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Background: The history of gestational diabetes mellitus (GDM) has been associated with breast cancer risk in some studies, particularly in young women, but results of cohort studies are conflicting.Methods: We pooled data from 257 290 young (age <55 years) women from five cohorts. We used multivariable Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between GDM history and risk of breast cancer, overall and by oestrogen receptor (ER) status, before age 55 years, adjusted for established breast cancer risk factors.Results: Five percent of women reported a history of GDM and 6842 women reported an incident breast-cancer diagnosis (median follow-up = 16 years; maximum = 24 years). Compared with parous women without GDM, women with a history of GDM were not at increased risk of young-onset breast cancer overall (HR = 0.90; 95% CI: 0.78, 1.03) or by ER status (HR = 0.96; 95% CI: 0.79, 1.16 for ER-positive; HR = 1.07; 95% CI: 0.78, 1.47 for ER-negative). Compared with nulliparous women, parous women with a history of GDM had a lower risk of breast cancer overall (HR = 0.79; 95% CI: 0.68, 0.91) and of ER-positive (HR = 0.82; 95% CI: 0.66, 1.02) but not ER-negative (HR = 1.09; 95% CI: 0.76, 1.54) invasive breast cancer. These results were consistent with the HRs comparing parous women without GDM to nulliparous women.Conclusions: Results of this analysis do not support the hypothesis that GDM is a risk factor for breast cancer in young women. Our findings suggest that the well-established protective effect of parity on risk of ER-positive breast cancer persists even for pregnancies complicated by GDM. [ABSTRACT FROM AUTHOR]

Early‐adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual‐level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18–24 years and other breast cancer risk factors showed that weight gain from ages 18–24 to 35–44 or to 45–54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.95–0.98) and with oestrogen‐receptor(ER)‐positive breast cancer (HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.94–0.98). Weight gain from ages 25–34 was inversely associated with ER‐positive breast cancer only and weight gain from ages 35–44 was not associated with risk. None of these weight gains were associated with ER‐negative breast cancer. Weight loss was not consistently associated with overall or ER‐specific risk after adjusting for initial weight. Weight increase from early‐adulthood to ages 45–54 years is associated with a reduced premenopausal breast cancer risk independently of early‐adulthood weight. Biological explanations are needed to account for these two separate factors. What's new? Body weight in childhood and early adulthood plays a key role in determining premenopausal breast cancer risk but little is conclusively known about how subsequent weight changes affect this risk. Here the authors pooled results from existing studies on weight changes and breast cancer risk including more than 600,000 premenopausal women. The results show that weight gain >10–15 kg from early adulthood on lowers the risk of developing premenopausal breast cancer, providing further evidence of body weight as an important determinant of breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated.Objective: To characterize breast cancer risk in relation to recent childbirth.Design: Pooled analysis of individual-level data from 15 prospective cohort studies.Setting: The international Premenopausal Breast Cancer Collaborative Group.Participants: Women younger than 55 years.Measurements: During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression.Results: Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)-positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns.Limitations: Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited.Conclusion: Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women.Primary Funding Source: The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Plausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent.Methods: We used serial questionnaire information from the Generations Study cohort (United Kingdom) to estimate HRs for breast cancer in relation to smoking adjusted for potentially confounding factors, including alcohol intake.Results: Among 102,927 women recruited 2003-2013, with an average of 7.7 years of follow-up, 1815 developed invasive breast cancer. The HR (reference group was never smokers) was 1.14 (95% CI 1.03-1.25; P = 0.010) for ever smokers, 1.24 (95% CI 1.08-1.43; P = 0.002) for starting smoking at ages < 17 years, and 1.23 (1.07-1.41; P = 0.004) for starting smoking 1-4 years after menarche. Breast cancer risk was not statistically associated with interval from initiation of smoking to first birth (P-trend = 0.97). Women with a family history of breast cancer (ever smoker vs never smoker HR 1.35; 95% CI 1.12-1.62; P = 0.002) had a significantly larger HR in relation to ever smokers (P for interaction = 0.039) than women without (ever smoker vs never smoker HR 1.07; 95% CI 0.96-1.20; P = 0.22). The interaction was prominent for age at starting smoking (P = 0.003) and starting smoking relative to age at menarche (P = 0.0001).Conclusions: Smoking was associated with a modest but significantly increased risk of breast cancer, particularly among women who started smoking at adolescent or peri-menarcheal ages. The relative risk of breast cancer associated with smoking was greater for women with a family history of the disease. [ABSTRACT FROM AUTHOR]

Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. [ABSTRACT FROM AUTHOR]

Background: Women diagnosed with breast cancer frequently attribute their cancer to psychological stress, but scientific evidence is inconclusive. We investigated whether experienced frequency of stress and adverse life events affect subsequent breast cancer risk.Methods: Breast cancer incidence was analysed with respect to stress variables collected at enrolment in a prospective cohort study of 106,000 women in the United Kingdom, with 1783 incident breast cancer cases. Relative risks (RR) were obtained as hazard ratios using Cox proportional hazards models.Results: There was no association of breast cancer risk overall with experienced frequency of stress. Risk was reduced for death of a close relative during the 5 years preceding study entry (RR = 0.87, 95 % confidence interval (CI): 0.78-0.97), but not for death of a spouse/partner or close friend, personal illness/injury, or divorce/separation. There was a positive association of divorce with oestrogen-receptor-negative (RR = 1.54, 95 % CI: 1.01-2.34), but not with oestrogen-receptor-positive breast cancer. Risk was raised in women who were under age 20 at the death of their mother (RR = 1.31, 95 % CI: 1.02-1.67), but not of their father, and the effect was attenuated after excluding mothers with breast or ovarian cancer (RR = 1.17, 95 % CI: 0.85-1.61).Conclusions: This large prospective study did not show consistent evidence for an association of breast cancer risk with perceived stress levels or adverse life events in the preceding 5 years, or loss of parents during childhood and adolescence. [ABSTRACT FROM AUTHOR]

Background: The history of gestational diabetes mellitus (GDM) has been associated with breast cancer risk in some studies, particularly in young women, but results of cohort studies are conflicting., Methods: We pooled data from 257 290 young (age <55 years) women from five cohorts. We used multivariable Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between GDM history and risk of breast cancer, overall and by oestrogen receptor (ER) status, before age 55 years, adjusted for established breast cancer risk factors., Results: Five percent of women reported a history of GDM and 6842 women reported an incident breast-cancer diagnosis (median follow-up = 16 years; maximum = 24 years). Compared with parous women without GDM, women with a history of GDM were not at increased risk of young-onset breast cancer overall (HR = 0.90; 95% CI: 0.78, 1.03) or by ER status (HR = 0.96; 95% CI: 0.79, 1.16 for ER-positive; HR = 1.07; 95% CI: 0.78, 1.47 for ER-negative). Compared with nulliparous women, parous women with a history of GDM had a lower risk of breast cancer overall (HR = 0.79; 95% CI: 0.68, 0.91) and of ER-positive (HR = 0.82; 95% CI: 0.66, 1.02) but not ER-negative (HR = 1.09; 95% CI: 0.76, 1.54) invasive breast cancer. These results were consistent with the HRs comparing parous women without GDM to nulliparous women., Conclusions: Results of this analysis do not support the hypothesis that GDM is a risk factor for breast cancer in young women. Our findings suggest that the well-established protective effect of parity on risk of ER-positive breast cancer persists even for pregnancies complicated by GDM., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)