e12627 Background: Response to neoadjuvant chemotherapy (NACT) in hormone receptor-positive, HER2-negative (ER+/HER2-) breast cancer (BC) is heterogeneous. Genomic assays predict chemotherapy benefit but are not widely available. We evaluated a clinicopathologic model estimating the probability of high genomic risk as a predictor of response to dose-dense NACT (AC q2w followed by Docetaxel q3w). Methods: We retrospectively analyzed 280 patients with stage II-III ER+/HER2- BC treated with NACT (median age 45 years; 70, 3% premenopausal) in a single center. Most patients had locally advanced disease (86, 8%), nodal involvement (93, 9%), and luminal B subtype (95, 4%). Pathologic response was assessed using Residual Cancer Burden (RCB). The probability of high genomic risk (corresponding to Recurrence Score ≥26) was calculated using the model developed by S. Yamamoto et al. according to the following formula: p = 1 / 1 + exp − (4. 611 + 1. 2342×HER2 − 0. 0813×ER − 0. 0489×PR + 0. 0857×Ki-67), where HER2=0-2; ER, PR, Ki-67=% positive nuclei. A cutoff of ≥50% was predefined as in the original study since the accuracy, sensitivity, specificity, positive predictive and negative predictive values are 90, 5%, 72, 2%, 94, 8%, 76, 4% and 93, 5%, respectively. Univariable and multivariable logistic regression analyses were performed to identify predictors of favorable response (RCB 0-1). RCB 0-1 as an end point was chosen due comparable long-term results in ER+/HER2- BC as per meta-analysis. Results: RCB 0 was achieved in 12, 9% of patients and RCB 0-1 in 24, 3%. Mean probability of high genomic risk was 40, 3%, with 36, 8% classified as high probability (≥50%). Germline testing was performed in 83, 2% of patients; mutations (BRCA1/2, ATM, PALB2, CHEK2) were identified by NGS in 18, 0% of all tested cases (BRCA2 being the most common - 9%) and were slightly more frequent in patients with high vs low genomic risk probability (22, 2% vs 15, 2%). In univariable analysis, factors associated with RCB 0-1 included age ≤50 years (OR 2, 09, 95% CI 1, 07-4, 07), initially operable disease (OR 2, 44, 95% CI 1, 19-5, 04), T1–3 stage (OR 1, 80, 95% CI 1, 03-3, 13), presence of germline mutations (OR 2, 82, 95% CI 1, 41-5, 67), and high genomic risk probability ≥50% (OR 2, 64, 95% CI 1, 51-4, 62; all p <0, 05). In multivariable analysis, high genomic risk probability ≥50% remained an independent predictor of RCB 0-1 (OR 2, 80, 95% CI 1, 48-5, 30; p =0, 001), together with germline mutation status (OR 2, 32, 95% CI 1, 11-4, 85; p =0, 025), while age, T stage and operability were not significant. Survival analysis is ongoing. Conclusions: A clinicopathologic model estimating the probability of high genomic risk independently predicts response to NACT in luminal breast cancer and may support selection of ER+/HER2- patients most likely to benefit from NACT when genomic testing is unavailable.
Kovalenko et al. (Thu,) studied this question.