Breast Conservation and Hypofractionation in Women with Hereditary Breast Cancer

Abstract

There is limited data on the use of breast conservation (BC) in women with non-BRCA related hereditary breast cancer (HBC) and on the use of hypofractionated radiation therapy (HRT) in women with HBC whether BRCA-related or not. This study examines the use of HRT as a component of BC in HBC with regard to outcomes and toxicity in women with germline DNA mutations that may confer increased risk of radio-sensitivity. From 2003-2015, 1303 patients were enrolled in 4 prospective protocols investigating HRT with a daily or weekly concomitant boost. Additional patients were identified through retrospective chart review. We identified patients who had genetic testing in this analysis and separated them into 2 groups: those with deleterious genetic mutations (MUT) and those with no mutation, benign variants, or variants of uncertain significance (NM). Overall survival (OS), Disease free survival (DFS), and Local recurrence free survival (LRFS) were estimated using the Kaplan Meier method. Patients with follow up <6 months were excluded for cosmetic endpoints. Clinician rated cosmesis, recorded on a scale from 1-4 (RTOG/Harvard scale) and patient rated cosmesis from 1-4 was collected. There were 329 patients with genetic testing, 300 with NM, and 29 with MUT. 98% of patients were enrolled on the prospective protocols. The MUT group included BRCA1 (21%), BRCA2 (28%), BRCA unclassified (10.3%), CHEK2 (17%), BRIP1 (7%), and 1 patient each (3%) with MUTYH, NF1, PALB2 and MUTYH, APC, and PMS2 mutations. There were no significant differences in baseline characteristics including race, stage, grade, estrogen or HER-2 receptor, or adjuvant therapy between the two groups with the exception of higher rates of progesterone receptor negativity in the MUT group and a higher frequency of a weekly concomitant boost (vs. daily concomitant boost) in the NM group. Median follow up was 90 months (mo) (MUT) and 74 mos for disease outcomes. There were no differences in OS, DFS, and LRFS. There was a higher rate of non-breast secondary cancer in the MUT group (21%) as compared to NM (4%) (p<0.001). With regard to clinician-rated cosmesis, rates of poor/fair cosmesis at a median follow up of 51 mo (MUT) and 48 mo (NM) were 13% (MUT) vs. 10% (NM) (p=0.09). Rates of patient rated cosmesis (median follow up 53 mo GM, 48 mo NM) of poor/fair were 13% (MUT) vs. 10% (NM) (p=0.81). There were no significant differences in the % grade ≥2 late toxicity in MUT vs NM: symmetry 11 vs. 7, edema 0 vs 1, skin thickening 0 vs 2, fibrosis 4 vs 3, retraction 15 vs 5, telangiectasia 4 vs 4, dimpling 0 vs 1, pigmentation changes 4 vs 1. There were no differences in disease-related outcomes, clinician and patient-rated cosmesis, or late toxicity between patients with known deleterious mutations and no mutations or benign variants. Though the numbers are small, this study provides preliminary data on the safety of hypofractionation in women with HBC.