Breast metastasis from BRCA1-mutated ovarian cancer: response to parp inhibition and a potential lymphatic route

Abstract

Abstract Background Breast metastasis from extramammary malignancies is rare, with ovarian cancer being an exceptionally uncommon primary source. These metastases frequently mimic primary breast carcinoma, posing substantial diagnostic and therapeutic challenges. Case presentation A 44-year-old woman presented with a breast mass initially suspected to be a primary breast carcinoma based on estrogen receptor (ER) (+, 80%), progesterone receptor (PR) (+, 5%), and Human Epidermal Growth Factor Receptor 2 (HER2) (0) staining. However, subsequent workup revealed a synchronous ovarian high-grade serous carcinoma (PAX8+/WT1+), raising the question of dual primary versus metastatic disease and prompting re-review of the breast biopsy, which ultimately confirmed the metastatic ovarian origin of the breast lesion. A pathogenic germline BRCA1 mutation c.964del (p.Ala322Leufs*19) was identified. After neoadjuvant chemotherapy and cytoreductive surgery, the patient received olaparib maintenance therapy, achieving 27 months of progression-free survival before platinum-resistant recurrence. Repeat HER2 testing of the breast lesion at recurrence showed conversion to IHC 2 + with FISH amplification, prompting enrollment in a clinical trial evaluating an anti-HER2 antibody–drug conjugate (ADC). Conclusions This case highlights three key points. First, the PAX8/WT1/GATA3 immunohistochemical panel is critical for distinguishing ovarian metastasis from primary breast carcinoma. Second, the route of spread from the ovary to the breast, possibly transdiaphragmatic via the cardiophrenic and internal mammary nodes, requires further investigation. Third, PARP inhibitor maintenance in the context of a germline BRCA1 mutation provided sustained disease control, and HER2 status conversion at recurrence opened a therapeutic window for sequential antibody–drug conjugate (ADC) therapy.