Ectopic breast cancer in vulva and other non-axillary sites: a systematic review

BACKGROUND: Ectopic breast cancer (EBC) is a rare malignancy (0.3–0.6% of all breast cancers) that arises along the embryological milk line. While axillary EBC is better characterised and typically managed similarly to orthotopic breast cancer, the clinical features and management of non-axillary EBC remain poorly defined. AIM: To synthesise available data on the clinical presentation, histopathology, management, and outcomes of non-axillary EBC to refine treatment strategies. METHODS: A systematic review of case reports and case series was conducted following PRISMA 2020 guidelines and registered with PROSPERO (CRD420251035771). PubMed, Ovid MEDLINE, Embase, Scopus, and Cochrane Library were searched up to April 2025. Study quality was assessed using the JBI checklist. Data were analysed descriptively using Microsoft Excel, focusing on clinical presentation, diagnosis, histopathology, treatment, and outcomes. RESULTS: Sixty-one studies (63 patients) were included: 37 vulvar and 26 non-vulvar cases. Median age at diagnosis was 62. Lesions typically presented as painless nodules, with ulceration prompting attention. Invasive ductal adenocarcinoma was the most common histological subtype (39.7%), and oestrogen receptor positivity (82.5%) was frequent. Lymph node involvement was reported in 50.8% of cases. Organ metastases commonly involved bone, lung, and liver. Surgery was the main treatment, with adjuvant systemic therapy. Among cases with available follow-up (n = 50), recurrence and mortality rates were 18.0% (n = 9) and 16.0% (n = 8), respectively. Follow-up methods were poorly documented. CONCLUSION: Non-axillary EBC shares clinical and pathological characteristics with orthotopic breast cancer. Multidisciplinary, site-adapted approach is recommended with applying breast cancer principles to systemic management. Increased clinical awareness and more consistent reporting are crucial to optimise future care and outcomes.