PS5-06-27: Reframing Breast Cancer Therapies in a Rare Context - A Case of Metastatic Mammary-Like Vulvar Carcinoma Treated with Breast Cancer Regimens

Abstract Background: Mammary-like adenocarcinoma of the vulva (MLVA) is a rare subtype of vulvar adenocarcinoma that exhibits morphological and immunohistochemical features similar to breast tissue. Arising from anogenital mammary-like glands, this entity poses unique diagnostic and therapeutic challenges due to its extreme rarity and overlapping features with both breast and gynecologic malignancies. Currently, there are no standardized treatment guidelines for MLVA, and clinical management is often extrapolated from therapeutic strategies used in breast cancer, particularly for tumors with hormone receptor or HER2 expression. Case: We report a case of a 60-year-old woman initially diagnosed with stage IV mammary-like adenocarcinoma of the vulva in August 2022. She underwent a modified radical vulvectomy with bilateral inguinal lymphadenectomy. Pathology confirmed adenocarcinoma arising from anogenital mammary-like gland, ER-negative and PR-negative, and HER2-positive. She received adjuvant radiation with concurrent cisplatin. Given HER2 positivity, she was treated with six cycles of docetaxel, trastuzumab, and pertuzumab, followed by maintenance trastuzumab and pertuzumab. In August 2021, staging scans revealed new lung metastasis. A lung biopsy confirmed moderately differentiated adenocarcinoma consistent with metastasis from the patient's known vulvar primary, HER2 2+ (FISH negative) and ER/PR negative, immunohistochemical stains - GATA3-positive, and PAX8-negative, SOX10-negative. Molecular testing revealed a germline BRCA2 mutation. She was treated with olaparib from February to November 2023. Following disease progression, she transitioned to trastuzumab deruxtecan for HER2-low disease, which resulted in temporary disease control between December 2022 to May 2024. Upon further progression, she received carboplatin, paclitaxel, and bevacizumab, completing six cycles in May 2024, followed by maintenance bevacizumab and pembrolizumab. With continued progression, she was re-challenged with paclitaxel. Staging scans in February 2025 showed disease progression including new brain metastasis. Repeat liver biopsy demonstrated moderately differentiated adenocarcinoma, HER2 1+. For brain metastases, she received local treatment with gamma knife radiosurgery. She was re-referred to the breast oncology clinic for co-management and discussion of next-line therapy. She was initiated on Sacituzumab Govitecan. Initial follow-up showed disease stability and good tolerance to therapy. Notably, the patient continues to work full-time as a dump truck driver, underscoring her preserved functional status and overall quality of life while on treatment. Conclusion: MLVA is an extremely rare malignancy with no established standards of care. Its histologic resemblance to breast cancer suggests it may respond to breast cancer-based therapies. In the absence of defined treatment pathways, applying breast cancer therapeutic strategies—particularly in the metastatic setting—may offer a rational and effective approach for managing this rare tumor type. While Sacituzumab Govitecan is not currently approved for vulvar malignancies, Sacituzumab govitecan targets the TROP2 protein, which is found on the surface of many cancer cells, including some mammary-like adenocarcinomas of the vulva. Trop-2-targeted mechanism of Sacituzumab Govitecan may offer a rational therapeutic approach in rare tumors with overlapping molecular features. Citation Format: D. Edwards, C. Coleman, A. Jamil. Reframing Breast Cancer Therapies in a Rare Context - A Case of Metastatic Mammary-Like Vulvar Carcinoma Treated with Breast Cancer Regimens [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 PS5-06-27.