We previously found that the risk of invasive breast cancer varied according to the progestagen component of combined postmenopausal hormone therapy (CHT): progesterone, dydrogesterone, or other ...progestagens. We conducted the present study to assess how these CHTs were associated with histology- and hormone receptor-defined breast cancer.
We used data from the French E3N cohort study, with 80,391 postmenopausal women followed for a mean duration of 8.1 years; 2,265 histologically confirmed invasive breast cancers were identified through biennial self-administered questionnaires completed from 1990 to 2002. The relative risks (RRs) were estimated using Cox proportional hazards models.
Compared with postmenopausal hormone therapy (HT) never-use, ever-use of estrogen+progesterone was not significantly associated with the risk of any breast cancer subtype, but increasing duration of estrogen+progesterone was associated with increasing risks of lobular (P = .06) and estrogen receptor-positive/progesterone receptor-negative (ER+/PR-; P = .02). Estrogen+dydrogesterone was associated with a significant increase in risk of lobular carcinoma (RR, 1.7; 95% CI, 1.1 to 2.6). Estrogen+other progestagens was associated with significant increases in risk of ductal and lobular carcinomas (RR, 1.6; 95% CI, 1.3 to 1.8; and 2.0; 95% CI, 1.5 to 2.7, respectively), of ER+/PR+ and ER+/PR- carcinomas (RR, 1.8; 95% CI, 1.5 to 2.1; and 2.6; 95% CI, 1.9 to 3.5, respectively), but not of ER-/PR+ or ER-/PR- carcinomas (RR, 1.0; 95% CI, 0.5 to 2.1; and 1.4; 95% CI, 0.9 to 2.0, respectively).
The increase in risk of breast cancer observed with the use of CHTs other than estrogen+progesterone and estrogen+dydrogesterone seems to apply preferentially to ER+ carcinomas, especially those ER+/PR-, and to affect both ductal and lobular carcinomas.
To investigate whether the relation between estrogen-progestagen menopausal hormone therapy (EP-MHT) and breast cancer risk varies according to the delay between menopause onset and treatment ...initiation.
Between 1992 and 2005, 1,726 invasive breast cancers were identified among 53,310 postmenopausal women from the French E3N cohort (mean duration of follow-up, 8.1 years). Hazard ratios (HRs) and CIs were estimated using Cox models, with MHT never users as the reference.
Among recent users of EP-MHT, the risk of breast cancer varied according to the timing of treatment initiation. This variation was confined to short durations of use (< or = 2 years): the HR was 1.54 (95% CI, 1.28 to 1.86) for short treatments initiated in the 3-year period following menopause onset and 1.00 (95% CI, 0.68 to 1.47) for short treatments initiated later (P = .04 for homogeneity). However, this pattern of risks was not observed in users of EP-MHT containing progesterone, among whom there was no significantly increased risk associated with short duration of use (HR was 0.87 95% CI, 0.57 to 1.32 for treatments initiated < or = 3 years after menopause, and HR was 0.90 95% CI, 0.45 to 1.81 for treatments initiated later). Longer durations of EP-MHT use were generally associated with increases in breast cancer risk, whatever the gap time.
Our results suggest that, for some EP-MHT, the timing of treatment initiation transiently modulates the risk of breast cancer and that, when initiated close to menopause, even short durations of use are associated with an increased breast cancer risk. Estrogen + progesterone combinations might be an exception in this regard.
Soy-based dietary supplements have been promoted as natural alternatives to menopausal hormone therapy, but their potential effect on breast cancer development is controversial.
We examined the ...relation between the consumption of soy supplements and the risk of breast cancer, overall and by tumor hormone receptor status, among women aged >50 y.
In total, 76,442 women from the Etude Epidemiologique aupres de Femmes de la Mutuelle Generale de l’Education Nationale (E3N) cohort, born between 1925 and 1950, were followed from 2000 to 2011 (11.2 y on average, starting at a mean age of 59.5 y; 3608 incident breast cancers), with soy supplement use assessed every 2–3 y. HRs of breast cancer were estimated with the use of multivariable Cox models.
Compared with never using soy supplements, the HRs associated with current use of soy supplements were 0.92 (95% CI: 0.76, 1.11) for all, 0.78 (95% CI: 0.60, 0.99) for estrogen receptor (ER)–positive, and 2.01 (95% CI: 1.41, 2.86) for ER-negative breast cancers. There was no association between past use of soy supplements and breast cancer. HRs for current use were 1.36 (95% CI: 0.95, 1.93) and 0.82 (95% CI: 0.65, 1.02) among women with and without a family history of breast cancer, respectively (P-interaction = 0.03) and 1.06 (95% CI: 0.87, 1.30) ≥5 y after menopause compared with 0.50 (95% CI: 0.31, 0.81) in premenopause or ≤5 y postmenopause (P-interaction = 0.04).
In this cohort of women aged >50 y, we report opposing associations of soy supplements with ER-positive and ER-negative breast cancer risk. Our results also caution against the use of these supplements in women with a family history of breast cancer. Whether the risk profile of soy supplements could be more favorable among premenopausal or recently postmenopausal women deserves further investigation.
Endometriosis and the risk of skin cancer Farland, Leslie V.; Lorrain, Simon; Missmer, Stacey A. ...
CCC. Cancer causes & control/CCC, Cancer causes & control,
10/2017, Volume:
28, Issue:
10
Journal Article
Peer reviewed
Open access
Purpose
Endometriosis has been associated with an increased risk of skin melanoma. However, associations with other skin cancer types and how they compare with melanoma are unclear. Our objective was ...to prospectively investigate the relationships between endometriosis and risk of non-melanoma and melanoma skin cancers.
Methods
E3N is a prospective cohort of 98,995 French women aged 40–65 years in 1990. Data on surgically confirmed endometriosis and skin cancer diagnoses were collected every 2–3 years through self-report, with skin cancer cases confirmed through pathology reports. Hazard Ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox regression models.
Results
Between 1990 and 2008, 535 melanoma, 247 squamous-cell carcinoma (SCC), and 1,712 basal-cell carcinoma (BCC) cases were ascertained. Endometriosis was associated with an increased overall risk of skin cancer (HR 1.28, 95% CI 1.05–1.55). When considering skin cancer type, endometriosis was associated with melanoma risk (HR 1.64, 95% CI 1.15–2.35), but not with SCC (HR 1.21, 95% CI 0.62–2.36) or BCC (HR 1.16, 95% CI 0.91–1.48) (non-melanoma skin cancers combined: HR 1.17, 95% CI 0.93–1.46), although no heterogeneity was detected across skin cancer types (Phomogeneity = 0.13).
Conclusion
These data support an association between a personal history of endometriosis and the risk of skin cancer and suggest that the association is strongest for melanoma.
•The only two longitudinal studies on menopause and asthma had conflicting findings.•We showed that surgical menopause is associated with an increased risk of asthma.•We found no change in asthma ...onset with natural menopause in women of normal weight.•The incidence of asthma increased after menopause only in overweight/obese women.•Metabolic factors, rather than female sex hormones alone, are likely to be involved.
The gender switch in asthma incidence around puberty has been put forward to suggest a role of sex hormones in asthma. However, there are limited and inconsistent findings on change in asthma incidence with menopause. We aimed to investigate the associations between menopause and asthma incidence, and interactions with overweight/obesity.
Asthma incidence was assessed in 67,872 women free of asthma at baseline (aged 41–68 years) and regularly followed up as a part of the French E3N cohort. Adjusted hazard ratios (aHR) were derived from Cox models considering age as the time-scale, menopausal status as a time-varying covariate and taking into account menopausal treatment.
During 843,243 person-years of follow-up, 1205 new-onset asthma cases were identified. Compared with pre-menopause, surgical menopause was associated with an increased risk of asthma onset (aHR = 1.33 95%CI 1.01–1.75) but no association was observed for natural menopause (aHR = 1.05 0.84–1.32). In women with natural menopause, a further analysis separating the transition through menopause and the later post-menopausal period did not show any change in asthma incidence with menopause in the total sample or in normal-weight women alone. However, in overweight/obese women, peri-menopausal and post-menopausal women had an increased risk of developing asthma compared with pre-menopausal women of the same age (aHR = 1.91 1.00–3.66 and aHR = 2.08 1.07–4.06 respectively).
Surgical menopause was associated with an increased risk of asthma onset. For natural menopause, no change in asthma incidence was observed in normal-weight women. However, overweight/obese women had an increased risk of developing asthma after natural menopause.
Abstract Purpose Early menarche has been associated with a greater risk of several major chronic diseases. Although largely genetically determined, age at menarche also has been related to ...environmental and lifestyle factors. Methods Using linear regression models, we explored simultaneously several pre- and postnatal factors as potential determinants of age at menarche and time to menstrual cycle regularity in 96,493 women participating, since 1990, in the French E3N prospective cohort. Results Younger age at recruitment, greater father's income index, urban birth place, greater birth length, and larger body silhouette during childhood were associated with an earlier age at menarche (from −1.3 to −4.6 months, Ptrend < .0001) whereas greater family size, food deprivation during childhood, and greater birth weight resulted in a delayed menarche (from +1.5 months to +5.3 months, Ptrend < .0001). Father's income index, urban birth place, and prematurity predicted a shorter time to menstrual cycle regularity (from −1.1 to −1.9 months, Ptrend < .04), whereas birth cohort, larger body silhouette at menarche, and childhood exposure to passive smoking were associated with a longer time to menstrual cycle regularity (from +1.1 months to +8.6 months, Ptrend < .006). Conclusions Age at menarche and menstrual cycle regularity are significantly influenced by several individual, environmental and lifestyle factors.
Background: C-reactive protein (CRP), a marker of lowgrade inflammation, has been associated with breast cancer risk, but results are scarce and inconsistent. Methods: A case–control study nested ...within the E3N prospective cohort included 549 postmenopausal breast cancer cases and 1,040 matched controls, all free of breast cancer at baseline. Serum levels of CRP were measured in samples collected between 1995 and 1999. Unconditional logistic regression models were used to evaluate the association between CRP and breast cancer risk, adjusting for matching factors and known breast cancer risk factors. Results: No association was observed between CRP levels and breast cancer risk overall. However, a significant interaction was observed between CRP levels and body mass index (BMI). A statistically significant increase in breast cancer risk was observed in overweight and obese women (BMI ≥ 25 kg/m²) (OR 1.92, 95 % CI 1.20–3.08 for CRP ≥ 2.5 mg/L compared with CRP < 1.5 mg/l, ptrend = 0.003, pinteraction between CRP and BMI = 0.03). Similar results were observed in women with waist circumference (WC) ≥ 88 cm (ptrend = 0.01, pinteraction = 0.06) and waistto-hip ratio (WHR) ≥ 0.80 (ptrend = 0.06, pinteraction = 0.35). CRP levels were not associated with breast cancer risk in women with normal BMI, WC, or WHR. Conclusions: We found a positive association between CRP levels and postmenopausal breast cancer risk restricted to women with excess adiposity. The suggested relationship between low-grade inflammation, abdominal adiposity, and postmenopausal breast cancer risk deserves further investigation.
Objective
To assess the association of body‐size from childhood to age 40 with depression in postmenopausal French women.
Methods
Participants of the E3N study reported birth characteristics and ...silhouettes matching theirs at age 8, at puberty, at 20‐25, and 35‐40 years (n = 41,144). Depression was assessed by the Center for Epidemiological Studies Depression Scale and split into new‐onset and recurrent depression according to women's history of psychological disorder. Risks were estimated with multinomial logistic regression models.
Results
Low or high birth weights were associated with risk of depression. A large body‐size at age 8 and a large body‐size over the life‐course were both associated with the risk of new‐onset depression specifically, while women with a large body‐size increase at puberty were at risk of recurrent depression. Largest body‐sizes at 20‐25 or 35‐40 years were associated with both the risk of new‐onset and recurrent depression, especially in normal weight women. However, a lean silhouette at 35‐40 years was associated with the risk of recurrent depression only.
Conclusions
Women with a large body‐size from childhood to adulthood might be at higher risk of new‐onset postmenopausal depression, while leanness in adulthood could be associated with a higher risk of recurrent depression.
The aim of this study was to obtain an overview of the associations between alcohol consumption and breast cancer risk at adulthood, by type of alcohol and subtype of breast cancer. Between 1993 and ...2008, 66 481 women from the French E3N-EPIC cohort were followed up and asked to report their alcohol consumption, by type of alcohol, through a 208-item diet-history questionnaire. A total of 2812 breast cancer cases were validated during the follow-up session. No association was found between high alcohol consumption, whatever its type, and increase in breast cancer risk in the premenopausal period. During the postmenopausal period, a linear association between total alcohol consumption and breast cancer risk was found (P<0.0001), mainly driven by the associations with wine and beer hazard ratio=1.33 (1.11–1.58) and 1.85 (1.19–2.89) for more than two glasses per day of wine and beer, respectively, compared with nondrinkers and with ER+/PR+ breast cancer subtypes. In the postmenopausal period, we observed interactions between total alcohol and folate intake levels (P=0.1192) and BMI (P=0.0367), with higher increased risks observed for high alcohol intake among women with low folate intake or who were overweight or obese. Our results make precise the current body of knowledge on the relationship between alcohol and breast cancer subtypes. Interactions between alcohol and other factors should further be taken into account in public health nutrition programs.
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