P5-13-08: Breast Cancer Index Predicts Likelihood of Breast Conservation Surgery after Neoadjuvant Chemotherapy

Introduction: Neoadjuvant chemotherapy increases the likelihood that breast conservation therapy for breast cancer patients will be successful. Breast Cancer Index (BCI), a gene expression assay combining HoxB13/IL17BR ratio and Molecular Grade Index (MGI), is prognostic for the risk of distant recurrence and overall survival in tamoxifen-treated and untreated breast cancer patients. It was previously reported that high risk patients, as determined by BCI, had a 10-fold greater probability of pathologic complete response (pCR) with neoadjuvant chemotherapy than low risk patients. The aim of the current study was to examine the relationship between BCI score and the use of breast conservation surgery (BCS) following treatment with neoadjuvant chemotherapy. Material and Methods: A total of 145 women (tumor size T1, T2 and T3) were treated with neoadjuvant cheomtherapy for stage I-III breast cancer. RNA was extracted from FFPE tumor samples and a real-time RT-PCR assay was completed to generate a BCI score and risk group categorization as previously described (Jerevall et al. Br J Cancer 2011). The relationship between BCS, BCI and clinicopathological factors was examined using univariate and multivariate logistic regression. Results: Of the 145 patients (67% ER+, 54% PR+, 57% >50 y old), 48 (33.1%) underwent BCS. BCI categorized 62 (43%) of patients as low, 50 (34%) as intermediate and 33 (23%) as high risk. The rate of BCS for the three BCI risk categories was 15% (low risk), 48% (intermediate risk) and 45% (high risk). In the low risk group, the rate of BCS was 15% corresponding to a NPV of 85%. This is consistent with previous data from the same cohort, where the NPV of BCI for pCR was 98.4% with only one patient in the low risk group achieving pCR. In univariate analysis, pathological tumor size (pT), ER, PR, grade and BCI were predictors of BCS. A higher BCI score was associated with higher likelihood of BCS (odds ratio of 3.90; CI: 1.45−10.49; p=0.0069). In multivariate analysis, pT and BCI remained significantly associated with BCS, while ER status was not (p=0.23). Results were similar in the subset of patients with T1 and T2 tumors (N=97). In this subset, BCI categorized 42% of patients as low, 37% as intermediate and 21% as high risk and the rate of BCS was 22%, 64% and 60%, respectively. In multivariate analysis of this subset, only BCI was significantly associated with BCS. In all patients, the concordance index based on a model with pT alone was 0.695. When BCI was incorporated into the model with pT, the concordance index increased to 0.801 (p= 0.0002). Conclusion: In this study, we have shown that patients with higher BCI scores were associated with a higher likelihood of receiving BCS after neoadjuvant chemotherapy. Addition of BCI to tumor size increased accuracy in predicting likelihood of BCS. BCI along with standard pathological factors may improve estimation of individual probability of BCS after neoadjuvant chemotherapy. This study gives rise to the hypothesis that patients with low BCI should not be eligible for neoadjuvant chemotherapy since the likelihood of breast conservation is low. Further large confirmatory studies are necessary. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-08.