Abstract P3-19-20: Are traditional indications for radiation therapy appropriate for small cell carcinoma of the breast: An NCDB outcomes analysis and treatment utilization report
Authors: Cantrell James Nathan , Pius Patricia , Acharya Pawan , Vesely Sara , Henson Christina , Algan Ozer 
Published: March 2022

Abstract
Background: Small-cell carcinomas (SCC) are poorly differentiated neuroendocrine tumors arising primarily in the lung. Extra-pulmonary SCC composes roughly 6% of all SCCs, with SCC arising in the breast (SCCB) accounting for roughly 4% of all extra-pulmonary sites. Due to its rarity, current practice is guided by traditional breast cancer studies and small-cell lung cancer experience. Prior database analyses of extra-pulmonary SCC’s have revealed mixed results regarding the effect of radiation therapy. The remaining literature regarding the treatment of SCCB is limited to case reports and small case series with no agreed upon “standard” radiation dose or regimen. Method: Using the NCDB, a retrospective observational cohort study was performed investigating survival outcomes and prognostic indicators for SCCB patients. Using cases from 2004-2017, females with primary SCCB and only one lifetime malignancy were included. Patients with in-situ or metastatic disease were excluded. Kaplan Meier method, log-rank test, and Cox proportional hazards regression were performed to determine characteristics associated with OS. Results: A total of 153 patients met criteria for descriptive analysis, with 142 patients having all outcomes information for survival analysis. Median age at diagnosis was 59 years. The majority of patients were white (79%), followed by Black (16%), with other reported races accounting for &lt;1% each. The cohort was composed of 19% stage I, 57.5% stage II, and 23.5% stage III patients. Triple negative (ER, PR, and HER2 negative) malignancies composed the largest group (37%), followed by ER or PR positive, HER2 negative cancers (28%), with ER or PR positive, HER2 positive group making up only 2%, and 33% having an unreported molecular subtype. Regarding surgical intervention, 42% received breast conserving surgery, 42% received mastectomy, and 16% had no surgery. Chemotherapy was administered to 82% of patients. Radiation therapy was administered to 65% of the cohort with a median dose of 6000cGy and a median of 33 fractions. Hormone therapy was administered to 19%. With median follow-up of 32 months, median survival was not met for stage I (75th percentile was 101 months) and was 57 months (95% CI 23-91) and 17 months (95% CI 6-28) for stage II and III respectively. On multivariate analysis (MVA), Age greater than 60 years old had a hazard ratio (HR) of 1.97 (95% CI 1.2-3.4, p = 0.01). When compared to stage I, stage II had a HR of 5.4 (95% CI 1.6-18.3, p = 0.007) and stage III a HR 5.8 (95% CI 1.6-21.3, p = 0.008). Receipt of hormone therapy had a HR of 0.32 (95% CI 0.15-0.72, p = 0.006). When compared to no surgery, breast conserving surgery (BCS) had a HR of 0.17 (95% CI 0.08-0.39 p = 0.0001) and mastectomy had a HR of 0.43 (95% CI 0.23-0.81 p = 0.009). Neither receipt of radiation or chemotherapy reached statistical significance. However, when looking at patients with traditional indications for radiation therapy, i.e., BCS or mastectomy with positive lymph nodes on pathology, the receipt of radiation was associated with better overall survival (median OS was 16.7 months (95% CI 0-36) without radiation versus 114 months (95% CI 93-137) with a p-value of 0.003). Conclusion: In one of the largest cohorts reported to date for SCCB, median survival was not met for stage I (75th percentile of 101 months) and was 57 months (95% CI 23-91) and 17 months (95% CI 6-28) for stage II and III respectively. Age &lt; 60, lower stage, use of hormone therapy, and receipt of surgery were positive prognostic factors on MVA. Receipt of radiation was associated with a significantly longer survival in patients possessing traditional indications for radiotherapy (BCS or mastectomy with positive lymph nodes). Median radiation dose was 6000cGy and median number of fractions was 33.
Citation Format: James Nathan Cantrell, Patricia Pius, Pawan Acharya, Sara Vesely, Christina Henson, Ozer Algan. Are traditional indications for radiation therapy appropriate for small cell carcinoma of the breast: An NCDB outcomes analysis and treatment utilization report [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 P3-19-20.