously reported that tumor hormone receptor level significantly influences response to trastuzumab containing NACT (Mod Pathol. 2011;24:367-374). In this study, we comprehensively evaluated various morphologic features and proliferative activity in 50 invasive breast carcinomas treated with trastuzumab containing NACT to determine if any of these features have the same predictive value as tumor hormone receptor content.
Design: Following morphologic parameters were analyzed: Nottingham score, grade and individual grading components, absolute mitosis count/10 high power fields, and type of growth pattern (infiltrative versus pushing). The following features were considered present if identified in >10% of the tumor: sheet-like growth pattern, spindle cells, apocrine differentiation, intra-tumoral lymphocytic infiltrate, and geographic necrosis. Nucleoli were considered prominent if visible at 10X objective and substantial apoptosis was considered present if easily visible at 10X. Cell proliferative activity was assessed by Ki-67 labeling index LI. Complete pathologic response was defined as absence of invasive carcinoma in the post-therapy resection specimen and within regional lymph nodes. Percentage tumor volume reduction was calculated based on pretherapy clinical tumor size and meticulous examination of the post-therapy resection specimen.
Results: Eighteen (36%) cases achieved pCR. Neither morphologic variables nor Ki-67 LI were predictive of pCR or >50% tumor volume reduction. Similar to our previous report, hormone receptor status and semi-quantitative H-scores for ER and PR were predictive of both pCR and >50% tumor volume reduction. The mean ER and PR H-scores for tumors that showed pCR were 44 and 10 respectively compared to 132 and 62 for cases that failed to achieve pCR (p value of 0.005 for ER and 0.018 for PR).
Conclusions: Only steroid hormonal receptor (ER and PR) content of the tumor are predictive of pCR and significant tumor volume reduction in HER2 positive patients treated with trastuzumab-containing NACT. Neither morphologic features (including Nottingham grading) nor Ki-67 LI are predictive of response or >50% tumor volume reduction. Semi-quantitative scoring for hormone receptors should be universally adopted by pathologists for proper patient management.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 27, Tuesday Morning