Early results of the French multicenter, randomized SHARE trial comparing whole breast irradiation versus accelerated partial breast irradiation in postmenopausal women with early-stage low risk breast cancer: Analysis of toxicity and cosmetic outcomes.

Abstract

514 Background: Locoregional management of early stage breast cancer (BC) has evolved from maximal tolerable to minimal effective therapies. Significant advancements in radiation therapy (RT), such as limited target volumes and hypofractionation, have led to accelerated partial breast irradiation (APBI). This study reports on toxicity and cosmetic outcomes of APBI in post-menopausal women with unifocal pT1-N0-M0 invasive BC. Methods: The SHARE trial (NCT01247233) is a non-inferiority, multicenter, randomized trial comparing local control of APBI versus Whole Breast Irradiation (WBI). Eligible patients were postmenopausal women over 50 years who had lumpectomy with surgical margins > 2mm. Only patients who had at least 4-5 clips placed in the tumor bed during surgery were eligible. Patients were randomized to receive either WBI (50Gy in 25 fractions (fr) with optional 16Gy-boost or 40Gy in 15 fr, or 42.5Gy in 16fr) or APBI (38.5Gy or 40Gy in 10fr twice daily). Primary endpoint was local recurrence. Secondary endpoints included grade >2 toxicity (NCI-CTCAE-v4) and cosmetic outcomes (good/excellent versus intermediate/poor) evaluated by both patients and doctors, over the follow-up time. We estimated the cumulative incidences (CI) using the Kalbfleisch-Prentice method due to competing events, and cause-specific Hazard Ratios (cs-HR APBI/WBI ) from Cox models adjusted on stratification factors. Results: Among 1006 patients (503 per arm) enrolled between December-2010 and July-2015, with a median follow-up of 5.8 years, 28 deaths and 11 local recurrences were reported. The risk of severe toxicity appeared significantly reduced in the APBI-arm when considering all type of toxicity (cs-HR APBI/WBI =0.74, [95%-CI: 0.61-0.89], p=0.001; 3-year CI=45% [41-49] in WBI vs 36% [32-40] in APBI), or only breast skin toxicity (cs-HR=0.55 [0.44-0.70], p<0.001; 3-year CI=36% [32-40] vs 21% [18-25], respectively). Conversely, for non skin breast toxicities, WBI was less toxic: cs-HR APBI/WBI =2.06 (1.49-2.86), p<0.001). We observed no significant difference of patient-reported cosmetic results: cs-HR APBI/WBI =1.08 (0.85-1.37), p=0.54. Findings were similar for doctor-evaluated results. Rib fractures incidence was nearly double in APBI compared to WBI. Conclusions: The SHARE trial showed that APBI is associated with reduced severe and skin-related toxicities compared to WBI, with no significant difference in cosmetic outcomes. Conversely, WBI was less toxic concerning non-skin breast toxicity, mainly breast fibrosis. The question that currently remains open on a practical level is how to consider APBI in the context of the widespread adoption of the “Fast Forward” regimen for patients at low risk of recurrence. Clinical trial information: 2010-A00243-36 .