J. Clin. Oncol. 2021 Aug 10
Management of Women With Breast Cancer and Pathogenic Variants in Genes Other Than BRCA1 or BRCA2.
Abstract
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.
Related Questions
When, if ever, would you recommend risk reducing BSO in patients with moderate penetrance breast cancer germline mutations?
RAD51C, RAD51D, and BRIP1 are all associated with significant risks of ovarian cancer and are appropriate for consideration of prophylactic oophorectomy, albeit perhaps at a slightly later age than BRCA1 and BRCA2. ATM and PALB2 may be associated with ovarian cancer risks that are similar to that of...
For which non-BRCA pathogenic germline variants, if any, might you consider recommending chemoprevention with SERM/AI?
The breast cancer prevention trials enrolled women with a risk of developing breast cancer equivalent to a 60-year old woman with no other risk factors. That is not a HIGH risk. Chemoprevention has been dramatically underused in both the truly high risk (if pathogenic mutation carriers) as well as t...
How do you counsel patients on the efficacy of breast cancer risk reduction strategies such as breast MRI surveillance or bilateral mastectomy for those considered high risk by polygenic risk score, pathogenic variants, and/or family history?
This is a difficult question with limited data to guide decisions. The ultimate goal of any screening effort is to identify disease earlier so that treatment is more effective (and hopefully less onerous) so that fewer patients die. We have good data that enhanced screening in high risk populations,...
Would you consider use of PARP inhibitors in patients with metastatic breast cancer with moderate penetrance germline mutations such as CHEK2, ATM, RAD51?
In the Olaparib Expanded (TBCRC 048) study published by @Dr. First Last in JCO, there were no responses to olaparib in metastatic breast cancer with germline or somatic CHEK2 or ATM pathogenic variants (mutations). In contrast, responses were seen in metastatic breast cancer with PALB2 pathogenic va...
Are CHEK2 mutations a contraindication for breast conservation therapy with lumpectomy + RT?
Among women with early-stage breast cancer and moderate penetrance breast cancer susceptibility genes, such as CHEK2, decisions about breast surgery are largely based upon personal preferences. According to data from large population-based studies, women with CHEK2 pathogenic variants have about a 2...