Ethnicity-Related Variation in Breast Cancer Risk Factors

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1 222 Summit Meeting on Breast Cancer Among African American Women Supplement to Cancer Ethnicity-Related Variation in Breast Cancer Risk Factors Leslie Bernstein, Ph.D. 1 Cayla R. Teal, M.A. 2 Sue Joslyn, Ph.D. 3,4 Jerome Wilson, Ph.D 5 1 Department of Preventive Medicine/USC Norris Cancer Center, University of Southern California, Los Angeles, California. 2 Center for Research on Minority Health, M. D. Anderson Cancer Center, Houston, Texas. 3 Department of Internal Medicine, College of Medicine, The University of Iowa, Iowa City, Iowa. 4 Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, Iowa. 5 Global Outcomes Research, Pfizer Pharmaceutical Group, New York, New York. Presented at the Summit Meeting on Breast Cancer Among African American Women, Washington, DC, September 8 10, Address for reprints: Leslie Bernstein, Ph.D., Department of Preventive Medicine/USC Norris Cancer Center, University of Southern California, 1975 Zonal Avenue, KAM 506, Los Angeles, CA 90033; Fax: (323) ; lbern@usc.edu. Received September 14, 2002, accepted September 14, *This article is a US Government work and, as such, is in the public domain in the United States of America. BACKGROUND. A variety of factors are predictors of breast cancer risk. However, the studies conducted to establish these risk factors have rarely included African American women. The few studies with sufficient numbers of African-American women suggest that risk factors for breast cancer among African-American women are similar to those of white women. Although risk factors may be similar for African-American and white women, differences in the prevalence of risk factors may explain the differences in patterns of incidence. METHODS. The authors reviewed the epidemiologic studies of breast cancer among African-American women and identified resources with information regarding the prevalence of risk factors among African American and white women. RESULTS. Considerable variation exists in the studies of breast cancer risk factors among African American women. Because few studies have included sufficient numbers of African-American women, no firm conclusions can be drawn regarding whether risk estimates for African American women differ from those of white women. Estimates of the prevalence of breast cancer risk factors indicate that African American and white women differ in terms of their ages at menarche, menstrual cycle patterns, birth rates, lactation histories, patterns of oral contraceptive use, levels of obesity, frequency of menopausal hormone use, physical activity patterns, and alcohol intake. CONCLUSIONS. The risk factor profile of African-American women appears to differ from that of white women. This may explain in part, the higher incidence rates for African Americans before age 45 years and the lower incidence rates at older ages. Discussions of these data at a workshop highlighted the need for future research on breast cancer risk among African Americans. This research should acknowledge the heterogeneous heritage, cultural beliefs, and cultural knowledge of African-American women. Studies conducted in collaboration with the African-American community of women and with the breast cancer advocacy community can benefit from assistance in the design of questionnaires and recruitment of participants. Cancer 2003;97(1 Suppl): Published 2003 by the American Cancer Society.* DOI /cncr KEYWORDS: breast cancer, risk factors, African Americans, higher incidence rates. Breast Cancer Risk Factors Breast cancer incidence rates are increasing worldwide, yet the relatively well established risk factors account for no more than 50 55% of the breast cancer risk among Westernized populations. 1 3 Age and race are established demographic risk factors for breast cancer. 4 Another well established risk factor is a family history of breast cancer. Ovarian hormones, particularly estrogens, play a major role in breast cancer development. 5 Many of the other established risk factors are surrogate measures of a woman s cumulative exposure to estrogen Published 2003 by the American Cancer Society*

2 Ethnic Variation in Risk Factors/Bernstein et al. 223 and, possibly, progesterone. These include early age at menarche, late age at menopause, nulliparity or late age at first birth, lack of or short-term breast-feeding, alcohol intake of at least one drink per day, obesity after menopause, and long-term use of hormone replacement therapy (HRT). 4,6,7 The effects of diet on breast cancer risk still are being debated. Evidence has accumulated over the past decade that physically active women have lower breast cancer risk Studies of Breast Cancer Risk among African American Women Much of the evidence on breast cancer risk factors has been accumulated in studies of white women. Information on risk factors among African-American women is limited because few studies of this population exist. In 1996, Moormeier 12 reviewed three studies of African American women with information or risk associated with early age at menarche, late age at first term pregnancy, nulliparity, older age at menopause, oral contraceptive use, positive family history of breast cancer, positive history of benign breast disease, and obesity. Although these data are insufficient for definitive conclusions, these studies suggest that risk factors for breast cancer among African American women are similar to those of white women. The results for obesity were inconsistent in these studies. Some of the variation in risk estimates for obesity may be due to the differences in the age composition of participants because obesity is associated with an increased risk of breast cancer among postmenopausal, not premenopausal, women. These three studies included 1146 breast cancer patients. Not included in this review was a hospital-based case control study of breast cancer among women aged years that included 524 African American breast cancer patients. 13 Among African-American women younger than age 45 years in this study, longer duration of oral contraceptive use was associated with an increased breast cancer risk; risk was not elevated for older women. Short stature was associated with a decreased risk of breast cancer among African American women aged years who participated in this study. 14 Brinton et al. 15 presented results for their multicenter case control study of breast cancer among women age years. Restricting their analyses to women living in Atlanta and New Jersey, they evaluated the prevalence of breast cancer risk factors among African American and white controls, the risk associated with these factors, and the population attributable risk for two age groups of women. This study included 281 African American breast cancer patients and 296 African-American controls. The prevalence of several breast cancer risk factors differed between the African American and white controls, particularly among the younger women (ages years). African-American women reported more births, younger age at first birth, shorter duration of breast-feeding, larger body size, and lower intake of alcoholic beverages. A similar pattern of risk factor prevalence was also noted for the older controls (ages years). In addition, older African-American women were less likely to have used oral contraceptives than white women. Odds ratio estimates also differed between African Americans and whites. Fewer births, younger age at menarche, and more years of oral contraceptive use among younger women were risk factors for breast cancer among white women. However, they were not predictive of breast cancer risk among African American women, although the results for oral contraceptive use suggest an increased risk. Based on this study, 15 well established breast cancer risk factors (number of births, age at first birth, age at menarche, history of breast biopsy, family history of breast cancer) accounted for 57% of the breast cancer risk among older white women, but only 30% of the risk among older African-American women. This difference in attributable risk and the relatively small number of African American women in this study highlight the need for large, comprehensive studies of breast cancer risk among African American women. The Carolina Breast Cancer Study (CBCS), a population-based case control study of breast cancer among African-American and white females aged years who resided in North Carolina, has attempted to address this shortcoming. 16 The CBCS has provided a number of published results on breast cancer risk factors, although not all of the publications provide results separately by race. 17 This study included approximately 350 breast cancer patients and 350 controls (different numbers are reported in some of the publications). 18 In Hall et al., 18 the CBCs confirmed that short stature is associated with reduced breast cancer risk among premenopausal African American women, but not among white women. Among postmenopausal women, the reverse was true, i.e., short stature was associated with lower risk for white women and no effect was observed for African American women. Hall et al. 18 also reported that a high body mass index (BMI) protected white but not African American premenopausal women and was not associated with an increased risk of breast cancer in either racial group of postmenopausal women. A high waist-to-hip ratio was associated with an increased risk among both premenopausal and postmenopausal women irregardless of race in that study. Overall, breast cancer risk was not significantly associated with

3 224 CANCER Supplement January 1, 2003 / Volume 97 / Number 1 oral contraceptive use among either African American or white women, but African American women who used oral contraceptives before age 18 years were at an increased risk. 19,20 Breast-feeding was associated with reduced breast cancer risk among parous women who had a first-term pregnancy before age 20 years; 20 however, results were not reported by race. Other studies will provide more data on breast cancer risk among African-American women. The Women s Contraceptive and Reproductive Events (CARE) Study, a population-based case control study conducted in five locations in the United States, focuses on breast cancer risk among women ages years. 21 In this study, 35% of cases and controls (1622 cases and 1661 controls) are African American women. The Black Women s Health Study, a nationwide cohort study of 64,530 African American women ages years, is expected to provide important information on factors associated with breast cancer risk, 22 as is the Hawaii/Los Angeles Multiethnic Cohort Study, 23 which includes 22,256 African American women ages years residing in Los Angeles. Prevalence of Established and Suspected Risk Factors Risk factors for which data exsit for African Americans include age at menarche, menstrual cycle patterns, birth rates, lactation history, oral contraceptive use, menopausal hormone use, body size and obesity, physical activity, and alcohol intake. When data are derived from federal surveys, we report results for non-hispanic African-American women and non-hispanic white women, although we do not make this qualification in the text below. Age at menarche and menstrual cycle patterns Age at menarche is considered an established risk factor for breast cancer. Modest elevations in breast cancer risk are associated with younger ages at menarche. 5 In general, breast cancer risk declines approximately 10 20% with each year that menarche is delayed. Age at onset of menses is not the only aspect of menarche that is important in determining breast cancer risk. Risk has also been associated with the time when regular or predictable menstrual cycles are first established. 24 During adolescence, not all menstrual cycles are ovulatory. Girls with early menarche establish ovulatory menstrual cycles more quickly than girls with later onset of menstruation. As a result, they are exposed to greater cumulative amounts of estrogen and progesterone during adolescence. 25 This effect persists into adulthood, with levels of estrogen higher among women with early menarche than among those with later menarche. 26,27 Menarche represents not only a chronologic marker for the onset of reproduction and exposure to estrogen and progesterone, it also conveys proportionally greater or lesser exposure to these hormones. Two cohort studies provide data on ages at menarche of African American and white women. In the CARDIA study, which includes young African-American and white women born between 1955 and 1968, the average age at menarche for African Americans was years compared with 12.7 years for whites. 28 In the Bogalusa Heart Study, the average age at menarche of African American girls declined from 12.3 years in to 11.4 years in , whereas it declined from 12.2 years to 11.5 years for white girls. 29 The average ages at menarche appear to be similar for the two groups, although historically African American women may have experienced menarche at a younger age than white women. Harlow et al. 30 studied the menstrual cycle patterns of 111 African American and 119 white postmenarcheal girls aged years over 2-years. Among these adolescent girls, menstrual cycle length was one-half day longer for whites than for African Americans, whites had greater variation in cycle length, and whites were more likely to have menstrual cycles that were more than 45 days in length. These menstrual cycle characteristics may represent a greater frequency of ovulatory menstrual cycles among African American women during adolescence. Pregnancy history, breast-feeding, and oral contraceptive use Parous women have a lower risk of breast cancer than nulliparous women. 6 Parous women with a younger age at first pregnancy are at lower risk than parous women who are older at first pregnancy. MacMahon et al. 31 reported that breast cancer risks of single women and nulliparous married women were similar and were approximately 1.4 times that of parous married women. 31 They also showed that women whose first child was born before they were 20 years of age had approximately 50% the breast cancer risk of women whose first birth was at age 30 years. Data on the effects of pregnancy history on risk have shown that each term pregnancy after the first results in a small additional reduction in breast cancer risk. 32 In contrast to the long-term protective effects of fullterm pregnancies on breast cancer risk, the immediate effect of full-term pregnancies is a temporary increase in risk. Women who have had a birth within the past 3 years have a greater risk than women of equivalent age whose most recent birth was at least 10 years earlier. 33 The immediate effect of a term pregnancy may be to enhance risk and the longterm benefit may be to reduce risk. Early studies heightened concern that

4 Ethnic Variation in Risk Factors/Bernstein et al. 225 FIGURE 2. Percentage of U.S. mothers (ages years) who breast feed based on year of baby s birth. 40 FIGURE and 1995 birth rates per 1000 women by age. 36 breast cancer risk was elevated among women who had incomplete pregnancies, particularly those who had induced abortions. A careful evaluation of the published literature on this topic revealed inconsistent findings across studies and concluded that breast cancer risk is not associated with an increased number of either spontaneous or induced abortions. 34 The average number of pregnancies per woman upon completion of her reproductive years differs between African Americans and whites but has declined during the 1990s. 35 In 1990, African American women had 5.2 pregnancies and an average of 2.6 live births per woman. These numbers have declined to 4.6 pregnancies and 2.2 live births per woman in The comparable figures for white women are a decline from 2.9 pregnancies in 1990 to 2.7 in 1995 and a decline from 1.9 live births in 1990 to 1.8 live births in African-American women also are younger than white women when they have children. 36 The birth rates of African-American women substantially exceed those of white women until age 30 years (Fig. 1). The birth rate for African American women younger than 20 years is more than twice that of white women. Given that pregnancy may confer a short-term increase in breast cancer risk and a longer-term reduction in risk, this pattern of pregnancies may account, in part, for the higher incidence rates of breast cancer among younger African American women relative to white women and the lower incidence rates at older ages. Lactation is an important behavior to study as it relates to breast cancer risk because this behavior is modifiable. We would expect that lactation would reduce breast cancer risk because it results in a substantial delay in reestablishing ovulation following a completed pregnancy. Evidence is fairly convincing that lactation reduces the risk of breast cancer among premenopausal women, but the data are less consistent for postmenopausal women Variations in the overall duration of breast-feeding (longer durations are protective), the time when supplementary feedings are introduced, and the frequency and duration of each breast-feeding episode may contribute to the inconsistent findings in the literature. White women are more likely to breast-feed their infants than African American women. 40,41 Over time, the proportion of African-American and white mothers aged years who breast-fed a newborn child more than doubled from and (Fig. 2). 40 Yet, white women are still more than twice as likely as African American women to breast-feed an infant. In , 60% of white mothers breast-fed compared with only 24% of African-American mothers. Data from the 1995 National Survey of Family Growth for the years indicate that white mothers breast-fed longer (average duration, 29.8 weeks) than African American women (average duration, 22.9 weeks). 41 It is important to establish whether breast-feeding reduces the risk of breast cancer among African-American women. If it does, then education and encouragement of new mothers to breastfeed are important steps to take in reducing breast cancer risk of African-American women. The most definitive work on the association of oral contraceptive use and risk of breast cancer is the reanalysis of data collected from 54 breast cancer studies conducted in 25 countries. 42,43 In this summary, a history of recent oral contraceptive use, rather than long duration of use, was more predictive of breast cancer risk. The effect of recent oral contraceptive use was strongest among women who first used oral contraceptives before the age of 20 years. The greatest increase in breast cancer risk was observed among women who were youngest at the time of their diagnoses. In this pooled analysis, the breast cancers diagnosed among oral contraceptive users were less advanced clinically than those diagnosed among women who had never used oral contraceptives. The results of several studies suggest that the long-term

5 226 CANCER Supplement January 1, 2003 / Volume 97 / Number 1 use of oral contraceptives increases the risk of breast cancer among African American women and that women who use them at a young age may particularly be at increased risk. 12,19,20 Data from the 1987 National Health Interview Survey indicate that approximately 80% of African American and white women born since 1945 have used oral contraceptives at some time in their lives. 44 African- American women began using contraceptives at a younger age than white women, but were less likely than white women to begin use before their first pregnancy. In this survey, the average duration of oral contraceptive use among women who had access to oral contraceptives for all of their reproductive lives was similar for African-American and white women (5 years). Menopausal hormone use The majority of studies that have included sufficiently large numbers of women who have used estrogen replacement therapy (ERT) for extended periods of time find a modest increase in breast cancer risk among exposed women. 45 In these studies, 5 years of use is associated with a 10% increase in risk and every additional 5 years of use doubles the increase in risk (e.g., 10 years, 20% increase; 15 years, 40% increase). Combined HRT regimens add a progestin to the estrogen regimen. Progestin may be added at the end of each cycle for days or it may be given continuously with the estrogen. Progestins in combined regimens may enhance the proliferative effects of estrogen on the breast and may increase breast cancer risk substantially. Three large population-based epidemiologic studies with sufficient data on combined regimens have shown that adding a progestin to the estrogen regimen changes the increase in breast cancer risk after 5 years of use from 10% (estrogen alone) to 30% (estrogen plus a progestin). 7,46,47 African-American women are less likely to be prescribed replacement hormones (ERT or HRT). 48,49 Data from the National Ambulatory Medical Care Surveys and the National Hospital Ambulatory Medical Care Surveys indicate that, although African-American and white women ages years have nearly the same number of ambulatory care visits, African-American women are roughly one-half as likely to be prescribed replacement hormones at a visit. 48 In a study of the use of ERT among older (age 65 years) community-dwelling postmenopausal women in North Carolina that took into account socioeconomic factors, white women were nearly 6 times more likely than African-American women to be current ERT users. 50 We can speculate as to the reasons why African- American women are less likely to use hormones. The reason may be the expense and lack of prescription coverage among African-American women. In addition, their risk of osteoporosis may be lower 49 and their body mass higher (see below) so that their need for replacement hormones may be less than that of white women. Body size, obesity, physical activity, and alcohol intake Two aspects of BMI, i.e., obesity and weight gain as an adult, are generally associated with higher breast cancer risk among postmenopausal women One explanation for the increased risk in heavy postmenopausal women is that thay have higher levels of circulating estrogens. The main source of endogenous estrogen after menopause is the conversion of the androgen precursor, androstenedione, to estrone in adipose tissue. 54 In contrast to the effects of obesity on postmenopausal women, heavy body weight is associated with a reduced breast cancer risk among premenopausal women. 53 One explanation for this effect for premenopausal women is that obese premenopausal women frequently experience anovulatory menstrual cycles translating into less exposure to estrogen and progesterone during their reproductive years. 55 Taller women are also at greater risk of breast cancer; this is particularly true among postmenopausal women. 53 The prevalence of overweight (weight in kilograms divided by height in meters squared [BMI] 25.0) and the prevalence of obesity (BMI 30.0) are substantially higher among African-American women than among white women (Table 1). 56 In general, African- American women are slightly taller than white women (Table 1). 57 The average height of women age 20 years is 64.2 inches for African-American women and 63.9 inches for white women. 57 Physical activity has been proposed as a means for reducing breast cancer risk because of its potential effects on hormone profiles and weight gain. 58 A number of epidemiologic studies on the relationship between physical activity and breast cancer risk published over the last decade have shown lower breast cancer risk cancer among more active women The 1996 National Longitudinal Study of Adolescent Health conducted in 1996 indicated that African- American girls watch more television each week than white girls (20 hours vs hours, respectively) and spend more time being inactive (African Americans, 27.6 hours per week; whites, 16.5 hours per week). 59 In addition, 18.1% of African-American girls participate in moderate to vigorous activity compared with 25.6% of whites. 59 Our own preliminary data regarding lifetime exercise activity among control participants in

6 Ethnic Variation in Risk Factors/Bernstein et al. 227 TABLE 1 Prevalence of Overweight (BMI > 25.0) and Obesity (BMI > 30.0), 1988, and Mean Height in inches, , for non-hispanic African-American and White women in the United States Age group (yrs) African Americans (%) Whites (%) BMI Overall, age-adjusted BMI Overall, age-adjusted Height (in.) Overall average BMI: body mass index. Data adapted from URL: and URL: the Women s CARE study indicate that African-American women are less likely to participate in exercise activities than white women. Among control subjects ages years, nearly 30% of the African-American women, but only 15% of the white women, reported no leisure time exercise activities over their lifetimes. Among women years, 37% of the African-American and 24% of the white women reported no participation in leisure time activity over their lifetimes. However these data do not take into account physical activities involved in these women s occupations or household activities. Interventions to reduce obesity and increase physical activity offer opportunities to reduce breast cancer risk. It is unclear whether these interventions will impact the risk of breast cancer among African Americans and whites similarly. Alcohol consumption is also a risk factor for breast cancer. Increases in breast cancer risk are observed with as little average intake as one alcoholic drink per day. 60 According to the 1998 National Health Interview Survey, at all adult ages (age 18 years) African American women are less likely to consume alcohol than white women. 61 Implications For Reducing Risk According to the available data, African-American women could decrease their risk of breast cancer by increasing breast-feeding, losing weight, and increasing physical activity. However, to develop appropriate approaches for reducing breast cancer risk among African-American women, we must obtain better data concerning factors that increase their risk and also gain understanding of the social and cultural issues associated with their varying risk factor profiles. Priorities For Research Efforts This workshop provided a number of suggestions for gaining a better understanding of the breast cancer risk profiles of African-American women and relating these to risk of the disease. Key among these is developing creative approaches to the conduct of studies of African-American women that encompass their broad cultural and ethnic backgrounds and their life experiences and perceptions of discrimination. Currently ongoing and previous studies of African-American women have limitations. The development of a multisite, long-term, longitudinal cohort study with representation of African-American women of varied heritage was discussed as a means for establishing risk factors for breast cancer. The ability to obtain full participation of African-American women is key to the success of any study. As reported for the CBCS, contact and cooperation rates were lower among African- American women than among white women. 16 One way to improve recruitment rates for breast cancer research studies is to use the advocacy community as a partner. Future studies should acknowledge the heterogeneity of African-American women with a focus on ethnic background and cultural history and emphasize the differences between the social and biologic contexts of breast cancer. Future studies should also incorporate questions on ethnic origin of parents and grandparents. Related to this issue is the need to separate race from social class. More creative methods for measuring socioeconomic status, beyond simply measuring education and income, are needed. Use of census-derived local area measures (i.e., census tract), that rely on summary measures of income and education of area residents, may misrepresent socioeconomic status among African Americans. Standardizing research questions in studies of African-American women will be difficult because the

7 228 CANCER Supplement January 1, 2003 / Volume 97 / Number 1 population is not homogeneous. It will be critical to tailor research approaches to the populations being studied. If researchers can achieve standardization in data collection methods across studies, comparison of results and pooling of data will be possible. Partnerships with community-based organizations and community leaders, as well as with breast cancer survivors and advocates, should be key elements of ongoing and new research efforts. Developing innovative methods by which these individuals and organizations are involved in the planning process can improve the success of a study. Nonprofit and community-based organizations have a vital role in collecting data and recruiting patients because underserved populations often mistrust the larger or unfamiliar institutions. Partnering can be an effective strategy for the education of African-American leaders about breast cancer risk in their community and the possible approaches for risk reduction. In summary, the workshop set the following priorities for future research efforts: 1. Focus on African-American women 2. Acknowledge the heterogeneity of African-American women 3. Emphasize differences between the social and biologic contexts of breast cancer among African- American women 4. Include measures of cultural beliefs, cultural knowledge, a woman s sense of fatalism, and level of perceived discrimination in epidemiologic studies 5. Develop an approach to initiate future studies that uses the resources of the African-American community and advocacy groups so that the study population represents all aspects of African-American heritage, socioeconomic groups, and cultural beliefs REFERENCES 1. Tavani A, Braga C, La Vecchia C, Negri E, Russo A, Franceschi S. Attributable risks for breast cancer in Italy: education, family history and reproductive and hormonal factors. Int J Cancer. 1997;70: Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN. Proportion of breast cancer cases in the United States explained by well-established risk factors. J Natl Cancer Inst. 1995;87: Bruzzi P, Green SB, Byar DP, Brinton LA, Schairer C. Estimating the population attributable risk for multiple risk factors using case control data. Am J Epidemiol. 1985;122: Kelsey JL, Bernstein L. Epidemiology and prevention of breast cancer. Annu Rev Public Health. 1996;17: Henderson BE, Ross RK, Bernstein L. Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1988;48: Henderson BE, Pike MC, Bernstein L, Ross RK. Breast cancer. In: Schottenfeld D, Fraumeni J Jr. editors. Cancer epidemiology and prevention, 2nd ed. New York: W.B. Saunders Co., 1996: Ross RK, Paganini-Hill A, Wan PC, Pike MC. Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J Natl Cancer Inst. 2000;92: Bernstein L, Henderson BE, Hanisch R, Sullivan-Halley J, Ross RK. Physical exercise and reduced risk of breast cancer in young women. J Natl Cancer Inst. 1994;86: Thune I, Brenn T, Lund E, Gaard M. Physical activity and the risk of breast cancer. N Engl J Med. 1997;336: Rockhill B, Willett WC, Hunter DJ, Manson JE, Hankinson SE, Colditz BA. A prospective study of recreational physical activity and breast cancer risk. Arch Intern Med. 1999;159: Friedenreich C, Bryant HE, Courneya KS. Case-control study of lifetime physical activity and breast cancer risk. Am J Epidemiol. 2001;154: Moormeier J. Breast cancer in black women. Ann Intern Med. 1996;124: Palmer JR, Rosenberg L, Rao RS, et al. Oral contraceptive use and breast cancer risk among African-American women. Cancer Causes Control. 1995;6: Palmer JR, Rosenberg L, Harlap S, et al. Adult height and risk of breast cancer among US black women. Am J Epidemiol. 1995;141: Brinton LA, Benichou J, Gammon MD, Brogan DR, Coates R, Schoenberg JB. Ethnicity and variation in breast cancer incidence. Int J Cancer. 1997;73: Moorman PG, Newman B, Millikan RC, Tse CK, Sandler DP. Participation rates in a case-control study: the impact of age, race, and race of interviewer. Ann Epidemiol. 1999;9: Furberg H, Newman B, Moorman P, Millikan R. Lactation and breast cancer risk. Int J Epidemiol. 1999;28: Hall IJ, Newman B, Millikan RC, Moorman PG. Body size and breast cancer risk in black women and white women. The Carolina Breast Cancer Study. Am J Epidemiol. 2000; 151: Moorman PG, Millikan RC, Newman B. Oral contraceptives and breast cancer among African-American women and white women. J Natl Med Assoc. 2001;93: Marcus P, Baird DD, Millikan R, Moorman P, Qaqish B, Newman B. Adolescent reproductive events and subsequent breast cancer risk. Am J Public Health. 1999;89: Marchbanks PA, McDonald JA, Wilson HG, et al. The NICHD Women s Contraceptive and Reproductive Experiences Study: methods and operational results. Ann Epidemiol. 2002;12: Rosenberg L, Adams-Campbell L, Palmer JR. The Black Women s Health Study a follow-up study for causes and prevention of illness. J Am Med Women Assoc. 1995;50: Kolonel LN, Henderson BE, Hankin JH, et al. A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am J Epidemiol. 2000;151: Henderson BE, Pike MC, Casagrande JT. Breast-cancer and the oestrogen window hypothesis. Lancet. 1981;2: Apter D, Vihko R. Early menarche, a risk factor for breast cancer, indicates early onset of ovulatory cycles. J Clin Endocrinol Metab. 1983;57:82 86.

8 Ethnic Variation in Risk Factors/Bernstein et al Vihko R, Apter DJ. Endocrine characteristics of adolescent menstrual cycles: impact of early menarche. Steroid Biochem. 1984;20: Apter D, Reinila M, Vihko R. Some endocrine characteristics of early menarche, a risk factor for breast cancer, are preserved into adulthood. Int J Cancer. 1989;44: Burke GL, Savage PJ, Manolio TA, et al. Correlates of obesity in young black and white women: the CARDIA study. Am J Public Health. 1992;82: Wattigney WA, Srinivasan SR, Chen W, Greenlund KJ, Berenson GS. Secular trend of earlier onset of menarche with increasing obesity in black and white girls: the Bogalusa Heart Study. Ethnicity Dis. 1999;9: Harlow SBD, Campbell B, Lin X, Raz J. Ethnic differences in the length of the menstrual cycle during the postmenarcheal period. Am J Epidemiol. 1997;156: MacMahon B, Cole P, Lin MT, et al. Age at first birth and cancer or the breast. A summary of an international study. Bull WHO. 1970;43: Yuan JM, Yu MC, Ross RK, Gao YT, Henderson BE. Risk factors for breast cancer in Chinese women in Shanghai. Cancer Res. 1988;48: Bruzzi P, Negri E, La Vecchia C, et al. Short term increase in risk of breast cancer after full term pregnancy. BM. 1988; 297: Wingo PA, Newsome K, Marks JS, Calle EE, Parker SL. The risk of breast cancer following spontaneous and induced abortion. Cancer Causes Control. 1997;8: Ventura SJ, Mosher WD, Curtin SC, Abma JC, Henshaw S. Highlights of trends in pregnancies and pregnancy rates by outcome: estimates for the United States, National vital statistics reports, vol 47, no. 29. Hyattsville, MD: National Center for Health Statistics, Ventura SJ, Mosher WD, Curtin SC, Abma JC, Henshaw S. Highlights of trends in pregnancies and pregnancy rates by outcome: estimates for the United States, National vital statistics reports, vol 21, no. 56. Hyattsville, MD: National Center for Health Statistics, Enger SM, Ross RK, Henderson BE, Bernstein L. Breast feeding history, pregnancy experience and risk of breast cancer. Br J Cancer. 1997;76: Newcomb PA, Storer BE, Longnecker MP, et al. Lactation and a reduced risk of premenopausal breast cancer. Engl J Med. 1994;330: Enger SM, Ross RK, Paganini-Hill A, Bernstein L. Breastfeeding experience and breast cancer risk among postmenopausal women. Cancer Epidemiol Biomark Prev. 1998;7: National Center for Health Statistics. Health, United States Hyattsville, MD: National Center for Health Statistics, 1995: Abma J, Chandra A, Mosher W, Peterson L, Piccinino L. Fertility, family planning, and women s health: new data from the 1995 National Survey of Family Growth. National Center for Health Statistics. Vital Health Statistics, vol 23, no. 19. Hyattsville, MD: National Center for Health Statistics, Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives. Lancet. 1996; 347: Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: further results. Contraception. 1996;54:1S 31S. 44. Dawson DA. Trends in use of oral contraceptives: data from the 1987 National Health Interview Survey. Fam Plan Perspect. 1990;22: Pike MC, Bernstein L, Spicer DV. The relationship of exogenous hormones to breast cancer risk. In: Niederhuber J. Current therapy in oncology. St. Louis: Mosby, 1993: Magnusson C, Baron JA, Correia N, Bergstrom R, Adami HO, Persson I. Breast cancer risk following long term oestrogenand oestrogen-progestin-replacement therapy. Int J Cancer. 1999;81: Shairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA. 2000;283; Marsh JVR, Brett KM, Miller LC. Racial differences in hormone replacement therapy prescriptions. Obstet Gynecol. 1999;93: Brown AF, Perez-Stable EJ, Whitaker EE, et al. Ethnic differences in hormone replacement prescribing patterns. J Gen Intern Med. 1999;14: Handa VL, Landerman R, Hanlon JT, Harris T, Cohen HJ. Do older women use estrogen replacement? Data from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). J Am Geriatr Soc. 1996;44: Hunter DJ, Willett WC. Diet, body size, and breast cancer. Epidemiol Rev. 1993;15: Huang Z, Hankinson SE, Colditz GA, et al. Dual effects of weight and weight gain on breast cancer risk. JAMA. 1997; 278: van den Brandt PA, Spiegelman D, Yaun SS, et al. Pooled analysis of prospective cohort studies on height, weight and breast cancer risk. Am J Epidemiol. 2000;152: Siiteri PK, MacDonald PC. Role of extraglandular estrogen in human endocrinology. In: Geiger SR, Astwood EB, Greep RO, editors. Handbook of physiology. Washington, DC: American Physiological Society, 1973: Pike MC. Reducing cancer risk in women through lifestylemediated changes in hormone levels. Cancer Detect Prev. 1990;14: National Center for Health Statistics. Prevalence of BMI, overwieght and obesity: United States, Hyattsville, MD: National Center for Health Statistics, [URL: Table A3; accessed 19-Feb-02]. 57. National Center for Health Statistics. Height in inches for females 20 years and over, number of examined persons, standard error of the mean, and selected percentiles by ethnicity/race, age: United States, Hyattsville, MD: National Center for Health Statistics, [URL: Table 1; accessed 19-Feb-02]. 58. Bernstein L, Ross RK, Henderson BE. Prospects for the primary prevention of breast cancer. Am J Epidemiol. 1992;135: Gordon-Larsen P, McMurray RG, Popkin BM. Adolescent physical activity and inactivity vary by ethnicity: the National Longitudinal Study of Adolescent Health. J Pediatr. 1999;135: Smith-Warner SA, Spiegelman D, Yaun SS, et al. Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA. 1998;279: Schoenborn CA, Adams PF. Alcohol use among adults: United States, Advance data from vital and health statistics, no Hyattsville, MD: National Center for Health Statistics, 2001.