Abstract PO1-14-12: Quantitative Biomarkers and 21-Gene Assay Results Predict Breast-Conserving Surgery Following Neoadjuvant Therapy in Early-Stage, Hormone Receptor-Positive, HER2-Negative Breast Cancer

Abstract Background: Neoadjuvant chemotherapy (NACT) and neoadjuvant endocrine therapy (NET) are often used to downstage tumors and/or enable breast-conserving surgery (BCS) in patients (pts) with early-stage, hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer. Given the increasing use of neoadjuvant therapy for HR+ breast cancer, studies are needed to better quantify the success of NACT/NET in downstaging tumors as a function of estrogen (ER), progesterone (PR), and Ki-67 expression, and 21-gene recurrence score (RS) in this patient population. Methods: Data were from pts with stage I-III, HR+/HER2- breast cancer diagnosed from 2010-2020 in the National Cancer Database (NCDB). Quantitative ER, PR, and Ki-67 data became available in 2018. We included pts who received either NACT or NET, with surgical plan categorized as mastectomy or BCS. Pts who received NACT for 12–30 weeks or NET for 4–36 months prior to surgery were eligible. Predicted rates of BCS by quantitative biomarkers (ER, PR, Ki-67 percentage, and RS) were estimated using restricted cubic spline logistic regression. Multivariable logistic regression models were fit to examine the associations between surgical plan and quantitative biomarkers for the two neoadjuvant cohorts. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated per 10% increase in percentages of ER, PR, and Ki-67 expression. Results: Of 44,589 pts treated with NACT, the mean age was 53 years, the median amount of time they were on NACT before surgery was 21 weeks, and 65% had cT1-2 disease. Of 10,466 pts treated with NET, the mean age was 68 years, the median amount of time they were on NET before surgery was 6 months, and 76% had cT1-2 disease. Overall, 42% of pts underwent BCS after NACT; while 64% did after NET. In the NACT cohort, 13,752 of the pts with available quantitative biomarker data were included in regression analyses; in the NET cohort, 4,003 were included. After adjusting for demographic and clinicopathologic factors, increasing ER% (aOR=0.96, 95% CI: 0.94–0.97) and PR% (aOR=0.98, 95% CI: 0.96–0.99) were associated with lower odds of BCS after NACT. Increasing Ki-67% was associated with greater odds of BCS after NACT (aOR=1.07, 95% CI: 1.04–1.10). Pts with a low (aOR=0.50, 95% CI: 0.29–0.88) or intermediate (aOR=0.58, 95% CI: 0.41–0.81) RS were significantly less likely than pts with a high RS to undergo BCS after NACT. Asian pts were less likely than White pts to have BCS (aOR=0.75, 95% CI: 0.56–0.99), while rates of BCS after NACT were similar to pts from other racial and ethnic groups. In the NET cohort, increasing ER% was associated with greater odds of BCS (aOR=1.09, 95% CI: 1.01–1.17). There was no significant association between baseline PR% or Ki-67% and BCS after NET. Pts with a low (aOR=0.92, 95% CI: 0.60–1.43) or intermediate (aOR=0.96, 95% CI: 0.65–1.41) RS were numerically less likely than pts with a high RS to have BCS after NET, though not statistically significant. Compared with White pts, Asian pts were less likely to have BCS after NET (aOR=0.60, 95% CI: 0.40–0.91). Conclusions: In this analysis of pts from the NCDB who received neoadjuvant therapy for early-stage, HR+/HER2- breast cancer, we found that BCS after NACT was higher for patients with a high RS or high Ki-67, suggesting that NACT is unlikely to downstage tumors with a low/intermediate RS or low Ki-67. Most pts receiving NET underwent BCS (likely due to a smaller clinical tumor size); BCT after NET was most dependent on ER expression. Asian pts were less likely to undergo BCS after either NACT or NET, which is consistent with previous reports. These data could facilitate appropriate neoadjuvant treatment selection based on tumor biology and improve patient counseling on the likelihood of successful BCS. Citation Format: Jincong Freeman, Sarah Shubeck, Nan Chen, Rita Nanda, Dezheng Huo, Frederick Howard. Quantitative Biomarkers and 21-Gene Assay Results Predict Breast-Conserving Surgery Following Neoadjuvant Therapy in Early-Stage, Hormone Receptor-Positive, HER2-Negative Breast Cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-14-12.