Having a family history of breast cancer was associated with a significant 2.2-fold increased risk of triple-negative breast cancer in Hispanic women, but not in black women, according to preliminary data from a study of 466 patients.
Moreover, Hispanic women were six times more likely to develop this aggressive form of cancer before age 50 years (odds ratio 6.1) when compared with black women (OR 1.5), Betsy C. Wertheim reported at the American Association for Cancer Research conference on the science of health disparities. The mean age at breast cancer diagnosis was 49 years for Hispanics and 52 years for blacks.
Subset analyses suggest that the increased risk for triple-negative breast cancer is confined to Hispanics who were born in Mexico and not in the United States.
Because the breast cancer tumors of affected women are negative for three important targets of available treatment regimens—estrogen receptors (ER), progesterone receptors (PR), and/or human epidermal growth factor receptor 2 (HER2)—their response to some treatments may be poor.
The association between family history of breast cancer and triple-negative breast cancer was increased nearly fivefold (OR 4.9) among Hispanic women living in Arizona, of whom 17% were American born. In contrast, there was no significant association among Hispanics living in Texas (OR 1.4), of whom 58% were American born.
“We aren't sure whether this association is due to environmental exposure or if it has to do with the ancestry of these women from Arizona versus Texas,” Ms. Wertheim, an assistant scientific investigator at the Arizona Cancer Center, University of Arizona, Tucson, told reporters at a press briefing.
The findings were based on 260 Hispanic women participating in the ongoing ELLA Binational Breast Cancer study and 206 black women studied with the same protocol at University of Texas M.D. Anderson Cancer Center, Houston. They ranged in age from 22 to 80 years. Family history was defined as self-reported history of breast or ovarian cancer in a relative before age 50 years.
Tumor marker data taken from medical records were used to determine if tumors were negative for ER, PR, and HER2/neu.
One genetic factor that may help explain the strong association between family history and triple-negative breast cancers is a higher burden of BRCA1 mutation carriers in the Mexican American cases, principal investigator Maria Elena Martinez, Ph.D., said in an interview.
This observation is supported by a recent study, led by Dr. Jeffrey N. Weitzel, that identified and characterized a novel large BRCA1 deletion in five unrelated high-risk families—four of Mexican ancestry (Cancer Epidemiol. Biomarkers Prev. 2007;16:1615–20). The families had a personal or family history of breast or ovarian cancer, but not necessarily triple-negative breast cancer.
Still, the findings suggest that the presence of these BRCA mutations may account for a higher proportion of breast cancer cases in young Mexican American women, similar to that of women of Ashkenazi ancestry, when compared with women who are black or non-Hispanic white.
“We're putting the pieces together,” Dr. Martinez said. “We believe there is possibly a BRCA1 mutation in these women based on his findings and extending those to our findings. Young onset, triple negative, and family history: It's crying out, as Dr. Weitzel would say, that there is a BRCA mutation in these women.”
The next logical step is to assess the rate of BRCA1 mutations in the current cohort and to confirm the findings of Dr. Weitzel, chief of the division of clinical cancer genetics at the City of Hope in Duarte, Calif.
Prior to the current study, very little was known about the rate of triple-negative breast cancer in Hispanic women, said Dr. Martinez, an epidemiology professor also with the university's Arizona Cancer Center.
If future research confirms a higher rate of BRCA1 mutations among Mexican American women, genetic counseling and advice regarding prophylactic mastectomy or oophorectomy is advisable. This must be done, however, in a culturally and language-sensitive environment, Dr. Martinez stressed.
The investigators reported no conflicts of interest. The ELLA study is supported by funding from the Avon Foundation and the National Cancer Institute.