PS5-06-19: Sacituzumab Govitecan Combined with Anti-angiogenic Therapy and Radiotherapy in a BRCA1-Mutated Triple-Negative Breast Cancer Patient with Multiple Recurrences: A Case Report

Abstract Introduction: Triple-negative breast cancer (TNBC), accounting for 10%-15% of breast cancers and defined by ER-/PR-/HER2- status, exhibits aggressive biological behavior with high proliferative indices, genomic instability, and limited targeted therapies. BRCA1-mutated TNBC may respond to PARP inhibitors and DNA-damaging agents. However, a significant proportion of BRCA1-mutated TNBC patients experience disease progression, underscoring the urgent need for novel treatment strategies. This case report details a young female with BRCA1-mutated TNBC presenting with extensive systemic and brain metastases. The treatment strategy combining Sacituzumab Govitecan (SG), Anlotinib, and concurrent whole-brain radiotherapy (WBRT) provides unique insights into managing complex, relapsed TNBC. Case Report: In March 2011, a 28-year-old female was diagnosed with left breast invasive ductal carcinoma (ER-/PR-/HER2-, pT2N0M0). She underwent left modified radical mastectomy, followed by 8 cycles of adjuvant chemotherapy (epirubicin + cyclophosphamide, followed by paclitaxel). In March 2017, a 2×2 cm invasive carcinoma was detected (ER-/PR-/HER2 1+) in her right breast. She received 6 cycles of neoadjuvant TAC chemotherapy (docetaxel + liposomal doxorubicin + cyclophosphamide), and then underwent right nipple-areolar-sparing mastectomy, axillary dissection, and breast reconstruction on August 7, 2017, followed by radiotherapy. In December 2020, right chest wall recurrence was found, treated with local extended resection in January 2021, and followed by one-year oral capecitabine. In June 2023, she developed lung metastases (germline BRCA1 mutation),then enrolled in an IIT trial (NCT05085626) where she received Fluzoparib + Chidamide, achieving partial response (PR) with a progression-free survival (PFS) of 14 months. In August 2024, the patient developed widespread metastases (brain, lung, soft tissues, liver, spleen, bone, ileum). She declined brain surgery and received Bevacizumab + Trastuzumab Deruxtecan. After two cycles, symptoms of intracranial hypertension improved, and the disease was assessed as stable disease (SD), but grade 3 or 4 nausea/vomiting/fatigue led to discontinuation. In December 2024, original lesions (brain, lung, liver, ileum) progressed with new metastases in retroperitoneum, kidneys, left 4th metacarpal, and phalanges. Treatment with SG in combination with Anlotinib was initiated, accompanied by concurrent WBRT during the first cycle. After two cycles, the disease achieved a PR. Grade 3 anemia occurred during treatment but was managed symptomatically. The PFS has exceeded 7 months to date, and the patient remains under continuous treatment. Discussion: Preclinical studies have shown that SG delivers SN-38 to induce DNA damage in homologous recombination deficiency (HRD) tumors (e.g., BRCA-mutated) with impaired repair. Anti-angiogenics enhance SG’s efficacy via VEGF-targeted vascular normalization and blockade of survival signaling pathways. Additionally, SG can penetrate into intracranial tumors and exhibit promising activity. Combining SG with WBRT can further induce DNA damage and enhance treatment efficacy. The patient’s positive response to this combination regimen suggests potential benefit for metastatic TNBC, especially in those with brain metastases, though grade 3 anemia highlights the need for close toxicity monitoring. Conclusion: This case report highlights the potential efficacy of SG in combination with anti-angiogenic therapy and radiotherapy in treating BRCA1-mutated TNBC patients with multiple recurrences and brain metastases. However, further studies are needed to confirm these findings and to optimize the use of these agents in this subset of patients. Citation Format: C. Hao, Z. Jie. Sacituzumab Govitecan Combined with Anti-angiogenic Therapy and Radiotherapy in a BRCA1-Mutated Triple-Negative Breast Cancer Patient with Multiple Recurrences: A Case Report [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-19.