A case‐control study on hormone therapy as a risk factor for breast cancer in Finland: Intrauterine system carries a risk as well

The purpose of this study was to evaluate the association between postmenopausal hormone therapy (HT) and the risk for breast cancer in recently postmenopausal Finnish women. All Finnish women with first invasive breast cancer diagnosed between the ages of 50 and 62 years during 1995–2007 (n = 9,956) were identified from the Finnish Cancer Registry. For each case, 3 controls of the same age were retrieved from the Finnish Population Register. The cases and controls were linked to the national medical reimbursement register to assess the use of HT. The odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer were calculated with conditional logistic regression analysis, adjusting for parity, age at the first birth and health care district. Estradiol‐only therapy (991 users with breast cancer, n) or oral progestagen (n = 138) was not accompanied by an increased risk. Estradiol‐progestagen therapy (EPT) (n = 1,731) was associated with an elevated risk in the whole series (OR 1.36; 95% CI 1.27–1.46). The risk became detectable in less than 3 years of use. Continuous EPT use tended to be associated with a higher risk for breast cancer than the sequential EPT use. The use of tibolone (n = 80) (1.36; 1.15–1.96), a levonorgestrel‐releasing intrauterine system (LNG–IUS) alone (n = 154) (1.45; 1.97–1.77) or as a complement to estradiol (n = 137) (2.15; 1.72–2.68) was also associated with an increased risk. The association between HT use and the risk for breast cancer shows a large variation between various forms of HT, and also the use of LNG‐IUS may carry a risk.     

Menopausal hormone therapy and risk of epithelial ovarian cancer.

Substantial increase in the use of menopausal hormone therapy (HT) throughout the 1990s, followed by widespread discontinuation after the 2002 publication of the Women's Health Initiative findings, has resulted in large numbers of former HT users among U.S. women. However, few studies have examined whether ovarian cancer risk varies according to recency and duration of specific HT regimens. We assessed risk of epithelial ovarian cancer among users of unopposed estrogen (ET) and combined estrogen/progestogen (EPT). In a population-based study in Washington state, 812 women with ovarian cancer diagnosed in 2002 to 2005 and 1,313 controls were interviewed in person about the use of HT and other characteristics. Women who used a single form of therapy (ET or EPT) were compared with women who never used HT using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CIs). Risk was increased among current or recent (within the last 3 years) users of ET with > or = 5 years of use (ORs, 95% CIs: 1.6, 1.1-2.5 and 1.8, 0.8-3.7, respectively). Little increase in risk was noted among long-term ET users who discontinued use in the more distant past (OR, 1.2; 95% CI, 0.6-2.6). No increase in risk was noted among women who used only EPT, regardless of duration. Compared with women who never used HT, current users of EPT had an OR of 1.1 (95% CI, 0.8-1.5), and risk declined with increasing time since stopping; the OR was 0.7 (95% CI, 0.4-1.0) among women who had discontinued EPT within the last 3 years and 0.5 (95% CI, 0.3-0.7) among women who stopped at an earlier point. Long-term ET may be associated with an increased ovarian cancer risk that wanes after use ceases. We did not observe an increased risk with EPT, and with increasing time after stopping, a reduction in risk became increasingly evident. The progestogen component of HT may confer a risk reduction that is masked by an opposing effect of estrogen until, among former users, estrogenic influences have diminished. These findings, if replicated, may have implications both for public health and development of chemoprevention strategies.     

Do the dose or route of administration of norethisterone acetate as a part of hormone therapy play a role in risk of breast cancer: National‐wide case‐control study from Finland

We examined the associations between various doses and routes of administration of norethisterone acetate (NETA) in estrogen–progestagen therapy (EPT) and the risk of breast cancer in Finland. All Finnish women with first invasive breast cancer diagnosed between the ages of 50–62 during 1995–2007 (n = 9,956) were identified from the Finnish Cancer Registry. For each case, 3 controls of the same age were retrieved from the Finnish Population Register. The use of estradiol+NETA‐therapy by the cases and controls was traced from the national Medical Reimbursement Registry. The data were analyzed with multivariate conditional logistic regression, adjusting for parity, age at the first birth, and health care district. The continuous mode of NETA use tended to be associated with a higher rate ratio for breast cancer than the sequential use. The use of continuous “low” dose (NETA 0.5 mg + estradiol 1.0 mg) was associated with an increased rate ratio of breast cancer already in less than 3 years of use (odds ratio 1.94; 95% confidence interval 1.39–2.70) while a risk elevation for “high” dose (NETA 1.0 mg + estradiol 2.0 mg) was seen after 3 years use (1.71; 1.51–2.54). Oral and transdermal use of NETA were accompanied with comparable risks for breast cancer. In conclusion, the dose or route of administration of NETA in EPT do not modify the risks for breast cancer.     

Postmenopausal hormone therapy and breast cancer risk: the Multiethnic Cohort

Epidemiological studies indicate that menopausal estrogen-progestin therapy (EPT) use is associated with an increase in breast cancer risk. Further data are needed on whether this association varies by specific prognostic factors and ethnicity. We conducted a cohort study among 55,371 African-American, Native Hawaiian, Japanese-American, Latina and White postmenopausal women aged 45-75 years old in the Multiethnic Cohort Study (MEC). A total of 1,615 incident invasive breast cancer cases were identified over an average of 7.3 years. Adjusted relative risks (RRs) were computed for the various forms of hormone therapy (HT). Assuming current users continued HT use to the end of follow-up, current EPT use was associated with a 29% increased risk of breast cancer per 5 years of use (95% confidence interval (CI) = 23-35%), and current estrogen therapy (ET) use with a 10% increase in risk per 5 years of use (95% CI = 5-16%). These figures increased to only a very small extent when we adjusted for the estimated 3% of such women who stop HT use per year of follow-up. EPT and ET use were associated with greater risk among leaner women, but the increase in risk with EPT use was still very evident in women with BMI > or =30 kg/m(2). Current EPT use was associated with increased risk for ER+/PR+, ER+/PR- and ER-/PR- tumors. There was little difference in risk by stage of disease or histologic subtype. The increase with EPT use was clearly seen in all 5 ethnic groups; and the increase with ET in 4 of the 5 groups.     

The effect of estrogen vs. combined estrogen-progestogen therapy on the risk of colorectal cancer

Studies suggest that estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) may have different associations with colorectal cancer (CRC) risk, but data are conflicting. Prior meta-analyses did not distinguish between ET and EPT. We conducted a meta-analysis to summarize the relative risks (RR) of CRC due to ET versus EPT among peri- or postmenopausal women. From a total of 2,661 articles, four randomized controlled trials, eight cohort and eight case-control studies were included. Variables assessed included study characteristics, duration and recency of menopausal hormone therapy (HT) use, method of assessment of HT use, outcome definition and its ascertainment method. RRs were synthesized by random-effects models. We found that EPT ever use was associated with a decreased risk of CRC (RR 0.74, 95% CI 0.68-0.81), and so was ET ever use (RR 0.79, 95% CI 0.69-0.91). While current use of ET was associated with a significantly reduced risk of CRC (RR 0.70, 95% CI 0.57-0.85), former use was not (RR 0.86, 95%CI 0.67-1.11). Recency did not significantly modify the association between EPT and CRC risk. EPT former use was associated with a lower RR of CRC compared to ET former use (p = 0.008) but no such difference was observed between EPT and ET current use (p = 0.12). Overall, we found consistent evidence supporting the association between EPT and CRC risk reduction, regardless of recency. While literature for the association between ET and CRC risk is heterogeneous, our analyses suggest only current use of ET is associated with a decreased CRC risk.     

Menopausal hormone therapy and risk of melanoma: Do estrogens and progestins have a different role?

The association between use of menopausal hormone therapy (HT) and occurrence of skin malignant melanoma (SMM) is controversial. We investigated the issue in a nationwide cohort of 684,696 Norwegian women, aged 45–79 years, followed from 2004 to 2008. The study was based on linkage between Norwegian population registries. Multivariable Poisson regression models were used to estimate the effect of HT use, different HT types, routes of administration and doses of estrogen and progestin on the risk of SMM. During the median follow‐up of 4.8 years, 178,307 (26%) women used HT, and 1,476 incident SMM cases were identified. Current use of HT was associated with increased risk of SMM (rate ratios (RR) = 1.19; 95% confidence interval (CI) 1.03–1.37). Plain estrogen therapy was associated with an increased risk of SMM (RR 1.45; 95% CI 1.21–1.73), both for oral (RR 1.45; 95% CI 1.09–1.93) and vaginal (RR 1.44; 95% CI 1.14–1.84) formulations, while combined estrogen and progestin therapy (EPT) was not (RR 0.91; 95% CI 0.70–1.19). We performed a dose–response analysis of estrogen and progestin in women using tablets, and found that use of estrogens was associated with increased risk (RR 1.24; 95% CI 1.00–1.53 per 1 mg/day) and use of progestins with decreased risk (RR 0.71; 95% CI 0.57–0.89 per 10 mg/month) of SMM. In conclusion, estrogens were associated with increased risk of SMM, while combinations of estrogens and progestins were not. Our results suggest that estrogens and progestins might affect the risk of SMM in opposite ways.     

Does hormone therapy counter the beneficial effects of physical activity on breast cancer risk in postmenopausal women?

Studies consistently demonstrate that physical activity is inversely associated with postmenopausal breast cancer. Whether this association is stronger among non-hormone users or former users of menopausal hormone therapy (HT) is of interest given the marked decline in HT use since 2002. The Women's Contraceptive and Reproductive Experiences Study, a population-based case-control study of invasive breast cancer, recruited white women and black women ages 35-64 years and collected histories of lifetime recreational physical activity and HT use including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT). Among postmenopausal women (1,908 cases, 2,013 control participants), breast cancer risk declined with increasing levels of lifetime physical activity among never HT users; among short-term HT users (fewer than 5 years); and among current ET users; P (trend) values ranged from 0.004 to 0.016. In contrast, physical activity had no significant association with risk among long-term and past HT users and among current EPT users. No statistical evidence of heterogeneity was demonstrated for duration or currency of HT use. Breast cancer risk decreases with increasing lifetime physical activity levels among postmenopausal women who have not used HT, have used HT for less than 5 years, or are current ET users, yet this study was unable to demonstrate statistically that HT use modifies the relationship between physical activity and breast cancer. With profound changes in HT use occurring since 2002, it will be important in future studies to learn whether or not any association between physical activity and breast cancer among former HT users is a function of time since last HT use.     

Age-related variation in the relationship between menopausal hormone therapy and the risk of dying from breast cancer

Multiple past studies have reported a reduced risk of breast cancer-related mortality (BCM) in relation to pre-diagnostic use of hormone therapy (HT); however, the extent to which this reduction is due to heightened screening or tumor biology is unknown. Using a population-based cohort of 1,911 post-menopausal women diagnosed with invasive breast cancer at ages 45–79 from 1993 to 1999, we investigated the extent to which the reduced risk in BCM observed in relation to HT might be explained by screening patterns or tumor features. Estrogen–progestin therapy (EPT) use was associated with a decreased risk of BCM (after adjustment for age, study, mammography, stage, and treatment), but only among older women (ever use: ≥65 years: HR = 0.45 [95% CI 0.26–0.80]; <65 years: HR = 1.03 [95% CI 0.60–1.79]). Estrogen-alone therapy (ET) use was not associated with risk of BCM (ever use: ≥65 years: HR = 0.76 [95% CI 0.51–1.12]; <65 years: HR = 1.20 [95% CI 0.71–2.02]). HT users had a much greater frequency of mammography (P value <0.001). EPT use was associated with tumor characteristics related to improved prognosis in older women after adjustment for screening, including an inverse association with poorly differentiated tumors (OR = 0.57 [95% CI 0.38–0.85]) and an association with lobular tumors (OR = 1.68 [95% CI 1.07–2.65]). Beyond the influence of EPT use on screening uptake, these data indicate that the improved survival associated with pre-diagnostic EPT use may be due in part to the development of more favorable tumor characteristics.     

Do breast cancer risk factors modify the association between hormone therapy and mammographic breast density? (United States)

Objective To evaluate whether the association between hormone therapy (HT) and breast density differs by levels of breast cancer risk factors. Methods We evaluated 80,867 screening mammograms from 39,296 postmenopausal women from Washington State. We estimated odds ratios and 95% confidence intervals for dense breasts (Breast Imaging Reporting and Data System categories 3 “heterogeneously dense” and 4 “extremely dense”) compared to fatty breasts (categories 1 “almost entirely fat” and 2 “scattered fibroglandular”) among HT users compared to never users. We separately examined former HT use and current HT use by type (estrogen plus progestin therapy (EPT) and estrogen-only therapy (ET)). We stratified the associations by age, BMI, race, family history, and reproductive and menopausal factors. Results Current EPT users had a 98% (1.87–2.09) greater odds of having dense breasts and current ET users had a 71% (1.56–1.87) greater odds compared to never users. Current HT users were more likely to have dense breasts if they were older, had more children, or younger at first birth compared to never users; these associations were stronger among EPT users than ET users. Conclusions HT, particularly EPT, may reduce protective effects of older age, parity, and younger age at first birth on mammographic density.     

Use of hormone therapy and risk of breast cancer detected at screening and between mammographic screens

Postmenopausal hormone therapy (HT) is associated with increased risk of breast cancer, but in women undergoing breast cancer screening it is not clear whether use of HT is associated with increased risk of breast cancer detected at screening or between screens (interval cancer). Further, it is unclear whether the use of the HTs that have been common in Scandinavia is associated with higher risk of breast cancer than the HTs used in other countries. Our study was based on data from 296,651 women aged 50-69 years, who participated in the Norwegian Breast Cancer Screening Program during 1995-2004. After a mean enrollment time of 3.8 years, 1,512 women were diagnosed with invasive screen detected breast cancer, and 814 with invasive interval breast cancer. Cox regression models were used to estimate hazard ratios (HRs) of breast cancer associated with HT use, after adjusting for confounders. Ever users of HT had a 58% increased risk of breast cancer, compared to never users. The HRs associated with HT use were 1.45 (95% confidence interval (CI) = 1.29-1.63) for screen detected and 1.89 (95% CI = 1.61-2.23) for interval cancer. The difference between screen detected and interval cancer was statistically significant (p = 0.011). The HR of breast cancer increased with duration of HT use, but significantly more so for interval than for screen detected cancer (use of HT for 5 or more years compared to never use; HR = 2.91, 95% CI = 2.10-4.04 and HR = 1.94, 95% CI = 1.51-2.50, respectively; p = 0.002). The population attributable fraction of breast cancer due to HT use was 19.8% overall. Ever users of HT tended to develop a cancer of lower grade. No other differences in histological tumor characteristics were observed between ever and never users of HT among screen detected or interval cancers. The estimated risks of either breast cancer overall with HT use are higher in Norway than reported in similar studies from the U.S. HT-use is a stronger risk factor for interval cancer than for screen detected cancer. The increased risk of interval cancer, which may partly be due to decreased sensitivity of mammograms in HT users, remains a challenge in breast cancer screening programs.     

Adiposity and estrogen receptor-positive,postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol

Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case–cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case–control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m² compared to women with BMI 18.5–25 kg/m², the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05–2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43–2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11–2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68–1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity–breast cancer relationship but does not explain all of the association.     

Variations in sex hormone metabolism genes, postmenopausal hormone therapy and risk of endometrial cancer

We investigated whether variants in sex steroid hormone metabolism genes modify the effect of hormone therapy (HT) on endometrial cancer risk in postmenopausal non-Hispanic white women. A nested case-control study was conducted within the California Teachers Study (CTS). We genotyped htSNPs in six genes involved in the hormone metabolism in 286 endometrial cancer cases and 488 controls. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each haplotype using unconditional logistic regression, adjusting for age. The strongest interaction was observed between duration of estrogen therapy (ET) use and haplotype 1A in CYP11A1 (p(interaction) = 0.0027; p(interaction) = 0.010 after correcting for multiple testing within each gene). The OR for endometrial cancer per copy of haplotype 1A was 2.00 (95% CI: 1.05-3.96) for long-term ET users and 0.90 (95% CI: 0.69-1.18) for never users. The most significant interaction with estrogen-progestin therapy (EPT) was found for two haplotypes on CYP19A1 and EPT use (haplotype 4A, p(interaction) = 0.024 and haplotype 3B, p(interaction) = 0.043). However, neither this interaction, nor the ET or EPT interactions for any other genes, was statistically significant after correction for multiple testing. Variations in CYP11A1 may modify the effect of ET use on risk of postmenopausal endometrial cancer; however, larger studies are needed to explore these findings further.     

Different types of postmenopausal hormone therapy and mammographic density in Norwegian women

Postmenopausal hormone therapy (HT) is associated with increased risk of breast cancer. The HTs used in Scandinavia is associated with higher risk estimates than those used in most other countries. Mammographic density is one of the strongest risk factors for breast cancer, and possibly an intermediate marker for breast cancer. We decided to examine the relationship between use of different types of HT and mammographic density in Norwegian women. Altogether, 1,007 postmenopausal participants in the governmental mammographic screening program were asked about current and previous HT use. Mammograms were classified according to percent and absolute mammographic density. Overall, current users of HT had on average 3.6% higher mean percent mammographic density when compared with never users (p < 0.001). After adjustment for age at screening, number of children and BMI in a multivariate model, women using the continuous estradiol (E(2)) plus norethisterone acetate (NETA) combination had a mean percent mammographic density significantly higher than never users (6.1% absolute difference). Those using the continuous E(2) plus NETA combination had an 4.8% (absolute difference) higher mean percent mammographic density after <5 years of use when compared with never users, while the corresponding number for >or=5 years of use was 7% (p-trend < 0.001). We found similar associations when absolute mammographic density was used as the outcome variable. In summary, our study shows a statistical significant positive dose-response association between current use of the continuous E(2) plus NETA combination and both measures of mammographic density.     

Endometrial cancer associated with various forms of postmenopausal hormone therapy: a case control study

This study evaluates the effect of different modes of estradiol-progestagen therapy (EPT) regimens on the postmenopausal endometrial cancer risk in Finland. Women diagnosed with endometrial cancer in 1995-2007 at the age of 50-80 years were identified from the Finnish Cancer Registry (N = 7,261). For each case, three age-matched controls were retrieved from the Finnish Population Register. The use of EPT since 1994 was ascertained from the national Medical Reimbursement Register. Odds ratios (ORs) for different EPT regimens were calculated with conditional logistic regression analysis, adjusted for parity and ages at the deliveries. For use of <5 years, the OR for sequential EPT was 0.67 (95% confidence interval 0.52-0.86), for continuous EPT 0.45 (0.27-0.73), and for estradiol plus levonorgestrel-releasing intrauterine device system (LNG-IUS) 0.39 (0.17-0.88). A decreased risk persisted for the use of continuous EPT and estradiol plus LNG-IUS of up to 10 years. The use of long-cycle EPT showed a tendency toward an elevated risk both for exposure of <5 years (1.40; 0.82-2.38) and for estimated use of >5 years (1.63; 1.12-2.38). For an estimated exposure of >10 years, the risk for endometrial cancer was elevated for both users of long-cycle EPT (2.95; 2.40-3.62) and sequential EPT (1.38; 1.15-1.66). Norethisterone acetate and medroxyprogesterone acetate as parts of EPT did not differ in their endometrial cancer risk. The use of tibolone showed no endometrial risk. The use of sequential and long-cycle EPT is associated with an increased risk of endometrial cancer, whereas the use of continuous EPT or estradiol plus LNG-IUS shows a decreased risk.     

Infectious mononucleosis and risk of breast cancer in a prospective study of women

Purpose

The association between infectious mononucleosis (IM) and risk of breast cancer is unclear; no prospective studies have examined this relationship. We examined self-reported history and age at IM in relation to risk of invasive breast cancer.

Methods

Self-reported history and age at IM were examined in relation to risk of invasive breast cancer in a large cohort of women, the Nurses’ Health Study II (81,807 women followed from 1989 to 2007). Through questionnaires, women were asked whether they ever had IM and if so, at what age. During follow-up, 2,349 cases of invasive breast cancer were documented. Cox proportional hazards regression was used to estimate relative risks (RR) and 95?% confidence intervals (CI) for the association of IM with breast cancer.

Results

The multivariable-adjusted RR for history of IM and risk of invasive breast cancer was 1.00 (95?% CI: 0.90–1.11). Similar null results were obtained when estrogen receptor/progesterone receptor positive and negative?tumors were considered separately. There were no clear patterns of association between age at IM and risk of breast cancer: compared to women with no history of IM, those who were ≤15?years old when they had IM were at lower risk (RR: 0.77; 95?% CI: 0.60, 0.97), but there was no association for women who had IM at ages 16–19, 20–24, or 30+. However, an increased RR (1.45; 95?% CI: 1.02–2.04) was observed for women who had IM at ages 25–29.

Conclusion

Results of this large prospective study do not support a clear association between history of clinical IM and risk of invasive breast cancer.     

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.     

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   

Hormone therapy use and mammographic density in postmenopausal Norwegian women

While studies have shown that use of postmenopausal hormone therapy with estrogen and progestogen (EPT) increases mammographic density, aspects of this association remain unclear. We examined whether mammographic density differed by type of hormone therapy (HT) used, dose, duration of use, time since last use, and whether the effects are modified by age and body mass index (BMI). Using a cross-sectional design, we recruited 2,424 postmenopausal women aged 50–69 years participating in the Norwegian Breast Cancer Screening Program. Mammographic density was assessed with a computer-assisted method, and we estimated mean absolute and percent mammographic density through multiple linear regression, and adjusting for possible confounders. Mammographic density was higher among current HT users (percent density: 22.6%; 95% CI: 22.1–23.2%) than among former (17.7%; 17.2–18.2%) or never users (16.3%; 15.7–16.8%). The highest density was seen in current EPT users of high-dose norethisterone acetate (NETA) regimens who had a percent density of 26.2% (24.3–28.1%). Results differed when considering the combined effect of age and BMI. The effect of EPT on mammographic density was modified by age and BMI, with no apparent association among the youngest women (aged 50–55) with the highest BMI (BMI ≥ 26). A higher mammographic density was found in EPT users compared to never HT users, particularly in women using high-dose NETA regimens. Age and BMI modified the association between EPT use and mammographic density.     

Type 2 diabetes mellitus,insulin‐use and risk of bladder cancer in a large cohort study

Type 2 diabetes mellitus (T2DM) is associated with increased bladder cancer incidence in some, but not all, studies. Many studies had limited statistical power and few examined risk by insulin‐use, duration of diabetes or cancer stage. We examined the association between T2DM and bladder cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a large prospective study with information on insulin‐use and duration of diabetes. Diabetes and insulin‐use were ascertained from a questionnaire at study enrollment in 1992 or 1993 and updated in 1997 and every 2 years thereafter. During follow‐up through 2007, 1,852 cases of incident bladder cancer were identified among 172,791 participants. Multivariable adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using extended Cox regression modeling. There were no associations of T2DM with the risk of bladder cancer overall (RR = 1.01, 95% CI: 0.87–1.17), noninvasive disease (RR = 0.93, 95% CI: 0.76–1.14) or invasive disease (RR = 1.13, 95% CI: 0.91–1.40). Compared to participants without T2DM, risk of invasive bladder cancer was higher among participants who had had T2DM for >15 years (RR = 1.63, 95% CI: 1.09–2.43) and among those using insulin (RR = 1.64, 95% CI: 1.18–2.27). These results do not support an association of T2DM with overall bladder cancer incidence, but do suggest positive associations of long‐term T2DM and insulin‐use or other factors correlated with severe diabetes, with invasive bladder cancer incidence.