BRCA1/2 Germline Mutations Linked To Guideline Nonconcordant Treatment

Author: By Laura Cowen, medwireNews Reporter

medwireNews: Treatment of women with pathogenic variants in breast cancer-associated genes appears to deviate from current practice guidelines, particularly for radiotherapy and chemotherapy, US population-based data suggest. 

Writing in JAMA Oncology, Allison Kurian, from Stanford University School of Medicine in California, USA, and colleagues report that, compared with other breast cancer patients, “women with pathogenic variants in BRCA1, BRCA2, and other breast cancer-associated genes were more likely to receive bilateral mastectomy, less likely to receive radiotherapy after lumpectomy, and more likely to receive chemotherapy for early-stage hormone receptor-positive disease.” 

Their findings are based on an analysis of Surveillance, Epidemiology and End Results registry data for 20,568 women aged 20 years or older who were diagnosed with stage 0 to III breast cancer between 2014 and 2016 and underwent genetic testing within 3 months of diagnosis. 

The researchers found that women with BRCA1/2 pathogenic variants were a significant 5.52 times more likely to receive bilateral mastectomy for a unilateral tumour than those without pathogenic variants, with rates of 61.7% versus 24.3%, despite both groups being eligible for a unilateral surgical procedure. 

They were also a significant 1.76 times more likely to receive chemotherapy for oestrogen receptor and/or progesterone receptor-positive, ERBB2-negative disease than those without the pathogenic variants (38.0 vs 30.3%). This occurred even though guidelines do not advise using genetic testing results to guide systemic therapy decision-making in early-stage disease. 

There is a “growing consensus” that patients with this favourable prognosis “may safely forgo chemotherapy”, the researchers observe. 

In addition, the team found that while guidelines recommend that genetic testing should not inform decision-making for radiotherapy (with the exception of TP53 pathogenic variants), women with the BRCA1/2 pathogenic variants were a significant 78% less likely to receive post-lumpectomy radiotherapy than those without, at rates of 50.2% versus 81.5%. 

And Allison Kurian and co-investigators note that similar patterns were observed with other pathogenic variants in breast cancer-associated genes (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN and TP53) but not with variants of uncertain significance. 

The authors conclude: “Multiplex sequencing for germline cancer susceptibility genes has quickly been adopted in oncology practice, sometimes outpacing the evidence base.” 

They add: “We believe more research is needed to confirm our results and to evaluate long-term outcomes of pathogenic variant carriers to understand treatment decision-making and consequences.” 

Reference  

Kurian AW, Ward KC, Abrahamse P, et al. Association of germline genetic testing results with locoregional and systemic therapy in patients with breast cancer. JAMA Oncol 2020; Advance online publication 6 February 2020. doi:10.1001/jamaoncol.2019.6400