Reproductive factors and family history of breast cancer in relation to plasma prolactin levels in premenopausal and postmenopausal women

Many reproductive factors are associated with breast cancer risk, potentially through a hormonal pathway. The peptide hormone prolactin is essential in mammary development and lactation and may be a link between risk factors and breast cancer. While higher prolactin levels are associated with increased breast cancer risk, few determinants of prolactin levels are known. We conducted a cross-sectional analysis among 1,089 premenopausal and 1,311 postmenopausal women within the Nurses' Health Study (NHS) and the NHS II to examine the associations of reproductive factors, benign breast disease and family history of breast cancer with plasma prolactin levels. Parous women had significantly lower prolactin levels than nulliparous women (parous vs. nulliparous multivariate-adjusted geometric means = 14.1 ng/mL vs. 16.6 ng/mL, p<0.001 for premenopausal and 9.1 vs. 10.1, p=0.04 for postmenopausal women), although levels did not decrease with increasing number of children for either premenopausal (p-trend = 0.23) or postmenopausal (p-trend = 0.07) parous women. Age at first birth was not associated with prolactin levels. The reduction in prolactin levels among parous premenopausal women appeared to attenuate with increasing time since first birth, but the trend was not statistically significant (p-trend = 0.12). Age at menarche, duration of lactation and benign breast disease were not associated with prolactin levels. Family history of breast cancer was associated with significantly higher prolactin levels when compared with no family history among premenopausal (15.9 ng/mL vs. 14.3 ng/mL, p=0.04) but not postmenopausal (p=0.73) women. In conclusion, the associations of parity and family history with breast cancer risk may be mediated, at least in part, by prolactin levels.     

Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the multiple outcomes of raloxifene evaluation study participants.

PURPOSE: To test the hypothesis that risk factors related to lifetime estrogen exposure predict breast cancer incidence and to test if any subgroups experience enhanced benefit from raloxifene. PATIENTS AND METHODS: Postmenopausal women with osteoporosis (N = 7,705), enrolled onto the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, were randomly assigned to receive placebo, raloxifene 60 mg/d, or raloxifene 120 mg/d for 4 years. Breast cancer risk was analyzed by the following baseline characteristics indicative of estrogen exposure: previous hormone replacement therapy, prevalent vertebral fractures, family history of breast cancer, estradiol level, bone mineral density (BMD), body mass index, and age at menopause. Therapy-by-subgroup interactions were assessed using a logistic regression model. RESULTS: Overall, women with the highest one-third estradiol levels (> or = 12 pmol/L) had a 2.07-fold increased invasive breast cancer risk compared with women with lower levels. Raloxifene significantly reduced breast cancer risk in both the low- and high-estrogen subgroups for all risk factors examined (P <.05 for each comparison). The women with the highest BMD and those with a family history of breast cancer experienced a significantly greater therapy benefit with raloxifene, compared with the two thirds of patients with lower BMD or those without a family history, respectively; the subgroup-by-therapy interactions were significant (P =.005 and P =.015, respectively). CONCLUSION: The MORE trial confirms that increased lifetime estrogen exposure increases breast cancer risk. Raloxifene therapy reduces breast cancer risk in postmenopausal osteoporotic women regardless of lifetime estrogen exposure, but the reduction is greater in those with higher lifetime exposure to estrogen.     

Serum concentrations of estrogens, sex hormone-binding globulin, and androgens and risk of breast cancer in postmenopausal women

We assessed the relationship between serum concentrations of estrogens, androgens, and sex hormone-binding globulin and risk of breast cancer among postmenopausal women. Study participants provided serum prior to breast biopsy or mastectomy in 3 hospitals in Grand Rapids, Michigan between 1977 and 1987. A total of 179 subjects with localized breast cancer were compared to 152 subjects with nonproliferative breast changes that have not been associated with elevated breast cancer risk. Increasing serum concentrations of estrone and estrone sulfate were associated with increases in breast cancer risk; the odds ratios (ORs) in the fourth quartiles compared to the first were 2.3 (95% confidence interval (CI) 1.1-4.6) for both (p-trend = 0.02 and 0.03, respectively). Estradiol and bioavailable estradiol concentrations were associated with nonstatistically significant increases in risk. Androstenediol levels were associated with risk (p-trend = 0.01); the OR in the fourth compared to the first quartile was 2.2 (95% CI 1.0-4.6). Testosterone, dehydroepiandrosterone and androstenedione levels were not associated with increased risk. Sex hormone-binding globulin was associated with a nonsignificant decrease in risk. Associations with estrone and estrone sulfate persisted after adjustment for androstenediol (ORs for fourth compared to first quartiles were 2.0 (95% CI 0.9-4.5) and 2.2 (95% CI 1.0-4.6), respectively (p-trend = 0.16 for both). The association with androstenediol was attenuated after adjustment for estrone (OR for fourth compared to first quartile was 1.6 (95% CI 0.7-3.6); p-trend = 0.13). Higher serum concentrations of estrogens were associated with increased breast cancer risk in postmenopausal women. Androgen levels were not independently associated with substantially increased risk.     

Impact of reproductive factors and lactation on breast carcinoma in situ risk

Incidence rates for breast carcinoma in situ (CIS) have increased markedly over the past 20 years. Breast CIS, detected primarily on mammography, now represents 30-45% of all screened detected breast cancers. We conducted a large population-based case-control study to evaluate the impact of reproductive factors and lactation on breast CIS risk. Case subjects were newly diagnosed with breast CIS at ages 35-64 years between March 1, 1995 and May 31, 1998 (n = 567), resided in Los Angeles County and were born in the United States. Control subjects (n = 614), identified through random digit dialing, fulfilled the same eligibility criteria and were required to have had at least one screening mammogram in the 2-year period before their interview. Women with a positive family history of breast cancer had a 2-fold increase in breast CIS risk. Parous women were at reduced risk relative to nulligravid women (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.46-1.00). Among nulliparous women, pregnancy was unrelated to breast CIS risk. Among parous women, risk declined with each additional term pregnancy (p-trend = 0.003). No associations were found with age at first term pregnancy, induced abortion or miscarriage. Long duration of breast-feeding (> or =24 months) was associated with increased risk (OR = 2.00, 95% CI = 1.11-3.60). The observed effects of family history and pregnancy on breast CIS risk are consistent with those observed for invasive breast cancer. The results for breast-feeding are contrary to what has been observed in studies of invasive breast cancer.     

Body mass index and the risk for developing invasive breast cancer among high-risk women in NSABP P-1 and STAR breast cancer prevention trials

High body mass index (BMI) has been associated with an increased risk for breast cancer among postmenopausal women. However, the relationship between BMI and breast cancer risk in premenopausal women has remained unclear. Data from two large prevention trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) were used to explore the relationship between baseline BMI and breast cancer risk. The analyses included 12,243 participants with 253 invasive breast cancer events from the Breast Cancer Prevention Trial (P-1) and 19,488 participants with 557 events from the Study of Tamoxifen and Raloxifene (STAR). Both studies enrolled high-risk women (Gail score ≥ 1.66) with no breast cancer history. Women in P-1 were pre- and postmenopausal, whereas women in STAR (P-2) were all postmenopausal at entry. Using Cox proportional hazards regression, we found slight but nonsignificant increased risks of invasive breast cancer among overweight and obese postmenopausal participants in STAR and P-1. Among premenopausal participants, an increased risk of invasive breast cancer was significantly associated with higher BMI (P = 0.01). Compared with BMI less than 25, adjusted HRs for premenopausal women were 1.59 for BMI 25 to 29.9 and 1.70 for BMI 30 or more. Our investigation among annually screened, high-risk participants in randomized, breast cancer chemoprevention trials showed that higher levels of BMI were significantly associated with increased breast cancer risk in premenopausal women older than 35 years, but not postmenopausal women.     

Physical exercise reduces risk of breast cancer in Japanese women

To evaluate the effects of physical exercise on breast cancer risk, a large-scale case-referent study of 2376 incident breast cancer cases and 18 977 non-cancer referents was conducted using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). To adjust appropriately for possible confounders, we examined the effects within subgroups of the study population. The multivariable-adjusted odds ratio (OR) was 0.81 (95% confidence interval (CI): 0.69–0.94) for twice a week or more regular exercise. We observed a decreased risk of breast cancer for women who regularly exercised for health twice a week or more, irrespective of menopausal status, and were able to detect greater risk reductions within particular subgroups, including women who were parous, without a family history or non-drinkers. Among premenopausal women, a particularly strong protective effect of physical exercise was observed (OR=0.57, 95%CI: 0.28–1.15) for those women whose body mass index (BMI) was high (BMI≥25). In contrast, risk reduction was found (OR=0.71, 95%CI: 0.50–1.01) among postmenopausal women whose BMI was medium (BMI: 22–25). Stratification of history of stomach cancer screening to adjust modifying effects of healthy consciousness allows a more precise assessment of the protective effect of exercise twice a week or more, independent of stomach cancer screening history. This study provides evidence that physical exercise, especially exercise twice a week or more, reduces the risk of breast cancer among Japanese women. (Cancer Sci 2003; 94: 193–199)     

Dietary Carbohydrate,Fiber and Sugar and Risk of Breast Cancer According to Menopausal Status in Malaysia

Background: Dietary carbohydrate, fiber and sugar intake has been shown to play a role in the etiology ofbreast cancer, but the findings have been inconsistent and limited to developed countries with higher cancerincidence. Objective: To examine the association of premenopausal and postmenopausal breast cancer risk withdietary carbohydrate, fiber and sugar intake. Materials and Methods: This population based case-control studywas conducted in Malaysia with 382 breast cancer patients and 382 controls. Food intake pattern was assessed viaan interviewer-administered food frequency questionnaire. Logistic regression was used to compute odds ratios(OR) with 95% confidence intervals (CI) and a broad range of potential confounders were included in analysis.Results: A significant two fold increased risk of breast cancer among premenopausal (OR Q4 to Q1=1.93, 95%CI:1.53-2.61, p-trend=0.001) and postmenopausal (OR Q4 to Q1=1.87, 95%CI: 1.03-2.61, p-trend=0.045) womenwas observed in the highest quartile of sugar. A higher intake of dietary fiber was associated with a significantlylower breast cancer risk among both premenopausal (ORQ4 to Q1=0.31, 95%CI: 0.12-0.79, p-trend=0.009) andpostmenopausal (ORQ4 to Q1=0.23, 95%CI: 0.07-0.76, p-trend=0.031) women. Conclusions: Sugar and dietaryfiber intake were independently related to pre- and postmenopausal breast cancer risk. However, no associationwas observed for dietary carbohydrate intake.     

Mammographic densities and risk of breast cancer among subjects with a family history of this disease.

BACKGROUND: A family history of breast cancer is known to increase risk of the disease, but other genetic and environmental factors that modify this risk are likely to exist. One of these factors is mammographic density, and we have sought evidence that it is associated with increased risk of breast cancer among women with a family history of breast cancer. METHODS: We used data from a nested case-control study based on the Canadian National Breast Screening Study (NBSS). From 354 case patients with incident breast cancer detected at least 12 months after entry into the NBSS and 354 matched control subjects, we analyzed subjects who were identified as having a family history of breast cancer according to one of three, nonmutually exclusive, criteria. We compared the mammographic densities of case patients and control subjects by radiologic and computer-assisted methods of measurement. RESULTS: After adjustment for other risk factors for breast cancer, the relative risks (RRs) between the most and least extensive categories of breast density were as follows: For at least one first-degree relative with breast cancer, RR = 11.14 (95% confidence interval [CI] = 1.54-80.39); for at least two affected first- or second-degree relatives, RR = 2.57 (95% CI = 0.23-28.22); for at least one first- or second-degree relative with breast cancer, RR = 5.43 (95% CI = 1.85-15.88). CONCLUSIONS: These results suggest that mammographic density may be strongly associated with risk of breast cancer among women with a family history of the disease. Because mammographic densities can be modified by dietary and hormonal interventions, the results suggest potential approaches to the prevention of breast cancer in women with a family history of breast cancer.     

Comparisons of two breast cancer risk estimates in women with a family history of breast cancer.

There is an increasing need for accurate prediction methods of assessing individual risk for breast cancer for both clinical and research purposes. The purpose of this study is to compare the Gail and Claus model risk estimates of breast cancer among women with a family history of breast cancer. This study presents risk estimates from two models of breast cancer risk in 491 women 18 to 74 years of age with a family history of breast cancer who were recruited to risk counseling clinical trials in Seattle, Washington between 1996 and 1997. These trials included women from the general population and additional samples of Ashkenazi Jewish, African-American, and lesbian women. We estimated and compared lifetime (to age 79) and 5-year risk for developing breast cancer using the National Surgical Adjuvant Breast and Bowel Project adaptation of the Gail model and the Claus model. About one-quarter of participants fell into the Gail "high" risk category (> or =1.7% risk of developing breast cancer in the next 5 years). The average lifetime risk was estimated at 13.2% by the Gail model and 11.2% by the Claus model. Estimates from the two models were moderately and positively correlated (r = 0.55) with the Gail model yielding a higher estimate than the Claus model for most participants. If women with a family history of breast cancer are being counseled regarding decisions on genetic testing, tamoxifen use, or other preventive measures, presenting both Claus and Gail estimates may be the best option.     

Variation in breast cancer hormone receptor and HER2 levels by etiologic factors: a population-based analysis

Evidence suggests that breast cancer hormone receptor status varies by etiologic factors, but studies have been inconsistent. In a population-based case-control study in Poland that included 2,386 cases and 2,502 controls, we assessed ER-alpha and PR status of tumors based on clinical records according to etiologic exposure data collected via interview. For 842 cancers, we evaluated ER-alpha, ER-beta, PR and HER2 levels by semiquantitative microscopic scoring of immunostained tissue microarrays and a quantitative immunofluorescence method, automated quantitative analysis (AQUAtrade mark). We related marker levels in tumors to etiologic factors, using standard regression models and novel statistical methods, permitting adjustment for both correlated tumor features and exposures. Results obtained with different assays were generally consistent. Receptor levels varied most significantly with body mass index (BMI), a factor that was inversely related to risk among premenopausal women and directly related to risk among postmenopausal women with larger tumors. After adjustment for correlated markers, exposures and pathologic characteristics, PR and HER2 AQUA levels were inversely related to BMI among premenopausal women (p-trend = 0.01, both comparisons), whereas among postmenopausal women, PR levels were associated directly with BMI (p-trend = 0.002). Among postmenopausal women, analyses demonstrated that BMI was related to an interaction of PR and HER2: odds ratio (OR) = 0.86 (95% CI = 0.69-1.07) for low PR and HER2 expression vs. OR = 1.78 (95% CI = 1.25-2.55) for high expression (p-heterogeneity = 0.001). PR and HER2 levels in breast cancer vary by BMI, suggesting a heterogeneous etiology for tumors related to these markers.     

Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women

The associations between endogenous sex hormone levels and breast cancer risk in postmenopausal women are well established. Mammographic density is a strong risk factor for breast cancer, and possibly an intermediate marker. However, the results from studies on the associations between endogenous sex hormones and mammographic density are conflicting. The authors examined the associations between circulating levels of sex hormones, sex hormone binding globulin (SHBG) and prolactin and mammographic densities among postmenopausal women not currently using postmenopausal hormone therapy (HT). The authors also examined if insulin-like growth factor-I (IGF-I) levels influenced the association between estrogen and mammographic density. Altogether, 722 postmenopausal participants in the Norwegian governmental mammographic screening program had endogenous hormone concentrations measured. Mammograms were classified according to percent and absolute mammographic density using a previously validated computer-assisted method. After adjustment for age, number of children, age at menopause, body mass index and HT use, both plasma concentrations of SHBG (p-trend = 0.003) and estrone (p-trend = 0.07) were positively associated with percent mammographic density. When the analyses were stratified according to median IGF-I concentration, the weak association between estrone and mammographic density was strengthened among women with IGF-I levels below median, while the association disappeared among women with over median IGF-I levels (p for interaction = 0.02). In summary, the authors found a positive association between plasma SHBG levels and mammographic densities among 722 postmenopausal Norwegian women not currently using HT. Further, the authors found a positive but weak association between plasma estrone concentration and mammographic density, which appeared to be modified by IGF-I levels.     

Risk Factors for breast cancer among japanese women: A case-control study in Ibaraki, Japan

BACKGROUND: The number of epidemiologic studies on breast cancer risk factorsin Japanese women is still quite limited. Our objective was to clarify the relationship between lifestyle, body size and breast cancer risk. METHODS: A matched case-control study was conducted in Ibaraki, Japan. The participants were 148 women aged 26-69 diagnosed with breast cancer at Tsukuba University Hospital or Tsukuba Medical Center Hospital between January, 1990 and March, 1997. Two controls were individually matched to the cases by age and residence. A self-administered questionnaire was used to obtain information on the family history of breast cancer, reproductive history, education, body size and lifestyle factors. Conditional logistic regression analysis was used to estimate oddsratios (ORs)and 95% confidence intervals (95% CI). RESULTS: After adjustment for potential confounders, heavy weight and higher body mass index were associated with an increased risk of breast cancer among postmenopausal women (OR = 1.76, 95% CI = 0.69, 4.48; OR = 1.57, 95% CI=0.61, 3.99, respectively). Current or ex-smokers were found to be at an increased risk for breast cancer (OR = 3.33; 95% CI = 1.63, 6.80). Women who take hot baths had a decreased risk for breast cancer (OR = 0.67; 95% CI = 0.43, 1.06). Recreational physical activity was associated with a reduced risk of breast cancer (PTrend = 0.005).OR for breast cancer among physically active women was 0.36 (95% CI = 0.19, 0.70), as compared with inactive women. Taller women had an increased risk of breast cancer relative to shorter women (OR = 1.49; 95% CI = 0.83, 2.70). No significant association between alcohol consumption and breast cancer risk was detected. CONCLUSION: Our results suggest that several potentially modifiable lifestyle factors may be useful for the prevention of breast cancer.     

Medical radiation,family history of cancer,and benign breast disease in relation to breast cancer risk in young women,USA

OBJECTIVE: In previous studies breast cancer risk has been increased among women who received high doses (above 100–200 cGy) of ionizing radiation or those exposed to lower doses prior to age 20. Some evidence suggests that such risk may be distinctly elevated among women with a family history of breast or ovarian cancer (probably only carriers of specific gene mutations) and women with benign breast disease (BBD).METHODS: A population-based case–control study in Los Angeles County obtained interview data from 744 women who were aged 40 or younger and diagnosed with breast cancer during 1983–1988, and from 744 matched controls. Women with a positive family history of breast or ovarian cancer reported cancer in a mother, sister, or grandmother. Women with BBD reported a physician diagnosis. Radiation exposure was defined as a history of either radiation therapy or moderate exposure to medical radiography.RESULTS: Breast cancer risk was elevated among women exposed to medical radiation prior to age 20 years (odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.2–1.8), relative to unexposed women. This increased risk was observed only among women with a history of BBD (OR = 2.4, 95% CI = 1.6–3.7). Overall, risk was not associated with exposure to medical radiation after age 20 years, although among women with a positive family history of breast or ovarian cancer, exposed women had an increased risk (OR = 1.8, 95% CI = 1.0–3.1). Breast cancer risk was not increased among women with a family history of breast/ovarian cancer exposed to medical radiation before age 20 years or those with BBD exposed to medical radiation after age 20 years.DISCUSSION: Study participants may have received radiation doses that are no longer common, hampering study generalizability. Although differences in recall between cases and controls cannot be completely excluded, women with BBD or a family history of breast cancer appear to have greater breast cancer risk following relatively low ionizing radiation exposure than other women in this study.     

Obesity,body size,and risk of postmenopausal breast cancer: the Women's Health Initiative (United States)

OBJECTIVE: Body size is an important modifiable risk factor for breast cancer. Although obesity has generally been found to be associated with increased risk for postmenopausal breast cancer, there remain questions concerning the role of body fat distribution, lifetime weight history, and effects within specific subgroups of women.METHODS: We assessed the relationship of several anthropometric measures and risk of postmenopausal breast cancer in 85,917 women aged 50–79 at entry in the Women's Health Initiative Observational Study. Women were enrolled during 1993–1998 at 40 clinics in the US and 1030 developed invasive breast cancer by April 2000. Upon entry, trained clinical center staff measured each woman's height, weight, and waist and hip circumference.RESULTS: Anthropometric factors were not associated with breast cancer among women who had ever used hormone replacement therapy (HRT). Among HRT non-users, heavier women (baseline body mass index (BMI) > 31.1) had an elevated risk of postmenopausal breast cancer (relative risk (RR) = 2.52; 95% confidence interval (CI) = 1.62–3.93), compared to slimmer women (baseline BMI 22.6). The elevation in risk associated with increasing BMI appeared to be most pronounced among younger postmenopausal women. Change in BMI since age 18, maximum BMI, and weight were also associated with breast cancer in HRT non-users. While both waist and hip circumference were associated with breast cancer risk, their ratio, a measure of fat distribution, was not (RR = 1.33; 95% CI = 0.88–2.01).CONCLUSIONS: Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.     

Family history of breast cancer as a risk factor for ovarian cancer in a prospective study

BACKGROUND: A family history of breast cancer has been associated with increased ovarian cancer risk. However, few studies have assessed risk according to characteristics that suggest an inherited cancer susceptibility disorder, such as earlier-than-usual age at cancer diagnosis, family members with double primary cancers of different types, multiple relatives with cancer, and cancer in both members of paired organs. METHODS: Ovarian cancer risk was assessed according to a detailed breast cancer family history among 49,975 participants in the Breast Cancer Detection Demonstration Project Breast Cancer Defection Demenstration Project (BCDDP) Follow-up Study (1979-1998). In all, 362 incident ovarian cancers were identified during follow-up and rate ratios (RRs) were calculated by Poisson regression. RESULTS.: Breast cancer in a first- or second-degree relative was associated with increased risk of ovarian cancer (RR = 1.4; 95% confidence interval [CI] = 1.1-1.7). Having 2 or more affected first-degree relatives was associated with increased risk (RR = 1.8; 95% CI = 1.1-2.8), especially for women diagnosed with ovarian cancer before age 60 (RR = 4.2; 95% CI = 1.9-9.2) or with a personal history of breast cancer (RR = 3.7; 95% CI 1.8-7.7). Risk was also particularly high for women with 2 or more first-degree relatives with breast cancer and at least 1 affected relative diagnosed before age 50 (RR = 2.6; 95% CI = 1.4-4.8) or with bilateral breast cancer (RR = 4.2; 95% CI = 1.7-10). CONCLUSIONS: A detailed breast cancer family history as well as an individual's age and personal history of breast cancer are useful for identifying women at elevated genetic risk of ovarian cancer.     

Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study

Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0–4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow‐up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR = 0.74; 95% confidence interval (CI): 0.66–0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR = 0.81, 95% CI: 0.67–0.98) and hormone receptor double negative breast cancer (adjusted HR = 0.60, 95% CI: 0.40–0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported.     

Lifetime recreational and occupational physical activity and risk of in situ and invasive breast cancer.

Numerous studies have observed reduced breast cancer risk with increasing levels of physical activity, yet these findings have been inconsistent about optimal times of activity and effect modification by other factors. We investigated the association between recreational and occupational physical activity and breast cancer risk in a population-based case-control study in Massachusetts, New Hampshire, and Wisconsin. During structured telephone interviews, 7,630 controls, 1,689 in situ, and 6,391 invasive breast cancer cases, ages 20 to 69 years, reported lifetime history of recreational physical activity and occupation. Neither lifetime recreational nor strenuous occupational physical activity appeared to be associated with risk of breast carcinoma in situ. In contrast, recreational physical activity was associated with a reduced risk of invasive breast cancer. After adjustment for potentially confounding factors, women averaging >6 h per week of strenuous recreational activity over their lifetime had a 23% reduction in the odds ratio of invasive breast cancer when compared with women reporting no recreational activity (95% confidence interval, 0.65-0.92; P(trend) = 0.05). However, this reduction in risk was limited to women without a first-degree family history of breast cancer (P(interaction) = 0.02). Inverse associations were observed for physical activity early in life, in the postmenopausal years, and in the recent past, but these findings were confined to women without a family history of breast cancer. Lifetime strenuous occupational activity was not associated with invasive breast cancer risk. These results provide further evidence that, for most women, physical activity may reduce the risk of invasive breast cancer.     

Breast cancer risk perception among women who have undergone prophylactic bilateral mastectomy

BACKGROUND: Prophylactic bilateral mastectomy is a preventive option for women who are at high risk of developing breast cancer. We compared the perceptions of breast cancer risk among women who had previously undergone prophylactic bilateral mastectomy with objective estimates of their breast cancer risk. METHODS: We asked 75 women in the Canadian province of Ontario who had undergone prophylactic bilateral mastectomy between 1991 and 2000 to provide a complete family history of the cancers that had occurred by the time of their surgery and to indicate their BRCA1 and BRCA2 gene mutation status. This information was used to generate estimates of each woman's risk for breast cancer by using the Gail model, the Claus model, and the BRCAPRO model. Sixty of the women also provided their own estimates of their lifetime risks of developing breast cancer before and after they had prophylactic mastectomy. Risk estimates were compared using Wilcoxon's signed-rank test and Pearson's product-moment correlation analysis. All statistical tests were two-sided. RESULTS: The women estimated that their lifetime risk of developing breast cancer before surgery was, on average, 76% (range = 20%-100%) and after surgery was 11.4% (range = 0%-60%). The mean estimated absolute risk reduction the women attributed to prophylactic mastectomy was 64.8%. The average computer-generated risk estimates were 59% for the 14 women who reported that they carried a BRCA1 or BRCA2 gene mutation and 17% for the other women (of whom 43 had a strong family history of breast cancer and 18 had a limited family history). Breast cancer risk was statistically significantly overestimated by all women except for the known BRCA1 and BRCA2 gene mutation carriers. CONCLUSION: Women who undergo prophylactic bilateral mastectomy have an exaggerated perception of their breast cancer risk before surgery. Formal genetic counseling and genetic testing may result in more accurate risk perceptions to guide women in choosing other preventive options.     

Circulating Sex Hormones and Mammographic Breast Density among Postmenopausal Women

The use of breast density as an intermediate or predictive marker of breast cancer risk is limited by an incomplete understanding of the etiology of breast density. High blood levels of endogenous estrogens and androgens are associated with increased risk of breast cancer among postmenopausal women. We sought to examine whether these hormones are also associated with breast density. The Wisconsin Breast Density Study enrolled 257 postmenopausal women, ages 55-70 years, with no history of postmenopausal hormone use, from mammography clinics in Madison, Wisconsin. Subjects provided a blood sample for sex hormone analysis, and breast density was measured from subjects' screening mammograms using a computer-assisted thresholding method. Numerous sex hormones were associated with breast density in age-adjusted analyses. However, further adjustment for body mass index and other potentially confounding factors substantially attenuated or eliminated these associations. In the fully adjusted model, there remained a positive association between percent breast density and serum progesterone (P=0.03), with percent density rising from 11.9% (95% CI: 9.8, 14.1%) among women in the lowest quartile of serum progesterone to 15.4% (12.9, 18.2%) among women in the highest quartile. There was also a positive association between sex hormone binding globulin and percent breast density (P=0.06). In contrast, there were no independent associations between percent breast density and estradiol (total, free, or bioavailable), estrone, estrone sulfate, or testosterone (total, free, or bioavailable). These results suggest that breast density has a hormonal etiology; however, it may differ in important ways from that of breast cancer risk.