Abstract PS5-04-10: Comparative analysis of second primary malignancies in invasive lobular versus ductal breast carcinoma: A SEER-based study

Abstract Background: Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two most common histologic subtypes of breast cancer (BC), with IDC accounting for approximately 70-80% of cases and ILC comprising 10-15%. Improved screening and advances in breast cancer treatment have increased survivorship but also heightened the risk of second primary malignancies (SPMs) among long-term survivors. Our study presents a comparative analysis of the types of SPMs among ILC and IDC survivors. Methods: Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results(SEER) 8 database registry, we identified a cohort of female patients diagnosed with ILC and IDC between 1975 and 2022. We analyzed the incidence of SPM using the SEER*Stat MultiplePrimary-Standardized Incidence Ratio (MP-SIR) session for the overall cohort of females with ILC and IDC. The cohort was further stratified by age (< 40 years and >/= 40 years). Standardized incidence ratios (SIRs) were calculated to compare the observed rates with the expected rates between ILC/IDC and the general population. Results: Both ILC and IDC had an increased risk of all types of SPMs, with SIRs of 1.09 (95%CI: 1.06-1.11) for ILC and 1.14 (95% CI: 1.14-1.15) for IDC. Some sites emerged as commonsites of SPMs for both ILC and IDC, and those with highest SIRs include soft tissue (ILC: SIR =1.72; IDC: SIR = 1.55, p < 0.05), thyroid (ILC: SIR = 1.42; IDC: SIR = 1.22, p < 0.05), skinexcluding basal and squamous (ILC: SIR = 1.19; IDC: SIR = 1.06, p < 0.05), and acute myeloidleukemia (ILC: SIR = 1.90; IDC: SIR = 1.78, p < 0.05). Sites for SPM unique to ILC include mainly the stomach (SIR = 1.58, CI 1.33 - 1.86) and melanoma of the skin (SIR = 1.18, CI 1.05 -1.32). Sites for SPM unique to IDC with p < 0.05 include salivary gland, esophagus, pleura, lung, bones and joints, corpus uteri, and acute lymphocytic leukemia (Table). Greater incidence of SPMs was observed for patients age< 40 for both ILC and IDC (ILC: age < 40 SIR = 1.84 vs age >/= 40 SIR = 1.08; IDC: age < 40SIR = 1.98 vs age >/= 40 SIR = 1.11). For ILC, SPM with involvement of the stomach is seen in the cohort of both age categories, but did not reach statistical significance for age < 40 (age < 40:SIR = 4.22, CI 0.87-12.33; age >/= 40: SIR = 1.56, CI 1.31-1.84). Conclusion: Our study provides a detailed understanding of the variation in the pattern of SPMs for both ILC and IDC. Patients with ILC exhibited a higher propensity to develop SPM at specific sites, such as the stomach and skin melanoma, highlighting the need for further investigation into the underlying biological mechanisms. Conversely, IDC has a broader distribution of unique SPMs involving the lung, pleura, salivary gland, esophagus, uterus, and bones. Younger patients exhibited a higher risk of SPMs in both ILC and IDC cohorts. These findings underscore the importance of a tailored surveillance strategy based on histological subtype. Citation Format: S. Singh, S. Sangam, B. Zengin, S. Modi, H. Jain, A. MariamRoy. Comparative analysis of second primary malignancies in invasive lobular versus ductal breast carcinoma: A SEER-based study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-04-10.