From the Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, GA
Correspondence to Dr. Marjorie McCullough, Department of Epidemiology and Surveillance Research, American Cancer Society, 1599 Clifton Road, NE, Atlanta, GA 30329-4251 (e-mail: marji.mccullough{at}cancer.org).
Received for publication March 28, 2005. Accepted for publication June 1, 2005.
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
African Americans; body mass index; breast neoplasms; cohort studies; education; exercise; reproductive behavior; risk factors
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
This disparity may have sociodemographic and/or biologic roots. Wojcik et al. (5) found that, among African-American women who were beneficiaries in the Department of Defense health-care system, death rates were closer to those of White women nationwide, suggesting that differences in access to care probably contribute to differences in survival. A recent report found that physicians treating African-American patients may be less well trained clinically and have less access to important clinical resources than do physicians treating White patients (6
). African-American women also differ from White women in risk factor profiles (7
), having a younger age at menarche, higher levels of obesity, and less physical activity. African-American women also present with later stage at diagnosis, more estrogen-receptornegative tumors (8
), and more aggressive tumors than do White women (9
, 10
), characteristics that have also been associated with lower socioeconomic status in both African-American women and White women (11
). Poorer breast cancer prognosis among African-American women has also been linked to specific mutations (12
) and cell-cycle defects (13
).
Relatively few studies have examined risk factors for breast cancer separately in African-American women, and the literature addresses primarily the risk of breast cancer incidence rather than mortality. However, because known risk factors for incident breast cancer are also associated with breast cancer mortality (1416
), there should be considerable overlap. A 1996 review of the literature, based on five case-control studies, concluded that associations for both established and probable breast cancer risk factors are similar in African-American women and White women, and that lower survival among African-American women is likely due to later stage at diagnosis (17
). In an analysis of data from the Multiethnic Cohort (18
), breast cancer risk was similar in both African-American women and White women after control for known risk factors.
Eight case-control analyses (1926
) published after the 1996 review are less consistent; two of these observed no association between body mass index and postmenopausal breast cancer risk in African-American women (19
, 26
). Only one published prospective study has examined breast cancer risk factors among African-American women (27
). After 4 years of follow-up in the Black Women's Health Study, African-American women over age 45 years who had their first child after age 30 years were not at higher breast cancer risk compared with those whose age at first birth was less than 20 years, but high parity (among parous women) was associated with lower risk. Conversely, later age at first birth and higher parity were associated with higher breast cancer risk among African-American women aged less than 45 years (27
).
The purpose of this study was to evaluate the relation between anthropometric, reproductive, and lifestyle breast cancer risk factors and fatal breast cancer among African-American women in a prospective cohort study. We focused our analysis on postmenopausal breast cancer because of the small number of premenopausal African-American women in the cohort. We included analyses of the same risk factors in White women in this cohort for comparison purposes.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We excluded participants from this analysis if they reported prevalent cancer other than nonmelanoma skin cancer at baseline (African-American women: n = 1,809; White women: n = 54,319); if they described themselves as "Hispanic," "Oriental," or "other"; or if information on race was missing (n = 14,718), if menopausal status was missing (African-American women: n = 1,710; White women: n = 12,767), or if the women were pre- or perimenopausal (African-American women: n = 8,550; White women: n = 151,169). The final analytical cohort consisted of 21,143 African-American women and 409,093 White women, among whom 257 and 4,265 deaths from breast cancer occurred, respectively.
The vital status of study participants was determined from the month of enrollment through December 31, 2002, using two approaches. American Cancer Society volunteers made personal inquiries in September 1984, 1986, and 1988 to determine whether their enrollees were alive or dead and to record the date and place of all deaths. Death certificates were then obtained from state health departments to verify the underlying cause of death. Automated linkage using the National Death Index was used to extend follow-up through December 31, 2002, and to identify deaths among 13,219 women (2 percent) lost to follow-up between 1982 and 1988. Details of the utility of the National Death Index for the ascertainment of participants in this study are given elsewhere (29). Death certificates or multiple cause-of-death codes were obtained for 98.5 percent of all women known to have died. The underlying cause of death from breast cancer was coded according to the International Classification of Diseases using Ninth Revision codes 174.0175.9 through 1998 and Tenth Revision codes C5050.9 through the year 2002 follow-up (30
, 31
).
Statistical analyses
Race-specific rates of breast cancer mortality were calculated by 5-year age intervals. In addition, age-standardized (to the entire study population), race-specific rates were calculated by risk factor and calendar year of follow-up. We examined several established risk factors for breast cancer separately among African-American women and White women, using Cox's proportional hazards modeling to calculate multivariate-adjusted hazard ratios (32). The time axis used was follow-up time since enrollment in 1982. Age adjustment was accomplished by stratifying on the exact year of age at enrollment within each Cox model.
The following self-reported variables assessed in 1982 were modeled categorically: height (centimeters: <160, 160165, >165170, >170, missing); body mass index (weight (kg)/height (m)2: <25, 25<30, 30<35, 35, missing); exercise at work or play (none/slight, moderate, heavy, missing); education (less than high school, high school, some college/trade, college graduate and beyond, missing); age at menarche (years: <12, 12, 13,
14, missing); age at menopause (years: <45, 4549, 5054,
55, menopausal but unknown age); history of physican-diagnosed breast cysts (yes/no); history of breast cancer in a mother or sister (yes/no); alcohol use (nondrinker, <1 drink/day,
1 drink/day, unknown or missing); and estrogen replacement therapy (never, ever, unknown or missing). We examined age at first livebirth (years: <20, 2024, 2529,
30) and number of livebirths (n = 1, 2, 3,
4) among parous women only, and we controlled each variable for the other in multivariate models. In the remainder of the multivariate models that included nulliparous women, we controlled for parity using a binary variable (nulliparous/parous). Because of the high percentage of missing data for alcohol and because only 4 percent of African-American women reported consuming one or more drinks per day, we did not include the association with alcohol independently, but this variable remained as a covariate in multivariate models. We evaluated the potential for confounding by vegetable, fruit, whole grain, and red and processed meat consumption, as assessed on the baseline questionnaire as follows: "On average, how many days per week do you eat the following foods?". As control for these diet variables did not change the overall findings materially, the diet variables are not included in the final multivariate models. All reported p values are two sided.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
Older age at first livebirth was statistically significantly associated only with greater risk of fatal breast cancer among White women. The age-adjusted hazard ratio among African-American women was 1.44 (95 percent CI: 0.86, 2.41; ptrend = 0.09); however, after adjustment for other risk factors, particularly the number of livebirths and education, the association was attenuated (HR = 1.13, 95 percent CI: 0.65, 1.98; ptrend = 0.64). Later age at menarche was inversely associated with risk of breast cancer in White women (HR = 0.86, 95 percent CI: 0.78, 0.95; p = 0.002) but not African-American women (HR = 1.00, 95 percent CI: 0.69, 1.45), but confidence intervals were wide. Although age at menopause was similarly related to risk among both groups, there was a high percentage of missing data, especially among African-American women.
When we combined all women in the same age-adjusted model, the hazard ratio of fatal breast cancer among African-American women (as a main exposure) was 1.24 (95 percent CI: 1.10, 1.41; p = 0.0007), compared with White women. Adjustment for other measured breast cancer risk factors attenuated but did not eliminate the association (HR = 1.15, 95 percent CI: 1.01, 1.31; p = 0.03). However, race as an exposure did not meet the assumption for proportional hazards. Thus, emphasis should be placed on the stratified results. As illustrated in figure 2, breast cancer death rates were higher in African-American women than in White women in our cohort until the 19982002 time period, when mortality rates converged. The lower rates observed in both races in 19821987 reflect our exclusion of all preexisting cancers at baseline.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Body mass has been consistently associated with higher breast cancer risk in postmenopausal White women (33), but results from case-control studies of African-American women are inconsistent (19
, 34
). We observed higher risk of fatal breast cancer with increasing body mass index at baseline in both groups, but the association was stronger in White women, possibly because of the comparatively smaller sample size for African-American women.
Several explanations may account for the weaker associations between fatal breast cancer risk and body mass index in African-American women compared with White women in our study. First, African-American women with a body mass index of less than 25 (who comprised the referent group) had higher rates of fatal breast cancer compared with White women of normal weight (64 vs. 45 per 100,000) (table 1), possibly because of factors affecting medical care or the racial differences in circulating estrogen levels (35). Higher serum estrone concentrations have been observed in African-American women compared with White women, even after controlling for obesity (36
). The increase in circulating estrogen levels with higher levels of obesity may not produce a linear increase in breast cancer risk in African-American women as has been reported in Whites (37
). Second, African-American women have more estrogen receptor-negative tumors (9
). Estrogen-mediated risk factors, including estrone synthesis in adipose tissue (38
), may be less important for estrogen receptor-negative tumors (39
). Finally, African-American women in our study were heavier than White women were and may also have had a higher body mass index during the premenopausal period when higher body mass is associated with lower subsequent risk of breast cancer (40
).
The inverse association with physical activity in African-American women (23), along with the suggestion that physical activity was slightly more strongly related to lower breast cancer mortality among African-American women than White women (22
), is consistent with limited data. In addition to its role in energy balance, physical activity is thought to lower breast cancer risk by influencing circulating hormone levels (22
).
Educational attainment was the strongest risk factor observed in African-American women. Those who were college educated had a 60 percent higher risk of fatal breast cancer than did those with less than a high school education, a finding not observed among White women in our cohort. Two previous case-control studies reported higher breast cancer incidence associated with higher education (24, 41
), even after controlling for age at first birth and number of births (24
), while two others observed no association (26
, 34
). Interestingly, spousal education was not related to risk in our study.
Because our study was of breast cancer mortality, one may hypothesize that higher education would predict lower mortality, not greater, if it reflected better access to screening and health care. Our findings may also be due to unmeasured confounders among college-educated women (17) or residual confounding. For example, women in our study with higher education were taller and experienced menarche at an earlier age, regardless of race. Thus, higher education may capture a combination of reproductive and other risk factors that acts as a stronger predictor of risk than do individual factors. Nevertheless, this finding varied by race.
Reproductive factors affect breast cancer risk partly by modulating lifetime exposure to the mitogenic effects of estrogen. We observed a 2030 percent statistically significant lower risk of fatal breast cancer in parous compared with nulliparous women of both races. However, among parous women, age at first birth and number of livebirthsboth clearly related to risk among White womenwere not clearly related to risk of postmenopausal breast cancer among African-American women. Later age at first birth was not related to increased breast cancer risk in African-American women, but having four or more births (vs. a single birth) was related to lower risk, controlling for age at first birth. This finding is similar to a recent report from the Black Women's Health Study cohort of breast cancer incidence (27). In that study, among African-American women over the age of 45 years, age at first birth was not related to risk, but the number of births was inversely related to risk; opposite patterns were observed in women aged less than 45 years of age (27
). Previous case-control studies have been equivocal, with some reporting increased breast cancer risk with later age at first birth in African-American women (34
, 42
44
), while others observed no association (21
, 24
, 26
, 27
). Likewise, having multiple births has been inversely associated with risk in three case-control studies of postmenopausal breast cancer in African-American women (21
, 26
, 34
) but not in another (45
). Although later age at menopause was similarly related to risk in both groups, later age at menarche was associated with lower risk only in White women, a finding not inconsistent with the literature (24
, 34
, 45
).
Most epidemiologic studies of breast cancer risk factors pertain almost exclusively to White women; risk factors are assumed to be similar across racial groups. In the Cancer Prevention Study II cohort, being African American is associated with higher risk of death from breast cancer after controlling for other measured risk factors (rate ratio = 1.15; p = 0.03). Even though our analysis controlled for most established breast cancer risk factors, we could not control for tumor characteristics associated with poor prognosis (8), screening behavior, or quality of health care.
Breast cancer mortality rates in African-American women in our cohort decreased over time and approached rates of White women by the end of follow-up in 2002. This is promising, because it suggests that the disparity in death rates by race in our cohort has diminished over time. The explanation for this phenomenon is unclear. It may be a chance finding, as the confidence interval around the death rate in African-American women for the most recent calendar period is wide, or it may reflect a shift toward greater screening and earlier diagnosis in our African-American women over time.
The strengths of this study include its prospective design and information on several important breast cancer risk factors. The follow-up of African-American women for breast cancer death is larger (in person-years) than in any other cohort. The limitations of our study were that we did not have information on breast cancer incidence, which would have allowed us to distinguish factors associated with incidence from those associated with survival. We had no information on access to health care, mammography screening, or treatment. Risk factors were assessed only at baseline in 1982; thus, misclassification of time-dependent risk factors, such as physical activity, body mass index, and hormone replacement therapy use, over the 20-year follow-up may attenuate associations.
In conclusion, established breast cancer risk factors associated with energy balance and estrogen metabolism generally influenced the risk of postmenopausal breast cancer similarly in both African-American women and White women. Our observation of an elevated risk of fatal breast cancer among African-American women with higher education deserves further study. Education may represent a combination of lifestyle factors closely tied with reproductive patterns that we are unable to fully control in our study. Our findings support health messages aimed at improving modifiable risk factor profiles in both African-American women and White women, including maintenance of ideal body weight and increased physical activity to reduce risk of breast cancer mortality.
![]() |
ACKNOWLEDGMENTS |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|