Severe radiodermatitis and implant loss associated with pembrolizumab and olaparib following pre-pectoral breast reconstruction in a 31-year-old female: a case report.

Background: Endoscopic nipple-sparing mastectomy (E-NSM) with immediate implant reconstruction is increasingly adopted to preserve breast appearance and quality of life. Immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase (PARP) inhibitors have substantially improved survival in BRCA-mutated triple-negative breast cancer (TNBC). However, the safety of sequential olaparib following concurrent pembrolizumab and radiotherapy in patients with pre-pectoral breast reconstruction remains poorly defined, and the risk of severe cutaneous toxicity and implant loss is underrecognized. Case Description: We herein report the case of a 31-year-old female who presented with a chief complaint of palpable masses in the left breast and ipsilateral axilla. Diagnostic core needle biopsies of the primary breast lesion and axillary lymph node were conducted, and histopathological examination confirmed invasive TNBC with ipsilateral axillary lymph node metastasis. Germline genetic testing further revealed a pathogenic BRCA1 mutation. After completion of multidisciplinary neoadjuvant systemic therapy, the patient underwent E-NSM with immediate pre-pectoral prosthetic breast reconstruction. Postoperatively, the patient received adjuvant pembrolizumab followed by locoregional radiotherapy. Although only grade 2 radiodermatitis (RD) was initially observed, the subsequent initiation of adjuvant olaparib triggered a rapid and catastrophic clinical deterioration. Within one week of commencing olaparib, the patient's condition progressed to grade 4 severe RD, characterized by extensive full-thickness skin necrosis and eventual implant extrusion, necessitating surgical explantation. Conclusions: This case highlights catastrophic synergistic cutaneous toxicity and implant loss caused by the sequential combination of pembrolizumab, radiotherapy, and olaparib in patients with pre-pectoral breast reconstruction. Olaparib serves as the dominant pathogenic factor, delivering a lethal "second hit" by inhibiting DNA repair in radiation-sensitized, hypovascular skin flaps overlying the implant. Weekly skin toxicity monitoring is mandatory from the initiation of radiotherapy until at least 2 months after the completion of radiotherapy. Pembrolizumab and olaparib should be initiated only after a mandatory washout period of 2 months following the end of radiotherapy, with monitoring performed every 1 to 2 weeks throughout the treatment course. No additional systemic anti-tumor agents shall be administered concurrently with radiotherapy. Upon detection of early skin reactions, prompt intervention with topical corticosteroids and temporary olaparib interruption is indicated, tailored to toxicity severity.