Non-steroidal anti-inflammatory drug use, hormone receptor status, and breast cancer-specific mortality in the Carolina Breast Cancer Study.

Epidemiologic studies report a protective association between non-steroidal anti-inflammatory drug (NSAID) use and hormone receptor-positive breast cancer risk, a finding consistent with NSAID-mediated suppression of aromatase-driven estrogen biosynthesis. However, the association between NSAID use and breast cancer-specific mortality is uncertain and it is unknown whether this relationship differs by hormone receptor status. This study comprised 935 invasive breast cancer cases, of which 490 were estrogen receptor (ER)-positive, enrolled between 1996 and 2001 in the Carolina Breast Cancer Study. Self-reported NSAID use in the decade prior to diagnosis was categorized by duration and regularity of use. Differences in tumor size, stage, node, and receptor status by NSAID use were examined using Chi-square tests. Associations between NSAID use and breast cancer-specific mortality were examined using age- and race-adjusted Cox proportional hazards analysis. Tumor characteristics did not differ by NSAID use. Increased duration and regularity of NSAID use was associated with reduced breast cancer-specific mortality in women with ER-positive tumors (long-term regular use (≥8 days/month for ≥ 3 years) versus no use; hazard ratio (HR) 0.48; 95 % confidence interval (CI) 0.23-0.98), with a statistically significant trend with increasing duration and regularity (p-trend = 0.036). There was no association for ER-negative cases (HR 1.19; 95 %CI 0.50-2.81; p-trend = 0.891). Long-term, regular NSAID use in the decade prior to breast cancer diagnosis was associated with reduced breast cancer-specific mortality in ER-positive cases. If confirmed, these findings support the hypothesis that potential chemopreventive properties of NSAIDs are mediated, at least in part, through suppression of estrogen biosynthesis.

Metformin does not affect risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database.

BACKGROUND: While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP). METHODS: We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses. RESULTS: Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1-22.5). CONCLUSIONS: Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

Oral contraceptives and breast cancer among African-american women and white women.

The higher incidence of breast cancer among African-American women younger than 50 as compared to white women points to the need to examine exposures that are common among younger women, including exposure to oral contraceptives (OC). We examined patterns of OC use and their associations with breast cancer in a population-based, case-control study conducted in North Carolina between 1993 and 1996. The study population was comprised of 858 cases and 789 controls, of whom 40% were African-American women. There was little evidence that breast cancer was associated with OC use among older women (age >50) of either race, most of whom discontinued use in the distant past. Among younger women, there was a modest, but nonsignificant, increase in risk associated with ever use of OCs for both African-American and white women. There was a trend of increasing risks with more recent use among African-American women, whereas no such trend was apparent for white women. Overall, we found more substantial age differences than race differences in patterns of OC use and the risk of breast cancer associated with their use. The similarity of the associations between African-American and white women suggest that racial differences in breast cancer incidence are not likely to be attributable to OC use.

Prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma.

BACKGROUND: A recent report suggested that the number of lymph nodes examined was a strong predictor of survival in patients with lymph node-negative breast carcinoma. Among women who had >or= 20 lymph nodes examined, the risk of dying from breast carcinoma within 5 years was increased nearly 4-fold compared with women who had fewer lymph nodes examined. Because these findings were based on a relatively small cohort of patients, corroborative studies with larger patient populations were needed. METHODS: The authors studied the relation between the number of lymph nodes examined and breast carcinoma survival among 911 women with lymph node-negative breast carcinoma with a median length of follow-up of 84 months. The association between other prognostic indicators and survival and the number of lymph nodes examined also was investigated. RESULTS: The number of lymph nodes examined was not found to be associated with either 5-year or long-term survival. The proportion of women dying from breast carcinoma was the same (8%) in both groups (those patients with >or= 20 lymph nodes examined vs. those in whom < 20 lymph nodes were examined) and the hazard ratio was 0.98 (95% confidence interval, 0.58-1.64). CONCLUSIONS: In this larger study population, the authors failed to confirm the findings of an earlier investigation in which having a larger number of lymph nodes examined was associated with poorer survival. This finding suggests that it is unlikely the number of lymph nodes examined is an important prognostic indicator in patients with lymph node-negative breast carcinoma.

Vitamin supplement use and breast cancer in a North Carolina population.

OBJECTIVE: Laboratory data suggest that several different vitamins may inhibit the growth of mammary cancers, however epidemiologic data on the relationship between vitamin supplement use and breast cancer are inconsistent. We examined the association between self-reported vitamin supplement use and breast cancer among black women and white women. DESIGN AND SETTING: The data came from a population-based, case-control study conducted in North Carolina between 1993 and 1996. Logistic regression models were used to calculate adjusted odds ratios (ORs) for breast cancer associated with the use of multivitamins or individual vitamin supplements. SUBJECTS: Eligible cases were aged 20 to 74, and approximately 40% of the study population were black women. The analyses included 861 cases and 790 controls. RESULTS: Among all women, there was little evidence for an association between any vitamin supplement and breast cancer. Modest inverse associations were observed among white women for use of multivitamins 95% confidence interval (CI): 0.59-1.12), vitamin C 95% CI: 0.54-1.14) and vitamin E 95% CI: 0.49-1.13). There was no evidence that vitamin supplements reduced the risk of breast cancer among black women. CONCLUSIONS: This study provided very limited support for the hypothesis that vitamin supplements may reduce the risk of breast cancer. Although dietary factors are likely an important influence in breast cancer aetiology, reductions in risk are most likely to be achieved through dietary modification rather than through vitamin supplementation.

Breast cancer: hormones and other risk factors.

UNLABELLED: In North America and Northern Europe, breast cancer incidence rates begin increasing in the early reproductive years and continue climbing into the late seventies, whereas rates plateau after menopause in japan and less developed countries. Female gender, age and country of birth are the strongest determinants of disease risk. Family history and mutations in the BRCA1 and BRCA2 genes are important correlates of lifetime risk. Genetic polymorphisms associated with estrogen synthesis and metabolism are currently under study. Atypical hyperplasia and molecular alterations in benign breast lesions appear to be involved in the pathogenesis of invasive carcinoma. In postmenopausal women, increased breast density on mammograms increases risk. Bone density and breast cancer are associated, presumably through the mechanism of endogenous estrogen levels. Serum estrogen levels are higher in breast cancer cases than controls. Many established risk factors for breast cancer may function through and endocrine mechanism. Current use of oral contraceptives and prolonged, current or recent use of hormone replacement therapy moderately increase risk. Tamoxifen and possibly other selective estrogen receptor modulators reduce breast cancer risk in high risk women. Relationships between various dietary micro and macronutrients and breast cancer have been suggested but require evaluation in clinical trials. Whereas alcohol consumption is associated with increased risk, most environmental factors, including polychlorinated compounds and electromagnetic fields, are not. CONCLUSION: Breast cancer etiology is becoming clearer through the study of molecular alterations in germline and somatic cell genes, and the interaction of these genes with steroid hormones and relevant growth factors. This knowledge should be useful for breast cancer prevention.

Race, anthropometric factors, and stage at diagnosis of breast cancer.

A recent study suggested that the greater prevalence of severe obesity among African-American women explained almost one third of the observed differences between African-American and White women in stage at diagnosis of breast cancer. The objective of this investigation was to attempt to replicate these findings in a second, larger population and to expand the analyses by including a measure of body fat distribution, the waist:hip ratio. The authors used data from a population-based study in North Carolina comprising 791 breast cancer cases (302 in African-American women and 489 in White women) diagnosed between 1993 and 1996. African-American women were more likely to have later-stage (TNM stage >/=II) breast cancer (odds ratio (OR) = 2.2; 95% confidence interval (CI): 1.6, 2.9). They also were much more likely to be severely obese (body mass index >/=32.3) (OR = 9.7; 95% CI: 6.5, 14.5) and to be in the highest tertile of waist:hip ratio (OR = 5.7; 95% CI: 3.8, 8.6). In multivariate logistic regression models, adjustment for waist:hip ratio reduced the odds ratio for later-stage disease in African-American women by 20%; adjustment for both waist:hip ratio and severe obesity reduced the odds ratio by 27%. These observations suggest that obesity and body fat distribution, in addition to socioeconomic and medical care factors, contribute to racial differences in stage at breast cancer diagnosis.

Body size and breast cancer risk in black women and white women: the Carolina Breast Cancer Study.

The relation between body size and breast cancer risk was investigated in a population-based, case-control study of Black women (350 cases, 353 controls) and White women (523 cases, 471 controls) from North Carolina, aged 20-74 years in 1993-1996. Logistic regression analyses compared tertiles of each body size variable, adjusting for age and breast cancer risk factors (results shown for highest relative to lowest tertile). Among premenopausal women, body mass index (kg/m2) was inversely associated with breast cancer (odds ratio (OR) = 0.46, 95% confidence interval (CI): 0.26, 0.80) for Whites but not for Blacks. There was essentially no association among postmenopausal women. Higher waist/hip ratio, adjusted for body mass index, increased risk for all women. Odds ratios for Black and White premenopausal women were 2.50 (95% CI: 1.10, 5.67) and 2.44 (95% CI: 1.17, 5.09), respectively; odds ratios for Black and White postmenopausal women were 1.62 (95% CI: 0.70, 3.79) and 1.64 (95% CI: 0.88, 3.07), respectively. Findings for body mass index differed among Black women when stratified by age (<50 years) (OR = 0.50, 95% CI: 0.25, 1.01) instead of menopausal status. Thus, the associations of breast cancer with body mass index and waist/hip ratio among Black women are similar to those documented for Whites, despite different body size profiles on average.

Alcohol consumption and breast cancer among black and white women in North Carolina (United States).

OBJECTIVE: The purpose of this study was to investigate the effects of alcohol consumption on breast cancer risk in black and white women. METHODS: We used data from the Carolina Breast Cancer Study, a population-based, case-control study of black and white women in North Carolina. Interviews were conducted with 890 cases and 841 controls frequency-matched on age and race. RESULTS: Overall, the prevalence of moderate to high levels of alcohol consumption was low. Compared with abstainers, the multivariate odds ratio for recent intake of one or two drinks per day was 1.4 (95% CI = 0.9-2.1) and two or more drinks a day was 1.0 (95% CI = 0.6-1.6); increasing consumption was not associated with risk (p for trend = 0.6). The associations were similar, but somewhat weaker, for average lifetime consumption. Among women who consumed 91 g/week or more of alcohol, a nonsignificant increased risk of breast cancer was observed for women reporting binge drinking (OR = 1.5; 95% CI = 0.9-2.3), but not for those who consumed less than 91 g/week reporting binge drinking (OR = 1.0; 95% CI = 0.6-1.5). Odds ratios did not differ meaningfully by race, age, menopausal status, exogenous hormone use, or body mass index. CONCLUSIONS: These data provide little evidence for an association between alcohol consumption and risk of breast cancer among either black or white women.

Menopausal hormones and breast cancer in a biracial population.

OBJECTIVES: This study examined the association between menopausal hormones and breast cancer in a biracial population. METHODS: Logistic regression was used to calculate odds ratios for breast cancer associated with hormone use among 397 cases and 425 controls, all menopausal women. RESULTS: Odds ratios for ever use of hormones were 0.8 (95% confidence interval [CI] = 0.5, 1.2) for White women and 0.7 (95% CI = 0.4, 1.2) for Black women. Risk was not increased with longer duration of use or more recent use. CONCLUSIONS: Breast cancer risk was not increased among White or Black women who used menopausal hormones, despite patterns of use varying considerably between races.

The associations of adolescent cigarette smoking, alcoholic beverage consumption, environmental tobacco smoke, and ionizing radiation with subsequent breast cancer risk (United States).

OBJECTIVES: Studies of breast cancer among survivors of the World War II atomic bomb blasts over Japan suggest that the adolescent breast may be particularly sensitive to carcinogenic insult. To further explore that possibility we examined the relationships of cigarette smoking, alcohol consumption, environmental tobacco smoke (ETS) exposure, and medical treatment with ionizing radiation during adolescence with subsequent breast cancer risk. METHODS: Data from the Carolina Breast Cancer Study, a population-based, case-control study of breast cancer in North Carolina women aged 20-74 years (864 cases, 790 controls), were analyzed. RESULTS: A modest increase in breast cancer risk was suggested for women who began to smoke cigarettes between the ages of 10 and 14 years (OR: 1.5, CI: 0.9-2.5), and for women exposed to ionizing radiation between ages 10 and 19 years to treat or monitor a medical condition (OR: 1.6, CI: 0.5-2.5). Neither exposure to ETS at home prior to age 18 years (OR: 1.1, CI: 0.9-1.3) nor initiation of alcoholic beverage consumption between ages 10 and 15 years (OR: 1.1, CI: 0.6-1.8) appeared to increase risk. CONCLUSIONS: Our results are consistent with previous evidence suggesting that some adolescent exposures could influence future breast cancer risk.

Hormone-related factors and risk of breast cancer in relation to estrogen receptor and progesterone receptor status.

Risk factors were examined for subgroups of breast cancer characterized by estrogen receptor (ER) and progesterone receptor (PR) status. Data from the Carolina Breast Cancer Study, a population-based, North Carolina case-control study of 862 breast cancer cases aged 20-74 years diagnosed during 1993-1996 and 790 controls frequency matched on race and age, were obtained by personal interview. ER and PR status was retrieved from medical records (80%) or was determined in the authors' laboratory (11%) but was missing for 9% of cases. The receptor status distribution was as follows: 53% ER+PR+, 11% ER+PR-, 8% ER-PR+, and 28% ER-PR-. Several hormone-related factors were associated with stronger increased risks for ER+PR+ than for ER-PR- breast cancer: the elevated odds ratios were strongest for ER+PR+ breast cancer among postmenopausal women who had an early age at menarche (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.4), nulliparity/late age at first full-term pregnancy (OR = 1.7, 95% CI: 0.9, 3.2 and OR = 1.6, 95% CI: 1.0, 2.7, respectively), or a high body mass index (OR = 1.6, 95% CI: 0.9, 3.0) and among pre-/perimenopausal women who had a high waist-hip ratio (OR = 1.9, 95% CI: 1.2, 3.1). In contrast, family history of breast or ovarian cancer and medical radiation exposure to the chest produced higher odds ratios for ER-PR- than for ER+PR+ breast cancer, especially among pre-/perimenopausal women.

Physical activity at age 12 and adult breast cancer risk (United States).

OBJECTIVES: Some epidemiologic studies suggest that adolescent physical activity reduces subsequent breast cancer risk. To examine this question further, we analyzed data on physical activity at age 12 that had been collected as part of the Carolina Breast Cancer Study (CBCS). METHODS: The CBCS is a population-based, case-control study of 527 white and 337 African-American cases and 790 controls, frequency-matched on age and race. Respondents were asked whether, and to what extent, they engaged in four specific activities at age 12 (walking to school, biking to school, competitive training, performing vigorous household chores). RESULTS: Women who reported participation in any of the four activities had a modest reduction in breast cancer risk (odds ratio (OR): 0.8, 95% confidence interval (CI): 0.6-1.0). Using an index measuring approximate number of activity episodes per week, analyses revealed modest inverse relationships for nearly all levels of activity relative to no reported activity; a weighting of the index by metabolic equivalent scores produced similar results. CONCLUSIONS: Our findings support the hypothesis that adolescent physical activity may protect against adult breast cancer, even at moderate levels.

Adolescent reproductive events and subsequent breast cancer risk.

OBJECTIVES: This study investigated the relationship between reproductive events during adolescence and subsequent breast cancer risk. METHODS: Logistic regression models used self-reported data from 862 case patients and 790 controls in the Carolina Breast Cancer Study. RESULTS: Miscarriage, induced abortion, and full-term pregnancy before 20 years of age were not associated with breast cancer. Among premenopausal women, breast-feeding before 20 years of age was inversely associated with disease. Oral contraceptive use before 18 years of age was positively associated with disease risk among African American women only. CONCLUSIONS: Pregnancy during adolescence does not appear to influence breast cancer risk, but breast-feeding may. A possible increased breast cancer risk among African American women who used oral contraceptives as adolescents warrants further study.

Participation rates in a case-control study: the impact of age, race, and race of interviewer.

PURPOSE: Despite concerns about declining participation rates in epidemiologic studies in recent years, relatively few papers have discussed obstacles to recruiting study participants or strategies for optimizing response rates. This report describes factors associated with nonparticipation in a population-based, case-control study of breast cancer and discusses ways to overcome barriers to participation. METHODS: Contact and cooperation rates were calculated for participants in the Carolina Breast Cancer Study (CBCS), stratified by case status, age, race, and race of interviewer. Demographic and breast cancer risk factor characteristics of partial and full responders also were compared. RESULTS: Contact rates and cooperation rates varied by case/control status and demographic characteristics. Contact rates were lower among controls, younger women, and black women. Cooperation rates were lower among controls, older women, and black cases. Cooperation rates were higher among both black and nonblack women when participants and interviewers were concordant on race. CONCLUSIONS: Obstacles to recruitment seem to differ among race and age subgroups, suggesting that recruitment strategies may need to be tailored to potential participants based upon demographic characteristics. Strategies have been implemented to improve response rates in this and other epidemiologic studies; however, additional research and innovation in this area are needed.

Catechol-O-methyltransferase and breast cancer risk.

Recent studies suggest that a polymorphism in catechol-O-methyltransferase (COMT) is associated with increased risk of breast cancer. Methylation by COMT is the principal pathway for inactivation of catechol estrogens, which are hypothesized to participate in estrogen-induced carcinogenesis. We examined the association of COMT genotype and breast cancer risk in a population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 654 cases and 642 controls, with approximately equal numbers of African-American and white women and women under the age of 50 and aged 50 or over. Contrary to previous reports, we did not observe an association between one or more copies of the low activity COMT allele (COMT-L) and breast cancer risk. Multivariate relative risks (RRs) were 0.8 (95% confidence interval: 0.6-1.1) for COMT-HL and 0.8 (0.6-1.1) for COMT-LL, compared with the COMT-HH genotype. RRs for COMT did not differ among African-American and white women and we did not observe strong modification of RR estimates by menopausal status, body mass index, physical activity or other covariates. Our results suggest that COMT genotype is not related to breast cancer risk.

Age at menarche, time to regular cycling, and breast cancer (North Carolina, United States).

OBJECTIVES: Later menarche, and a longer time until onset of regular cycling, are considered markers of lower lifetime exposure to circulating ovarian hormones. While later age at menarche is associated with reduced breast cancer risk, evidence for the relationship between time until onset of regular cycles and breast cancer is inconsistent. We evaluated both associations with breast cancer risk. METHODS: We used data from the Carolina Breast Cancer Study, a population-based case-control study of breast cancer among White and Black women aged 20 to 74 years, residing in central and eastern North Carolina (United States). Cases were diagnosed between May 1993 and June 1996. Unconditional logistic regression models were limited to women with complete data for the risk factors considered (n = 830 cases, 758 controls). RESULTS: We observed an inverse relationship between age at menarche and breast cancer risk, but found little support for the hypothesis that a longer time until onset of regular menstrual cycling was associated with reduced risk of breast cancer (odds ratios = 1.0 [95 percent confidence interval (CI) = 0.7-1.5], and 1.2 [CI = 0.8-1.6], respectively, for 1-4 years and < 1 year until onset of regular cycling, relative to 5+ years). There was little relationship between age at menarche and time until regular cycling. We found strong evidence that delays in onset of regular cycling were associated with increased frequency of irregular cycles throughout young adulthood. CONCLUSIONS: Given the inconsistent findings regarding the links between menstrual cycle characteristics and breast cancer, and recent recommendations to delay menarche and alter the patterns of cycles of young women in order to reduce breast cancer risk, this topic calls for further, innovative study.

Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk.

To examine the effects of smoking and N-acetylation genetics on breast cancer risk, we analyzed data from an ongoing, population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 498 cases and 473 controls, with approximately equal numbers of African-American and white women, and women under the age of 50 and age 50 years or older. Among premenopausal women, there was no association between current smoking [odds ratio (OR), 0.9; 95% confidence interval (CI), 0.5-1.5] or past smoking (OR, 1.0; 95% CI, 0.6-1.6) and breast cancer risk. Among postmenopausal women, there was also no association with current smoking (OR, 1.2; 95% CI, 0.7-2.0); however, a small increase in risk was observed for past smoking (OR, 1.5; 95% CI, 1.0-2.4). For postmenopausal women who smoked in the past, ORs and 95% CIs were 3.4 (1.4-8.1) for smoking within the past 3 years, 3.0 (1.3-6.7) for smoking 4-9 years ago, and 0.6 (0.3-1.4) for smoking 10-19 years ago. Neither N-acetyltransferase 1 (NAT1) nor N-acetyltransferase 2 (NAT2) genotype alone was associated with increased breast cancer risk. There was little evidence for modification of smoking effects according to genotype, except among postmenopausal women. Among postmenopausal women, ORs for smoking within the past 3 years were greater for women with the NAT1*10 genotype (OR, 9.0; 95% CI, 1.9-41.8) than NAT1-non*10 (OR, 2.5; 95% CI, 0.9-7.2) and greater for NAT2-rapid genotype (OR, 7.4; 95% CI, 1.6-32.6) than NAT2-slow (OR, 2.8; 95% CI, 0.4-8.0). Future studies of NAT genotypes and breast cancer should investigate the effects of environmental tobacco smoke, diet, and other exposures.

Association between high-density lipoprotein cholesterol and breast cancer varies by menopausal status.

A nested case-control study was conducted to investigate the hypothesis that women with high levels of high-density lipoprotein cholesterol (HDL-C) are at an increased risk of breast cancer. The source population was a cohort of 95,000 women enrolled in the Kaiser Permanente Medical Care Program who underwent a routine multiphasic health examination between 1964 and 1971. From the more than 2,000 breast cancer cases diagnosed in this cohort, 200 cases were randomly selected for this study. For each case, one control who matched on age and date of examination was chosen. Lipid and lipoprotein levels were measured in archived serum samples collected at the time of the women's examinations. Breast cancer risk factor information was obtained from questionnaires completed by the women when their blood was drawn and was supplemented with information from medical records. HDL-C levels were not significantly different between the cases and controls overall; however, a statistically significant interaction between the HDL-C level and menopausal status at diagnosis was detected. Premenopausal cases had mean HDL-C levels 3.48 mg/dl lower than matched controls [95% confidence interval (CI), -7.05, 0.09], whereas postmenopausal cases had levels 2.05 mg/dl higher than controls (95% CI, -0.94, 5.03). In multivariate conditional logistic regression analyses, the odds ratio associated with each 1 mg/dl increase in HDL-C was 0.96 (95% Cl, 0.93-1.0) for premenopausal women and 1.02 (95% CI, 0.99-1.05) for postmenopausal women. Although many breast cancer risk factors are associated with high HDL-C, the relationship between breast cancer and HDL-C was independent of other factors evaluated.