Abstract PD14-06: Does chemotherapy benefit patients with HR+/HER2- invasive lobular breast cancer?
Authors: Yaghi Marita , Jabbal Iktej , Bilani Nadeem , Zerdan Maroun Bou , Elson Leah , Li Hong , Saravia Diana , Stone Elizabeth , Nahleh Zeina 
Published: March 2022

Introduction Invasive lobular breast cancer (ILBC) is the second most common subtype of breast cancer. More evidence is emerging on the unique clinical features of ILBC. However, most systemic therapy guidelines for ILBC are derived from clinical trials with no specific focus on ILBC. Also, the benefit of chemotherapy for the treatment ILBC has been questioned. Using a large national registry, we aimed at comparing outcomes of various systemic therapy regimens in hormone receptor-positive (HR+) and HER2- ILBC. Methods We performed a year-stratified simple random sampling method to select 10% of ER+ or PR+ (HR+) and HER2- female patients with ILBC with AJCC stages I-III who underwent surgery from the National Cancer Database (NCDB) (2010-2017). Patients were grouped into four treatment cohorts: surgery only (S), chemotherapy alone (CT), endocrine therapy alone (ET), combined chemotherapy followed by endocrine therapy (CET). Overall survival (OS) among groups was first examined using the Kaplan-Meier method and Cox proportional hazard modeling. Focusing on ET and CET, propensity score (PS) match in logistic regression was performed to reduce selection biases due to demographical and clinical characteristics. OS between PS matched ET and CET pairs were evaluated again using the same methods. OS differences between ET and CET by lobular histology group and by disease stage were also examined. Results Approximately 90% of ILBC were HR+ and HER2+. N=17,789 patients were included in this analysis: 59.7% received ET, 26.2% CET, 2.3% CT and 11.9% S. 5-years OS was significantly better for patients who received ET (90.7%) or CET (90.4%) as compared to CT (79.4%) or S only (79.7%) (p&lt;.001). Of interest, after adjusting for other demographic and clinical characteristics, 5-years OS was similar for both ET and CET (p=.064). Increased ET administration (52.6% to 67.4%, p for trend &lt;.001) and decreased CET (30.4% to 20.2%, p for trend &lt;0.001) were observed from 2010 to 2017. Among n=15,273 patients who underwent ET (n=10,616; 69.5%) or CET (n=4,657; 30.5%), both groups had similar histology findings (45.5% vs 47.7% lobular histology mixed with other features). However, significant demographic and clinical characteristics differences were identified between both cohorts. Patients in the CET group were younger (mean age 56.9±10.5 vs. 65.5±11.6) (p&lt;.001), had a higher stage at diagnosis (34.8% stage III vs. 4.2%), more positive regional LN (67.5% vs. 13.7%), and received more radiation therapy (74.1% vs. 58.5%) as compared to those in the ET group. 5-years OS remained similar between ET and CET when adjusting for age, stage, LN involvement, histology, and radiation therapy (adjusted HR, 95% CI: 1.04, 0.89-1.20). Importantly, OS was similar between ET and ECT among patients with OncotypeDX (ODX) score &lt; 26 (96.4% vs 97.5%) and ODX score ≥ 26 (5-year OS: 92.2% vs 91.4%). PS match yielded 3,002 pairs; 5-years OS remained similar between ET (92.6%) and CET (91.6%) (p=0.94). In addition, no significant difference was detected when stratifying by disease stage and histology. Conclusion In this large analysis , chemotherapy did not improve survival in patients with HR+ and HER2- lobular cancer treated with ET, regardless of stage or lymph node involvement, or ODX score. The majority of patients with early stage HR+/HER2- with ILBC in the US receive ET, and one-fourth receive CET. Research investigating de-escalated chemotherapy-free regimens for ILBC are warranted. Exploring biomarkers-based approach to identify subgroups who would benefit from chemotherapy would better define systemic treatment options for ILBC.

Citation Format: Marita Yaghi, Iktej Jabbal, Nadeem Bilani, Maroun Bou Zerdan, Leah Elson, Hong Li, Diana Saravia, Elizabeth Stone, Zeina Nahleh. Does chemotherapy benefit patients with HR+/HER2- invasive lobular breast cancer? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD14-06.