The present findings of a 78% increased risk of breast cancer for African American women who have a first degree relative with breast cancer demonstrate a familial component to breast cancer in African-American women. The association with family history was stronger for breast cancer diagnosed before age 45, and also stronger if the relative with cancer had been diagnosed at a young age. An association with family history of breast cancer was observed for both ER+ and ER- breast cancer.
There have been only three studies, each with a case-control design, that provide data on family history of breast cancer in black women [10
]. In a hospital-based case-control study, the odds ratio for having a first-degree relative with breast cancer was 2.8 [10
]. The other two case-control studies used a cohort approach in which the relative's cancer status was the outcome. In the Cancer and Steroid Hormone study, the relative risk estimates were 2.02 for mothers of cases relative to mothers of controls, and 1.65 for sisters of cases relative to sisters of controls [11
]. In the more recent Women's CARE study, the estimated relative risk for breast cancer among all first degree relatives of the cases was 1.78 [12
]. Our prospective cohort study yielded an identical overall relative risk estimate of 1.78.
The present results are also similar to results from studies of Asian and Caucasian women. In the most informative data on Asian women, from a large cohort study of women in Shanghai, the estimated relative risk for having at least one first degree relative with breast cancer was 1.74 [13
]. In the most informative study of family history and breast cancer risk in Caucasian women, a pooled analysis of 52 case-control and cohort studies, the estimated relative risk associated with having a single first degree relative with the disease was 1.80, for two relatives it was 2.93, and for three or more it was 3.90 [14
]. The similarity of findings in different ethnic groups suggests that genetic factors probably do not explain ethnic disparities in breast cancer incidence, such as the disproportionately high incidence of breast cancer in young African American women.
We found that the association of family history of breast cancer with breast cancer risk was present in all combinations of ER/PR status except for ER-/PR+, a group for which numbers were too small for informative analysis. These results are in agreement with findings from a large cohort of women from the Group Health screening program from Western Washington state [15
]. The Iowa Women's Health Study cohort found that an association was present in all categories of receptor status except ER+/PR- [16
]. In our study, the IRR for positive family history was highest for ER+/PR+ tumors although not statistically different from IRRs for the other subtypes. These results illustrate the importance of assessing family history in relation to specific subtypes of breast cancer.
Relatively few studies have examined whether having a family history of other types of cancer predicts risk of breast cancer. In the CARE study, family history of ovarian cancer was associated with breast cancer risk in white women but not in black women [12
]. On the other hand, family history of cervical cancer was associated with breast cancer in black, but not white women [12
]. In the Shanghai Women's Health Study, a family history of leukemia was associated with increased risk of breast cancer overall and family histories of lung cancer and esophageal cancer were associated with early onset breast cancer [14
]. In a Danish population-based registry linkage study, family histories of ovarian and cervical cancers were associated with overall breast cancer risk, and family histories of colon and gall bladder cancer were associated with early breast cancer [17
]. In a Swedish registry study, family histories of colorectal, ovarian, and pancreatic cancers were associated with breast cancer risk [18
]. Family history of colon cancer, but not ovarian cancer, was associated with an increased risk of breast cancer in a primarily Caucasian population from the Southwestern U.S [19
]. In the present study of African American women, no association was observed with family history of lung, prostate, or ovarian cancer. However, women who reported a first degree relative with colon cancer had a 35% increased risk of breast cancer. This is of interest because African Americans have a higher incidence of colon cancer than do other U.S. ethnic groups [20
]. We also observed an increased IRR, not statistically significant, for leukemia, in agreement with results from the Shanghai study. In the only study that reported on the accuracy of self-reports of family history of cancer by ethnic group, there was no difference in accuracy by race/ethnicity [21
A potential limitation of the present study, shared by previous epidemiologic studies of family history of breast cancer, is the lack of information on which participants had mutations in the BRCA1 or BRCA2 genes. As a result, it was not possible to estimate the magnitude of the IRR associated with a positive family history of breast cancer separate from the effects of these rare, high-penetrance genes. However, the prevalence of these genes is quite low in African American women, with the best estimates indicating a prevalence of 1.4% for the BRCA1 gene and 2.6% for the BRCA2 gene [22
Strengths of the study are the large size of the cohort and the duration of follow-up which resulted in a large number of breast cancer cases, thus permitting estimation of IRRs with narrow confidence bounds. One advantage of studying this relation in a cohort versus a case-control study is that it was possible to directly compare incidence rates in persons with and without a family history. Another is that there would not have been differential reporting of family history of cancer based on the respondents' own case status. While there was undoubtedly underreporting of family members with cancers, the underreporting would have been non-differential.
In summary, our prospective study of African American women supports a genetic etiology for breast cancer in this population group. The magnitude of the association and the relatively stronger association with early onset disease are consistent with findings from Asian-ancestry and European-ancestry populations. In addition, our data suggest a familial link of colon cancer, and possibly leukemia, with breast cancer.