BAP1-defficient breast cancer in a patient with BAP1 cancer syndrome

• Published in: Breast cancer (Tokyo, Japan) Vol. 29; no. 5; pp. 921 - 927
• Main Authors: Blatnik, Ana, Ribnikar, Domen, Šetrajčič Dragoš, Vita, Novaković, Srdjan, Stegel, Vida, Grčar Kuzmanov, Biljana, Boc, Nina, Perić, Barbara, Škerl, Petra, Klančar, Gašper, Krajc, Mateja
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01-09-2022; Springer
• Subjects: Breast cancer; Cancer; Cancer patients; Cancer Research; Case Report; Development and progression; Genetic aspects; Immunohistochemistry; Immunotherapy; Medicine; Medicine & Public Health; Melanoma; Metastasis; Oncology; Prevention; Surgery; Surgical Oncology; Hereditary cancer syndromes; Immunotherapy; Breast cancer; BAP1
• ISSN: 1340-6868; 1880-4233
• DOI: 10.1007/s12282-022-01354-0

BAP1 cancer syndrome is a rare and highly penetrant hereditary cancer predisposition. Uveal melanoma, mesothelioma, renal cell carcinoma (RCC) and cutaneous melanoma are considered BAP1 cancer syndrome core cancers, whereas association with breast cancer has previously been suggested but not confirmed so far. In view of BAP1 immunomodulatory functions,
BAP1
alterations could prove useful as possible biomarkers of response to immunotherapy in patients with BAP1-associated cancers. We present a case of a patient with BAP1 cancer syndrome who developed a metastatic breast cancer with loss of BAP1 demonstrated on immunohistochemistry. She carried a germline
BAP1
likely pathogenic variant (c.898_899delAG p.(Arg300Glyfs*6)). In addition, tumor tissue sequencing identified a concurrent somatic variant in
BAP1
(partial deletion of exon 12) and a low tumor mutational burden. As her triple negative tumor was shown to be PD-L1 positive, the patient was treated with combination of atezolizumab and nab-paclitaxel. She had a complete and sustained response to immunotherapy even after discontinuation of nab-paclitaxel. This case strengthens the evidence for including breast cancer in the BAP1 cancer syndrome tumor spectrum with implications for future cancer prevention programs. It also indicates immune checkpoint inhibitors might prove to be an effective treatment for BAP1-deficient breast cancer.