Concordance of Biomarkers and Tumor Location for in-Breast Tumor Recurrences in Early Stage Breast Cancer Patients Treated with Breast Conserving Surgery and Adjuvant RT

Abstract

Patients with an in-breast tumor recurrence (IBTR) after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality. Identifying clinical parameters that increase risk for recurrence after IBTR remains a challenge. Our purpose is to describe clinical and treatment parameters of primary and IBTRs that may predict decreased disease free survival after IBTR. Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution. Overall survival (OS), Disease free survival (DFS), and Local recurrence free survival (LRFS) were estimated using the Kaplan Meier method. We subsequently identified patients who experienced an isolated IBTR. Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated using chi-squared tests. The effect of clinical and treatment parameters with time interval to the first IBTR was evaluated using ANOVA. We identified 2217 patients who met eligibility criteria. The median follow-up (FU) was 44 months (IQR: 25.7 – 70.9). OS at 5-years was 97.7%, DFS was 96.1% and LRFS was 97.9%. The median time to IBTR was 33.8 months (IQR: 21 – 44). We identified 37 patients with isolated IBTR, 51.4% as DCIS, and 48.6% as invasive disease, of whom 83.3% had an in situ component. Radiotherapy information was available for 30 patients. Median whole-breast dose was 40.5Gy; 23 patients received a boost to the tumor bed, with the median dose with boost of 48Gy. In 80.6% of patients, hormone receptor status at recurrence was concordant with the primary tumor. ER and PR receptor status from primary to IBTR were highly associated (ER: χ2, p = 0.006; PR: χ2, p=0.001). There were no changes in HER2 status from primary to IBTR. There was a high level of concordance between quadrant of tumor from primary to IBTR (62.2% of IBTRs, χ2, p=0.008). Tumor size greater than 1.5 cm and endocrine therapy upfront were associated with longer interval to IBTR (ANOVA p=0.02, p=0.004, respectively). At the time of IBTR, 86.5% of patients underwent salvage surgery (43.2% bilateral mastectomy, 24.3% unilateral mastectomy, and 16.2% local excision), 21.6 % received chemotherapy, and 43.2% received endocrine therapy. DFS after IBTR was 81.1% (median FU = 25.5 months, IQR: 11.6 – 56.4) with 57% local, 14% regional and 29% distant recurrences after IBTR. DFS after IBTR was not associated with histology at initial presentation (p=0.4), concordance of biomarkers (p=0.8), concordance of tumor location (p=0.8), or presence of an in situ component with IBTR (p=0.9). Among patients with early stage breast cancer patients who had BCS treated with adjuvant RT, ER/PR status and quadrant are highly concordant from primary to IBTR. The overall recurrence rate in this modern series was low. There was no correlation between concordance of biomarkers and tumor location and the presence of an in situ component at recurrence with improved DFS after IBTR.