Role of chemotherapy in early-stage hormone receptor positive HER2-negative (HR+) breast cancer patients with variant histology.
Authors: Roy Arya Mariam , Catalfamo Kayla , Attwood Kristopher , Muthusamy Kumarasamy Vasanthan , Gupta Kush , Gandhi Shipra 
Published: June 2023

e12514

Background: Breast cancer (BC) is a heterogenous disease with several different subtypes and histological variants (HV) with varied levels of aggressiveness, survival, and response to treatments. National Comprehensive Cancer Network (NCCN) guidelines do not recommend chemotherapy (CT) for some of these HR+ HVs. Given the rarity of these HVs, there is a paucity of data regarding optimal management. We aim to study the benefit of CT in these rare HVs of BC. Methods: We queried the National Cancer Database for stage I, II, III BC patients (pts) with mucinous, papillary, tubular, and medullary HVs from the years 2010-2019. Pts > 18 years (yrs) treated with surgery were included and the population was divided into two cohorts based on the receipt of CT (CT and no CT). Cox Proportional Hazards regression was used to adjust for covariates associated with overall survival (OS) including age, race, gender, income, stage, grade, insurance status, education, comorbidities, and treatments received. Results: In the mucinous histology, out of 16,162 pts, 10% (n = 1,620) received CT. Pts who received CT were younger (54 vs 68 yrs p < 0.001). When stratified by T and N-stage, 5-yr (OS) was higher in the CT compared to the no CT cohort, with higher survival differences observed in higher T (T1: 96% vs 90%, T2: 94% vs 84%, T3: 90% vs 74%, T4: 80% vs 50%) and N-stages (Node negative (N0): 95% vs 88%, Node positive (N+): 88% vs 72%) (all p < 0.001). Although, pts who received CT had better OS on univariate (UV) analysis (no CT: HR 2.04, 95% CI = 1.71-2.43, p < 0.001), this difference was not observed on multivariate (MV) analysis (no CT: HR 1.1, 95% CI = 0.9-1.3, p = 0.28). In the papillary and tubular histology, 12% (280/2324) and 4.3% (211/4980) pts received CT respectively. No significant survival benefit with CT was observed in both papillary and tubular histology in any T or N stages (overall 5-yr OS: Papillary 88% vs 85%, p = 0.2; Tubular 93% vs 94%, p = 0.8). The administration of CT was associated with poor outcomes in both (MV HR: Papillary 1.76, 95% CI = 1.2-2.6, p < 0.001; Tubular 1.87, 95% CI = 1.13-3.1, p < 0.001). In the medullary histology, out of 472 pts, 81% (n = 382) received CT. Those who received CT were younger (51 vs 65 yrs) and node positive (18.5% vs 4%) (both p < 0.001). The OS was higher in CT group compared to no CT (3-yr OS: 97% vs 94%, 5-yr OS: 96% vs 85%, MV HR for CT: 0.34, 95% CI = 0.17-0.67, all p < 0.001). The observed survival difference in CT vs no CT groups was irrespective of the T- and N-stages (5-yr OS:- T1: 100% vs 91%, T2: 95% vs 76%, N0: 97% vs 88%, N+: 95% vs 50%, all p < 0.001). Conclusions: As consistent with the NCCN guidelines, in this large retrospective study, we did not observe any benefit with CT among mucinous, papillary and tubular histology. However, in medullary histology, CT has OS benefit in HR+ BC subtype. Multicenter clinical trials would be beneficial to assess the impact of CT in HVs and to reassess guidelines.