Abstract P5-10-14: Early Invasive Lobular or Ductal Carcinoma with Differential Clinical Outcomes Across Molecular Subtypes among Young Women Who Received Neoadjuvant Chemotherapy

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Abstract Background: Young women in the US are experiencing rising rates of breast cancer, necessitating effective treatment strategies. Neoadjuvant chemotherapy (NACT) is widely used in clinical practice, yet research on post-NACT outcomes among young women is limited, especially for those with less common histology, e.g., invasive lobular carcinoma (ILC) or invasive ductal and lobular carcinoma (IDLC). In this study, we examined differential pathologic complete response (pCR) and overall survival (OS) between invasive ductal carcinoma (IDC), ILC, or IDLC among female patients (pts) aged ≤40 years with stage I-III disease who received NACT, stratified by molecular subtype. Methods: This hospital-based, retrospective study analyzed data from the 2010-2020 National Cancer Database. We assessed 4 molecular subtypes: HR+/HER2–, HR+/HER2+, HR–/HER2+, and TNBC. pCR, defined as ypT0/Tis ypN0, was modeled using logistic regression, and adjusted odds ratios (aOR) were calculated. OS was event or censored at the time of death from any cause or last known contact, with 5-/10-year OS rates estimated using the Kaplan-Meier method and compared using log-rank tests. We performed Cox regression to generate adjusted hazard ratios (aHR). All models were stratified by molecular subtype, adjusting for clinical T/N stage, tumor grade, PR status (HR+ only), race/ethnicity, year of diagnosis, and comorbidity score. Results: Of 26,480 young women (median follow-up 52.9 [IQR 32.9, 79.2] months), 95.8% had IDC, 2.1% ILC, and 2.1% IDLC. In the HR+/HER2– cohort, 14.9% of IDC pts achieved pCR compared to 3.3% of ILC and 4.1% of IDLC pts (p<.001). After covariate adjustment, pts with ILC (aOR 0.45, 95% CI: 0.23-0.86) or IDLC (aOR 0.49, 95% CI: 0.27-0.89) had lower odds of pCR than IDC pts. In the HR+/HER2+ cohort, a higher pCR rate was observed among IDC pts (33.8%) than ILC (24.3%) or IDLC (27.5%) pts (p=.033). However, the odds of pCR were not significantly different between IDC and ILC (aOR 0.90, 95% CI: 0.56-1.43) or IDLC (aOR 0.77, 95% CI: 0.52-1.13). In the HR–/HER2+ cohort, pCR rates were similar across histologic types (IDLC: 70.6%; ILC: 58.8%; IDC: 49.9%; p=.180). On multivariable regression, pts with ILC (aOR 1.68, 95% CI: 0.60-4.70) or IDLC (aOR 1.96, 95% CI: 0.67-5.73) had similar odds of pCR as those with IDC. In the TNBC cohort, IDC pts achieved a higher rate of pCR than ILC or IDLC pts (36.0%, 21.3% vs. 18.0%; p=.003). Compared to IDC pts, IDLC pts had lower odds of pCR (aOR 0.40, 95% CI: 0.18-0.9) while ILC pts had similar odds of pCR (aOR 0.70, 95% CI: 0.34-1.42). IDC was associated with significantly longer 5-/10-year OS rates (compared to ILC or IDLC) among pts with HR+/HER2– (p=.012) or TNBC (p<.001). In the adjusted models, pts with HR+/HER2– ILC (aHR 1.55, 95% CI: 1.15-2.10) or IDLC (aHR 1.52, 95% CI: 1.15-2.03) had a greater mortality risk than IDC pts. HR–/HER2+ ILC pts also had a higher risk of death than IDC pts (aHR 3.51, 95% CI: 1.10-11.15). In the TNBC cohort, ILC was associated with an increased mortality risk compared to IDC (aHR 2.28, 95% CI: 1.41-3.69). Conclusions: In this US national registry of young women with early-stage breast cancer who received NACT, pts with ILC or IDLC consistently exhibited lower pCR rates and poorer OS than those with IDC across molecular subtypes. These disparities underscore the need for tailored treatment interventions that account for histologic type, particularly for ILC, among young women. Our findings not only highlight the importance of informed NACT counseling, but also underscore the necessity for oncology programs to optimize therapeutic approaches and continue multidisciplinary efforts to reduce disparities specifically for young women with ILC. Citation Format: Jincong Freeman, Jared H. Hara, Olasubomi J. Omoleye, Ted O. Akhiwu, Shreyas Kalantri, Heather J. Hoffman. Early Invasive Lobular or Ductal Carcinoma with Differential Clinical Outcomes Across Molecular Subtypes among Young Women Who Received Neoadjuvant Chemotherapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-10-14.

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