Researchers examined the germline DNA of Hispanic women with BRCA-negative breast cancer to pinpoint pathogenic variants.
A new study aiming to characterize the incidence of genetic susceptibility variants for breast cancer among BRCA-mutation-negative Hispanic women found a number of specific variants occurring in almost 5% of the cohort.
“One in 12 Hispanic women will be diagnosed with breast cancer, and it is more likely to be at a later, less curable stage than in non-Hispanic women,” wrote study authors led by Jeffrey N. Weitzel, MD, of the City of Hope Cancer Center in Duarte, California. “Yet, there is a dearth of Hispanic-specific health care research, particularly in the area of genomic predisposition to breast cancer.”
The new study, published in Cancer, examined germline DNA from 1,054 Hispanic women who are negative for BRCA mutations with hereditary breast cancer. Hereditary disease was defined as breast cancer diagnosed at an age below 51 years, bilateral breast cancer, breast and ovarian cancer, or breast cancer diagnosed between the ages of 51 and 70 years along with the existence of at least two first-degree or second-degree relatives with breast cancer diagnosed before age 70 years. The researchers considered 12 known and suspected cancer susceptibility genes.
The women in the study were compared with 312 local control patients, and 887 multiethnic control patients. In the 1,054 Hispanic women, a total of 49 pathogenic variants were identified in seven of the 12 genes. These included variants in CHEK2 (20 patients), PALB2 (18 patients), ATM (5 patients), BRIP1 (2 patients), TP53 (3 patients), CDH1 (1 patient), and NF1 (1 patient). In total, pathogenic variants were detected in 47 patients (4.4%). Three of the 47 carried two variants.
Age at diagnosis and tumor characteristics were not significantly different between the patients with pathogenic variants and those without. The recurrent pathogenic variants in PALB2 and CHEK2 represented 47% of all the variants observed, which the authors wrote suggests a founder effect.
“This is the first study of Hispanic women with breast cancer that reports on the spectrum and frequency of pathogenic variants in breast cancer susceptibility genes beyond BRCA,” the authors wrote. “This important information can enable enhanced screening, prevention, and therapeutic strategies for patients and their families.”
In an accompanying editorial, Steven A. Narod, MD, of the Women’s College Research Institute in Toronto, noted there are more considerations surrounding genetic testing than simply whether or not relevant variants are present.
“I am not convinced that just because we have the opportunity to find rare mutations that we should do so,” he wrote, noting that PALB2 may be an exception given increasing evidence of its role in breast cancer. “The clinical and social implications of genetic testing in the Hispanic population are not discussed here.”
He added that the women in the study were selected at clinical centers and are not necessarily representative of all Hispanic women with breast cancer.
“I think that all patients with breast cancer, regardless of ethnicity, should be offered full gene sequencing for three genes,” he wrote. “I do not see the evidence showing that we should test beyond BRCA1, BRCA2, and PALB2-but I get the feeling that I am too late in the game.”