Impact of Neoadjuvant Concurrent Chemoradiation (NACCRT) on Operability and Survival in Locally Advanced Inoperable Breast Cancer

Abstract

Inoperable locally advanced breast cancers (LABC) are treated with neoadjuvant chemotherapy (NACT). However, many patients remain inoperable after NACT due to an inadequate response. We, therefore, investigated the role of neoadjuvant concurrent chemoradiation (NACCRT) in this setting. Patients with inoperable Stage III LABC were prospectively recruited in the study between May 2017 and December 2021. NACT consisted of 4 cycles of q3weekly Adriamycin (60 mg/m2) and Cyclophosphamide (600mg/m2), and 4 cycles of q3weekly Paclitaxel (175 mg/m2). Concurrent radiotherapy with 6 MV X-rays was given using a 3D conformal technique to a total dose of 46 Gy (2 Gy/fraction, 5 days/week) to the involved breast, axilla, supraclavicular fossa, and internal mammary chain (upper 3 intercostal spaces) along with the first two cycles of paclitaxel. A 0.5 cm bolus was used to boost the skin till the appearance of hyperpigmentation. All patients were assessed for surgery after the completion of the planned neoadjuvant treatment. Adjuvant treatments were given based on the receptor status. The impact of neoadjuvant CTRT on the pathological complete response (pCR), operability, and survival was analyzed. Event-free survival (EFS) and Overall Survival (OS) were analyzed using the Kaplan-Meier method. The study enrolled 202 female patients with a median age of 52 years, with 23.7% having IIIA, 65.3% IIIB, and 10.8% having IIIC disease. Hormone-receptor (HR) positive disease was observed in 90/202 (44.6%) patients, triple-negative (TNBC) in 50/202 (24.8%) and Her2/neu positive in 62/202 (30.7%) patients. Modified radical mastectomy was performed in 88.1% of patients, with 8.5% remaining inoperable and 3.4% declining surgery due to clinical complete response (cCR). Among the patients who underwent MRM, 65/178 (32.2%) patients had a pCR. pCR was observed in 13/81 (16%) with HR-positive disease, 21/46 (45.6%) with TNBC, and 31/51 (60.7%) patients with Her2/neu-positive disease. Grade 3 skin reactions were observed in 39/202 (19.3%). Postoperative wound morbidity requiring hospitalization was observed in 19/178 (10.6%) patients. The median follow-up was 42 months, with 4-year EFS and OS of 63.8% and 71.5%, respectively. Six out of 7 patients who were in cCR and declined surgery are alive and remain in cCR. On subgroup analysis of Her 2 positive patients, pCR was significantly associated with improved EFS and OS (89.8% vs 33.3%, p = 0.001 and 89.1% vs 44.4%, p = 0.001 respectively). Our study demonstrates the feasibility and efficacy of NACCRT in improving operability, pCR rates and survival outcomes in patients with inoperable LABC. The results suggest that NACCRT can be considered for use in clinical practice with careful patient selection. These findings contribute to the ongoing efforts to optimize treatment for this patient population and warrant further investigation in larger, randomized trials.