Postmenopausal hormone use and incident ovarian cancer: Associations differ by regimen

Ovarian cancer has been associated in epidemiologic studies with postmenopausal hormone use. Whether associations differ by hormone regimen, current status or duration of use is unclear. We examined epithelial ovarian cancer incidence in relation to unopposed estrogen (E-only) and estrogen plus progestin (E + P) among 54,436 postmenopausal women of the Cancer Prevention Study II Nutrition Cohort, a US cohort prospectively followed for cancer incidence since 1992. Demographic, medical, reproductive and lifestyle information was collected at enrollment and updated throughout follow-up via self-administered questionnaire. Extended Cox models were used to estimate age- and multivariate-adjusted relative risk (RR) of ovarian cancer according to hormone regimen, current status and duration of use. During 15 years of follow-up, 297 incident cases were identified. Relative to "never" use of hormones, current E-only use was associated with a twofold higher risk [RR 2.07, 95% confidence interval (CI) 1.50-2.85]; each 5-year increment of use was associated with a 25% higher risk (RR 1.25, 95% CI 1.15-1.36); ≥ 20 years of use was associated with a near threefold higher risk (RR 2.89; 95% CI 1.71-4.87; trend p = 0.01). Past E-only use was not significantly associated with ovarian cancer, although a modest increase in risk per each 5-year increment of use was suggested (RR 1.14, 95% CI 0.92-1.41). Neither current nor former E + P use was associated with ovarian cancer risk (RR 1.08, 95% CI 0.86-1.35; RR 1.08, 95% CI 0.68-1.71, respectively, per 5-year increment). These findings suggest that progestins may mitigate some of the detrimental effects of estrogen on the ovarian epithelium.     

A prospective study of smoking and risk of breast cancer in young adult women.

OBJECTIVES: To investigate the association between smoking and invasive breast cancers characterized by their estrogen receptor status in a large prospective study of mainly premenopausal women. METHODS: 112,844 women aged 25-42 years in 1989 were followed 10 years; questionnaire information on medical illnesses and risk factors was collected biennially and information on diet was collected in 1991 and 1995. During this period of follow-up (1,077,536 person-years), 1009 incident breast cancer cases were documented. RESULTS: In the multivariate-adjusted models, smoking status was not significantly related to overall breast cancer risk: compared with never smokers, the relative risks (RRs) were 1.18 [95% confidence interval (CI) 1.02-1.36] for past smokers and 1.12 (95% CI 0.92-1.37) for current smokers. Increasing duration of smoking before the first pregnancy was associated with a greater risk of breast cancer, although little increase was seen in the highest category: compared with never smokers, RRs were 1.42 (95% CI 1.10-1.83) for 15-19 years of smoking and 1.10 (95% CI 0.80-1.52) for >/=20 years of smoking (P for trend = 0.01). Smoking was related most strongly to the risk of estrogen receptor-positive breast cancers. For women who had smoked for >/=20 years, the RR of estrogen receptor-positive cancer was 1.37 (95% CI 1.07-1.74) and the RR of estrogen receptor-negative cancer was 1.04 (95% CI 0.71-1.53). For smoking before age 15, the RRs were 1.49 (95% CI 1.03-2.17) for estrogen receptor-positive cancer and 1.19 (95% CI 0.69-2.08) for estrogen receptor-negative cancer. CONCLUSIONS: Our results suggest that longer duration of smoking may be related to the risk of estrogen receptor-positive breast cancer but possibly less so for estrogen receptor-negative breast cancer.     

Postmenopausal estrogen and progestin use in relation to breast cancer risk.

Epidemiological evidence now consistently supports a modest increase in breast cancer risk among women using postmenopausal hormones, usually estrogens.Less is known regarding how the addition of progestin affects breast cancer risk. The objective of this study was to investigate the type and duration of postmenopausal therapy and breast cancer risk. We performed a multicenter population-based case-control study set in Massachusetts, New Hampshire, and Wisconsin. The subjects were 5298 postmenopausal women (age range, 50-79 years) with a new diagnosis of invasive breast cancer from statewide tumor registries. For comparison, 5571 controls were randomly selected from population lists. Participants completed a structured telephone interview covering hormone use and breast cancer risk factors. Multivariable regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). The RR for breast cancer increased with longer durations of hormone use, about 2%/year for estrogen alone (RR, 1.02; 95% CI, 1.01-1.03) and 4%/year for estrogen-progestin use (RR, 1.04; 95% CI, 1.01-1.08). Estrogen-progestin use that was both recent and long term (>5 years in duration) was more strongly associated with breast cancer risk (RR, 1.57; 95% CI, 1.15-2.14) than similar use of estrogen alone (RR, 1.39; 95% CI, 1.17-1.65). In estrogen-progestin users, risks were similar for sequential and continuous use regimens but perhaps stronger for lobular than ductal breast cancer. Use of progestin alone was associated with a doubling of risk (RR, 2.09; 95% CI, 1.07-4.07 for ever use versus nonuse). Estrogen-progestin use, both sequential and continuous, appears to be more strongly associated with risk of breast cancer than use of estrogen alone.     

A prospective study of postmenopausal hormone use and ovarian cancer risk

The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk is unclear, particularly for specific hormone formulations, but recent studies suggest that there is a positive association. We conducted a prospective observational study with 82,905 postmenopausal women, including 389 ovarian cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users of PMH, both current and past users of > or =5 years had a significantly elevated risk of ovarian cancer (RR=1.41, 95% confidence interval (CI) 1.07-1.86 and relative risk (RR)=1.52, 95% CI 1.01-2.27, respectively). Examined by hormone type in continuous years, use of unopposed estrogen was associated with a significant increase in the risk of epithelial ovarian cancer (P for trend <0.001; RR for 5-year increment of use=1.25, 95% CI 1.12-1.38). Use of estrogen plus progestin (RR for 5-year increment of use=1.04, 95% CI 0.82-1.32) was not significantly associated with ovarian cancer risk. Generally, results were similar for serous tumours (RR for 5-year increment of unopposed estrogen use=1.23, 95% CI 1.07-1.40) and slightly stronger for endometrioid tumours (RR for 5-year increment of unopposed estrogen use=1.53, 95% CI 1.20-1.94). Recency of use was not significantly associated with ovarian cancer risk, but statistical power was limited here.     

Prognostic characteristics of breast cancer among postmenopausal hormone users in a screened population.

PURPOSE: We determined the risk of breast cancer and tumor characteristics among current postmenopausal hormone therapy users compared with nonusers, by duration of use. METHODS: From January 1996 to December 2000, data were collected prospectively on 374,465 postmenopausal women aged 50 to 79 years who underwent screening mammography. We calculated the relative risk (RR) of breast cancer (invasive or ductal carcinoma-in-situ) and type of breast cancer within 12 months of postmenopausal therapy use among current hormone users with a uterus (proxy for estrogen and progestin use) and without a uterus (proxy for estrogen use), compared with nonusers. RESULTS: Compared with nonusers, women using estrogen and progestin for >/= 5 years were at increased risk of breast tumors of stage 0 or I (RR, 1.51; 95% CI, 1.37 to 1.66), stage II or higher (RR, 1.46; 95% CI, 1.30 to 1.63), size 相似文献   

Endometrial cancer and menopausal hormone therapy in the National Institutes of Health-AARP Diet and Health Study cohort

BACKGROUND: Menopausal hormone therapy formulations for women without hysterectomy have included estrogen plus progestin for years, but endometrial cancer risks associated with the use of sequential and continuous estrogen-plus-progestin regimens remain unclear. METHODS: The National Institutes of Health-AARP Diet and Health Study included 73,211 women who were ages 50 years to 71 years at baseline and who completed 2 questionnaires (1995-1996 and 1996-1997). Linkage to state cancer registries and mortality indices identified 433 incident endometrial cancers through 2000. Using proportional hazards regression, the authors estimated relative risks (RRs) and 95% confidence intervals (95% CIs) relative to never-use of hormone therapy. RESULTS: In 51,312 women who never used hormones or only used estrogen-plus-progestin regimens at doses consistent with current practice, neither sequential estrogen plus progestin (daily estrogen plus progestin for 10-14 days per cycle: RR, 0.74; 95% CI, 0.39-1.40) nor continuous estrogen plus progestin (daily estrogen plus progestin for >/=20 days per cycle: RR, 0.80; 95% CI, 0.55-1.15) had any statistically significant association with endometrial cancer. Long durations (>/=5 years) of sequential regimen use (RR, 0.79; 95% CI, 0.38-1.66) and of continuous regimen use (RR, 0.85; 95% CI, 0.53-1.36) were not associated with endometrial cancer. CONCLUSIONS: Confirmation that these estrogen-plus-progestin regimens neither increase nor decrease the risk of endometrial cancer could influence menopausal symptom management for women who are considering estrogen-plus-progestin therapy.     

Active and passive smoking and breast cancer risk in middle-aged Japanese women

To examine the hypothesis that tobacco smoke is associated with the risk of female breast cancer, we estimated the relative risks of active and passive smoke in middle-aged Japanese women in a population-based prospective study. The cohort consisted of residents in 4 public health center areas, aged 40 to 59 years. A self-administered questionnaire survey was conducted in 1990. This analysis included 21,805 subjects, 180 of whom had developed breast cancer by December 31, 1999. When the reference was defined as never-active smokers without passive smoking, adjusted relative risks (RRs) were 1.9 (95% confidence interval [CI] = 1.0-3.6) in current active smokers, 1.2 (95% CI = 0.4-4.0) in ex-active smokers and 1.2 (95% CI = 0.8-1.6) in never-active smokers with passive smoking. The elevated risk for ever-smokers was clearly observed in premenopausal women at baseline (RR = 3.9, 95% CI = 1.5-9.9) but not in postmenopausal women (RR = 1.1, 95% CI = 0.5-2.5). In never-active smokers, the adjusted RR for passive smoking, residential or occupational/public tobacco smoke exposure was 1.1 (95% CI = 0.8-1.6). In premenopausal women, passive smoking increased the risk (RR = 2.6; 95% CI = 1.3-5.2) but not in postmenopausal women (RR = 0.7; 95% CI = 0.4-1.0). We conclude that tobacco smoking increases the risk of female breast cancer in premenopausal women.     

Hormonal risk factors for endometrial cancer: modification by cigarette smoking (United States)

Objectives: To evaluate whether smoking modifies the risk of endometrial cancer associated with body mass index (BMI), postmenopausal hormone use, and other hormonal factors. Methods: Using multivariate adjusted models we examined interview data from a population-based case–control study of Wisconsin women (n = 740 cases, n = 2372 controls). Results: The relative risk for endometrial cancer associated with current smoking was 0.8 (95% CI: 0.6–1.0) compared to never smokers. No clear dose–response relationship was evident for pack-years smoked. When examined according to smoking status the risk associated with the highest quartile of BMI seemed to be greater among non-smokers (OR = 3.6, 95% CI: 2.4–5.3) than among current smokers (OR = 2.8, 95% CI: 1.4–5.6). Among postmenopausal women the risk associated with current use of postmenopausal hormones appeared to be greater among non-smokers (OR = 3.3, 95% CI: 2.3–4.9) than among current smokers (OR = 2.7, 95% CI: 1.3–5.5). Risk for long-term use (10 or more years) compared with never users was 8.3 (95% CI: 4.6–15.1) among never smokers and 2.5 (95% CI: 0.8–7.9) among current smokers. The risk associated with non-insulin-dependent diabetes was greater among non-smokers (OR = 2.5, 95% CI: 1.7–3.6) than current smokers (OR = 1.1, 95% CI: 0.4–3.1). There was no modifying effect of smoking on the risk associated with parity. Conclusion: These results suggest that smoking moderates the risk associated with endometrial cancer among women at greatest risk, specifically women who are obese or who use postmenopausal hormones.     

Risk of endometrial cancer in relationship to cigarette smoking: results from the EPIC study

Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53-0.93), while it was 1.75 (95% CI = 1.13-2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59-1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54; 95% CI = 1.47-4.38 and HR = 2.23; 95% CI = 1.04-4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer.     

Endometrial carcinoma risks among menopausal estrogen plus progestin and unopposed estrogen users in a cohort of postmenopausal women.

BACKGROUND: Because unopposed estrogen substantially increases endometrial carcinoma risk, estrogen plus progestin is one menopausal hormone therapy formulation for women who have not had a hysterectomy. However, endometrial carcinoma risks among estrogen plus progestin users and among former unopposed estrogen users are not firmly established. METHODS: We evaluated endometrial carcinoma risks associated with estrogen plus progestin and unopposed estrogen therapies in 30,379 postmenopausal Breast Cancer Detection Demonstration Project follow-up study participants. We ascertained hormone therapy use and other risk factors during telephone interviews and mailed questionnaires between 1979 and 1998. We identified 541 endometrial carcinomas via self-report, medical records, the National Death Index, and state cancer registries. Poisson regression generated time-dependent rate ratios (RR) and 95% confidence intervals (95% CI). RESULTS: Endometrial carcinoma was significantly associated with estrogen plus progestin only use (n = 68 cancers; RR, 2.6; 95% CI, 1.9-3.5), including both sequential (progestin <15 days per cycle; n = 32 cancers; RR, 3.0; 95% CI, 2.0-4.6) and continuous (progestin at least 15 days per cycle; n = 15 cancers; RR, 2.3; 95% CI, 1.3-4.0) regimens. The RR increased by 0.38 (95% CI, 0.20-0.64) per year of estrogen plus progestin use, and RRs increased with increasing duration of use for both regimens. The strong association with unopposed estrogen use declined after cessation but remained significantly elevated > or =10 years after last use (RR, 1.5; 95% CI, 1.0-2.1). CONCLUSIONS: Both estrogen plus progestin regimens significantly increased endometrial carcinoma risk in this study. Risks among unopposed estrogen users remained elevated long after last use. The prospect that all estrogen plus progestin regimens increase endometrial carcinoma risk deserves continued research.     

Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts

We examined the associations of body mass index (BMI), waist circumference, a history of diabetes, and cigarette smoking with risk of pancreatic cancer among 37,147 women and 45,906 men followed up during 560,666 person-years in the Swedish Mammography Cohort and the Cohort of Swedish Men; 136 incident cases of pancreatic cancer were diagnosed. The multivariate rate ratio (RR) of pancreatic cancer for obese women and men (BMI > or =30 kg/m(2)) was 1.81 (95% CI: 1.04-3.15) compared to those with a BMI of 20-25 kg/m(2). For a difference of 20 cm (about two standard deviations) in waist circumference, the multivariate RRs were 1.32 (95% CI: 0.73-2.37) among women and 1.74 (95% CI: 1.00-3.01) among men. Pancreatic cancer risk was associated with history of diabetes (multivariate RR: 1.88; 95% CI: 1.09-3.26) and cigarette smoking (multivariate RR for current compared with never smokers: 3.06; 95% CI: 1.99-4.72). Current smokers of > or =40 pack-years had a five-fold elevated risk compared with never smokers. Risk among past smokers approached the RR for never smokers within 5-10 years following smoking cessation. Findings from this prospective study support positive relationships of overall obesity, abdominal adiposity, diabetes and smoking with risk of pancreatic cancer.     

Alcohol consumption and endometrial cancer risk: the multiethnic cohort

The role of alcohol intake in the etiology of endometrial cancer is unclear. We examined the impact of alcohol intake on endometrial cancer risk among 41,574 postmenopausal African-American, Japanese-American, Latina, Native-Hawaiian and White women recruited to the prospective Multiethnic Cohort Study in 1993-1996. During an average of 8.3 years of follow-up, 324 incident invasive endometrial cancer cases were identified among these women. Data on alcohol intake and endometrial cancer risk factors were obtained from the baseline questionnaire. Relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with alcohol intake were estimated using log-linear (Cox) proportional hazard models stratified by age, year of recruitment, ethnicity and study center, and adjusted for several confounding factors. Increased alcohol consumption was associated with increased risk (p trend = 0.013). Compared to nondrinkers, women consuming >or=2 drinks/day had a multivariate RR of 2.01 (95% CI: 1.30, 3.11). There was no increase in risk associated with <1 drink/day (RR = 1.01; 95% CI: 0.77, 1.33) and 1 to <2 drinks/day (RR = 1.09; 95% CI: 0.62, 1.93). There was no clear effect modification by body mass index, postmenopausal hormone use, parity, oral contraceptive use or smoking status, though our power to detect such interactions was limited. Our results suggest that only alcohol consumption equivalent to 2 or more drinks per day increases risk of endometrial cancer in postmenopausal women.     

Risk of endometrial cancer following estrogen replacement with and without progestins.

BACKGROUND: Unopposed estrogen replacement therapy (i.e., estrogen without progestins) increases the risk of endometrial cancer. In this study, we examined the endometrial cancer risk associated with combined estrogen-progestin regimens currently in use, since the safety profiles of these regimens have not been clearly defined. METHODS: We conducted a nationwide population-based, case-control study in Sweden of postmenopausal women aged 50-74 years. We collected information on use of hormone replacement from 709 case patients with incident endometrial cancer and from 3368 control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) as estimates of relative risks. All individual comparisons were made with women who never used the respective hormone replacement regimens. RESULTS: Treatment with estrogens alone was associated with a marked duration- and dose-dependent increase in the relative risk of endometrial cancer. Five or more years of treatment had an OR of 6.2 for estradiol (95% confidence interval [CI] = 3.1-12.6) and of 6.6 for conjugated estrogens (95% CI = 3.6-12.0). Following combined estrogen-progestin use, the association was considerably weaker than that for estrogen alone; the OR was 1.6 (95% CI = 1.1-2.4) after 5 or more years of use. This increase in risk was confined to women with cyclic use of progestins, i.e., fewer than 16 days per cycle (most commonly 10 days per cycle [OR = 2.9; 95% CI = 1.8-4.6 for 5 or more years of use]), whereas continuous progestin use along with estrogens was associated with a reduced risk (OR = 0.2; 95% CI = 0.1-0.8 for 5 or more years of use). CONCLUSION: The risk of developing endometrial cancer is increased after long-term use of estrogens without progestins and with cyclically added progestins. Continuously added progestins may be needed to minimize the endometrial cancer risk associated with estrogen replacement therapy.     

Postmenopausal hormone therapy is associated with a reduced risk of colorectal cancer lacking CDKN1A expression

Experimental studies have shown that estrogen- or progesterone-activated signaling leads to growth inhibition effects on colon cancer cells through the upregulation of several cell-cycle regulators. However, epidemiologic studies evaluating hormone therapy use and colorectal cancer risk by the status of cell-cycle regulators are lacking. In this study, we used data from the prospective Nurses' Health Study to evaluate whether the association between hormone therapy use and colorectal cancer risk differs by the molecular pathologic status of microsatellite instability (MSI) and expression of cell-cycle-related tumor biomarkers, including CDKN1A (p21, CIP1), CDKN1B (p27, KIP1), and TP53 (p53) by immunohistochemistry. Duplication Cox regression analysis was used to determine an association between hormone therapy use, cancer risk, and specific tumor biomarkers in 581 incident colon and rectal cancer cases that occurred during 26 years of follow-up among 105,520 postmenopausal women. We found a difference between hormone therapy use and colorectal cancer risk according to CDKN1A expression (P(heterogeneity) = 0.01). Current hormone therapy use was associated with a reduced risk for CDKN1A-nonexpressed [multivariate relative risk (RR), 0.61; 95% confidence interval (CI), 0.46-0.82] but not for CDKN1A-expressed (RR, 1.32; 95% CI, 0.76-2.31) tumors. The lower risk for CDKN1A-nonexpressed but not for CDKN1A-expressed cancers was also present among current users of estrogen-alone therapy. We found no significant difference in the relations between hormone therapy use and cancer risk according to MSI, CDKN1B, or TP53 status. Together, our molecular pathological epidemiology findings suggest a preventive effect of hormone therapy against colorectal carcinogenesis that depends, in part, on loss of cyclin-dependent kinase inhibitor CDKN1A.     

Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project

The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk. Among postmenopausal women, the joint exposure to higher body mass index (BMI) and the variant C allele was associated with an increased risk of breast cancer [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.15-2.22]. The joint exposure to the variant C allele and long-term use of hormone replacement therapy (HRT) (>51 months) was related to an increased risk of breast cancer (OR, 1.51; 95% CI, 0.99-2.31) especially estrogen receptor-positive, progesterone receptor-positive breast cancer (OR, 1.87; 95% CI, 1.08-3.25). Among the control population, the CYP17 variant C allele was inversely associated with long-term use of postmenopausal HRT and a higher BMI in postmenopausal women. In conclusion, the findings suggest that the CYP17 variant C allele may increase breast cancer risk in conjunction with long-term HRT use and high BMI in postmenopausal women.     

Plasma prolactin concentrations and risk of postmenopausal breast cancer

Prolactin is important in human breast development, and substantial laboratory and in vitro data suggest a role in mammary carcinogenesis. Therefore, we conducted a prospective case-control study nested within the Nurses' Health Study cohort to examine, in detail, the association between plasma prolactin concentrations and postmenopausal breast cancer by cancer invasiveness, estrogen receptor/progesterone receptor status, and other subject characteristics, including postmenopausal hormone use. Blood samples were collected from 1989 to 1990 and prolactin was measured by microparticle enzyme immunoassay. The analysis included 851 cases of postmenopausal breast cancer diagnosed after blood collection and before June 2000, in which there were one or two controls (n=1,275) matched on age, postmenopausal hormone use, fasting status, and time of day and month of blood collection. Prolactin was associated with a modestly increased risk of postmenopausal breast cancer [relative risk, top versus bottom quartile, 1.34; 95% confidence interval (CI), 1.02-1.76; P-trend = 0.01]. The association differed by estrogen receptor/progesterone receptor status (P-heterogeneity=0.03). The relative risk was 1.78 (95% CI, 1.28, 2.50; P-trend < 0.001) for estrogen receptor+/progesterone receptor+, 0.76 (95% CI, 0.43, 1.32; P-trend=0.28) for estrogen receptor-/progesterone receptor-, and 1.94 (95% CI, 0.99, 3.78; P-trend=0.12) for estrogen receptor+/progesterone receptor- breast cancers. Associations generally were similar for ductal and lobular carcinomas (P-heterogeneity=0.43) and by tumor size (P-heterogeneity=0.24). Among estrogen receptor+/progesterone receptor+ cancers, the association did not significantly differ by postmenopausal hormone use, years between blood draw and diagnosis, or after adjustment for estradiol (relative risk, 1.93; 95% CI, 1.16, 3.22; P-trend=0.01). Our prospective data suggest that plasma prolactin concentrations are associated with an increased risk of postmenopausal breast cancer, particularly for estrogen receptor+/progesterone receptor+ cancers, and independently of estradiol.     

Cigarette smoking and subsequent risk of lung cancer by histologic type in middle-aged Japanese men and women: the JPHC study

In order to update the findings of relative risk associated with cigarette smoking for lung cancer by histologic type in Japan, the data from a population-based cohort study of 91,738 men and women were analyzed. During 1990-1999, 422 lung cancer incident cases were identified. The relative risk for all incident cases associated with current smokers versus non-smokers was 4.5 [95% confidence interval (CI): 3.0-6.8] and 4.2 (95% CI: 2.4-7.2), for men and women, respectively. When divided by histologic type, relative risk for squamous cell carcinoma and small cell carcinoma was 12.7 (95% CI: 4.7-34.7) and 17.5 (95% CI: 4.9-62.1), while for adenocarcinoma it was 2.8 (95% CI: 1.6-4.9) and 2.0 (95% CI: 0.8-5.0) for men and women, respectively. We confirmed that the lung cancer risk in men rose with increasing cigarette smoking, especially the duration of smoking among current smokers and decreased after the cessation of smoking among former smokers. Unlike the US or European countries, the relative risk did not increase in this updated study, compared with previous studies in 1960s to 1990s in Japan either for all incident cases or for specific histologic types and the magnitude of relative risks was substantially lower than that observed in the US or European countries, especially for adenocarcinoma.     

Body mass and endometrial cancer risk by hormone replacement therapy and cancer subtype.

Epidemiologic studies unequivocally show that greater body mass increases the risk of endometrial cancer, but whether risk varies by use of postmenopausal hormone therapy (HT), location of fat deposition, or cancer subtype is still unclear. We examined these associations among 33,436 postmenopausal women in the Cancer Prevention Study II Nutrition Cohort, who completed questionnaires on diet, lifestyle, and medical history at baseline in 1992. A total of 318 cases were eligible through June 2003. Cox-proportional hazards analyses were used to estimate multivariate-adjusted rate ratios (RR). As expected, adult body mass index (BMI) was a strong predictor of risk [RR, 4.70; 95% confidence interval (CI), 3.12-7.07 for BMI 35+ versus 22.5-25.0, P trend < 0.0001]. Use of estrogen plus progestin postmenopausal HT modified the association. Among never-users, risk was significantly linear across the entire range of BMI examined (RR, 0.51; 95% CI, 0.29-0.92 for <22.5 versus 22.5-25.0; RR, 4.41; 95% CI, 2.70-7.20 for > or =35 versus 22.5-25.0, P trend < 0.0001), but among ever estrogen plus progestin users, the association was not significant (P trend = 1.0; P interaction < 0.0001). We observed no difference in risk according to tendency for central versus peripheral fat deposition. Greater BMI (> or =30 versus <25.0) increased risk of both "type I" (classic estrogen pathway, RR, 4.22; 95% CI, 3.07-5.81) and "type II" (serous, clear cell, and all other high grade) cancers (RR, 2.87; 95% CI, 1.59-5.16). The increased risk of endometrial cancer across the range of BMI in women who never used postmenopausal HT stresses the need to prevent both overweight and obesity in women.     

Reproductive factors, hormone use and the risk of lung cancer among middle-aged never-smoking Japanese women: a large-scale population-based cohort study

Although a link between female hormonal factors and the risk of lung cancer has been suggested, few studies have examined this association in detail. We investigated the associations between reproductive factors, hormone use and the risk of lung cancer in a population-based prospective study. Self-administered questionnaires were distributed to 44,677 lifelong never-smoking women in 1990-1994 to assess menstrual and reproductive factors and hormone use. After 8-12 years of follow-up, 153 lung cancer cases were diagnosed. Relative risk (RR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazards model. Age at menopause, age at menarche, number of children, age at first live birth, breast feeding and use of hormones were not associated with a risk of lung cancer, either overall or among postmenopausal women or women with natural menopause. Compared to women with both late age at menarche (> or =16) and early age at menopause (< or =50), those with either early age at menarche or late age at menopause had a >2-fold, significant increase in the risk of lung cancer. Induced menopausal women with experience of hormone replacement therapy had a significantly elevated risk compared to naturally menopausal women without female hormone use, with an RR of 2.40 (95% CI 1.07-5.40). These findings suggest that both endogenous and extraneous estrogen may be involved in the etiology of lung cancer.     

Smoking and survival after breast cancer diagnosis

We examined whether a history of smoking is associated with an increased risk of death from any cause or from breast cancer, among women diagnosed with breast cancer. This was a prospective observational study among 5,056 women from the Nurses' Health Study with Stages I-III invasive breast cancer diagnosed between 1978 and 2002 and for whom we had information on smoking, and who were followed until January 2002 or death, whichever came first. Subjects were classified as current, former or never smokers based upon smoking status at the biennial questionnaire immediately preceding the breast cancer diagnosis. In multivariate-adjusted analyses, compared with never smokers, women who were current smokers had a 43% increased adjusted relative risk (RR) [95% confidence interval (95% CI): 1.24-1.65] of death from any cause. A strong linear gradient was observed with the number of cigarettes per day smoked, p-trend <0.0001; the RR (95% CI) for 1-14, 15-24 and 25 or more cigarettes per day was 1.27 (1.01-1.61), 1.30 (1.08-1.57) and 1.79 (1.47-2.19). In contrast, there was no association with current smoking and breast cancer death; the RR (95% CI) was 1.00 (0.83-1.19). Current and past smokers were more likely than never smokers to die from primary lung cancer, chronic obstructive pulmonary disease and other lung diseases. We conclude that a history of smoking increased mortality following diagnosis with breast cancer, but did not increase mortality from breast cancer.