Prospective Clinical Trial of Premastectomy Radiotherapy Followed by Immediate Breast Reconstruction for Operable Breast Cancer

Abstract

Radiation delivered prior to mastectomy and autologous breast reconstruction may avoid the adverse effects of radiation on autologous donor tissue while providing the psychologic benefit of immediate reconstruction. We aimed to study the feasibility of premastectomy radiation therapy (PreMRT). A total of 50 women enrolled in a prospective trial of preoperative radiation to the breast and regional nodes followed by mastectomy with axillary evaluation and immediate breast reconstruction. The trial was embedded in a randomized trial of hypofractionated versus conventionally fractionated regional nodal irradiation (NCT02912312). Eligible women enrolled from 2018-22, had cT0-T3 N0-3 breast cancer, and a pre-operative recommendation for radiation. The primary outcome was frequency of complete free flap loss. Mastectomy skin flap necrosis was assessed by validated SKIN grading score. The Satisfaction with Breast Cosmetic Outcomes Scales evaluated patient satisfaction with cosmetic result. Descriptive statistics and 95% exact confidence intervals were calculated. One patient withdrew prior to any treatment and one elected not to have breast reconstruction. Median age of the 48 women completing PreMRT and reconstruction was 48 [range 31-72]. Most had ER-positive HER2-negative (77%), cT3 (54%) or cT2 (38%), cN1 (79%) disease and received 50 Gy in 25 fractions (n = 24) or 40.05 Gy in 15 fractions (n = 23). Four received 10-16 Gy internal mammary or infraclavicular boost. 35% VMAT, 48% matched photon-electron, and 17% partially-wide-tangent technique. Median time to surgery was 23 days [14-85]. Skin reaction delayed surgery for one patient. Most had skin-sparing mastectomy (92%) and axillary lymph node dissection (67%). 12 surgeons performed the reconstructions: 35 deep inferior epigastric perforators; 4 profunda artery perforator; 2 muscle-sparing transverse rectus abdominis myocutaneous; 1 latissimus dorsi (LD); 2 LD/implant; 2 LD/tissue expander (TE); and 2 subpectoral (SP) TE. There were no complete flap losses. Two patients (4.4%, 95% CI 0.5%-14.8%) with free flaps had partial flap loss with revision surgery. Both patients with SP TEs had infections and unplanned reoperation. The protocol was subsequently amended to not allow SP TE reconstruction. Eight patients had skin flap necrosis: 5 partial and 3 full thickness necrosis; only 1 required operative debridement. Seven had pathologic complete response. At six months 19/31 (61%) reported being "quite a bit" or "very much" satisfied with how they looked in the mirror clothed. There are no recurrences with a median follow up of 33 months [5-119]. Radiation treatment of the breast and lymph node basins prior to mastectomy with immediate autologous reconstruction is feasible. There were no autologous flap loses and complication rates are similar to reconstruction after radiation series. This promising strategy reduces time to autologous reconstruction and merits further prospective study.