Contemporary Hormonal Contraception and the Risk of Breast Cancer

Mørch, Lina Steinrud; Skovlund, Charlotte Wessel; Hannaford, Philip Christopher; Iversen, Lisa; Fielding, Shona; Lidegaard, Øjvind

doi:10.1056/nejmoa1700732

Cited by 420 publications

(293 citation statements)

References 37 publications

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“…Although the increased risk of breast cancer for premenopausal women associated with any regular alcohol consumption and increased duration of current OC use has been reported previously, this is the first study to quantify the excess burden of breast cancer for premenopausal women attributable to any regular alcohol consumption (12.6%), current OC use for five or more years (7.1%) and these two factors combined (18.8%). Our results did not support an association of low body fatness, physical inactivity and non‐breastfeeding with breast cancer for premenopausal women .…”

Section: Discussionmentioning

confidence: 77%

The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: A pooled cohort study

Arriaga

Vajdic

Canfell

et al. 2019

Intl Journal of Cancer

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Estimates of the future breast cancer burden preventable through modifications to current behaviours are lacking. We assessed the effect of individual and joint behaviour modifications on breast cancer burden for premenopausal and postmenopausal Australian women, and whether effects differed between population subgroups. We linked pooled data from six Australian cohort studies (n = 214,536) to national cancer and death registries, and estimated the strength of the associations between behaviours causally related to cancer incidence and death using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We combined these estimates to calculate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), and compared PAFs for population subgroups. During the first 10 years follow‐up, there were 640 incident breast cancers for premenopausal women, 2,632 for postmenopausal women, and 8,761 deaths from any cause. Of future breast cancers for premenopausal women, any regular alcohol consumption explains 12.6% (CI = 4.3–20.2%), current use of oral contraceptives for ≥5 years 7.1% (CI = 0.3–13.5%), and these factors combined 18.8% (CI = 9.1–27.4%). Of future breast cancers for postmenopausal women, overweight or obesity (BMI ≥25 kg/m2) explains 12.8% (CI = 7.8–17.5%), current use of menopausal hormone therapy (MHT) 6.9% (CI = 4.8–8.9%), any regular alcohol consumption 6.6% (CI = 1.5–11.4%), and these factors combined 24.2% (CI = 17.6–30.3%). The MHT‐related postmenopausal breast cancer burden varied by body fatness, alcohol consumption and socio‐economic status, the body fatness‐related postmenopausal breast cancer burden by alcohol consumption and educational attainment, and the alcohol‐related postmenopausal breast cancer burden by breast feeding history. Our results provide evidence to support targeted and population‐level cancer control activities.

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Section: Discussionmentioning

confidence: 77%

The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: A pooled cohort study

Arriaga

Vajdic

Canfell

et al. 2019

Intl Journal of Cancer

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“…A recent large Danish cohort study reported a relative risk of breast cancer of 1.19 (95% CI 1.13–1.26) for current or recent users of COC compared to never-users of hormonal contraception 277. Risk appeared to increase with duration of use.…”

Section: Health Risks Associated With Chc Usementioning

confidence: 97%

FSRH Guideline (January 2019, amended October 2023) Combined Hormonal Contraception

2019

BMJ Sex Reprod Health

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“…35 Considering the fact that ~16% of women between 15 and 44 years of age in the US are on oral contraceptives (~9.7 million women) at any given time 36 and that ~1.5 million are on oestrogen compounds for non-reproductive reasons, 37 further study of the concentrations of these genotoxic oestrogenic metabolites in women using these products long-term is important, and now possible. 35 Considering the fact that ~16% of women between 15 and 44 years of age in the US are on oral contraceptives (~9.7 million women) at any given time 36 and that ~1.5 million are on oestrogen compounds for non-reproductive reasons, 37 further study of the concentrations of these genotoxic oestrogenic metabolites in women using these products long-term is important, and now possible.…”

Section: Discussionmentioning

confidence: 99%

Impact of route of administration on genotoxic oestrogens concentrations using oral vs transdermal oestradiol in girls with Turner syndrome

Mauras

Torres-Santiago

Santen

et al. 2018

Clinical Endocrinology

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Objective:The established link between oestrogen and breast cancer occurs via both oestrogen receptor (ER)-mediated and non ER-mediated mechanisms. The term genotoxic estrogens describes mutagenic metabolites, including oestrogen catechols and quinones, which have been linked to breast carcinogenesis in post-menopausal women. We aimed to assess whether the route of administration of 17β oestradiol (E 2 ) affects the accumulation of genotoxic oestrogen metabolites in a model of ovarian failure in young girls with Turner syndrome.Methods: Stored plasma samples obtained at 0 and 12 months were used from 40 adolescents with Turner syndrome who participated in a 12 months randomized controlled trial of the metabolic impact of E 2 orally (2 mg/d) vs transdermally (100 µg/d);dose escalation allowed matching of unconjugated E 2 levels in the parent study. We measured 12 oestrogen metabolites (total concentrations = conjugated and unconjugated) using a highly sensitive LCMSMS assay. Results from 48 normally menstruating adolescents were used for comparison. Results: After treatment, least square mean (SE) total E 2 concentrations were higher in the oral vs transdermal group (6784 pmol/L vs 1123 [1614], P < 0.0001), as was oestrone (E 1 ) (91 060 pmol/L vs 19 278 [16 534], P < 0.0001). Also, higher after oral treatment were catechol-oestrogens 4-hydroxy-E 2 (149 vs 28 [±49] pmol/L), 2-hydroxy-E 2 (300 vs 76 [±52]), 4-hydroxy-E 1 (450 vs 105 [±113]), 2-hydroxy-E 1 (3094 vs 740 [±684]) and 16α-hydroxy-E 1 (3,007 vs 157 [±534]) (<0.001 between groups). Levels were much closer to controls in the transdermal group. Conclusions: Common feminizing doses of oral oestradiol for 12 months result in substantial accumulation of unphysiologic, genotoxic oestrogens compared to transdermal oestradiol, expanding concerns about oral oestrogens' first hepatic passage.Further studies assessing long-term risks of these metabolites in women taking different forms of oestrogen are needed. K E Y W O R D Sbreast cancer, children, genotoxic oestrogens, LCMSMS assay, oestradiol, transdermal, Turner syndrome

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Contemporary Hormonal Contraception and the Risk of Breast Cancer

Cited by 420 publications

References 37 publications

The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: A pooled cohort study

The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: A pooled cohort study

FSRH Guideline (January 2019, amended October 2023) Combined Hormonal Contraception

Impact of route of administration on genotoxic oestrogens concentrations using oral vs transdermal oestradiol in girls with Turner syndrome

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