Surgical outcomes of prepectoral two-stage breast reconstruction in patients treated with pembrolizumab or CDK4/6 inhibitors

Authors: Ibrahim Y, Alnaseri T, Gupta N, Hall A, Carter M, Kwan L, Demirjian M, McCann KE, Teshome M, Delong MR

Affiliation: University of California, Los Angeles

Journal: Plastic and Reconstructive Surgery, March 2026

PMID: 41825078

Key takeaways

• Pembrolizumab (PD-1 inhibitor) exposure was associated with more seromas during tissue expansion (44.4% vs 27.0%) and more major complications (4x) and reoperations (5.4x) after implant exchange.

• CDK4/6 inhibitor use showed no increase in major complications or reoperations under this center’s practice of holding therapy for about 1 week preoperatively.

• This is a retrospective study and it may be underpowered, as it includes a relatively small number of patients receiving either pembrolizumab or CDK4/6 inhibitors

Background

Pembrolizumab and CDK4/6 inhibitors are increasingly used in breast cancer treatment, but their effects on staged implant reconstruction are poorly characterized. This study examines complications after immediate prepectoral tissue expander placement and subsequent implant exchange.

Objective

Evaluate whether pembrolizumab or CDK4/6 inhibitor exposure is associated with surgical complications during two-stage prepectoral breast reconstruction.

Methods

• Design: Retrospective, single-center review of immediate two-stage prepectoral reconstructions performed January 2018-October 2024.

• Population: 472 patients (823 breasts); median age 46.7 years, median BMI 23.5 kg/m², median follow-up 12 months. Twenty-seven received pembrolizumab and 30 received a CDK4/6 inhibitor.

• Exclusions: Autologous, delayed, or direct-to-implant reconstruction; chemotherapy after implant exchange; <3 months follow-up.

• Perioperative practice: Surgery generally 3-6 weeks after chemotherapy; implant exchange generally after adjuvant chemotherapy or immunotherapy. CDK4/6 inhibitors were typically held 1 week before surgery; surgery could be delayed for ANC <1.0 or active issues.

• Outcomes: Infection, hematoma, seroma, mastectomy-flap necrosis, implant removal, reoperation, and major complications (readmission or return to OR), assessed separately after expander and implant surgery.

• Statistics: Chi-square/Fisher exact tests and Wilcoxon rank-sum tests. Pembrolizumab analyses were additionally adjusted for chemotherapy type. No prespecified primary endpoint, power calculation, alpha plan, or multiple-comparison correction was reported.

Results

Pembrolizumab:  n = 27

• After tissue expander placement, seroma was more common in patients receiving Pembro than in those not receiving Pembro: 44.4% vs 27.0% (p=0.049).

• Major complications after expander placement were not increased with Pembro (22.2% vs 26.6% without, p=0.61). Other complication rates were also similar.

• After implant exchange, major complications were higher with Pembro (26.3% vs 8.0% without, p=0.019).

• Reoperation after implant exchange was also higher: 19.1% vs 3.7% without (p=0.011).

• After adjustment for chemotherapy type, Pembro was associated with approximately 4× higher odds of major complications and 5.4× higher odds of reoperation after implant exchange.

CDK4/6 inhibitors: n = 30

• After tissue expander placement, major complication rates were essentially identical: 26.4% with CDK4/6 inhibitors vs 26.3% without (p=0.97).

• Reoperation rates were also similar: 23.3% vs 23.1% without (p=0.97).

• Minor infection was lower in the CDK4/6 group: 0% vs 12.4% (p=0.037), although this was based on a small treated cohort.

• After implant exchange, CDK4/6 inhibitor use was not associated with significantly higher rates of major complications, reoperation, infection, explantation, necrosis, or capsular contracture.

• The rate of seroma after implant exchange was higher with CDK4/6 inhibitors (8.0% vs 1.5%), but this did not reach statistical significance (p=0.076).

Conclusion

The authors conclude that pembrolizumab exposure is associated with increased seroma during expansion and increased major complications and reoperations after implant exchange, warranting further study. CDK4/6 inhibitor use was not associated with increased wound healing complications in this cohort.

Strengths

• Addresses a timely, clinically relevant question with stage-specific reconstructive outcomes.

• Includes the institution’s full prepectoral experience over more than 6 years and reports practical perioperative management.

Limitations

• Retrospective, single-center design with very small cohorts (27 pembrolizumab; 30 CDK4/6), which may be underpowered to detect complications

• Major confounding by indication and treatment intensity: the groups differed in chemotherapy, radiation, axillary surgery, age, race, and corticosteroid exposure; adjustment was limited mainly to chemotherapy type.

• Only 21/27 pembrolizumab patients reached implant exchange versus 402/445 controls, creating potential selection/survivorship bias in second-stage comparisons.

• Many outcomes were tested without reported multiplicity correction; the expander-seroma result was borderline (p=0.0494). Long-term implant outcomes remain inadequately studied.

Clinical relevance

Given the very small cohorts (27 pembrolizumab and 30 CDK4/6 inhibitor patients), these findings should be considered preliminary. Patients receiving pembrolizumab warrant closer counseling regarding reconstructive complications and careful coordination of implant-exchange timing with systemic therapy. CDK4/6 inhibitors were not associated with increased surgical complications when held for 1 week preoperatively, but the study is too small to establish equivalence or definitive safety.