Abstract PS6-16: Outcomes for metaplastic breast cancer differ by histologic subtype
Authors: Tadros Audree B , Sevilimedu Varadan , Zabor Emily , Giri Dilip , Morrow Monica , Plitas George 
Published: February 2021

Background: Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer. The majority of MBC has triple negative (TN) receptor status and has been associated with poorer overall survival compared to other TN breast cancers. MBCs constitute a histopathologically distinct and diverse entity, which can be further classified into subtypes. In this study, we report the largest single-institution study of MBC. We aimed to compare survival outcomes among the histologic subtypes of MBC and to compare MBC to a cohort of non-metaplastic TN breast cancer patients.

Methods: All pure MBC patients undergoing surgery from 1995-2017 were identified from our prospectively maintained institutional database. Based upon the World Health Organization classification of MBC, tumors were classified by subtype: squamous, spindle, heterologous mesenchymal, or mixed. Primary endpoints included overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS). A contemporary cohort of non-metaplastic TN breast cancer patients was also identified from our institutional database. Clinicopathologic, treatment, and survival outcomes were compared between the 2 groups.

Results: In total, 132 MBC patients were included: 45 heterologous mesenchymal (34.1%), 26 squamous (19.7%), 26 spindle (19.7%), 30 mixed (22.7%), and 6 other (4.5%). Median follow-up time among survivors with MBC was 5.8 years (0-19.4 years). Five-year OS rate was 76% (95% CI 0.68-0.84). Five-year BCSS rate was 79% (95% CI 0.71-0.87). OS and BCSS varied among MBC subtypes. Patients with heterologous mesenchymal subtype had the best OS and BCSS rates, 88% (95% CI 0.78-0.98) and 88% (95% CI 0.78-0.99), respectively. Patients with squamous subtype had the worst OS and BCSS rates, 50% (95%CI 0.26-0.73) and 56% (95%CI 0.32-0.79), respectively. No difference in locoregional recurrence was seen between the groups. TN breast cancer patients presented with smaller tumors than patients with MBC (1.7 vs 2.35 cm, p &lt; 0.001) (Table). However, they were more likely to be pathologically node positive (40% vs 24%, p &lt; 0.001). Kaplan-Meier survival analysis demonstrated improved OS, DSS, and RFS for patients with TN breast cancer compared to MBC. The RFS hazard ratio for MBC compared to TN breast cancer, adjusted for age, year of surgery, type of surgery, and pathologic tumor and nodal staging, was 2.38 (range 1.63-3.26, p &lt; 0.001). Of the 10 MBC patients who received neoadjuvant chemotherapy, 4 progressed while on treatment and 3 had no response.

Conclusions: Metaplastic breast cancer is associated with poor survival outcomes compared to TN non-metaplastic breast cancer. The heterologous mesenchymal subtype is associated with the highest BCSS, while the squamous subtype is associated with the lowest BCSS. These data suggest that standard-of-care therapy for TN is not effective for MBC and that research is needed to identify therapies tailored to the unique biology of MBC.

Table. Patient, tumor, and treatment characteristicsMetaplastic (n = 132)Non-Metaplastic TN (n = 1767)p-valueMedian Age at Surgery (range)56 years (46, 65)54 years (44,63)0.13Tumor Size (range)2.4 cm (1.5, 3.5)1.7 cm (1.0, 2.5)&lt; 0.001Breast ProcedureMastectomy62 (47%)787 (45%)0.65Lumpectomy70 (53%)980 (55%)Tumor SubtypeHR-/HER2-114 (97%)1767 (100%)&lt; 0.001HR-/HER2+1 (0.9%)0 (0%)HR+/HER2-2 (1.7%)0 (0%)Unknown150 (0%)Family History of Breast CancerNo70 (55%)914 (52%)0.6Yes58 (45%)849 (48%)Unknown44Genetic MutationBRCA1 Pathogenic Mutation9 (27%)145 (31%)0.11BRCA2 Pathogenic Mutation3 (9.1%)42 (9%)Other mutation1 (3%)0 (0%)Negative20 (61%)279 (60%)Not Tested991301Menopausal StatusPostmenopausal83 (63%)1007 (57%)&lt; 0.001Axillary ProcedureSentinel Lymph Node Biopsy91 (69%)1018 (58%)&lt; 0.001Axillary Dissection37 (28%)742 (42%)None4 (3%)7 (0.4%)Pathologic Tumor Staget01 (0.8%)32 (1.8%)&lt; 0.001t156 (42%)1082 (61%)t259 (45%)585 (33%)t311 (8.3%)51 (2.9%)t45 (3.8%)17 (1.0%)Pathologic Nodal Stagen0100 (76%)1065 (60%)&lt; 0.001n125 (19%)486 (28%)n22 (1.5%)126 (7.1%)n31 (0.8%)86 (4.9%)nx4 (3%)4 (0.2%)Radiation TherapyNo59 (45%)585 (33%)&lt; 0.001Yes71 (55%)1164 (67%)Unknown218ChemotherapyAdjuvant118 (92.2%)1358 (77.6%)&lt; 0.001Neoadjuvant10 (7.8%)81 (5%)No0312 (17.8%)Unknown416HR, hormone receptor; TN, triple negative

Citation Format: Audree B Tadros, Varadan Sevilimedu, Emily Zabor, Dilip Giri, Monica Morrow, George Plitas. Outcomes for metaplastic breast cancer differ by histologic subtype [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 PS6-16.