Considerations for radiation
Radiation therapy in the context of breast-conserving therapy or mastectomy should not be withheld because of hereditary mutations, except in the case of TP53 mutations, according to the guidelines.
There’s no evidence that radiotherapy increases toxicity or contralateral breast cancer risk for most BRCA1/2 or moderate-penetrance gene mutations. However, the intact breast shouldn’t be irradiated in germline TP53 mutation carriers, the guidelines say, because of the important role that TP53 plays in the ability to repair DNA damage after cellular stress.
“Carriers of a TP53 mutation would be expected to be unable to repair tissue damage from DNA damaging radiotherapy and be at risk for significant [radiotherapy]-associated sequelae,” the guidelines state.
Chemotherapy and PARP inhibitors
For women with metastatic breast cancer harboring germline BRCA1/2 mutations, the guidelines say platinum chemotherapy should be preferred over taxanes for platinum-naive patients.
Provided the breast cancer is HER2 negative, the PARP inhibitors olaparib or talazoparib “should be offered as an alternative to chemotherapy in the first- to third-line settings,” the guidelines state.
The guidelines confirm that PARP inhibitors are a “valid starting point” for treatment of BCRA1/2–associated metastatic breast cancer, Dr. Gradishar said.
“When a patient progresses on a PARP inhibitor, assuming they’re not going on some other investigational drug or clinical trial, they’re going to get chemotherapy,” he said. “So the argument is that, if you have something that’s at least as good or maybe a little bit better and has fewer side effects, why not start with that and then move on to other things?”
By contrast, there’s not enough evidence to recommend PARP inhibitors for germline BRCA mutation carriers with nonmetastatic breast cancers, according to the guidelines, and there’s “no robust data” for using PARP inhibitors in patients with breast cancers with mutations in moderate-penetrance genes.
The guideline authors disclosed relationships with AstraZeneca, Myriad Genetics, Pfizer, Lilly, and other companies. Dr. Gradishar has relationships with AstraZeneca, Celltrion, Genentech, MacroGenics, Merck, Pfizer, and Seattle Genetics.
SOURCE: Tung NM et al. J Clin Oncol. 2020 Apr 3;JCO2000299. doi: 10.1200/JCO.20.00299.