Risk of Premenopausal and Postmenopausal Breast Cancer among Multiple Sclerosis Patients.
ABSTRACT: To investigate risk of premenopausal and postmenopausal breast cancer among Multiple Sclerosis (MS) patients, considering tumor stage.The Swedish Patient Register identified 19,330 women with MS between 1968 and 2012, matched individually with a cohort of 193,458 without MS. Matching variables were year of birth, sex, region of residence and vital status at the time of diagnosis. The cancer register identified 471 and 5,753 breast cancer cases among the MS and non-MS cohorts, respectively. Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (CI) for premenopausal and postmenopausal breast cancer.Overall risk of postmenopausal breast cancer was 13% higher among MS patients compared with women without MS (HR = 1.13, 95% CI 1.02-1.26). Stratified analyses showed that the risk was statistically significantly increased in women diagnosed between 1968 and 1980 and those who were diagnosed at age 65 or older age. We observed a non-statistically significant risk only for stage 0-1 postmenopausal breast cancer (HR = 1.17, 95% CI 0.93-1.48). MS was not associated with premenopausal breast cancer.The modest increased risk of postmenopausal breast cancer in women with MS may be due to surveillance bias, where contact with health services for one disease increases the risk of a second diagnosis being recorded.
Project description:Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as a risk factor for breast cancer; however few studies - most confined to postmenopausal women - have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women.We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models.Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004).These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of metabolic syndrome through lifestyle changes could confer protection against breast cancer.
Project description:Obesity is a well-established cause of postmenopausal breast cancer. However, early life adiposity is inversely associated with breast cancer incidence. To understand these conflicting relations, we use validated measures to assess adiposity in childhood and late adolescence, as well as weight change, in relation to total invasive breast cancer incidence and receptor subtypes. We conducted a prospective observational study among 74,177 women from the Nurses' Health Study from 1980-2012, with updated risk factors every 2 years during which 4,965 incident invasive breast cancers occurred. Overall, weight at age 18 was inversely associated with both premenopausal (HR per 30 kg?=?0.52, 95% CI?=?0.39-0.71) and postmenopausal (HR per 30 kg?=?0.81, 95% CI?=?0.72-0.92) breast cancer which was largely explained by adiposity at age 10. Long-term weight gain from age 18 both during premenopause and postmenopause were positively associated with postmenopausal breast cancer risk. However, premenopausal weight gain was not related to premenopausal breast cancer risk. Furthermore, weight gain since age 18 was positively associated with ER+/PR+ postmenopausal breast cancer (HR per 30 kg?=?1.50, 95% CI?=?1.36-1.65) but not ER+/PR- (HR per 30 kg?=?0.96, 95% CI?=?0.78-1.19) or ER-/PR- (HR per 30 kg?=?1.16, 95% CI?=?0.95-1.42) postmenopausal breast cancer. Overall, 17% of ER+/PR+ postmenopausal breast cancer and 14% of total postmenopausal breast cancer are attributable to weight gain of?>?5 kg since age 18.
Project description:BACKGROUND:Greater body mass index (BMI), a measure of overall adiposity, is associated with a higher risk of postmenopausal breast cancer. The role of central adiposity, often measured by waist circumference, is less well understood, especially among premenopausal women. The objective of the current study was to examine multiple measures of adiposity in relation to breast cancer in a prospective cohort study. METHODS:A total of 50,884 Sister Study cohort participants aged 35 to 74 years were enrolled from 2003 through 2009. Inclusion criteria for the cohort included having a sister previously diagnosed with breast cancer. Trained study personnel measured height, weight, and waist and hip circumference during a home visit and study participants completed a detailed questionnaire. Using Cox regression analysis, we estimated multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk associated with adiposity measurements, considering tumor subtype and menopausal status. RESULTS:In total, 2009 breast cancers were diagnosed during follow-up (mean?=?5.4 years). Weight, BMI, waist circumference, and waist-to-hip ratio were found to be positively associated with overall breast cancer risk and HRs were greater among postmenopausal women, those with hormonally responsive tumors, and women who were not currently using postmenopausal hormones. In models that adjusted for BMI, waist circumference associations persisted among both postmenopausal women (81-88 cm vs ?80 cm: HR?=?1.16 [95% CI 1.01-1.35] and >88 cm vs ?80 cm: HR?=?1.30 [95% CI 1.10-1.54]) and premenopausal women (81-88 cm vs ?80 cm: HR?=?1.56 [95% CI 1.19-2.04] and >88 cm vs ?80 cm: HR?=?1.30 [95% CI 0.91-1.87]). CONCLUSIONS:Findings from this large, prospective study with examiner-measured body size indicate that waist circumference is independently and positively associated with both premenopausal and postmenopausal breast cancer risk.
Project description:Soy food intake has previously been associated with reduced breast cancer risk. Epidemiological evidence for subgroups of breast cancer, particularly by menopausal and hormone receptor status, is less consistent. To evaluate the role of hormone receptor and menopausal status on the association between soy food intake and breast cancer risk, we measured usual soy food intake in adolescence and adulthood via food frequency questionnaire in 70,578 Chinese women, aged 40-70 years, recruited to the Shanghai Women's Health Study (1996-2000). After a median follow-up of 13.2 years (range: 0.01-15.0), 1,034 incident breast cancer cases were identified. Using Cox models, we found that adult soy intake was inversely associated with breast cancer risk [hazard ratio (HR) for fifth versus first quintile soy protein intake?=?0.78; 95% confidence interval (CI):0.63-0.97]. The association was predominantly seen in premenopausal women (HR?=?0.46; 95% CI:0.29-0.74). Analyses further stratified by hormone receptor status showed that adult soy intake was associated with significantly decreased risk of estrogen receptor (ER)+/progesterone receptor (PR)+ breast cancer in postmenopausal women (HR?=?0.72; 95% CI:0.53-0.96) and decreased risk of ER-/PR- breast cancer in premenopausal women (HR?=?0.46; 95% CI:0.22-0.97). The soy association did not vary by human epidermal growth factor-2 (HER2) status. Furthermore, we found that high soy intake during adulthood and adolescence was associated with reduced premenopausal breast cancer risk (HR?=?0.53; 95% CI: 0.32-0.88; comparing third vs. first tertile) while high adulthood soy intake was associated with postmenopausal breast cancer only when adolescent intake was low (HR?=?0.63; 95% CI: 0.43-0.91). Our study suggests that hormonal status, menopausal status and time window of exposure are important factors influencing the soy-breast cancer association.
Project description:BACKGROUND: The influence of parity and time interval between age at first pregnancy (AFP) and age at diagnosis on breast cancer survival is not established in the same way as their influence on breast cancer risk. We aimed to investigate the association of time interval or parity with prognosis in pre- and postmenopausal women in Korea. METHODS: We conducted a retrospective study of 29,167 women with breast cancer through the Korean Breast Cancer Registry from 1993-2009. Information on reproductive factors, including breastfeeding, AFP, and parity were collected from a routine questionnaire. Conditional logistic regression was used to estimate the associations between menopausal status and overall mortality (OM) and breast-cancer-specific mortality (BCSM), adjusting for treatment and stage. RESULTS: High parity (?5) increased the hazard ratios (HR) of BCSM (HR?=?1.33, 95% confidence interval (CI): 0.83-2.11, p?<?0.001) and OM (HR?=?1.20, 95% CI: 0.85-1.68.73, p?<?0.001) in premenopausal and postmenopausal women (BCSM, HR: 1.62, 95% CI: 0.93-2.82, p?<?0.001; OM, HR?=?1.58, 95% CI: 1.14-2.21, p <0.001). A longer time interval between age at breast cancer diagnosis and AFP reduced the HRs of BCSM (HR?=?0.97, 95% CI: 0.96-0.98, p?=?0.001) and OM (HR?=?0.98, 95% CI: 0.97-0.98, p?<?0.001) in premenopausal women, but had an adverse effect on the HR of OM (HR?=?1.03, 95% CI: 1.02-1.03, p?<?0.001) in postmenopausal women. CONCLUSIONS: High parity (?5) was associated with poor breast cancer prognosis in both pre- and postmenopausal women. The time intervals between reproductive events had different effects on breast cancer outcomes depending on menopausal status.
Project description:Importance:Many established breast cancer risk factors are used in clinical risk prediction models, although the proportion of breast cancers explained by these factors is unknown. Objective:To determine the population-attributable risk proportion (PARP) for breast cancer associated with clinical breast cancer risk factors among premenopausal and postmenopausal women. Design, Setting, and Participants:Case-control study with 1:10 matching on age, year of risk factor assessment, and Breast Cancer Surveillance Consortium (BCSC) registry. Risk factor data were collected prospectively from January 1, 1996, through October 31, 2012, from BCSC community-based breast imaging facilities. A total of 18?437 women with invasive breast cancer or ductal carcinoma in situ were enrolled as cases and matched to 184?309 women without breast cancer, with a total of 58?146 premenopausal and 144?600 postmenopausal women enrolled in the study. Exposures:Breast Imaging Reporting and Data System (BI-RADS) breast density (heterogeneously or extremely dense vs scattered fibroglandular densities), first-degree family history of breast cancer, body mass index (>25 vs 18.5-25), history of benign breast biopsy, and nulliparity or age at first birth (?30 years vs <30 years). Main Outcomes and Measures:Population-attributable risk proportion of breast cancer. Results:Of the 18?437 women with breast cancer, the mean (SD) age was 46.3 (3.7) years among premenopausal women and 61.7 (7.2) years among the postmenopausal women. Overall, 4747 (89.8%) premenopausal and 12?502 (95.1%) postmenopausal women with breast cancer had at least 1 breast cancer risk factor. The combined PARP of all risk factors was 52.7% (95% CI, 49.1%-56.3%) among premenopausal women and 54.7% (95% CI, 46.5%-54.7%) among postmenopausal women. Breast density was the most prevalent risk factor for both premenopausal and postmenopausal women and had the largest effect on the PARP; 39.3% (95% CI, 36.6%-42.0%) of premenopausal and 26.2% (95% CI, 24.4%-28.0%) of postmenopausal breast cancers could potentially be averted if all women with heterogeneously or extremely dense breasts shifted to scattered fibroglandular breast density. Among postmenopausal women, 22.8% (95% CI, 18.3%-27.3%) of breast cancers could potentially be averted if all overweight and obese women attained a body mass index of less than 25. Conclusions and Relevance:Most women with breast cancer have at least 1 breast cancer risk factor routinely documented at the time of mammography, and more than half of premenopausal and postmenopausal breast cancers are explained by these factors. These easily assessed risk factors should be incorporated into risk prediction models to stratify breast cancer risk and promote risk-based screening and targeted prevention efforts.
Project description:BACKGROUND:Recreational physical activity has been consistently associated with reduced breast cancer risk. Less is known about how family history of breast cancer affects the association and whether it varies by menopausal status. METHODS:The Sister Study is a cohort of 50,884 women who had a sister with breast cancer but no prior breast cancer themselves at enrollment. Women reported all recreational sport/exercise activities they participated in over the past 12 months. Hours/week and MET-hours/week of physical activity were considered in association with breast cancer risk. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated with Cox regression. Extent of family history, examined as a modifier, was characterized by a Bayesian score incorporating characteristics of the family structure. RESULTS:During follow-up (average 8.4 years), 3,023 cases were diagnosed. Higher hours/week (HR?7vs<1 = 0.77; 95% CI, 0.66-0.90) and MET-hours/week (HRquartile4vs1 = 0.75; 95% CI, 0.67-0.85) of physical activity were associated with reduced postmenopausal breast cancer risk. Hours/week and MET-hours/week were associated with suggestively increased premenopausal breast cancer risk (MET-hours/week HRquartile4vs1 = 1.25; 95% CI, 0.98-1.60). Associations did not vary with extent of family history. However, the increased risk in premenopausal women may be limited to those with stronger family history. CONCLUSIONS:In women with a family history of breast cancer, physical activity was associated with reduced postmenopausal, but not premenopausal, breast cancer risk and was not modified by extent of family history. IMPACT:This was the first study to examine the association between physical activity and breast cancer risk in a large population with a family history of breast cancer.
Project description:Preeclampsia and hyperemesis gravidarum are pregnancy complications associated with altered sex hormone levels. Previous studies suggest preeclampsia may be associated with a decreased risk of subsequent breast cancer and hyperemesis with an increased risk, but the evidence remains unclear. We used data from the Generations Study, a large prospective study of women in the United Kingdom, to estimate relative risks of breast cancer in relation to a history of preeclampsia and hyperemesis using Cox regression adjusting for known breast cancer risk factors. During 7.5 years average follow-up of 82,053 parous women, 1,969 were diagnosed with invasive or in situ breast cancer. Women who had experienced preeclampsia during pregnancy had a significantly decreased risk of premenopausal breast cancer (hazard ratio (HR) =0.67, 95% confidence interval (CI): 0.49-0.90) and of HER2-enriched tumours (HR = 0.33, 95% CI: 0.12-0.91), but there was no association with overall (HR = 0.90, 95% CI: 0.80-1.02) or postmenopausal (HR = 0.97, 95% CI: 0.85-1.12) breast cancer risk. Risk reductions among premenopausal women were strongest within 20 years since the last pregnancy with preeclampsia. Hyperemesis was associated with a significantly increased risk of HER2-enriched tumours (HR = 1.76, 95% CI: 1.07-2.87), but not with other intrinsic subtypes or breast cancer risk overall. These results provide evidence that preeclampsia is associated with a decreased risk of premenopausal and HER2-enriched breast cancer and that hyperemesis, although not associated with breast cancer risk overall, may be associated with raised risk of HER2-enriched tumours.
Project description: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.
Project description:<h4>Background</h4>MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen.<h4>Patients and methods</h4>Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis.<h4>Results</h4>At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03).<h4>Conclusions</h4>Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.