Predictors of Response to Standard Neoadjuvant Chemotherapy in Estrogen Receptor Positive, HER2 Negative Breast Cancer
Rohit Bhargava. Magee-Womens Hospital of UPMC, Pittsburgh, PA
Background: In contrast to estrogen receptor (ER) negative tumors, ER+/HER2– tumors rarely achieve pathologic complete response (pCR) to standard neoadjuvant chemotherapy. Nevertheless, tumor volume reduction secondary to NACT in ER+/HER2– tumors help these patients undergo breast conserving therapy, which is the primary goal of NACT. Therefore, it is important to know which routinely assessed parameters predict for >50% tumor volume reduction (TVR), so that patients are appropriately selected for NACT. We performed subset analysis (from a previously reported dataset of 359 cases: Cancer. 2010;116:1431-1439) of 119 ER+/HER2– cases treated with standard NACT at our institution form 1999-2006.
Design: Semi-quantitative H-scores for ER, progesterone receptors (PR), age, pre-therapy tumor size were available on all cases. H&E slides were available on 75 cases. Numerous morphologic parameters were analyzed in the pre-therapy biopsy including Nottingham score, grade and individual grading components, and absolute mitosis count/10 high power fields (hpf). The following features were considered present if identified in >10% of the tumor: lobular-like growth pattern, 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. All parameters were statistically analyzed using t-test to determine if they predict for >50%TVR.
Results: Of the 119 patients, 24 (20%) showed >50% tumor volume reduction and 95 (80%) showed ≤50% TVR. The mean and median PR H-scores for tumors that showed >50% TVR were 90 and 70 respectively compared to 132 and 140 for cases that showed ≤50%TVR (p=0.03). The other parameters that predicted >50% TVR were mitotic activity score of 2/3 (p=0.01), Nottingham score of 7 or higher (p=0.04), Nottingham grade of 3 (p=0.02). Patient's younger age and tumor high absolute mitotic count/10 hpf showed a trend for >50% TVR (p=0.07). All other clinical and morphologic parameters including ER H-score did not reach statistical significance in predicting >50%TVR.
Conclusions: Semiquantitative PR H-score and tumor mitotic activity are the 2 most important parameters that predict for significant tumor volume reduction to standard NACT in ER+/HER2– tumors. Although not analyzed in this study, Ki-67 labeling index may also provide information similar to tumor mitotic activity. Therefore PR H-score and some measure of tumor cell proliferation should be taken into account in selecting ER+/HER2– patients for standard NACT.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 11, Wednesday Afternoon