Prior BRCA1/2 Status Knowledge Beneficial On Breast Cancer Diagnosis

Author: By Lynda Williams, Senior medwireNews Reporters 

medwireNews: Study findings suggest that prior knowledge of a pathogenic BRCA variant before breast cancer diagnosis is helpful regardless of whether individuals choose to undergo risk-reducing bilateral mastectomy (RRBM). 

In a research letter to JAMA Oncology, the Israeli investigators describe “measurable downstream benefits” for the 42 women who were aware of their BRCA1/2 carrier status before being diagnosed with breast cancer but did not undergo RRBM, compared with the 63 patients who found out their BRCA1/2 status after diagnosis. 

The patients were aged an average 50.4 years at the time of breast cancer diagnosis in 2005–2016 at a single institution and 83% were Ashkenazi Jewish.  

Patients who knew their genotype before breast cancer diagnosis were more likely to have a suggestive family history and a higher socioeconomic index than those who did not, and were significantly more likely to be diagnosed by magnetic resonance imaging rather than examination or mammography than those who did not (64.3 vs 1.6%). 

Awareness of BRCA1/2 status before diagnosis was also significantly associated with earlier clinical stage at diagnosis, in that aware patients were more likely to have ductal carcinoma in situ (38.1 vs 3.2%) or T1N0 disease (42.9 vs 27.0%) than those who were unaware. 

By contrast, awareness of BRCA1/2 status before diagnosis was independent of other tumour characteristics, such as grade, hormone receptor status and HER2 expression.  

Patients aware of their BRCA1/2 status before diagnosis were significantly more likely to undergo bilateral mastectomy as their initial surgery than those who were not (64.3 vs 15.9%), report Ephrat Levy-Lahad, from the Shaare Zedek Medical Center in Jerusalem, and co-authors. 

But patients in the prediagnosis cohort were also significantly less likely to undergo axillary lymph node dissection (7.2 vs 34.9%) or to require chemotherapy (28.6 vs 79.4%). Indeed, the prediagnosis BRCA1/2 status cohort completely avoided neoadjuvant chemotherapy whereas this treatment was given to 22.2% of those who found out their status later. 

Logistic regression analysis confirmed that prediagnosis awareness and better socioeconomic index significantly reduced the risk of advanced clinical disease, while prediagnosis awareness alone reduced the risk of an advanced pathological stage. 

Five-year overall survival (OS) was achieved by 94% of the prediagnosis patients versus 78% of postdiagnosis patients. After adjusting for age, socioeconomic status and other factors, the hazard ratio (HR) for death in the prediagnosis versus postdiagnosis groups was a nonsignificant 0.16, but OS was significantly predicted by higher socioeconomic status (HR=0.76), BRCA2 versus BRCA1 status (HR=0.15) and age at diagnosis (HR=1.05). 

“To our knowledge, this is the first report to document a possible survival advantage for presymptomatic identification of BRCA carrier status in carriers who decline RRBM”, the researchers say.

While acknowledging that the study did not consider use of risk-reducing salpingo-oophorectomy among patients, they believe that the identical age at diagnosis in the two cohorts “suggests lack of substantial bias”. 

The team concludes: “These results provide further support for BRCA1/BRCA2 screening in unaffected women, particularly in populations such as Ashkenazi Jews, with high BRCA1/BRCA2 carrier rates.” 

Reference  

Hadar T, Mor P, Amit G, et al. Presymptomatic awareness of germline pathogenic BRCA variants and associated outcomes in women with breast cancer. JAMA Oncol; Advance online publication 9 July 2020. doi:10.1001/jamaoncol.2020.2059