NEW YORK – Women carrying pathogenic germline BRCA1/2 variants who develop breast cancer appear to fare better if their germline risk variants were uncovered prior to their cancer diagnosis, even if they do not undergo preventative procedures such as risk-reduction surgery, according to new research from Israel.
"The findings of this study suggest that prior awareness of BRCA pathogenic variant carrier status may be beneficial even in carriers who decline [risk-reduction bilateral mastectomy] and later develop breast cancer," co-corresponding authors Ephrat Levy-Lahad, a researcher at the Medical Genetics Institute at Shaare Zedek Medical Center and the Hebrew University of Jerusalem, and Tal Hada, an investigator with the Shaare Zedek breast surgery unit, and their colleagues wrote.
As they reported in a research letter appearing in JAMA Oncology on Thursday, investigators in Israel and the US retrospectively assessed outcomes for 105 BRCA1/2 germline mutation carriers diagnosed with breast cancer from 2005 to 2016. More than half of the women — 63 of them — learned that they carried pathogenic BRCA1 or BRCA2 variants through testing performed after being diagnosed with breast cancer, while 42 of the women knew they were BRCA1/2 mutation carriers beforehand.
Using clinical, pathological, and other information gleaned from Israel's National Cancer Registry, the team found that women with knowledge of their BRCA1/2 mutation status prior to their breast cancer diagnosis tended to have higher socioeconomic status and family histories that pointed to increased cancer risk. From that group of 42 women, 40 had been followed at clinics for high-risk individuals.
Though women with pre- and post-breast cancer knowledge of their germline BRCA1/2 risk were roughly the same age when diagnosed with cancer, those with prior knowledge of their mutation status were diagnosed with less invasive forms of breast cancer or with noninvasive ductal carcinoma in situ compared to women who were unaware of their germline risk.
Likewise, learning of their germline risk earlier appeared to lend patients an overall survival advantage, despite similar breast cancer grades, hormone receptor status patterns, and subtypes in both groups, the team reported Those with previous knowledge had a five-year survival rate of 94 percent, compared to 78 percent for those who learned about their BRCA1/2 status post diagnosis.
The researchers noted that women with previous knowledge of their germline cancer risk were also significantly more likely to go through bilateral — rather than unilateral — mastectomy as a first cancer surgery, but they had lower rates of chemotherapy or axillary dissection surgery involving the lymph nodes.
"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," the authors wrote. More than 80 percent of the women assessed for the analysis had Ashkenazi Jewish ancestry.
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July 11, 2020 at 12:15AM
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