Evidence map›Paper›PMID 42584510›Full record

ArticleBreast cancer research and treatment2026

When immunotherapy hurts: neoadjuvant PD-1 inhibitors increase opioid use after mastectomy with reconstruction.

Tyler P Shern, Victoria Chamberlain, Logan R Holt, Michele A Gadd, Francys C Verdial, Tolga Ozmen, Michelle C Specht, Charles S Dai, Barbara L Smith

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Article in Breast cancer research and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

9 authors.

Tyler P ShernDivision of Breast Surgery, Mass General Brigham, 55 Fruit Street, Boston, MA, 02114, USA.
Victoria Chamberlain *Division of Breast Surgery, Mass General Brigham, 55 Fruit Street, Boston, MA, 02114, USA.
Logan R Holt *Division of Breast Surgery, Mass General Brigham, 55 Fruit Street, Boston, MA, 02114, USA.
Michele A GaddDivision of Breast Surgery, Mass General Brigham, 55 Fruit Street, Boston, MA, 02114, USA.
Francys C VerdialDivision of Breast Surgery, Mass General Brigham, 55 Fruit Street, Boston, MA, 02114, USA.
Tolga OzmenDivision of Breast Surgery, Mass General Brigham, 55 Fruit Street, Boston, MA, 02114, USA.
Michelle C SpechtDivision of Breast Surgery, Mass General Brigham, 55 Fruit Street, Boston, MA, 02114, USA.
Charles S DaiDivision of Hematology Oncology, Mass General Brigham Cancer Institute, 55 Fruit Street, Boston, MA, 02114, USA.
Barbara L SmithDivision of Breast Surgery, Mass General Brigham, 55 Fruit Street, Boston, MA, 02114, USA. BLSMITH1@mgh.harvard.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeProgrammed cell death protein-1 (PD-1) inhibitors have transformed cancer therapy, but evidence suggests PD-1 signaling modulates µ-opioid receptor activity, potentially attenuating opioid analgesia. This study evaluated the effect of PD-1-based neoadjuvant chemotherapy (NAC) on perioperative opioid use and pain outcomes following mastectomy with immediate reconstruction.

methodsWe retrospectively reviewed consecutive mastectomies with immediate reconstruction following NAC between 2020 and 2024. Patients were grouped by PD-1-based NAC (NAC + PD-1) versus NAC without PD-1 inhibitors (NAC). Patient and procedural characteristics, perioperative opioid use, pain scores, and post-discharge opioid refills were analyzed. Multivariable analysis identified predictors of post-anesthesia care unit (PACU) opioid use per hour, postoperative pain, and post-discharge refills.

resultsAmong 277 patients, 54 received NAC + PD-1 and 223 received NAC. BRCA1/2 mutations (38.9% vs. 7.2%, p < 0.001), bilateral surgery (92.6% vs. 67.7%, p < 0.001), and sentinel lymph node biopsy (87.0% vs. 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 PACU opioid use per hour (3.5 vs. 2.1 OMEs/hour, p = 0.029), higher maximum PACU pain scores (6.3 vs. 5.4 p = 0.011), and post-discharge opioid refills (38.9% vs. 17.0%, p = 0.001). On multivariable analysis, NAC + PD-1 (β = 1.189, p = 0.044), breast volume > 700 cm

conclusionNeoadjuvant PD-1 inhibitors were associated with increased perioperative opioid requirements. Clinicians should consider potential PD-1-related alterations in analgesic response when managing pain in this population.

Indexed as

Analgesics, OpioidBreast NeoplasmsImmune Checkpoint InhibitorsMammaplastyMastectomyPostoperative PainAdultAgedFemaleHumansMiddle AgedNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorRetrospective StudiesAnalgesics, OpioidImmune Checkpoint InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 ReceptorAnalgesiaMastectomyNeoadjuvant chemotherapyOpioidsPainPD-1 inhibitors

Identifiers

PMID42584510

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