Oral contraceptives and breast cancer. A prospective cohort study

In 1976, information on oral contraceptive (OC) use as well as numerous risk factors for breast cancer was provided by 121,964 married female registered nurses aged 30 to 55 years. Ninety-two percent of women in the cohort completed follow-up questionnaires, and vital records were systematically searched to ascertain deaths among nonrespondents. After four years of follow-up, 592 incident cases of breast cancer were identified. Compared with never users, the age-adjusted relative risk (RR) of breast cancer, regardless of menopausal status, among all women who had ever used OCs was 1.0. Among premenopausal women compared with those who had never used OCs, the RR of breast cancer was 1.5 for current use of OCs in 1976 and 1.0 for past use. Among postmenopausal women, the RR for past use of OCs was 1.0. These estimates were essentially unaltered after controlling for other known risk factors for breast cancer in multiple logistic regression analysis. Furthermore, there was no modification of these effects by family history of breast cancer, age at first use, timing of the first birth, or other breast cancer risk factors. Data on past use of OCs provide substantial reassuring evidence that there is no large excess risk of breast cancer within a few years of cessation of pill use. The observed moderate elevation of breast cancer risk with current use was of borderline statistical significance. However, the observation was based on 29 cases and may reflect the effect of sampling variability, as most other studies have not observed a relationship between current use of OCs and breast cancer in women of this age.     

Oral contraceptives and risk of breast cancer

Use of oral contraceptives (OCs) by women before age 25 or first full-term pregnancy has been theorized to increase the risk of breast cancer. While multiple studies have reported a positive relationship between early use and subsequent breast cancer development, numerous researchers have concluded there is no effect. One reason for the varied results may be the case control methodology utilized by the majority of studies and its associated biases including selection, information, and recall bias. Other theories include an undetected latent effect, changing dosages and formulations, earlier breast cancer diagnosis and follow-up among OC users, and chance. While more research is needed, the weight of evidence supports no increased risk of breast cancer among OC users, including women less than 25 years of age and before first full-term pregnancy. Hence, it seems unnecessary to change the current approach toward OC use.     

Breast cancer in relation to early use of oral contraceptives. No evidence of a latent effect

A long-term effect of oral contraceptives (OCs) on breast cancer risk has been suggested as an explanation for some studies' failure to detect an association between OCs and breast cancer. To address this latency hypothesis, we analyzed data on 4714 case subjects and 4540 control subjects from the population-based Cancer and Steroid Hormone Study. No support was evident for a latent effect of OCs on breast cancer risk through age 54 years: among parous women who had cumulated more than six years of OC use before their first term pregnancy, the risk of breast cancer, relative to nonusers before first term pregnancy, was 0.6 at zero to four years after first term pregnancy (95% confidence interval [Cl], 0.2 to 1.8), 0.7 at five to nine years (95% Cl, 0.3 to 1.7), and 1.1 at ten to 14 years (95% Cl, 0.3 to 3.9). Among nulliparous women with more than six years of OC use in total, the relative risk of breast cancer, by interval from last use of OCs, was 1.3 at zero to four years (95% Cl, 0.8 to 2.0), 1.1 at five to nine years (95% Cl, 0.5 to 2.0), and 0.6 at ten to 14 years (95% Cl, 0.1 to 3.7).     

A prospective study of folate intake and the risk of breast cancer

CONTEXT: Folate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption. OBJECTIVES: To assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol. DESIGN: Prospective cohort study performed in 1980, with 16 years of follow-up. SETTING AND PARTICIPANTS: A total of 88818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer by levels of folate and alcohol intake. RESULTS: A total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 microg/d compared with 150 to 299 microg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend = .001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 microg/d (for alcohol intake > or =15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 microg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93). CONCLUSIONS: Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.     

Hormone replacement therapy after a diagnosis of breast cancer: cancer recurrence and mortality

OBJECTIVE: To determine whether hormone replacement therapy (HRT) after treatment for breast cancer is associated with increased risk of recurrence and mortality. DESIGN: Retrospective observational study. PARTICIPANTS AND SETTING: Postmenopausal women diagnosed with breast cancer and treated by five Sydney doctors between 1964 and 1999. OUTCOME MEASURES: Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes and to death from primary tumour were compared between women who used HRT for menopausal symptoms after diagnosis and those who did not. Relative risks (RRs) were determined from Cox regression analyses, adjusted for patient and tumour characteristics. RESULTS: 1122 women were followed up for 0-36 years (median, 6.08 years); 154 were lost to follow-up. 286 women used HRT for menopausal symptoms for up to 26 years (median, 1.75 years). Compared with non-users, HRT users had reduced risk of cancer recurrence (adjusted relative risk [RR], 0.62; 95% CI, 0.43-0.87), all-cause mortality (RR, 0.34; 95% CI, 0.19-0.59) and death from primary tumour (RR, 0.40; 95% CI, 0.22-0.72). Continuous combined HRT was associated with a reduced risk of death from primary tumour (RR, 0.32; 95% CI, 0.12-0.88) and all-cause mortality (RR, 0.27; 95% CI, 0.10-0.73). CONCLUSION: HRT use for menopausal symptoms by women treated for primary invasive breast cancer is not associated with an increased risk of breast cancer recurrence or shortened life expectancy.     

Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk

CONTEXT: Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown. OBJECTIVE: To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone. DESIGN: Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. SETTING: Twenty-nine screening centers throughout the United States. PARTICIPANTS: A total of 46355 postmenopausal women (mean age at start of follow-up, 58 years). MAIN OUTCOME MEASURE: Incident breast cancers by recency, duration, and type of hormone use. RESULTS: During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval [CI], 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin-only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only. CONCLUSION: Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone.     

Oral contraceptives and cervical cancer risk in Costa Rica. Detection bias or causal association?

To examine the relationship between cervical cancer and oral contraceptive (OC) use, we analyzed data from a population-based, case-control study in Costa Rica. Women aged 25 to 58 years in whom cervical cancer was diagnosed and reported to the National Tumor Registry were examined as two separate case groups: invasive cervical cancer and carcinoma in situ (CIS). Controls were women aged 25 to 58 years identified through a national survey. Women who had used OCs had no increased risk of invasive cervical cancer compared with women who had never used OCs (relative risk, 0.8; 95% confidence interval, 0.5 to 1.3). Women who had used OCs had an increased risk of CIS compared with those who had never used OCs (relative risk, 1.6; 95% confidence interval, 1.2 to 2.2). However, further analyses indicated that this increased risk was confined to those who had recently used OCs. Also, the risk of CIS was not elevated in subgroups in which a history of cervical smears was not strongly linked to OC use. The elevated risk of CIS among OC users may therefore reflect a bias caused by enhanced detection of disease rather than a causal association.     

Family history and the risk of breast cancer

To investigate whether a family history of breast cancer increases a woman's risk of developing breast cancer, we analyzed data from the Centers for Disease Control's Cancer and Steroid Hormone Study. The 4,735 cases were women 20 to 54 years old with a first diagnosis of breast cancer ascertained from eight population-based cancer registries; the 4,688 controls were women selected at random from the general population of these eight areas. Compared with women without a family history of breast cancer, women who had an affected first-degree relative had a relative risk of 2.3; women with an affected second-degree relative had a relative risk of 1.5; and women with both an affected mother and sister had a relative risk of 14. The risk of breast cancer for a woman was higher if her first-degree relative had unilateral rather than bilateral breast cancer or had breast cancer detected at a younger rather than older age. For women aged 20 to 39, 40 to 44, and 45 to 54 years, the estimated annual incidence of breast cancer per 100,000 women attributable to a first-degree family history of breast cancer was 51.9, 115.1, and 138.6, respectively, and that attributable to a second-degree family history of breast cancer was 12.1, 19.2, and 92.4, respectively.     

Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women

CONTEXT: Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers. The effect of postmenopausal estrogen use on ovarian cancer is not established. OBJECTIVES: To examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use. DESIGN AND SETTING: The American Cancer Society's Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996. PARTICIPANTS: A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment. MAIN OUTCOME MEASURE: Ovarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT). RESULTS: A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up. Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96). Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was associated with increased risk in both baseline and former users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users. Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use <15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use >/=15 years ago, 1.31; 95% CI, 0.79-2.17). CONCLUSIONS: In this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.     

Oral contraceptive agents and breast cancer: a population-based case-control study

In this population-based case-control study that was conducted in Adelaide, South Australia, and which involved 395 case subjects and 386 control subjects who were aged 20 years to 69 years, the adjusted relative risk of breast cancer for women who had ever used oral contraceptive agents was 1.06 (95% confidence interval [CI], 0.70-1.60). Relative risks that were associated with use of oral contraceptive agents for one month to 18 months and for 19 months or more before a first pregnancy were 1.09 (95% CI, 0.45-2.62) and 1.67 (95% CI, 0.63-4.42), respectively, but the trend was not statistically significant. Relatively-little variation in risk was found in association with the total duration of the use of oral contraceptive agents and with years since the first and the last use of oral contraceptive agents. When the risk of breast cancer in association with the use of oral contraceptive agents was examined across levels of risk factors of breast cancer (history of benign breast disease, family history of breast cancer and parity), the only relative risk which deviated markedly from unity was that which was associated with use of oral contraceptive agents in women with a history of benign breast disease; however, the relative risk of 1.77 (95% CI, 0.35-8.97) was not statistically significant. In conclusion, the results of this study support those of the majority of previous studies in showing no overall relationship between the use of oral contraceptive agents and the risk of breast cancer.     

Changes in breast density associated with initiation, discontinuation, and continuing use of hormone replacement therapy

CONTEXT: Initiation of hormone replacement therapy (HRT) has been shown to increase breast density. Evidence exists that increased breast density decreases mammographic sensitivity. The effects on breast density of discontinuing and continuing HRT have not been studied systematically. OBJECTIVE: To examine the effects of initiation, discontinuation, and continued use of HRT on breast density in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 5212 naturally postmenopausal women aged 40 to 96 years and enrolled in a large health maintenance organization in western Washington State who had 2 screening mammograms between 1996 and 1998. MAIN OUTCOME MEASURES: Breast density, assessed using the clinical radiologists' BI-RADS 4-point scale, compared among women who did not use HRT before either mammogram (nonusers); who used HRT before the first but not before the second mammogram (discontinuers); who used HRT before the second but not before the first mammogram (initiators); and who used HRT prior to both mammograms (continuing users). RESULTS: Relative to nonusers, women who initiated HRT were more likely to show increases in breast density (relative risk [RR], 2.57; 95% confidence interval [CI], 2.12-3.08), while women who discontinued HRT use were more likely to show decreases in density (RR, 1.81; 95% CI, 1.06-2.98) and women who continued to use HRT were more likely to show both increases in density (RR, 1.33; 95% CI, 1.13-1.55) and sustained high density (RR, 1.45; 95% CI, 1.33-1.58). CONCLUSIONS: These results indicate that breast density changes associated with HRT are dynamic, increasing with initiation, and decreasing with discontinuation.     

A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer

To quantify the effect of estrogen replacement therapy on breast cancer risk, we combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies. Using this summary dose-response slope, we calculated the proportional increase in risk of breast cancer for each year of estrogen use. For women who experienced any type of menopause, risk did not appear to increase until after at least 5 years of estrogen use. After 15 years of estrogen use, we found a 30% increase in the risk of breast cancer (relative risk, 1.3; 95% confidence interval [CI], 1.2 to 1.6). The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. Among women with a family history of breast cancer, those who had ever used estrogen replacement had a significantly higher risk (3.4; CI, 2.0 to 6.0) than those who had not (1.5; CI, 1.2 to 1.7).     

Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies

CONTEXT: Some epidemiologic studies suggest that elevated fruit and vegetable consumption is associated with a reduced risk of breast cancer. However, most have been case-control studies in which recall and selection bias may influence the results. Additionally, publication bias may have influenced the literature on associations for specific fruit and vegetable subgroups. OBJECTIVE: To examine the association between breast cancer and total and specific fruit and vegetable group intakes using standardized exposure definitions. DATA SOURCES/STUDY SELECTION: Eight prospective studies that had at least 200 incident breast cancer cases, assessed usual dietary intake, and completed a validation study of the diet assessment method or a closely related instrument were included in these analyses. DATA EXTRACTION: Using the primary data from each of the studies, we calculated study-specific relative risks (RRs) that were combined using a random-effects model. DATA SYNTHESIS: The studies included 7377 incident invasive breast cancer cases occurring among 351 825 women whose diet was analyzed at baseline. For comparisons of the highest vs lowest quartiles of intake, weak, nonsignificant associations were observed for total fruits (pooled multivariate RR, 0.93; 95% confidence interval [CI], 0.86-1.00; P for trend =.08), total vegetables (RR, 0.96; 95% CI, 0.89-1.04; P for trend =.54), and total fruits and vegetables (RR, 0.93; 95% CI, 0.86-1.00; P for trend =.12). No additional benefit was apparent in comparisons of the highest and lowest deciles of intake. No associations were observed for green leafy vegetables, 8 botanical groups, and 17 specific fruits and vegetables. CONCLUSION: These results suggest that fruit and vegetable consumption during adulthood is not significantly associated with reduced breast cancer risk.     

Cancer risks and the contraceptive pill. What is the evidence after nearly 25 years of use?

The question of whether the steroidal components in oral contraceptives (OCs) may have an initiating or promotional influence on the development of cancer continues to be raised as a public health issue. It is estimated that since the introduction of OCs nearly 25 years ago, more than 150 million women have used 1 or more types of the formulation and nearly 1 billion woman-years of exposure to the steroids have accumulated. Contraceptive practice in Australia would indicate that about 25% of women of reproductive age are using OCs. The debate about the OC's carcinogenic potential has recently been reopened with 2 reports in "The Lancet" of an association between the incidence of breast and cervical cancer and OC usage. Biologically the relationship between the contraceptive steroids and cancer must continue to be regarded as the most important concern with the longterm use of OCs. The demonstration of receptors to these steriods in these organs, in both normal and malignant tissues, further increases the speculation that the steroid hormones have a biological role in carcinogenesis in these target organs. Theoretical reasons exist for the concern about carcinogenesis and contraceptive steroids. This paper reviews the available evicence. Data can be derived only from large-scale epidemiological research, by means of case-control or cohort studies. No clear evidence exists that OCs cause or increase the chance of developing any cancer in the female genital tract and the breast. In fact, OC offers a significant protection against the development of endometrial and ovarian cancer, especially to those women who have taken OCs for a long time. The association between the risk of breast cancer and OC use is less certain, but factors such as the history of benign breast disease, a close relationship with breast cancer, or nulliparity -- previously considered to be important -- do not appear to contribute significantly to the risk. The weight of evidence indicates that no increased risk of breast cancer exists, even in those younger women aged less than 25 years who decide to use OCs before their 1st full-term pregnancy. There is some evidence that suggests that the risk of cervical neoplasia -- dysplasia, carcinoma-in-situ and invasive carcinoma -- may increase slightly in OC users but the actual part played by the patient's sexual history under these circumstances remains to be defined. There is now strong evidence to implicate multiplicity of sexual partners and wart virus infection in carcinogenesis of the uterine cervix. There does not appear to be an overall relationship between OCs and malignant melanoma. Overall, the evidence is reassuring. The low-dose combined OC can be considered safe, not only in terms of cardiovascular and thromboembolic risks, but also in relation to carcinogenesis.     

Ischemic stroke risk with oral contraceptives: A meta-analysis

CONTEXT: The relationship between ischemic stroke and oral contraceptive (OC) use has been studied for 40 years, but disagreement about an association persists. OBJECTIVE: To review available literature to determine whether OC use is associated with increased stroke risk. DATA SOURCES: Studies published from January 1960 through November 1999 were identified from electronic databases (MEDLINE, BIOSIS, and Dissertation Abstracts Online), Index Medicus, bibliographies of pertinent review articles and pertinent original articles, textbooks, and expert consultation. STUDY SELECTION: From 804 potentially relevant references retrieved, 73 were studies investigating risk of ischemic stroke with OC use. Two reviewers independently applied the following inclusion criteria: more than 10 stroke cases sampled, clear stroke subtype differentiation, concurrent controls included, adequate data included to determine relative risks (RRs) and confidence intervals (CIs), analysis controlled for age, and no later publication of identical data. A third investigator adjudicated disagreements. Sixteen studies met all inclusion criteria and were included in the meta-analysis. DATA EXTRACTION: Two investigators independently extracted data, with disagreements resolved through discussion. DATA SYNTHESIS: The 16 studies were analyzed using random effects modeling. Current OC use was associated with increased risk of ischemic stroke (RR, 2.75; 95% CI, 2.24-3.38). Smaller estrogen dosages were associated with lower risk (P=.01 for trend), but risk was significantly elevated for all dosages. Studies that did not control for smoking (P=.01) and those using hospital-based controls (P<.001) found higher RRs, but no other patient characteristics or elements of study design were important. The summary RR was 1.93 (95% CI, 1.35-2.74) for low-estrogen preparations in population-based studies that controlled for smoking and hypertension. This translates to an additional 4.1 ischemic strokes per 100,000 nonsmoking, normotensive women using low-estrogen OCs, or 1 additional ischemic stroke per year per 24,000 such women. The RR of stroke due to OC use was not different in women who smoked, had migraines, or had hypertension. CONCLUSIONS: Summary results indicate that risk of ischemic stroke is increased in current OC users, even with newer low-estrogen preparations. However, the absolute increase in stroke risk is expected to be small since incidence is very low in this population. JAMA. 2000;284:72-78     

Decrease in breast cancer incidence following a rapid fall in use of hormone replacement therapy in Australia

OBJECTIVE: To determine if the recent rapid fall in use of hormone replacement therapy (HRT) in Australia has been followed by a reduction in breast cancer incidence among women aged 50 years or older, but not among younger women. DESIGN AND SETTING: Analysis of trends in annual prescribing of HRT, using Pharmaceutical Benefits Scheme data, and in annual age-standardised breast cancer incidence rates in Australian women for the period 1996-2003. RESULTS: In Australia, prescribing of HRT increased from 1996 to 2001, but dropped by 40% from 2001 to 2003. Age-standardised breast cancer incidence rates in women aged > or = 50 years also increased to 2001 but declined thereafter. The incidence rates in this age group were lower by 6.7% (95% CI, 3.9%-9.3%; P < 0.001) in 2003 compared with 2001, equivalent to 600 (95% CI, 350-830) fewer breast cancers (out of about 9000 incident breast cancers annually for women this age). There was no significant change in breast cancer incidence for women aged < 50 years. CONCLUSIONS: While other factors may have contributed to a recent reduction in breast cancer incidence among Australian women aged > or = 50 years, the available evidence suggests that much of the decrease is due to the recent fall in use of HRT. This is consistent with other evidence that the HRT-associated increase in risk of breast cancer is reversible after ceasing use of HRT.     

Adult weight change and risk of postmenopausal breast cancer

Context  Endogenous hormones are a primary cause of breast cancer. Adiposity affects circulating hormones, particularly in postmenopausal women, and may be a modifiable risk factor for breast cancer. Objective  To assess the associations of adult weight change since age 18 years and since menopause with the risk of breast cancer among postmenopausal women. Design, Setting, and Participants  Prospective cohort study within the Nurses' Health Study. A total of 87 143 postmenopausal women, aged 30 to 55 years and free of cancer, were followed up for up to 26 years (1976-2002) to assess weight change since age 18 years. Weight change since menopause was assessed among 49 514 women who were followed up for up to 24 years. Main Outcome Measure  Incidence of invasive breast cancer. Results  Overall, 4393 cases of invasive breast cancer were documented. Compared with those who maintained weight, women who gained 25.0 kg or more since age 18 years were at an increased risk of breast cancer (relative risk [RR], 1.45; 95% confidence interval [CI], 1.27-1.66; P<.001 for trend), with a stronger association among women who have never taken postmenopausal hormones (RR,1.98; 95% CI, 1.55-2.53). Compared with weight maintenance, women who gained 10.0 kg or more since menopause were at an increased risk of breast cancer (RR, 1.18; 95% CI, 1.03-1.35; P  = .002 for trend). Women who had never used postmenopausal hormones, lost 10.0 kg or more since menopause, and kept the weight off were at a lower risk than those who maintained weight (RR, 0.43; 95% CI, 0.21-0.86; P = .01 for weight loss trend). Overall, 15.0% (95% CI, 12.8%-17.4%) of breast cancer cases in this population may be attributable to weight gain of 2.0 kg or more since age 18 years and 4.4% (95% CI, 3.6%-5.5%) attributable to weight gain of 2.0 kg or more since menopause. Among those who did not use postmenopausal hormones, the population attributable risks are 24.2% (95% CI, 19.8%-29.1%) for a weight gain since age 18 years and 7.6% (95% CI, 5.9%-9.7%) for weight gain since menopause. Conclusions  These data suggest that weight gain during adult life, specifically since menopause, increases the risk of breast cancer among postmenopausal women, whereas weight loss after menopause is associated with a decreased risk of breast cancer. Thus, in addition to other known benefits of healthy weight, our results provide another reason for women approaching menopause to maintain or lose weight, as appropriate.      

Effect of breast self-examination techniques on the risk of death from breast cancer

OBJECTIVE: To measure the effect of breast self-examination (BSE) technique and frequency on the risk of death from breast cancer. DESIGN: Case-control study nested within the Canadian National Breast Screening Study (NBSS). SETTING: The Canadian NBSS, a multicentre randomized controlled trial of screening for breast cancer in Canadian women. SUBJECTS: The case subjects were 163 women who had died from breast cancer and 57 women with distant metastases. Ten control subjects matched by 5-year age group, screening centre, year of enrolment and random allocation group were randomly selected for each case subject. EXPOSURE MEASURES: Self-reported BSE frequency before enrolment in the NBSS, annual self-reports of BSE frequency during the program and annual objective assessments of BSE technique. OUTCOME MEASURES: Odds ratios (ORs) associated with BSE practice were estimated by conditional multiple logistic regression modelling, which permitted control of covariates. RESULTS: Relative to women who, when assessed 2 years before diagnosis, examined their breasts visually, used their finger pads for palpation and examined with their 3 middle fingers, the OR for death from breast cancer or distant metastatic disease for women who omitted 1, 2 or 3 of these components was 2.20 (95% confidence interval [CI] 1.30 to 3.71, p = 0.003). The OR for women who omitted 1 of the 3 components was 1.82 (95% CI 1.00 to 3.29, p = 0.05), for those who omitted 2 of the 3 components, 2.84 (95% CI 1.44 to 5.59, p = 0.003), and for those who omitted all 3 components, 2.95 (95% CI 1.19 to 7.30, p = 0.02). The results remained unchanged after adjustment for potential confounders. CONCLUSION: The results, obtained with the use of prospectively collected data, suggest that the performance of specific BSE components may reduce the risk of death from breast cancer.     

Risk of Dementia Among White and African American Relatives of Patients With Alzheimer Disease

Context  Evidence exists that the incidence of Alzheimer disease (AD), as well as risk attributable to specific genetic factors such as apolipoprotein E (APOE) genotype, may vary considerably among ethnic groups. Family studies of probands with AD offer an opportunity to evaluate lifetime risk of dementia among relatives of these probands. Objective  To compare lifetime dementia risk estimates among relatives of white and African American probands with probable or definite AD. Design and Setting  Risk analysis using data collected by questionnaire and supplemental records between May 1991 and March 2001 at 17 medical centers contributing to the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study. Participants  A total of 17 639 first-degree biological relatives and 2474 spouses of 2339 white AD probands, and 2281 first-degree biological relatives and 257 spouses of 255 African American AD probands. Main Outcome Measures  Cumulative risk of dementia by age 85 years, stratified by ethnicity and sex of relatives and by APOE genotype of probands. Results  Cumulative risk of dementia in first-degree biological relatives of African American AD probands by age 85 years was 43.7% (SE, 3.1%), and the corresponding risk in first-degree biological relatives of white AD probands was 26.9% (SE, 0.8%), yielding a relative risk (RR) of 1.6 (95% confidence interval [CI], 1.4-1.9; P<.001). The risk in spouses of African American AD probands of 18.5% (SE, 8.4%) was also higher than the risk in white spouses of 10.4% (SE, 1.7%) but did not reach statistical significance (RR, 1.8; 95% CI, 0.5-6.0; P = .34), likely due to the smaller sample size of African Americans. The proportional increase in risk of dementia among white first-degree biological relatives compared with white spouses of 2.6 (95% CI, 2.1-3.2) was similar to that of 2.4 (95% CI, 1.3-4.4) in African American first-degree biological relatives compared with African American spouses. Female first-degree biological relatives of probands had a higher risk of developing dementia than did their male counterparts, among whites (31.2% vs 20.4%; RR, 1.5; 95% CI, 1.3-1.7; P<.001) as well as among African Americans, although this was not significant among African Americans (46.7% vs 40.1%; RR, 1.2; 95% CI, 0.9-1.7, P = .30). The patterns of risk among first-degree biological relatives stratified by APOE genotype of the probands were similar in white families and African American families. Conclusion  First-degree relatives of African Americans with AD have a higher cumulative risk of dementia than do those of whites with AD. However, in this study, the additional risk of dementia conferred by being a first-degree relative, by being female, or by the probability of having an APOE 4 allele appeared similar in African American and white families. These data provide estimates of dementia risk that can be used to offer counseling to family members of patients with AD.      

Hereditary aspects of prostate cancer.

OBJECTIVE: To review current literature on the hereditary aspects of prostate cancer and to evaluate the importance of family history in history taking and screening for prostate cancer. DATA SOURCES: MEDLINE was searched for articles in English or French published between Jan. 1, 1956, and Oct. 31, 1994, with the use of MeSH headings "prostatic neoplasms," "genetics" and "chromosomes." Additional references were selected from the bibliographies of articles found during the search. STUDY SELECTION: Case-control studies involving the incidence of prostate cancer and relative risk (RR) of such cancer in the families of men with this disease, compared with a control group, were included. Only studies in which prostate cancer was diagnosed on the basis of histologic tests were included. Animal investigations were excluded. DATA EXTRACTION: Ten case-control studies were evaluated critically in terms of design, case and control groups, the size of the samples and statistical results. The incidence of prostate cancer in the families of cases, compared with that in the families of controls, and differences in RR were reviewed. DATA SYNTHESIS: The lifetime risk of prostate cancer is 9.5% and of death from prostate cancer is 2.9% for a man 50 years of age. For first-degree male relatives of men with prostate cancer, the calculated RR ranges from 1.7 to 8.73. "Hereditary" prostate cancer is a term applied to a specific subset of patients with prostate cancer. This form of prostate cancer is transmitted by a rare, autosomal, dominant allele with high penetrance; it accounts for an estimated 43% of early-onset disease (affecting men less than 55 years of age) but only 9% of all prostate cancer in men up to 85 years of age. A greater number of affected family members and early onset among family members are the most significant predictors of risk. CONCLUSIONS: Recent confirmation of the familial clustering and Mendelian inheritance patterns of some prostate cancer has important implications. It increases the potential for directed research into the causes of prostate cancer and for refinements in the current screening practices to detect this common disease. Manoeuvres to detect prostate cancer should be started earlier among men with one or more first-degree relatives with the disease than among other men.