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

Our plain-English summary of BAP1-defficient breast cancer in a patient with BAP1 cancer syndrome, by A. Blatnik, D. Ribnikar, V. Šetrajčič Dragoš, et al (Breast Cancer, 2022).

The study

• Authors: A. Blatnik, D. Ribnikar, V. Šetrajčič Dragoš, S. Novaković, V. Stegel, B. Grčar Kuzmanov, N. Boc, B. Perić, P. Škerl, G. Klančar, M. Krajc
• Journal: Breast Cancer
• Published: 2022;29(5):921-927
• Type of article: Case report
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© 2022. The Author(s).

In plain English

This case report described one woman with BAP1 cancer syndrome, an inherited condition the authors noted is linked mainly to uveal melanoma, mesothelioma, kidney cancer and skin melanoma. The article did not discuss asbestos. At age 35 she was diagnosed with locally advanced triple negative breast cancer. Genetic testing of her blood found a likely disease-causing BAP1 variant. Her breast tumor had lost the BAP1 protein, and tumor sequencing suggested a partial deletion in BAP1 as the second hit. Her two sisters and her mother did not carry the variant, and her father was not tested. After the cancer spread to lymph nodes, it tested PD-L1 positive. She was treated with atezolizumab (an immunotherapy drug) plus nab-paclitaxel. CT scans at 5 and 8 months showed a complete response, and she was still in remission in January 2021. The authors concluded that their report implies an association between BAP1 cancer syndrome and breast cancer. They stated that a single case is by no means evidence that BAP1 loss explains her response to immunotherapy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (one patient)
• Who was studied: One 35-year-old woman with locally advanced left breast cancer, reported by authors at the Institute of Oncology Ljubljana, Slovenia. Immunotherapy began in September 2019 and follow-up ran to January 2021.
• Exposure: No asbestos or other environmental exposure was reported. The factor studied was an inherited (germline) BAP1 likely pathogenic variant, c.898_899delAG p.(Arg300Glyfs*6).
• Main results:
  • Blood (germline) testing of the patient found the BAP1 variant c.898_899delAG p.(Arg300Glyfs*6) as a secondary finding.
  • The patient's breast tumor cells had lost BAP1 protein on immunohistochemistry.
  • Tumor DNA analysis suggested a partial deletion of exon 12 in BAP1 as the second hit. It also showed a low tumor mutational burden and a somatic TP53 variant.
  • The patient's tumor was PD-L1 positive, with 5–7% of lymphocytes within the tumor expressing PD-L1.
  • On atezolizumab with nab-paclitaxel, CT scans at 5 and 8 months showed a complete response of the lymph node lesions.
  • Nab-paclitaxel was stopped because of nerve damage (peripheral neuropathy) and patient preference.
  • She stayed in remission on atezolizumab alone, still in remission at her January 2021 check-up.
  • She had no immune-related side effects.
  • Her two sisters and her mother did not carry the variant. Her father was not tested.
  • A skin nodule removed from the patient was confirmed as an MBAIT, a benign skin growth typical of BAP1 cancer syndrome.
• The authors' conclusion: The authors concluded that their report implies an association between BAP1 cancer syndrome and breast cancer. They hypothesized that BAP1 loss might explain the patient's response to immunotherapy, and said this warrants further investigation.
• Limitations the authors state:
  • The authors stated that a single case is not evidence that BAP1 inactivation plays a role in response to immunotherapy.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, BAP1 Tumor Predisposition Syndrome, Mesothelioma, Carcinoma, Biomarker, Immunotherapy, Immunohistochemistry, Tumor Mutational Burden (TMB).

Related studies

• Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1-associated cancer susceptibility syndrome — Z. Marušić, M. Buljan, et al. (2015)
• Histologically Diverse BAP1-Deficient Melanocytic Tumors in a Patient With BAP1 Tumor Predisposition Syndrome — A. Louw, J. Creaney, et al. (2020)
• Ocular melanoma and the BAP1 hereditary cancer syndrome: implications for the dermatologist — L.M. Martorano, R.R. Winkelmann, et al. (2014)
• BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs — M. Carbone, L.K. Ferris, et al. (2012)
• Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations — M. Carbone, H.I. Pass, et al. (2022)
• CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma — M. Betti, A. Aspesi, et al. (2016)

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