Caffeinated coffee, decaffeinated coffee and endometrial cancer risk: a prospective cohort study among US postmenopausal women

There is plausible biological evidence as well as epidemiologic evidence to suggest coffee consumption may lower endometrial cancer risk. We evaluated the associations between self-reported total coffee, caffeinated coffee and decaffeinated coffee, and endometrial cancer risk using the Women's Health Initiative Observational Study Research Materials obtained from the National Heart, Lung, and Blood Institute Biological Specimen and Data Repository Coordinating Center. Our primary analyses included 45,696 women and 427 incident endometrial cancer cases, diagnosed over a total of 342,927 person-years of follow-up. We used Cox-proportional hazard models to evaluate coffee consumption and endometrial cancer risk. Overall, we did not find an association between coffee consumption and endometrial cancer risk. Compared to non-daily drinkers (none or <1 cup/day), the multivariable adjusted hazard ratios for women who drank ≥4 cups/day were 0.86 (95% confidence interval (CI) 0.63, 1.18) for total coffee, 0.89 (95% CI 0.63, 1.27) for caffeinated coffee, and 0.51 (95% CI 0.25, 1.03) for decaf coffee. In subgroup analyses by body mass index (BMI) there were no associations among normal-weight and overweight women for total coffee and caffeinated coffee. However among obese women, compared to the referent group (none or <1 cup/day), the hazard ratios for women who drank ≥2 cups/day were: 0.72 (95% CI 0.50, 1.04) for total coffee and 0.66 (95% CI 0.45, 0.97) for caffeinated coffee. Hazard ratios for women who drank ≥2 cups/day for decaffeinated coffee drinkers were 0.67 (0.43-1.06), 0.93 (0.55-1.58) and 0.80 (0.49-1.30) for normal, overweight and obese women, respectively. Our study suggests that caffeinated coffee consumption may be associated with lower endometrial cancer risk among obese postmenopausal women, but the association with decaffeinated coffee remains unclear.     

Empirically derived dietary patterns and risk of postmenopausal breast cancer in a large prospective cohort study

BACKGROUND: Inconsistent associations have been reported between diet and breast cancer. OBJECTIVE: We prospectively examined the association between dietary patterns and postmenopausal breast cancer risk in a US-wide cohort study. DESIGN: Data were analyzed from 40 559 women who completed a self-administered 61-item Block food-frequency questionnaire in the Breast Cancer Detection Demonstration Project, 1987-1998; 1868 of those women developed breast cancer. Dietary patterns were defined by using principal components factor analysis. Cox proportional hazard regression was used to assess breast cancer risk. RESULTS: Three major dietary patterns emerged: vegetable-fish/poultry-fruit, beef/pork-starch, and traditional southern. The vegetable-fish/poultry-fruit pattern was associated with higher education than were the other patterns, but was similar in nutrient intake to the traditional southern pattern. After adjustment for confounders, there was no significant association between the vegetable-fish/poultry-fruit and beef/pork-starch patterns and breast cancer. The traditional southern pattern, however, was associated with a nonsignificantly reduced breast cancer risk among all cases (in situ and invasive) that was significant for invasive breast cancer (relative hazard = 0.78; 95% CI = 0.65, 0.95; P for trend = 0.003). This diet was also associated with a reduced risk in women without a family history of breast cancer (P = 0.05), who were underweight or normal weight [body mass index (in kg/m(2)) < 25; P = 0.02], or who had tumors positive for estrogen receptor (P = 0.01) or progesterone receptor (P = 0.003). Foods in the traditional southern pattern associated with reduced breast cancer risk were legumes, low mayonnaise-salad dressing intake, and possibly cabbage. CONCLUSIONS: The traditional southern diet or its components are associated with a reduced risk of invasive breast cancer in postmenopausal women.     

Lactation and risk of breast cancer in a cohort of US women

The relation between lactation and risk of breast cancer was examined in a cohort of 89,413 parous female US registered nurses aged 30-55 years and free from cancer in 1976 who provided information on total duration of lactation in 1986. Between 1976 and 1986, 1,262 cases of breast cancer occurred during 785,958 person-years of follow-up. There was no independent association between lactation and the risk of breast cancer. After adjustment for age and parity, compared with women who had never lactated, the relative risks (and 95% confidence intervals (CI] were 0.95 (95% CI 0.84-1.08) for women with less than 7 months of lactation, 0.87 (95% CI 0.71-1.08) for 7-11 months, 0.94 (95% CI 0.77-1.14) for 12-23 months, and 0.98 (95% CI 0.76-1.28) for greater than or equal to 24 months (test for trend: z = -0.80, p = 0.42). The association did not differ by age or menopausal status. These results do not confirm reports that relatively short durations of lactation reduce the risk of breast cancer among younger women.     

A prospective study of multivitamin supplement use and risk of breast cancer

The authors evaluated the association between multivitamin supplement use and breast cancer risk in a completed trial. At baseline (1992-1995), 37,920 US women aged > or =45 years and free of cancer provided detailed information on multivitamin supplement use. During an average of 10 years of follow-up, 1,171 cases of invasive breast cancer were documented. Multivitamin use was not significantly associated with overall risk of breast cancer. Compared with the risk for never users, the multivariable relative risks were 0.97 (95% confidence interval: 0.81, 1.16) for past users and 0.99 (95% confidence interval: 0.82, 1.19) for current users. Current multivitamin use for > or =20 years or > or =6 times/week was also not significantly associated with risk. Multivitamin use was nonsignificantly inversely associated with risk of breast cancer among women consuming > or =10 g/day of alcohol and with risk of estrogen receptor negative-progesterone receptor negative breast cancer. Multivitamin use was nonsignificantly associated with a reduced risk of developing < or =2-cm breast tumors but an increased risk of >2-cm tumors. The authors' data indicate no overall association between multivitamin use and breast cancer risk but suggest that multivitamin use might reduce risk for women consuming alcohol or decrease risk of estrogen receptor negative-progesterone receptor negative breast cancer.     

Risk factors for fatal breast cancer in African-American women and White women in a large US prospective cohort

African-American women have a higher lifetime risk of fatal breast cancer than do White women. Recent studies suggest that breast cancer risk factors may vary by race. The authors examined risk factors for fatal breast cancer in postmenopausal African-American women and White women in a large US prospective cohort. In 1982, 21,143 African-American women and 409,093 White women in the Cancer Prevention Study II completed a questionnaire on reproductive, medical, anthropometric, and demographic factors. During a 20-year follow-up, 257 deaths from breast cancer occurred among African-American women and 4,265 among Whites. Cox proportional hazards modeling was used to calculate multivariate-adjusted rate ratios, stratified by race. Higher body mass index, taller height, and physical inactivity were associated with increased breast cancer mortality rates in both groups. A college education was associated with higher mortality from breast cancer only in Africa-American women (hazard ratio = 1.62, 95% confidence interval: 1.13, 2.30; p(trend) = 0.01, vs. less than a high school education). Most other risk factors were associated with breast cancer rates similarly in both groups. With few exceptions, established breast cancer risk factors were similarly associated with risk of death from breast cancer among African-American women and White women.     

Interaction of waist/hip ratio and family history on the risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women

The authors previously reported an interaction of waist/hip ratio and family history on the risk of breast cancer in the Iowa Women's Health Study. Here they reexamine this association based on 9 additional years of follow-up, stratifying on tumor receptors for estrogen and progesterone. Data on risk factors and family history of breast cancer were ascertained in 1986. The occurrences of breast cancer and estrogen receptor/progesterone receptor were determined through the Iowa Surveillance, Epidemiology, and End Results' registry. Rate ratios were elevated with increasing weight and body mass index and decreasing body mass index at age 18 years, but they did not vary by family history. There was no association with height, waist circumference, or waist/hip ratio. A linear trend of increasing risk with increasing waist/hip ratio was observed among family history-positive women (p = 0.06) but not among family history-negative women (p = 0.87). This apparent interaction (p = 0.09) was examined by estrogen receptor or progesterone receptor status. When stratified on family history and estrogen receptor, no clear patterns were evident. In contrast, family history-positive women in the upper quintile of the waist/hip ratio were at 2.2-fold greater risk of progesterone receptor-negative tumors compared with those in the lowest quintile (95% confidence interval: 0.9, 5.8). Thus, the previously reported interaction between family history and waist/hip ratio is still (weakly) evident and appears to reflect risk for progesterone receptor-negative tumors.     

Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women.

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels: <10th, 11th-30th, 31st-50th, and >50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95% confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile: RR = 1.21 (95% CI = 0.91--1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (>50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95% CI = 0.78--1.49) among nondrinkers, 1.33 (95% CI = 0.86--2.05) among drinkers of < or = 4 gm per day, and 1.59 (95% CI = 1.05--2.41) among drinkers of > 4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.     

Lifetime alcohol consumption and postmenopausal breast cancer rate in Denmark: a prospective cohort study

Alcohol intake may be one of the few modifiable risk factors for breast cancer. In a prospective cohort of 29,875 women with 423 cases of breast cancer during 1993-2000, we examined the relationship between postmenopausal breast cancer incidence rate and alcohol consumption in different life periods. When alcohol intake during four age ranges, twenties, thirties, forties and fifties was evaluated, only the intake in the fifties increased the risk of breast cancer [rate ratio (RR)=1.12 (95% CI: 1.05-1.19)] per 10 g/d increase in alcohol intake. After adjustment for intake at study entry, this association was no longer present [RR=1.01 (95% CI: 0.91-1.13)]. The cumulative lifetime alcohol intake, adjusted for recent intake, showed no association with postmenopausal breast cancer risk. Recent alcohol intake, adjusted for the alcohol intake in the other life time periods, showed a significant association of RR=1.09 (95% CI: 1.00-1.18) per 10 g/d. There was no indication of a higher risk among women with early drinking start, nor did women who started to drink before their first birth have a higher risk than women who started to drink later in life. Our results suggest that baseline intake of alcohol is a more important determinant of postmenopausal breast cancer risk than earlier lifetime exposure.     

Bone mineral density and breast cancer risk in postmenopausal women

Two recent studies have shown a woman's bone mineral density (BMD) (a composite measure of exposure to many different factors throughout one's lifetime) predicts breast cancer. In a prospective cohort study, we examined whether hip BMD was associated with breast cancer risk among 8203 postmenopausal women. During an average follow-up of 3.7 years, 131 incident breast cancer cases (102 invasive) were identified. Cox proportional hazards models were used to obtain estimates of the relative risk of breast cancer. Our results demonstrate an increase in breast cancer risk among women with higher BMD. Independent of age, geographic area, and body mass index, relative to the lowest BMD quartile the risk of breast cancer (95% confidence interval) by increasing quartile was 1.9 (1.1, 3.2), 1.5 (0.8, 2.6), and 1.5 (0.8, 2.7), respectively. An examination of other factors important in determining BMD may help explain the positive association between BMD and breast cancer.     

Dietary fat,calories, and the risk of breast cancer in postmenopausal women: a prospective population-based study.

We tested the hypothesis that a high-fat diet increases the risk of breast cancer in a population-based study of 590 women aged 40-79 years who were without known breast cancer when they provided a quantitative 24-hour diet recall. Fifteen postmenopausal women were diagnosed with incident breast cancer during the next 15 years (approximately 7600 person-years of follow-up). These women had significantly higher age-adjusted intake of all fats (monounsaturated, polyunsaturated, and saturated), and oleic, linoleic, and linolenic acids, with a stepwise increase in risk across tertiles of intake. Fat intake was associated with total calories, protein, and carbohydrates, and women with incident breast cancer consumed more calories, protein, and carbohydrates than did other subjects. When each nutrient variable (calories, fats, protein, and carbohydrates) was adjusted for age, body mass index, age at menopause, parity, and alcohol consumption, the strongest risks for incident breast cancer were associated with total calories (relative risk per standard deviation = 2.72, 95% confidence interval = 1.51-4.89, p = 0.002) and total fats (relative risk per standard deviation = 2.01, 95% confidence interval = 1.19-3.41, p = 0.01). Fat composition of the diet, expressed either as percent of energy or as fat intake adjusted for calories by regression analysis, was not significantly associated with risk of breast cancer. These results support the hypothesis that total calorie consumption, as well as dietary fat consumption, is a risk factor for breast cancer in postmenopausal women, and parallel observations in animal models.     

Occupation and breast cancer risk among Shanghai women in a population-based cohort study

INTRODUCTION: A total of 74,942 female subjects were recruited in a population-based cohort study in Shanghai, China between 1997 and 2000. We examined the relationship between occupation and breast cancer risk. METHODS: Cases were 586 women previously diagnosed with breast cancer at baseline and 438 women newly diagnosed with breast cancer during follow-up through December 2004. Eight controls were randomly selected for each case from cancer-free cohort members and frequency-matched to the cases by year of birth and age at diagnosis. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk associated with occupations, adjusting for established breast cancer risk factors. RESULTS: In the prevalent breast cancer data analysis, increased risks of breast cancer were associated with technicians in engineering/agriculture/forestry (OR = 1.6, CI: 1.0-2.4), teaching personnel (OR = 1.5, CI:1.1-2.0), tailoring/sewing workers (OR = 1.6, CI:1.0-2.7), and examiners/measurers/testers (OR = 1.5, CI:1.1-2.1) among those who started the jobs at least 20 years ago. Among incident breast cancer cases, significantly increased risks were associated with medical/health care workers (OR = 1.4, CI:1.0-2.0), administrative clerical workers (OR = 1.5, CI:1.0-2.4), postal/telecommunication workers (OR = 2.2, CI:1.0-5.5), and odd-job workers (OR = 1.7, CI:1.1-2.8) among those who started the jobs at least 20 years ago. The excess risks were found in both prevalent and incident cases for postal/telecommunication workers and purchasing/marketing personnel, although ORs reached only marginal significance. CONCLUSIONS: This study suggests that white-collar professionals and several production occupations may be associated with an increased risk of breast cancer.     

Left-handedness in relation to breast cancer risk in postmenopausal women

Breast cancer risk may be influenced by intrauterine exposure to steroid hormones. We evaluated left-handedness, a marker of intrauterine hormone exposure, in relation to breast cancer risk in our population-based, case-control study. Case women 50-79 years of age with a first diagnosis of invasive breast cancer were ascertained through statewide cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control women were identified in each state through lists of licensed drivers (for ages 50-64) and Medicare beneficiaries (for ages 65-79), and selected at random to correspond with the age distribution of case women. Exposure information, including handedness, was obtained through a telephone interview. Our results indicated a modest association between left-handedness and breast cancer risk (OR = 1.42; 95% CI = 1.10-1.83). The effect of left-handedness was modified by age; we observed the greatest risk ratio in the oldest age group. Left-handedness was not associated with breast tumor laterality. Our results are consistent with the hypothesis that intrauterine hormone exposures play a role in the development of breast cancer.     

Diabetes and risk of prostate cancer in a prospective cohort of US men

One previous study has suggested that diabetes may decrease risk of prostate cancer but only several years after diagnosis of diabetes. The authors examined the role of timing of diabetes diagnosis in relation to risk of prostate cancer among men in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a mailed questionnaire including information on diabetes at enrollment in 1992 and at follow-up questionnaires in 1997 and 1999. Historical information on diabetes was also available from a previous study in 1982. The authors documented 5,318 cases of incident prostate cancer through August 31, 2001, among 72,670 men. Results from Cox proportional hazards models showed that diabetes was associated with a lower incidence of prostate cancer (rate ratio (RR) = 0.67, 95% confidence interval (CI): 0.60, 0.75). This association differed significantly by time since diagnosis of diabetes (p < 0.0002); risk of prostate cancer was slightly increased during the first 3 years after diagnosis of diabetes (RR = 1.23, 95% CI: 0.92, 1.65) but was reduced among men diagnosed 4 or more years before (RR = 0.63, 95% CI: 0.56, 0.71). Study results are consistent with the hypothesis that diabetes is associated with reduced risk of prostate cancer but only several years after diagnosis of diabetes.     

Anthropometric indicators of breast cancer risk in postmenopausal women in Hawaii

As part of a case-control study of breast cancer in Hawaii, self-reported data on height, weight at various ages, breast size, shoe size, and triceps skinfold thickness were collected from 138 Japanese postmenopausal cases, 134 Caucasian postmenopausal cases, 154 Japanese neighborhood controls, and 142 Caucasian neighborhood controls. In a multiple covariance analysis, cases of both ethnic groups were slightly heavier (at all ages) and more obese (based on a weight-corrected-for-height index) than were controls, although none of the differences was statistically significant. Among the Japanese only, cases were also taller, had a greater body surface area (computed from the height and weight data), and had a larger shoe size than did the controls. The latter finding was statistically significant (p less than 0.05). Odds ratios were computed by multiple logistic regression analysis and revealed no additional relationships; however, there were suggested dose-response gradients for height, weight at age 20, and body surface area in the Japanese women and for breast size in the Caucasian women. A further analysis of risks based on changes in relative body weight between young adult life (age 20) and current age was also negative. Overall, these findings offer only weak support for an association between weight or obesity and breast cancer risk and suggest that anthropometric indices are at best very indirect indicators of true etiologic factors for breast cancer.     

Carbohydrate intake, glycemic index, glycemic load, and risk of postmenopausal breast cancer in a prospective study of French women

BACKGROUND: Diets high in carbohydrates may result in chronically elevated insulin concentrations and may affect breast cancer risk by stimulation of insulin receptors or through insulin-like growth factor I (IGF-I)-mediated mitogenesis. Insulin response to carbohydrate intake is increased in insulin-resistant states such as obesity. OBJECTIVE: We sought to evaluate carbohydrate intake, glycemic index (GI), and glycemic load (GL) and subsequent overall and hormone-receptor-defined breast cancer risk among postmenopausal women. DESIGN: A prospective cohort analysis of dietary carbohydrate and fiber intakes was conducted among 62 739 postmenopausal women from the E3N French study who had completed a validated dietary history questionnaire in 1993. During a 9-y period, 1812 cases of pathology-confirmed breast cancer were documented through follow-up questionnaires. Nutrients were categorized into quartiles and energy-adjusted with the regression-residual method. Cox model-derived relative risks (RRs) were adjusted for known determinants in breast cancer. RESULTS: Dietary carbohydrate and fiber intakes were not associated with overall breast cancer risk. Among overweight women, we observed an association between GI and breast cancer (RR(Q1-Q4): 1.35; 95% CI: 1.00, 1.82; P for trend = 0.04). For women in the highest category of waist circumference, the RR(Q1-Q4) was 1.28 (95% CI: 0.98, 1.67; P for trend = 0.10) for carbohydrates, 1.35 (95% CI: 1.04, 1.75; P for trend = 0.01) for GI, and 1.37 (95% CI: 1.05, 1.77; P for trend = 0.003) for GL. We also observed a direct association between carbohydrate intake, GL, and estrogen receptor-negative breast cancer risk. CONCLUSIONS: Rapidly absorbed carbohydrates are associated with postmenopausal breast cancer risk among overweight women and women with large waist circumference. Carbohydrate intake may also be associated with estrogen receptor-negative breast cancer.     

Fat and protein intake and subsequent breast cancer risk in postmenopausal women

The role of diet in the etiology of breast cancer has been extensively evaluated. Case-control studies generally support an association, while cohort studies have produced inconsistent results. This study, carried out on the ORDET cohort, is the first prospective Italian study to address the relation between diet and breast cancer. Female volunteers were recruited from 1987 to 1992 among residents of Varese Province, Northern Italy, an area covered by a cancer registry. A semiquantitative self-administered food questionnaire was completed by participants. After a mean 5.5 yr of follow-up, 56 cases of invasive breast cancer were identified among the 3,367 postmenopausal members; 214 controls were randomly chosen from the cohort, matched to cases for age, menopausal status at recruitment, recruitment center, and recruitment period. The adjusted odds ratios for the highest tertile of intake vs. the lowest were 3.47 [95% confidence interval (CI) = 1.43-8.44] for total fat, 3.78 (95% CI = 0.95-15.0) for animal protein, and 0.42 (95% CI = 0.18-0.95) for total carbohydrates. These findings indicate a significant positive association between total fat and animal protein and risk of breast cancer and an inverse association with carbohydrates and constitute new evidence for a role of diet in the etiology of breast cancer.     

Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16alpha-hydroxyestrone ratio in premenopausal and postmenopausal women

Experimental and clinical evidence suggests that 16alpha-hydroxylated estrogen metabolites, biologically strong estrogens, are associated with breast cancer risk, while 2-hydroxylated metabolites, with lower estrogenic activity, are weakly related to this disease. This study analyzes the association of breast cancer risk with estrogen metabolism, expressed as the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone, in a prospective nested case-control study. Between 1987 and 1992, 10,786 women (ages 35-69 years) were recruited to a prospective study on breast cancer in Italy, the "Hormones and Diet in the Etiology of Breast Cancer" (ORDET) study. Women with a history of cancer and women on hormone therapy were excluded at baseline. At recruitment, overnight urine was collected from all participants and stored at -80 degrees C. After an average of 5.5 years of follow-up, 144 breast cancer cases and four matched controls for each case were identified among the participants of the cohort. Among premenopausal women, a higher ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone at baseline was associated with a reduced risk of breast cancer: women in the highest quintile of the ratio had an adjusted odds ratio (OR) for breast cancer of 0.58 [95% confidence interval (CI) = 0.25-1.34]. The corresponding adjusted OR in postmenopausal women was 1.29 (95% CI = 0.53-3.10). Results of this prospective study support the hypothesis that the estrogen metabolism pathway favoring 2-hydroxylation over 16alpha-hydroxylation is associated with a reduced risk of invasive breast cancer risk in premenopausal women.     

Stressful life events and risk of breast cancer in 10,808 women: a cohort study

The authors prospectively investigated the relation between stressful life events and risk of breast cancer among 10,808 women from the Finnish Twin Cohort. Life events and breast cancer risk factors were assessed by self-administered questionnaire in 1981. A national modification of a standardized life event inventory was used, examining accumulation of life events and individual life events and placing emphasis on the 5 years preceding completion of the questionnaire. Through record linkage with the Finnish Cancer Registry, 180 incident cases of breast cancer were identified in the cohort between 1982 and 1996. The multivariable adjusted hazard ratio for breast cancer per one-event increase in the total number of life events was 1.07 (95% confidence interval (CI): 1.00, 1.15). This risk estimate rose to 1.35 (95% CI: 1.09, 1.67) when only major life events were taken into account. Independently of total life events, divorce/separation (hazard ratio (HR) = 2.26, 95% CI: 1.25, 4.07), death of a husband (HR = 2.00, 95% CI: 1.03, 3.88), and death of a close relative or friend (HR = 1.36, 95% CI: 1.00, 1.86) were all associated with increased risk of breast cancer. The findings suggest a role for life events in breast cancer etiology through hormonal or other mechanisms.     

A population-based cohort study of HRT use and breast cancer in Korea

The incidence of breast cancer has recently been ranked first in Korea. This is a population-based cohort study that aims to evaluate the risk of breast cancer from the use of hormone replacement therapy (HRT). A total of 9579 participants were observed between January 1998 and June 2004; 6108 women who took HRT constituted the HRT group, and 3471 women who did not take HRT constituted the non-HRT group. Using the database from the Korea Central Cancer Registry, the authors examined the incidence of breast cancer from HRT. A total of 26 cases of breast cancer developed in the HRT group as compared with the 13 cases in the non-HRT group, during the follow-up period. The relative risk of developing breast cancer in the HRT group was 1.16 times higher than in the non-HRT group, with a population attributable risk of 29.9%. The risk of breast cancer in the HRT group increased when the risk factors were adjusted in the model.