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

Introduction

Radiation therapy is a core component of comprehensive breast cancer treatment, and radiodermatitis (RD) is its most common cutaneous adverse event, whose incidence and severity are modulated by the complex interplay of treatment regimens, individual risk factors, and intrinsic biological variability (1).

While immune checkpoint inhibitors (ICIs; e.g., pembrolizumab) and poly (ADP-ribose) polymerase (PARP) inhibitors (e.g., olaparib) have dramatically improved outcomes for high-risk breast cancer, the synergistic risk of catastrophic RD from sequential use of these agents with radiotherapy remains poorly defined, especially in patients with pre-pectoral prosthetic reconstruction.

We herein report a case of a young patient with germline BRCA1-mutated triple-negative breast cancer, who developed rapidly progressive grade 4 RD and implant loss after endoscopic nipple-sparing mastectomy (E-NSM) with immediate pre-pectoral reconstruction, followed by sequential adjuvant pembrolizumab, locoregional radiotherapy, and olaparib.

Pembrolizumab may induce a hyper-reactive cutaneous immune microenvironment via CD5⁺ immune cell modulation (2-5), while olaparib drives off-target toxicity in irradiated normal skin through synthetic lethality and PARP-DNA trapping in the context of BRCA deficiency (6,7), which together amplify radiation-induced skin injury.

Despite a growing understanding in the academic community of the pathophysiologic mechanisms by which ICIs and PARP inhibitors may mediate RD, critical gaps remain in clinical practice and guideline recommendations.

The landmark OlympiA clinical trial has confirmed that 1 year of adjuvant olaparib therapy confers a survival benefit in patients with germline BRCA-mutated early breast cancer. However, guidelines from the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN), as well as core clinical trial data, provide no specific guidance on the optimal and safe timing of olaparib initiation following adjuvant radiotherapy—a critical oversight, particularly for the growing population of young patients undergoing E-NSM with pre-pectoral prosthetic breast reconstruction.

In this cohort, the thin, potentially hypovascular skin flaps created during surgery have inherent impairments in DNA repair capacity and radiation tolerance, creating a uniquely high-risk local microenvironment for the development of synergistic treatment-related toxicity. This clinical intersection of immunotherapy, radiotherapy, PARP inhibition, and pre-pectoral prosthetic reconstruction represents an understudied, high-risk frontier of treatment-related toxicity. In existing literature, the risk of severe RD and catastrophic reconstructive failure that can severely impair patient quality of life in this setting is underrecognized and markedly underreported.

To our knowledge, this report is one of the first well-characterized cases to fully describe fulminant grade 4 RD and subsequent implant extrusion triggered by sequential administration of pembrolizumab, locoregional radiotherapy, and adjuvant olaparib in this high-risk reconstructive population. Beyond documenting this catastrophic adverse event, our case delineates the mechanistic basis of this synergistic toxicity, provides actionable, evidence-based safety recommendations for clinicians managing this vulnerable patient population, and fills a critical gap in current clinical guidelines. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0028/rc).

Case presentation

A 31-year-old female presented on December 2, 2024, after discovering a left breast lump. The patient presented with primary clinical manifestations of breast pain and nipple discharge. For personal background, she was unemployed, married at the age of 20, and had given birth to three daughters. She had regular menstrual cycles, a past medical history of hepatitis B virus (HBV) infection, and no other remarkable medical or personal history. Physical examination revealed a palpable mass approximately 5 cm × 5 cm at the 10 o’clock position of the left breast, 2 cm from the nipple. The mass was hard with indistinct boundaries. An enlarged lymph node (approximately 2 cm × 2 cm) was palpable in the left axilla, tough in texture with fair mobility. Core needle biopsies of the breast mass and axillary lymph node were performed, confirming metastatic carcinoma in the lymph node. Consequently, the preoperative diagnosis was established as left triple-negative breast cancer (TNBC), clinical stage cT2N1M0 (stage IIB; Figure 1A). Following multidisciplinary team (MDT) discussion, neoadjuvant therapy was initiated. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 Breast magnetic resonance imaging. (A) Baseline; (B) after 4 cycles; (C) after 8 cycles.

The patient was treated according to the KEYNOTE-522 regimen, consisting of two phases: phase 1 (cycles 1–4) with pembrolizumab [200 mg every 3 weeks (q3w)], nab-paclitaxel [130 mg once weekly (qw)], and carboplatin (600 mg q3w) (Figure 1B); followed by phase 2 (cycles 5–8) with pembrolizumab (200 mg q3w), epirubicin (150 mg/m² q3w), and cyclophosphamide (1,000 mg/m² q3w). On June 2025, therapeutic evaluation achieved a clinical complete response (cCR) ultimately (Figure 1C).

On June 11, 2025, given the patient’s high aesthetic requirements and eligibility for surgery, an E-NSM with pre-pectoral implant reconstruction was performed. Intraoperatively, the resected mammary glandular tissue weighed approximately 335 g. Based on the contralateral breast morphology (mild ptosis) and the volume of the resected native breast tissue, a 235 cc textured anatomical silicone gel breast implant (Model CPG™311, MENTOR^®, Johnson & Johnson MedTech, Leiden, The Netherlands) was selected and placed in the pre-pectoral plane.

Immediate postoperative results were satisfactory with near-symmetrical breasts (Figure 2A). Two months postoperatively, mild capsular contracture caused slight superior displacement of the implant; however, skin color and temperature were normal, with no evidence of ulceration (Figure 2B).

Figure 2 Postoperative breast contour. (A) Postoperative day 10. (B) 2 months postoperatively.

On July 3, 2025, genetic testing revealed a positive germline BRCA1 mutation. Maintenance monotherapy with pembrolizumab (200 mg q3w) was initiated on July 11, 2025. Subsequently, adjuvant radiotherapy was administered from August 4 to September 3, 2025, during which pembrolizumab was continued concurrently.

Two weeks after the completion of radiotherapy (September 16), the patient developed erythema and hyperpigmentation on the skin of the left breast, consistent with grade 2 RD. On September 29, oral olaparib [300 mg twice daily (BID)] was initiated. One week later (October 5), the cutaneous lesions of the left breast deteriorated rapidly, presenting with exudation and focal necrosis. The patient returned to the clinic on November 4. Physical examination revealed extensive skin ulceration and necrosis in the lower pole of the left breast (at the 7 and 5 o’clock positions), measuring approximately 5 and 8 cm, respectively, with implant exposure. The final diagnosis was grade 4 RD and post-reconstruction implant extrusion (Figure 3).

Figure 3 Grade 4 radiodermatitis and post-reconstruction implant extrusion.

On November 12, the operation of left breast implant removal and debridement of necrotic tissue was performed. Due to excessive skin defect precluding primary closure, the Negative Pressure Wound Therapy (NPWT) was applied. On November 26, the defect was repaired via a left thoracodorsal artery perforator (TDAP) flap transplantation. The patient demonstrated a good recovery (Figure 4).

Figure 4 Changes in wound condition. (A) November 12, 2025, implant explantation and debridement; (B) November 26, 2025, left thoracodorsal artery perforator flap transplantation; (C) postoperative view following flap transplantation.

Findings from the patient’s follow-up assessment on February 5, 2026: the patient underwent left TDAP flap transplantation on November 25, 2025, with a smooth postoperative recovery. Findings from the patient’s follow-up assessment on February 5, 2026: the surgical incision had healed completely, the skin of the operative field presented normal coloration without erythema, swelling, ulceration or wound breakdown, and no significant morphological deformity was observed (Figure 5).

Figure 5 Cutaneous manifestations at 3 months after surgery.

The treatment timeline is summarized in Figure 6.

Figure 6 The treatment timeline. IV, intravenous; q3w, every 3 weeks; RT, radiotherapy; TDAP, thoracodorsal artery perforator.

Discussion

The patient’s rapid clinical deterioration and subsequent skin ulceration following the sequential addition of olaparib strongly suggest that the PARP inhibitor played a dominant role in the catastrophic failure of the reconstruction. In a study on olaparib combined with radiotherapy for soft tissue sarcoma, Sargos et al. noted an RD incidence rate of over 90%, with grade 3/4 severe RD accounting for 31.7% (8). This data strongly evidences the potent local tissue toxicity sensitization of PARP inhibitors. De Haan et al. similarly found in non-small cell lung cancer studies that olaparib combined with radiotherapy exacerbated pulmonary and esophageal toxicities, essentially reflecting olaparib-mediated radiosensitization in normal tissues (7). While the temporal correlation between olaparib initiation and rapid progression of skin necrosis is notable, a rigorous, balanced analysis demonstrates that this adverse outcome is not attributable to a single causative agent, but rather to the synergistic interaction of three interrelated risk factors, which explain the stark difference in safety profile compared to published data.

The landmark phase 1 RADIOPARP trial, with a median follow-up of 59 months, established the long-term safety of concurrent olaparib (up to 200 mg twice daily) and breast radiotherapy in high-risk TNBC patients, with no grade ≥3 late toxicities reported and only rare grade 2 cutaneous adverse events. These data confirm the general tolerability of olaparib combined with radiotherapy in appropriately selected patients (9). However, two critical, defining differences between the RADIOPARP trial population and our patient directly account for the divergent safety outcomes: first, none of the patients who underwent post-mastectomy radiotherapy in the RADIOPARP trial received immediate breast reconstruction, eliminating the anatomical and physical risks associated with a pre-pectoral implant; second, the RADIOPARP trial excluded patients treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) ICIs, thus not capturing the immune-mediated amplification of radiation toxicity observed in our case.

The catastrophic skin necrosis and reconstructive failure in this case arose from the synergistic convergence of three core risk factors, which created a high-risk microenvironment not present in the RADIOPARP trial cohort:

• Anatomical and physical risks of pre-pectoral prosthetic reconstruction: the thin, hypovascular skin flaps created during E-NSM and pre-pectoral implant placement have inherently impaired microcirculation and reduced radiation tolerance. Furthermore, the subcutaneous implant acts as a tissue-equivalent bolus, increasing radiation dose deposition at the skin surface and exacerbating basal cell DNA damage from radiotherapy. Sustained skin tension from the implant further compromises flap perfusion and reparative capacity, establishing the anatomical foundation for severe toxicity.
• Immune sensitization mediated by pembrolizumab: pembrolizumab therapy pre-activated the systemic and cutaneous immune microenvironment, which acted as a critical amplifier of synergistic toxicity from subsequent radiotherapy and olaparib. This immune-mediated amplification of radiation injury is well characterized: Sibaud et al. observed localized inflammatory erythema emerging shortly after pembrolizumab infusion within previously irradiated fields (3). Mechanistically, this phenomenon is attributed to the reactivation of a latent inflammatory microenvironment or subclinical radiation-induced cellular damage by anti-PD-1 inhibition. In our patient, radiation-induced tissue damage triggered an exaggerated, uncontrolled immune-inflammatory response in this pre-sensitized microenvironment, which markedly exacerbated the severity of cutaneous radiation injury. Critically, this sustained hyperactive inflammatory state further depleted the residual DNA repair capacity of the already compromised skin flaps, creating a vulnerable cellular state that was exquisitely sensitive to the lethal “second hit” of olaparib-mediated PARP inhibition.
• Second-hit effect of olaparib-mediated DNA repair inhibition: olaparib blocks PARP-mediated single-strand DNA break repair, which is the primary compensatory pathway for resolving radiation-induced DNA damage in normal tissues. In skin flaps already compromised by hypoperfusion, radiation injury, and immune hyperactivation, olaparib eliminated the remaining cellular repair capacity, delivering a synergistic lethal hit to the irradiated tissue. Importantly, this effect was only catastrophic in the context of the aforementioned pre-existing risk factors, rather than acting as an independent, dominant pathogenic agent.

We provide the following actionable, evidence-based recommendations for clinicians managing high-risk TNBC patients with pre-pectoral prosthetic reconstruction who require sequential immune therapy, radiotherapy, and PARP inhibitor treatment:

• Mandatory minimum washout period & concomitant medication rule: for this high-risk population, we strongly recommend a mandatory minimum 2-month washout period after the completion of radiotherapy before the initiation of adjuvant pembrolizumab and olaparib treatment. Pembrolizumab and olaparib should only be initiated after acute radiation dermatitis has completely resolved to ≤ grade 1. Additionally, no additional systemic anti-tumor agents shall be administered concurrently with radiotherapy.
• Standardized skin monitoring protocol: a structured monitoring schedule is mandatory for early detection of progressive toxicity, with all assessments performed uniformly per National Cancer Institute (NCI)-CTCAE v5.0 criteria: weekly skin toxicity assessment from the initiation of radiotherapy through the entire minimum 2-month post-radiotherapy washout period; standardized skin assessment once every 1 to 2 weeks during the full course of pembrolizumab and olaparib treatment.
• Early intervention thresholds: for patients developing ≥ grade 2 cutaneous toxicity during olaparib treatment, immediate temporary interruption of olaparib is indicated, along with prompt initiation of topical high-potency corticosteroids, moisturizing barrier repair, and anti-infective therapy as needed. Olaparib should only be restarted after complete resolution of toxicity to ≤ grade 1, to prevent progression to irreversible full-thickness skin necrosis and implant loss.

This study is limited by its nature as a single case report, and the safety recommendations proposed here require validation in larger, prospective cohort studies of high-risk reconstructed TNBC patients.

Conclusions

This case demonstrates that the combined use of pembrolizumab, olaparib and radiotherapy correlates with synergistic radiosensitizing cutaneous toxicity in BRCA1-mutated triple-negative breast cancer. Patients undergoing pre-pectoral implant-based breast reconstruction have inherently reduced local skin tolerance to radiation injury, requiring rigorous risk assessment before using this combined regimen. Clinicians should optimize treatment sequencing, implement standardized skin toxicity monitoring, and initiate early intervention for RD to avoid severe, irreversible adverse events.

Acknowledgments

We thank the patient for her invaluable contributions to this research.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0028/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0028/prf

Funding: The study was supported by the Special Research Project for Clinical Research of Innovative Drugs after Market Launch (No. WKZX2024CX103103), Key Research and Development Program of Hunan Province (No. 2025JK2123) and Wu Jieping Medical Foundation (No. 320.6750.2024-21-37).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0028/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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