Abstract P6-01-15: Breast cancer patients with different hormone receptor subtypes receiving neoadjuvant chemotherapy (NAC) experience differential overall survival according to their resistance to NAC
Authors: Prabhakaran Sangeetha , Pankratz V. Shane , McNicoll Christopher , Falk Nadja , Nemunaitis Jacklyn , Zhou Jain , Sandoval-Belt Payton 
Published: March 2023

Abstract
Background: Response to neoadjuvant chemotherapy (NAC) is an indicator of outcomes and can be quantified as achievement of pathologic complete response (pCR) (absence of residual invasive disease in breast and lymph nodes) and residual percent cellularity. However, the significance of residual tumor cellularity post-NAC is not well understood. We assessed the impact of NAC-induced reduction in tumor cellularity among hormone receptor subtypes and the effect of these reductions on overall survival (OS).
Methods: An IRB-approved retrospective review identified demographics, disease presentation, response to treatment, and outcomes. ER and PR status were categorized as low positive (1-9%), positive (≥ 10%) and negative. Treatment response was noted as percent residual cellularity (complete 0%, almost complete &lt; 10%, good 10-30%, moderate &gt;30-80% and poor &gt;80%) in the surgical specimen and pathologic stage. We examined measures of response to NAC within breast tumor subtypes and the effect of these responses on associations with OS among hormone receptor subtypes.
Results: The clinical series comprised 384 patients who received curative intent NAC. This series was diverse in presentation, displayed considerable variability in response to NAC (Table 1). 88 (23.6%) patients did not experience tumor down staging, and of those presenting with clinical nodal Stage 1 or higher (n=197), 94 (47.7%) did not experience nodal down staging. Although Triple Negative Breast Cancer (TNBC) status was not significantly associated with post-NAC residual tumor cellularity (p=0.74), ER, PR, and HER2 status were individually associated with this measure of response to NAC (p=0.04, 0.01, and 0.01, respectively). However, none of these associations explained more than 2.5% of the variability in this marker of treatment response. Median non-censored follow-up time was 4.26 years. Accounting for censoring, median survival was 13.65 years (lower 95% confidence limit was 11.79 years). Differential associations with OS were observed for three hormone receptor subtypes (ER: p&lt; 0.001, HER2: p=0.04, and TNBC: p&lt; 0.001) according to residual tumor cellularity, classified by percent residual cellularity categories of complete or almost complete response versus all others. Importantly, although ER negative patients with poor residual cellularity response had worse OS than ER positive patients with good response (Hazard Ratio [HR], 95% Confidence Interval [CI] = 4.74, 2.2-10.2), ER negative patients with good response did not have significantly worse OS than ER positive patients with good response (HR, 95% CI = 1.37, 0.57-3.26). Similar patterns were seen for patients with HER2 negative breast cancer or TNBC. Chemo resistant TNBC patients had higher risks for mortality than if they were not chemo resistant (HR, 95% CI: 2.41, 1.02-5.71).
Conclusions: Our data suggest that OS associated with different hormone subtypes differs according to response to NAC. Differential OS according to response to NAC is greatest for patients classified according to ER status influences, with good response eliminating much of the differential mortality risk between ER negative and positive patients. There is a similar difference according to TNBC, although the difference appears to be less complete. Further studies should focus on understanding the chemo resistance of ER negative tumors, and perhaps TNBC, to identify mechanisms that may ultimately drive treatment response and survival.
Table 1. Demographic and other characteristics
Citation Format: Sangeetha Prabhakaran, V. Shane Pankratz, Christopher McNicoll, Nadja Falk, Jacklyn Nemunaitis, Jain Zhou, Payton Sandoval-Belt. Breast cancer patients with different hormone receptor subtypes receiving neoadjuvant chemotherapy (NAC) experience differential overall survival according to their resistance to NAC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-15.