Abstract PS7-15: Mixed invasive ductal lobular carcinomas (mDLC) are clinically more similar to invasive lobular carcinoma (ILC) than to invasive ductal carcinoma (IDC)
Authors: Nasrazadani Azadeh , Li Yujia , Fang Yusi , Shah Osama , Atkinson Jennifer M , Lee Joanna S , McAuliffe Priscilla F , Lee Adrian V , Tseng George , Lucas Peter , Oesterreich Steffi , Wolmark Norman 
Published: February 2021

Abstract
Clinicopathologic differences between histological subtypes of invasive breast cancer are increasingly being appreciated. Mixed invasive ductal lobular carcinomas (mDLC) are thought to be composed of both ductal and lobular components, and we sought to determine whether mDLC clinically align more closely with invasive ductal (IDC) or invasive lobular (ILC) carcinoma subtypes or if they display intermediate or unique features dissimilar to either type. Key clinical and histologic parameters were compared between cohorts of patients with mDLC (N = 410), IDC (N = 12,979), and ILC (N = 1,569) identified from cancer registry data of a single large healthcare system.Patients with mDLC were older (59 years (49 - 68)) than those with IDC (57 years (48 - 67), p = 0.014)) and younger than those with ILC (61 years (51 - 70), p = 0.006). Tumor size in mDLC was larger (19mm (12 - 27)) than IDC (16mm (10 - 25), p &lt; 0.001) and smaller than ILC (20mm (12 - 35), p = 0.036). Similar to ILC, mDLC were more likely than IDC to be ER+ (92% vs 78% in IDC, p &lt; 0.001), and less likely to be HER2+ (8% vs 15% in IDC, p = 0.04). mDLC were also similar to ILC with regards to higher likelihood of diagnosis at higher stage (p &lt; 0.001), yet with lower grade (p &lt; 0.001), at diagnosis as compared to IDC. Heatmap visualization, as well as dimension reduction by multidimentional scaling (MDS), demonstrates significant overlap of the mDLC and ILC cohorts. Furthermore, an elastic net regression model based on clinicopathologic parameters predicts mDLC to align more closely with ILC than IDC. For patients for whom oncotype Dx scores were available, there was a trend for enrichment of low risk RS scores with rare high-risk RS tumors in mDLC, similar to ILC. With regards to response to neoadjuvant chemotherapy, a subset of the aforementioned cohorts who had received neoadjuvant chemotherapy, mDLC (N = 17), IDC (N = 180), and ILC (N = 57), were compared. Among patients in whom breast conserving surgery (BCS) was attempted, patients with IDC were more likely to have a successful BCS than those with ILC, with less margin positivity thereby avoiding re-excision and/or completion mastectomy (70% vs 32%, respectively; p = 0.003). Successful BCS was achieved with mDLC 56% of the time, although compared to IDC and ILC statistical significance was not reached. In a limited cohort receiving neoadjuvant endocrine therapy (mDLC (N = 7), IDC (N = 37), and ILC (N = 21)) no differences with regard to rates of successful BCS were identified. Pathologic complete response rates (pCR) were additionally evaluated, although small study numbers precluded our ability to perform statistical analysis.Collectively, the aforementioned findings support a higher concordance between mDLC and ILC as compared to IDC. It is feasible that the lobular component of mDLC tumors is predominant, leading to the observed histopathologic similarities noted between mDC and ILC cohorts. We are planning meta-analyses including data from other institutions, and molecular studies to further understand complexities of mDLC.The authors acknowledge grant support from ASCO Conquer Cancer (to NW and AN).
Citation Format: Azadeh Nasrazadani, Yujia Li, Yusi Fang, Osama Shah, Jennifer M Atkinson, Joanna S Lee, Priscilla F McAuliffe, Adrian V Lee, George Tseng, Peter Lucas, Steffi Oesterreich, Norman Wolmark. Mixed invasive ductal lobular carcinomas (mDLC) are clinically more similar to invasive lobular carcinoma (ILC) than to invasive ductal carcinoma (IDC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-15.