Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994–2016) and the NHSII (1995–2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81–1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90–1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74–1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48–0.94), current use (HR = 1.01; 95% CI = 0.80–1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95–1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.     

Sleep characteristics,light at night and breast cancer risk in a prospective cohort

Increasing numbers of women in the US are getting too little sleep. Inadequate sleep has been associated with impaired metabolic function and endocrine disruption. Sister Study cohort participants (n = 50,884), completed baseline and follow‐up questionnaires on sleep patterns. Incident breast cancers estrogen receptor (ER) status of the tumor were ascertained from questionnaires and medical records. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). Analyses of sleep characteristics reported at the first follow‐up interview included only participants who were breast cancer‐free at time of follow‐up interview. Over ～7 years of follow‐up, 2,736 breast cancer cases (invasive and ductal carcinoma in situ) were diagnosed. There was little evidence that usual sleep duration or other sleep characteristics were associated with breast cancer. However, relative to those with no difficulty sleeping, women who reported having difficulty sleeping ≥ 4 nights a week were at an increased risk of overall (HR = 1.32, 95% CI: 1.09–1.61) and postmenopausal breast cancer (HR = 1.51, 95% CI 1.24–1.85). Risk of ER+ invasive cancer was elevated for women who reported having a light or television on in the room while sleeping (HR = 1.20, 95% CI: 0.97–1.47) or who typically got less sleep than they needed to feel their best (HR = 1.21, 95% CI: 0.98–1.50). In our study, most sleep characteristics, including sleep duration, were not associated with an increased risk although higher risk was observed for some markers of inadequate or poor quality sleep.     

Mammographic density and estrogen receptor status of breast cancer.

BACKGROUND: The density of breast tissue on a mammogram is a strong predictor of breast cancer risk and may reflect cumulative estrogen effect on breast tissue. Endogenous and exogenous estrogen exposure increases the risk of estrogen receptor (ER)-positive breast cancer. We determined if mammographic density is associated more strongly with ER-positive breast cancer than with ER-negative breast cancer.METHODS: We analyzed data from 44,811 participants in the San Francisco Mammography Registry of whom 701 developed invasive breast cancer. Mammographic density was measured using the Breast Imaging Reporting and Data System (BI-RADS) classification system (1 = almost entirely fat, 2 = scattered fibroglandular, 3 = heterogeneously dense, 4 = extremely dense). We tested for associations between mammographic density and ER-positive and ER-negative breast cancer separately. Analyses were adjusted for age, body mass index, postmenopausal hormone use, family history of breast cancer, menopausal status, parity, and race/ethnicity.RESULTS: Mammographic density was strongly associated with both ER-positive and ER-negative breast cancers. Compared with women with BI-RADS 2, women with BI-RADS 1 (lowest density) had a lower risk of ER-positive cancer [adjusted hazard ratio (HR), 0.28; 95% confidence interval (95% CI), 0.16-0.50] and ER-negative cancer (adjusted HR, 0.17; 95% CI, 0.04-0.70). Women with BI-RADS 4 (highest density) had an increased risk of ER-positive breast cancer (adjusted HR, 2.21; 95% CI, 1.64-3.04) and an increased risk of ER-negative breast cancer (adjusted HR, 2.21; 95% CI, 1.16-4.18).CONCLUSION: Surprisingly, women with high mammographic density have an increased risk of both ER-positive and ER-negative breast cancers. The association between mammographic density and breast cancer may be due to factors besides estrogen exposure.     

Reproductive factors,hormone use and gastric cancer risk: The Singapore Chinese Health Study

Gastric cancer incidence varies greatly worldwide, but is consistently twice as high in men than in women. The hormone‐related factors hypothesized to be associated with lower risk of gastric cancer in women have not been fully explored in populations with a high background risk of gastric cancer. The Singapore Chinese Health Study (SCHS) is a prospective cohort study in which 34,022 of the participants enrolled between 1993 and 1998 were women between 45 and 74 years of age. Information on reproductive histories, hormone replacement therapy (HRT) and oral contraceptive (OC) use was collected through in‐person interviews at baseline. As of December 31, 2013, 269 incident gastric cancer cases were identified. Multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate gastric cancer risk associations. Older age at natural menopause (≥55 versus <45 years: HR = 0.50, 95% CI: 0.25–0.99), type of menopause (other versus natural: HR = 0.48, 95% CI: 0.27–0.87) and greater years of menstrual cycling (fourth versus first quartile: HR = 0.67, 95% CI: 0.46–0.96) were associated with a decreased risk of gastric cancer. Ever use of OCs and HRT was also associated with reduced risk of gastric cancer; the multivariable‐adjusted HRs (95% CIs) were 0.40 (0.17–0.90) for use of HRT >3 years and 0.67 (0.47–0.94) for ever use of OCs, compared with never use. Reproductive factors associated with a longer window of fertility and the use of exogenous hormones were shown to reduce gastric cancer development in a cohort of Chinese women with a high background risk of gastric cancer.     

Breast cancer risk in relation to history of preeclampsia and hyperemesis gravidarum: Prospective analysis in the Generations Study

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.     

Bladder cancer risk and personal hair dye use

Several cohort and case-control studies have found an increased risk of bladder cancer among hairdressers and barbers who are occupationally exposed to hair dyes. However, the carcinogenic risk associated with personal use of hair dyes remains uncertain since several large case-control and cohort studies did not find an association between personal hair dye use and bladder cancer. To address this question, the authors used data collected on 459 bladder cancer cases and 665 controls who were interviewed as part of a case-control study conducted in New Hampshire between 1994 and 1998. Participants underwent a structured personal interview with regard to history of hair dye use and bladder cancer risk factors. Unconditional logistic regression analysis was used to compute odds ratios that were associated with hair dye use, while controlling for potential confounding factors. A history of any hair dye use was inversely associated with bladder cancer incidence in men [adjusted odds ratio (OR) = 0.5; 95% confidence interval (CI)=0.3-0.8], although risk reductions were not statistically significant for individual dye types. In women, use of permanent (adjusted OR = 1.5; 95%CI = 0.8-2.7) and rinse-type hair dye (adjusted OR = 1.7; 95%CI = 0.8-3.6) were associated with a modestly elevated risk of bladder cancer but with limited statistical precision; no association was found with use of semi-permanent dyes (adjusted OR = 0.7; 95%CI = 0.3-1.4). For permanent hair dye use, odds ratios were most pronounced for younger age at first use, higher frequency and prolonged time since first use; however there were no clear trends in risk by these factors. In light of the prevalence of hair dye use, further studies are needed that address the effects of specific colors and types of hair dyes along with the possible role of individual susceptibility.     

The association between metabolic health,obesity phenotype and the risk of breast cancer

Beyond the current emphasis on body mass index (BMI), it is unknown whether breast cancer risk differs between metabolically healthy and unhealthy normal weight or overweight/obese women. The Sister Study is a nationwide prospective cohort study. Data came from 50,884 cohort participants aged 35 to 74 years enrolled from 2003 through 2009. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for breast cancer risk. Metabolic abnormalities considered included: high waist circumference (≥88 cm); elevated blood pressure (≥130/85 mm Hg or antihypertensive medication); previously diagnosed diabetes or antidiabetic drug treatment; and cholesterol‐lowering medication use. During follow‐up (mean, 6.4 years), 1,388 invasive breast cancers were diagnosed at least 1 year after enrollment. Compared to women with BMI <25 kg/m² with no metabolic abnormalities (metabolically healthy normal weight phenotype), women with a BMI <25 kg/m² and ≥1 metabolic abnormality (metabolically unhealthy, normal weight phenotype) had increased risk of postmenopausal breast cancer (HR = 1.26, 95% CI: 1.01–1.56), as did women with a BMI ≥25 kg/m² and no metabolic abnormalities (metabolically healthy overweight/obese phenotype) (HR = 1.24, 95% CI: 0.99–1.55). Furthermore, risk of postmenopausal breast cancer was consistently elevated in women with normal BMI and central obesity (normal weight central obesity phenotype) regardless of the criterion used to define central obesity, with HR for waist circumference ≥88 cm, waist circumference ≥80 cm, and waist‐hip ratio ≥0.85 of 1.58, 95% CI: 1.02–2.46; 1.38, 95% CI: 1.09–1.75; and 1.38, 95% CI: 1.02–1.85, respectively. There was an inverse association between premenopausal breast cancer and metabolically healthy overweight/obese phenotype (HR = 0.71, 95% CI: 0.52–0.97). Our findings suggest that postmenopausal women who are metabolically unhealthy or have central adiposity may be at increased risk for breast cancer despite normal BMI.     

A dietary pattern based on estrogen metabolism is associated with breast cancer risk in a prospective cohort of postmenopausal women

Increased exposure to estrogen is a risk factor for postmenopausal breast cancer, and dietary factors can influence estrogen metabolism. However, studies of diet and breast cancer have been inconclusive. We developed a dietary pattern associated with levels of unconjugated estradiol and the ratio of 2‐ and 16‐hydroxylated estrogen metabolites in a subsample of Prostate, Lung, Colorectal and Ovarian Screening Trial (PLCO) participants (n = 653) using reduced rank regression, and examined its association with postmenopausal breast cancer prospectively in the larger PLCO cohort (n = 27,488). The estrogen‐related dietary pattern (ERDP) was comprised of foods with positively‐weighted intakes (non‐whole/refined grains, tomatoes, cruciferous vegetables, cheese, fish/shellfish high in ω‐3 fatty acids, franks/luncheon meats) and negatively‐weighted intakes (nuts/seeds, other vegetables, fish/shellfish low in ω‐3 fatty acids, yogurt, coffee). A 1‐unit increase in the ERDP score was associated with an increase in total (HR: 1.09, 95% CI: 1.01–1.18), invasive (HR: 1.13; 95% CI: 1.04–1.24) and estrogen receptor (ER)‐positive (HR: 1.13, 95% CI: 1.02–1.24) breast cancer risk after adjustment for confounders. Associations were observed for the fourth quartile of ERDP compared with the first quartile for overall breast cancer (HR: 1.14; 95% CI: 0.98–1.32), invasive cases (HR: 1.20, 95% CI: 1.02–1.42) and ER‐positive cases (HR: 1.19; 95% CI: 0.99–1.41). The increased risk associated with increasing ERDP score was more apparent in strata of some effect modifiers (postmenopausal hormone therapy non‐users and non‐obese participants) where the relative estrogen exposure due to that factor was lowest, although the p values for interaction were not statistically significant. Results suggest a dietary pattern based on estrogen metabolism is positively associated with postmenopausal breast cancer risk, possibly through an estrogenic influence.     

Association between sleep duration and breast cancer incidence: The multiethnic cohort

Breast cancer is the most common cancer and the second-leading cause of cancer-related death among women. Inconsistent findings for the relationship between melatonin levels, sleep duration and breast cancer have been reported. We investigated the association of sleep duration at cohort entry and its interaction with body mass index (BMI) with risk of developing breast cancer in the large population-based Multiethnic Cohort study. Among the 74,481 at-risk participants, 5,790 breast cancer cases were identified during the study period. Although we detected no significant association between sleep duration and breast cancer incidence, higher risk estimates for short (HR = 1.03; 95% CI: 0.97–1.09) and long sleep (HR = 1.05; 95% CI: 0.95–1.15) compared to normal sleep (7–8 hr) were found. The patterns for models stratified by age, BMI, ethnicity and hormone receptor status were similar but did not indicate significant interaction effects. When examining the combined sleep duration and BMI interaction effect, in comparison to the normal BMI-normal sleep group, risk estimates for underweight, overweight and obesity were similar across categories of sleep duration (≤6, 7–8, and ≥9 hr). The underweight-normal sleep group had lower breast cancer incidence (HR = 0.66, 95% CI: 0.50–0.86), whereas the overweight-short sleep, overweight-normal sleep group and all obese women experienced elevated breast cancer incidence. The respective HRs for short, normal and long sleep among obese women were 1.35 (95% CI: 1.20–1.53), 1.27 (95% CI: 1.15–1.42) and 1.46 (95% CI: 1.21–1.76). Future perspectives need to examine the possibility that sleep quality, variations in circadian rhythm and melatonin are involved in breast cancer etiology.     

Personal use of hair dye and cancer risk in a prospective cohort of Chinese women

Although widely studied over the past 40 years, personal use of hair dye generally has not been associated with overall cancer risk. The association between hair dye use and risk of bladder and hematopoietic cancers has been less conclusive. Most hair dye studies have been case-control studies conducted in Caucasian populations. We examined the relationship between personal hair dye use and cancer risk in a prospective cohort of 70 366 Chinese women. After an average of 7 years of follow up, 2437 women were newly diagnosed with cancer by 31 December 2005. Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI) of cancer risk associated with hair dye use, adjusting for potential confounding factors. Compared with women who reported no hair dye use, ever users had an overall cancer risk of 0.89 (95% CI 0.82, 0.97). No significant association was observed for several common cancers, including cancers of the breast (RR 0.93, 95% CI 0.78, 1.09), lung (RR 0.81, 95% CI 0.62, 1.09), stomach (RR 0.90, 95% CI 0.66, 1.21), and colorectum (RR 1.04, 95% CI 0.84, 1.28). We also found no significant association with most other cancers, including bladder cancer (RR 1.14, 95% CI 0.56, 2.35) and hematopoietic cancers overall (RR 0.89, 95% CI 0.59, 1.35) or their subtypes, including non-Hodgkin lymphoma, multiple myeloma, and leukemia. We generally found no evidence of an association between personal use of hair dye and cancer risk, although our study is limited by small numbers for certain cancer types. ( Cancer Sci 2009; 100: 1088–1091)     

Prospective study of breast cancer in relation to coffee,tea and caffeine in Sweden

Studies of coffee and tea consumption and caffeine intake as risk factors for breast cancer are inconclusive. We assessed coffee and tea consumption, caffeine intake, and possible confounding factors among 42,099 women from the Swedish Women's Lifestyle and Health study, the participants of which were aged 30–49 years at enrollment in 1991–1992. Complete follow‐up for breast cancer incidence was performed through 2012 via linkage to national registries. Poisson regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer. During follow‐up 1,395 breast cancers were diagnosed. The RR was 0.97 (95% CI 0.94–0.99) for a 1‐unit increase in cups of coffee/day, 1.14 (95% CI 1.05–1.24) for a 1‐unit increase in cups of tea/day, and 0.97 (95% CI 0.95–1.00) for a 100 mg/day increase in caffeine intake. Although the RR for no consumption (RR = 0.86, 95% CI 0.69–1.08), a group with a relatively small number of women, was not statistically significant, women with higher consumption had a decreased breast cancer risk (3–4 cups/day: RR = 0.87, 95% CI 0.76–1.00; ≥5 cups/day: RR = 0.81, 95% CI 0.70–0.94) compared to women consuming 1–2 cups of coffee/day. Compared to no consumption, women consuming >1 cups tea/day showed an increased breast cancer risk (RR = 1.19, 95% CI 1.00–1.42). Similar patterns of estimates were observed for breast cancer risk overall, during pre‐ and postmenopausal years, and for ER+ or PR+ breast cancer, but not for ER? and PR? breast cancer. Our findings suggest that coffee consumption and caffeine intake is negatively associated with the risk of overall and ER+/PR? breast cancer, and tea consumption is positively associated with the risk of overall and ER+/PR+ breast cancer.     

Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta‐analysis

Statins have shown antineoplastic properties in preclinical studies with breast cancer cells. They inhibit the enzyme “HMG CoA reductase” and the expression of this enzyme in cancer cells has been implicated as a favorable prognostic factor in patients with breast cancer. After a search of MEDLINE and Embase from inception through November 2015, 817 abstracts were reviewed to identify studies that described an association between statin use and outcomes in breast cancer. A total of 14 studies which included 75,684 women were identified. In a meta‐analysis of 10 studies, statin use was associated with improved recurrence‐free survival (RFS; HR 0.64; 95% CI 0.53–0.79, I² = 44%). Furthermore, this RFS benefit appeared to be confined to use of lipophilic statins (HR 0.72; 95% CI 0.59–0.89) as hydrophilic statin use was not associated with improvement in RFS (HR 0.80; 95% CI 0.44–1.46). Statin users similarly showed improved overall survival in a meta‐analysis with substantial heterogeneity (8 studies, HR 0.66; 95% CI 0.44–0.99, I² = 89%). Statin users also had improved cancer‐specific survival, although this relationship was measured with less precision (six studies, HR 0.70; 95% CI 0.46–1.06, I² = 86%). In conclusion, breast cancer patients who use statins, or specifically, lipophilic statins show improved recurrence‐free survival. Statin users also had improved overall survival and cancer‐specific survival. These findings should be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs should be identified.     

The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status

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.     

Personal use of hair dyes and risk of bladder cancer: a meta-analysis of epidemiologic data

OBJECTIVE: We compared, updated, and expanded the analyses of two previous meta-analyses of personal hair dye exposure and bladder cancer, and briefly discussed the biological plausibility of a systemic hazard to human health from exposure to para-phenylenediamine (PPD), a key chemical in hair dyes. METHODS: The meta-analysis included 11 case-control studies and one cohort study. We evaluated heterogeneity across studies and conducted sensitivity and influence analyses. RESULTS: No association was found between any personal use of hair dye and bladder cancer among women (meta-relative risk [mRR] = 1.01, 95% CI: 0.89-1.14), men (mRR = 0.82, 95% CI: 0.60-1.14), or both sexes combined (mRR = 0.97, 95% CI: 0.87-1.08). No statistically significant mRRs were found among the studies that reported data for permanent hair dye use (mRR = 1.06, 95% CI: 0.89-1.27), duration of any hair dye use (mRR = 1.00, 95% CI: 0.85-1.19), duration of permanent hair dye use (mRR = 1.31 95% CI 0.78-2.19), lifetime applications of any hair dye use (mRR = 1.12 (95% CI: 0.72-1.72) or permanent hair dye use (mRR = 1.59, 95% CI 0.69-3.64), or dark color hair dye use (mRR = 0.94, 95% CI: 0.74-1.19). CONCLUSION: The results of this meta-analysis of epidemiologic studies do not indicate a causal association between personal hair dye use and bladder cancer.     

Weight and weight changes in early adulthood and later breast cancer risk

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.     

Tea consumption and breast cancer risk in a cohort of women with family history of breast cancer

Laboratory studies have observed chemopreventive effects of black and green tea on breast cancer development, but few epidemiologic studies have identified such effects. We investigated the association between tea consumption and breast cancer risk using data from 45,744 U.S. and Puerto Rican women participating in the Sister Study. Frequency and serving size of black and green tea consumption were measured at cohort enrollment. Breast cancer diagnoses were reported during follow-up and confirmed by medical record review. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We further investigated potential variation according to estrogen receptor (ER) status, menopausal status and body mass index (BMI). Overall, 81.6 and 56.0% of women drank black or green tea, respectively. A total of 2,809 breast cancer cases were identified in the cohort. The multivariable model suggested an inverse association between black (≥5 vs. 0 cups/week: HR = 0.88, 95% CI 0.78, 1.00, p-trend = 0.08) and green tea (≥5 vs. 0 cups/week: HR = 0.82, 95% CI 0.70, 0.95, p-trend < 0.01) consumption and breast cancer risk. We did not observe differences by ER characteristics, menopausal status or BMI. In conclusion, our study suggests drinking at least five cups of green or black tea per week may be associated with decreased breast cancer risk.     

Chemical exposures in the workplace and breast cancer risk: A prospective cohort study

We investigated the relationship between workplace chemical exposures and breast cancer risk among women enrolled in the Sister Study, a prospective cohort study of US and Puerto Rican women. A total of 47,640 participants reported work outside of the home. Workplace exposure to eleven agents (acids, dyes or inks, gasoline or other petroleum products, glues or adhesives, lubricating oils, metals, paints, pesticides, soldering materials, solvents and stains or varnishes) was characterized based on self‐reports of frequency and duration of use. Approximately 14% of the study population reported exposure to only one agent and 11% reported working with two or more of the 11 agents in their lifetime. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for each agent, adjusting for established breast cancer risk factors. During follow‐up, 1,966 cases of breast cancer were reported. Although there were no significant associations between ever use of the eleven agents evaluated and breast cancer risk, women with cumulative exposure to gasoline or petroleum products at or above the highest quartile cutoff had an elevated risk of total (HR: 2.3, 95%CI: 1.1–4.9) and invasive (HR: 2.5, 95%CI: 1.1–5.9) breast cancer compared with women in the lowest quartile group (p_trend = 0.03). Workplace exposure to soldering materials was associated with an increased risk of premenopausal breast cancer (HR = 1.8, 95% CI = 1.1–3.0). Findings support the need for further studies to elucidate the role of occupational chemicals in breast cancer etiology.     

Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer

Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta‐analyses have been null for late‐life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p′‐DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p′‐DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer. A population‐based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996–1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow‐up of 5 and 15 years, we identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer‐related. Using Cox regression models, we estimated the multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lipid‐adjusted organochlorine concentrations with all‐cause and breast cancer‐specific mortality. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all‐cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer‐specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all‐cause and breast cancer‐specific mortality. Third tertile DDE concentrations were inversely associated with 15‐year all‐cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population‐based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals.     

Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone women's health initiative clinical trials

The associations between breast tenderness during use of conjugated equine estrogen (CEE) therapy with or without medroxyprogesterone (MPA) therapy and subsequent breast cancer risk are unknown. We analyzed data from the Women’s Health Initiative Estrogen plus Progestin (N = 16,608, 5.6 years intervention) and estrogen-alone (N = 10,739, 6.8 years intervention) clinical trials until trial close-out (Spring 2005). At baseline and annually, participants underwent mammography and clinical breast exam. Self-reported breast tenderness was assessed at baseline and 12 months. Invasive breast cancer was confirmed by medical record review. The risk of new-onset breast tenderness after 12 months was significantly higher among women assigned to active therapy than placebo (CEE-alone vs. placebo risk ratio [RR] 2.15, 95% confidence interval [CI] 1.97–2.35; CEE + MPA vs. placebo RR 3.07, 95% CI 2.85–3.30). CEE + MPA doubled the risk of invasive breast cancer among women with baseline breast tenderness (hazard ratio [HR] 2.16, 95% CI 1.29–3.74), but had a smaller effect among women without baseline breast tenderness (HR 1.17; 95% CI 0.97–1.41). New-onset breast tenderness was associated with a higher risk of breast cancer among women assigned to CEE + MPA (HR 1.33, 95% CI 1.02–1.72, P = 0.03), but not among women assigned to CEE-alone (HR 0.98, 95% CI 0.62–1.53). New-onset breast tenderness during use of CEE + MPA was associated with increased subsequent breast cancer risk. The association of CEE + MPA therapy with increased breast cancer risk was especially pronounced among women with baseline breast tenderness.