Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations

Our plain-English summary of Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations, by M. Carbone, H.I. Pass, G. Ak, et al (Journal of Thoracic Oncology, 2022).

The study

• Authors: M. Carbone, H.I. Pass, G. Ak, H.R. Alexander, P. Baas, F. Baumann, A.M. Blakely, R. Bueno, A. Bzura, G. Cardillo, J.E. Churpek, I. Dianzani, A. De Rienzo, M. Emi, S. Emri, E. Felley-Bosco, D.A. Fennell, R.M. Flores, F. Grosso, N.K. Hayward, M. Hesdorffer, C.D. Hoang, P.A. Johansson, H.L. Kindler, M. Kittaneh, T. Krausz, A. Mansfield, M. Metintas, M. Minaai, L. Mutti, M. Nielsen, K. O'Byrne, I. Opitz, S. Pastorino, F. Pentimalli, M. de Perrot, A. Pritchard, R.T. Ripley, B. Robinson, V. Rusch, E. Taioli, Y. Takinishi, M. Tanji, A.S. Tsao, A.M. Tuncer, S. Walpole, A. Wolf, H. Yang, Y. Yoshikawa, A. Zolondick, D.S. Schrump, R. Hassan
• Journal: Journal of Thoracic Oncology
• Published: 2022;17(7):873-889
• Type of article: Review
• Cited by: 83 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and less frequently, breast cancer, several types of skin carcinomas, and other tumor types. Mesotheliomas in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy. Others may grow aggressively but very often respond to therapy. Detecting BAP1 germline mutations has, therefore, substantial medical, social, and economic impact. Close monitoring of these patients and their relatives is expected to result in prolonged life expectancy, improved quality of life, and being cost-effective. The co-authors of this paper are those who have published the vast majority of cases of mesothelioma occurring in patients carrying inactivating germline BAP1 mutations and who have studied the families affected by the BAP1 cancer syndrome for many years. This paper reports our experience. It is intended to be a source of information for all physicians who care for patients carrying germline BAP1 mutations. We discuss the clinical presentation, diagnostic and treatment challenges, and our recommendations of how to best care for these patients and their family members, including the potential economic and psychosocial impact.

Copyright © 2022 International Association for the Study of Lung Cancer. All rights reserved.

In plain English

This article was a review in which the authors, who describe themselves as having published most reported cases of mesothelioma in carriers of inherited (germline) BAP1 mutations, drew on their experience and the published literature to discuss care of these patients and their relatives. They described three women from one family who carried the same BAP1 mutation and had no history, radiological or histological evidence of asbestos exposure. A 43-year-old with peritoneal mesothelioma was treated with cytoreductive surgery, HIPEC and cisplatin/pemetrexed and remained tumor-free almost 6 years later. Her 46-year-old sister, whose peritoneal mesothelioma was found incidentally, chose no further treatment and remained asymptomatic six years after diagnosis. A 39-year-old half-niece with an 8-year history of pleural effusion was diagnosed with mesothelioma and had a partial response to chemotherapy. The authors compiled published reports covering 689 mutation carriers, of whom 553 developed cancer. They stated that no biomarkers identify which patients will survive long term and that no consensus on surveillance exists. The authors recommended offering germline genetic testing to all patients diagnosed with mesothelioma.

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: Review and expert recommendations based on the authors' collective experience and the published literature, illustrated with three case reports from one family
• Who was studied: Carriers of germline BAP1 mutations and their relatives. The case examples were three female patients from one family (the 'P-family') who carried the same BAP1 mutation. The literature compilation covered 689 carriers from 97 papers published from 2011 to January 2022.
• Exposure: The paper's focus was inherited (germline) BAP1 mutations rather than asbestos. The three case patients had no history, radiological or histological evidence of asbestos exposure.
• Main results:
  • Patient 1 was a 43-year-old woman with peritoneal mesothelioma, epithelioid type. She was treated with cytoreductive surgery, HIPEC and adjuvant cisplatin/pemetrexed. As of January 2022, almost 6 years after diagnosis and therapy, she remained tumor-free.
  • Patient 2 was a 46-year-old woman, the sister of Patient 1. Her peritoneal mesothelioma, epithelioid type, was found during surgery for breast cancer treatment. She chose no further treatment for the mesothelioma, which did not progress. She was asymptomatic six years after diagnosis.
  • Patient 3 was a 39-year-old woman, a half-niece of the proband, with an 8-year history of recurrent right pleural effusion. Pleural nodules were diagnosed as diffuse malignant mesothelioma, epithelioid type. After 6 cycles of cisplatin/pemetrexed she had a partial response.
  • In the authors' compilation of 97 published papers covering 689 carriers of germline BAP1 mutations (309 female, 268 male, 112 unknown), 553 developed cancer.
  • Using the ACMG guidelines, the authors mapped pathogenic BAP1 mutations identified up to January 2022 in 234 families and 510 subjects from the US, Europe, Australia and Asia.
• The authors' conclusion: The authors recommended that germline genetic testing be offered to all patients diagnosed with mesothelioma. They concluded that a subset of mesothelioma patients with germline BAP1 (and less often other) mutations have prolonged survival and benefit from tailored care for themselves and their relatives who carry the same mutation.
• Limitations the authors state:
  • There are no biomarkers to identify which carriers with mesothelioma will survive long term and which may benefit from immediate therapy.
  • No clear consensus exists on how to screen carriers for mesothelioma.
  • The authors stated they do not know why mesotheliomas in these carriers are less aggressive.
  • Measured survival may be influenced by lead-time bias, because nodules can be present for years before diagnosis.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, BAP1 Tumor Predisposition Syndrome, BAP1, Germline Mutation, Carcinoma, Multidisciplinary Team, Genetic Counseling, Pathology.

Related studies

• CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma — M. Betti, A. Aspesi, et al. (2016)
• Prevalence and Preliminary Validation of Screening Criteria to Identify Carriers of Germline BAP1 Mutations — M.G. Zauderer, G. Jayakumaran, et al. (2019)
• Clinical Implications of Real-time Integrative Sequencing in Management of Patients With Suspected Germline BAP1 Mutations — S. Sengupta, A.C. Weyand, et al. (2019)
• Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma — A. Bononi, K. Goto, et al. (2020)
• Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer — M. Carbone, J.W. Harbour, et al. (2020)
• Germline BAP1-positive patients: the dilemmas of cancer surveillance and a proposed interdisciplinary consensus monitoring strategy — P. Star, A. Goodwin, et al. (2018)

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