Retrospective analysis of impact of neoadjuvant PD-1 inhibitors on opioid use after mastectomy with reconstruction

PD-1 inhibitors have transformed cancer therapy, but evidence suggests that PD-1 signaling modulates μ-opioid receptor activity, potentially attenuating opioid analgesia. A retrospective study at Mass General Brigham (Boston, MA) evaluated the effect of PD-1-based neoadjuvant chemotherapy (NAC) on perioperative opioid use and pain outcomes following mastectomy with immediate reconstruction. Between 2020 and 2024, 277 patients were treated: 54 received NAC plus PD-1 (NAC+PD-1), and 223 received NAC without PD-1 (NAC). BRCA1/2 mutations (38.9% versus 7.2%; p<0.001), bilateral surgery (92.6% versus 67.7%; p<0.001), and sentinel node biopsy (87.0% versus 64,6%; p=0.001) were more common in the NAC+PD-1 group. Despite comparable preoperative analgesia and intraoperative opioids, NAC+PD-1 patients had higher post-anesthesia care unit (PACU) opioid use per hour, higher maximum PACU pain scores, and higher post-discharge opioid refills. On multivariable analysis, NAC+PD-1 (β=1.189; p=0.044), breast volume > 700 cm³ (β=1.065; p=0.029), and preoperative analgesia medications (β=-0.541; p=0.034) predicted PACU opioid use per hour, while NAC+PD-1 (OR 3.574; p<0.001) and axillary lymph node dissection (OR 1.935; p=0.048) predicted opioid refill likelihood. The authors conclude that neoadjuvant PD-1 inhibitors were associated with increased perioperative opioid requirements.