Abstract P6-01-32: Evaluation of pathologic response and residual tumor cellularity following neo-adjuvant chemotherapy predict prognosis in breast cancer patients
Authors: Gentile Damiano , Sagona Andrea , De Carlo Camilla , Fernandes Bethania , Grimaldi Simone Di Maria , Barbieri Erika , Gatzemeier Wolfgang , Scardina Lorenzo , Biondi Ersilia , Jacobs Flavia , Vatteroni Giulia , Tinterri Corrado 
Published: March 2023

Abstract
Introduction: Treatment of early-stage beast cancer (BC) has changed since recent evidence showed that neoadjuvant chemotherapy (NAC) can reduce residual tumor cellularity (RTC) and improve patient outcomes. Achieving a pathologic complete response (pCR) has been associated with significantly improved disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). However, among patients treated with NAC, few experience pCR, while approximately 60-80% of them achieve a pathologic partial response (pPR). In previous studies, BC patients with different grades of pPR have been usually grouped and analyzed together, with inconsistent results and unclear prognostic significance. Objectives: The primary aims of this study were to describe the clinical and treatment characteristics of BC patients treated with NAC, to identify independent predictive factors of pCR, and to compare the oncologic outcomes between patients achieving pCR or pPR. The secondary aim of this study was to measure the RTC of BC patients with pPR and to compare the outcomes of patients with different RTC in order to improve prognostic information. Methods: All the consecutive BC patients undergoing NAC at the Breast Unit of IRCCS Humanitas Research Hospital (Milan, Italy) between October 2006 and April 2020 and their corresponding post-operative pathology slides were reviewed. The following exclusion criteria were used: excisional biopsy or debulking surgery as first BC operation, patients with a previous BC diagnosis or other prior or synchronous malignancies, male patients, unknown NAC regimen, disease progression during NAC, and follow-up ≤12 months. Results: A total of 495 BC patients received NAC. Overall, 148 (29.9%) patients achieved pCR, while 347 (70.1%) had pPR, and median RTC was 40%. At multivariable analysis, 3 independent factors predicting pCR were identified. Tumor stage pre-NAC (cT1-2 84.5% versus cT3-4 15.5%, odds ratio (OR)=0.119, 95% confidence interval (95%CI)=0.048-0.189, p=0.001), BC sub-type (HER2-enriched 54.7% versus triple-negative 29.8% versus luminal-like 15.5%, OR=2.178, 95%CI=2.055-2.301, p=0.001), and vascular invasion (absence 98.0% versus presence 2.0%, OR=0.022, 95%CI=0.004-0.090, p=0.001). Patients with BC undergoing NAC and achieving pCR presented statistically significant longer DFS, DDFS, and OS (p = &lt; 0.001). Patients with RTC &lt; 40% presented statistically significant better DFS and DDFS (p = 0.033, p = 0.015, respectively). However, no statistically significant difference in terms of OS was observed between RTC &lt; 40% and RTC ≥40% groups (p = 0.148). Conclusions: Tumor stage pre-NAC, BC sub-type, and vascular invasion are significantly and independently associated with pCR. Patients with pCR present a better prognosis compared to patients with pPR in terms of DFS, DDFS, and OS. Measurement of RTC in BC patients with pPR improves the prognostic information that can be obtained from the assessment of the pathologic response. Different patterns of residual disease play an important role in predicting the risk of subsequent loco-regional and distant recurrence, and patients with RTC &lt; 40% present significantly better DFS and DDFS.
Citation Format: Damiano Gentile, Andrea Sagona, Camilla De Carlo, Bethania Fernandes, Simone Di Maria Grimaldi, Erika Barbieri, Wolfgang Gatzemeier, Lorenzo Scardina, Ersilia Biondi, Flavia Jacobs, Giulia Vatteroni, Corrado Tinterri. Evaluation of pathologic response and residual tumor cellularity following neo-adjuvant chemotherapy predict prognosis in breast cancer patients [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 P6-01-32.