scholarly journals Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases

BMJ ◽  
2020 ◽  
pp. m3873 ◽  
Author(s):  
Yana Vinogradova ◽  
Carol Coupland ◽  
Julia Hippisley-Cox
Keyword(s):  
Breast Cancer ◽  
General Practice ◽  
Hormone Replacement Therapy ◽  
Index Date ◽  
Hormone Replacement ◽  
Case Control ◽  
Case Control Studies ◽  
Increased Risk ◽  
Nested Case Control

Abstract Objective To assess the risks of breast cancer associated with different types and durations of hormone replacement therapy (HRT). Design Two nested case-control studies. Setting UK general practices contributing to QResearch or Clinical Practice Research Datalink (CPRD), linked to hospital, mortality, social deprivation, and cancer registry (QResearch only) data. Participants 98 611 women aged 50-79 with a primary diagnosis of breast cancer between 1998 and 2018, matched by age, general practice, and index date to 457 498 female controls. Main outcome measures Breast cancer diagnosis from general practice, mortality, hospital, or cancer registry records. Odds ratios for HRT types, adjusted for personal characteristics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. Separate results from QResearch or CPRD were combined. Results Overall, 33 703 (34%) women with a diagnosis of breast cancer and 134 391 (31%) controls had used HRT prior to one year before the index date. Compared with never use, in recent users (<5 years) with long term use (≥5 years), oestrogen only therapy and combined oestrogen and progestogen therapy were both associated with increased risks of breast cancer (adjusted odds ratio 1.15 (95% confidence interval 1.09 to 1.21) and 1.79 (1.73 to 1.85), respectively). For combined progestogens, the increased risk was highest for norethisterone (1.88, 1.79 to 1.99) and lowest for dydrogesterone (1.24, 1.03 to 1.48). Past long term use of oestrogen only therapy and past short term (<5 years) use of oestrogen-progestogen were not associated with increased risk. The risk associated with past long term oestrogen-progestogen use, however, remained increased (1.16, 1.11 to 1.21). In recent oestrogen only users, between three (in younger women) and eight (in older women) extra cases per 10 000 women years would be expected, and in oestrogen-progestogen users between nine and 36 extra cases per 10 000 women years. For past oestrogen-progestogen users, the results would suggest between two and eight extra cases per 10 000 women years. Conclusion This study has produced new generalisable estimates of the increased risks of breast cancer associated with use of different hormone replacement preparations in the UK. The levels of risks varied between types of HRT, with higher risks for combined treatments and for longer duration of use.

scholarly journals Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases

BMJ ◽  
2019 ◽  
pp. k4810 ◽  
Author(s):  
Yana Vinogradova ◽  
Carol Coupland ◽  
Julia Hippisley-Cox
Keyword(s):  
Hormone Replacement Therapy ◽  
Venous Thromboembolism ◽  
Replacement Therapy ◽  
Odds Ratio ◽  
Index Date ◽  
Adjusted Odds Ratio ◽  
Hormone Replacement ◽  
Case Control ◽  
Case Control Studies ◽  
Nested Case Control

AbstractObjectiveTo assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy.DesignTwo nested case-control studies.SettingUK general practices contributing to the QResearch or Clinical Practice Research Datalink (CPRD) databases, and linked to hospital, mortality, and social deprivation data.Participants80 396 women aged 40-79 with a primary diagnosis of venous thromboembolism between 1998 and 2017, matched by age, general practice, and index date to 391 494 female controls.Main outcome measuresVenous thromboembolism recorded on general practice, mortality, or hospital records. Odds ratios were adjusted for demographics, smoking status, alcohol consumption, comorbidities, recent medical events, and other prescribed drugs.ResultsOverall, 5795 (7.2%) women who had venous thromboembolism and 21 670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date. Of these two groups, 4915 (85%)and 16 938 (78%) women used oral therapy, respectively, which was associated with a significantly increased risk of venous thromboembolism compared with no exposure (adjusted odds ratio 1.58, 95% confidence interval 1.52 to 1.64), for both oestrogen only preparations (1.40, 1.32 to 1.48) and combined preparations (1.73, 1.65 to 1.81). Estradiolhad a lower risk than conjugated equine oestrogen for oestrogen only preparations (0.85, 0.76 to 0.95) and combined preparations (0.83, 0.76 to 0.91). Compared with no exposure, conjugated equine oestrogen with medroxyprogesterone acetate had the highest risk (2.10, 1.92 to 2.31), and estradiol with dydrogesterone had the lowest risk (1.18, 0.98 to 1.42). Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens (overall adjusted odds ratio 0.93, 95% confidence interval 0.87 to 1.01).ConclusionsIn the present study, transdermal treatment was the safest type of hormone replacement therapy when risk of venous thromboembolism was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations.

scholarly journals Population-Based Estimates of the Age-Specific Cumulative Risk of Breast Cancer for Pathogenic Variants in CHEK2: Findings from the Australian Breast Cancer Family Registry

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1378
Author(s):  
Tú Nguyen-Dumont ◽  
James G. Dowty ◽  
Jason A. Steen ◽  
Anne-Laure Renault ◽  
Fleur Hammet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cumulative Risk ◽  
Population Based ◽  
Case Control ◽  
Cancer Information ◽  
Case Control Studies ◽  
Breast Cancer Family ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Control Family

Case-control studies of breast cancer have consistently shown that pathogenic variants in CHEK2 are associated with about a 3-fold increased risk of breast cancer. Information about the recurrent protein-truncating variant CHEK2 c.1100delC dominates this estimate. There have been no formal estimates of age-specific cumulative risk of breast cancer for all CHEK2 pathogenic (including likely pathogenic) variants combined. We conducted a population-based case-control-family study of pathogenic CHEK2 variants (26 families, 1071 relatives) and estimated the age-specific cumulative risk of breast cancer using segregation analysis. The estimated hazard ratio for carriers of pathogenic CHEK2 variants (combined) was 4.9 (95% CI 2.5–9.5) relative to non-carriers. The HR for carriers of the CHEK2 c.1100delC variant was estimated to be 3.5 (95% CI 1.02–11.6) and the HR for carriers of all other CHEK2 variants combined was estimated to be 5.7 (95% CI 2.5–12.9). The age-specific cumulative risk of breast cancer was estimated to be 18% (95% CI 11–30%) and 33% (95% CI 21–48%) to age 60 and 80 years, respectively. These findings provide important information for the clinical management of breast cancer risk for women carrying pathogenic variants in CHEK2.

scholarly journals Oral Contraceptive Use and Breast Cancer Risk Assessment: A Systematic Review and Meta-Analysis of Case-Control Studies, 2009–2020

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5654
Author(s):  
Agnieszka Barańska ◽  
Agata Błaszczuk ◽  
Wiesław Kanadys ◽  
Maria Malm ◽  
Katarzyna Drop ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oral Contraceptive ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Case Control ◽  
Cochrane Library ◽  
Control Group ◽  
Case Control Studies ◽  
Increased Risk ◽  
Breast Cancer Risk Assessment

To perform a meta-analysis of case-control studies that addressed the association between oral contraceptive pills (OC) use and breast cancer (BrCa), PubMED (MEDLINE), Embase, and the Cochrane Library were searched to identify case-control studies of OC and BrCa published between 2009 and 2020. We used the DerSimonian–Laird method to compute pooled odds ratios (ORs) and confidence intervals (CIs), and the Mantel–Haenszel test to assess the association between OC use and cancer. Forty-two studies were identified that met the inclusion criteria and we included a total of 110,580 women (30,778 into the BrCa group and 79,802 into the control group, of which 15,722 and 38,334 were using OC, respectively). The conducted meta-analysis showed that the use of OC was associated with a significantly increased risk of BrCa in general, OR = 1.15, 95% CI: 1.01 to 1.31, p = 0.0358. Regarding other risk factors for BrCa, we found that increased risk was associated significantly with early menarche, nulliparous, non-breastfeeding, older age at first parity, postmenopause, obesity, smoking, and family history of BrCa. Despite our conclusion that birth control pills increase the cancer risk being supported by extensive previous studies and meta-analyzes, further confirmation is required.

Postscript: starting oral contraceptives (25 May, page 41)

1992 ◽  
Vol 30 (14) ◽  
pp. 56.1-56
Keyword(s):  
Breast Cancer ◽  
Oral Contraceptives ◽  
Contraceptive Use ◽  
Causal Relation ◽  
Case Control ◽  
Term Pregnancy ◽  
Oral Contraceptive Use ◽  
Increased Risk ◽  
The Uk

In our article on oral contraceptives (OCs) we state that ‘oral contraceptives increase the risk of breast cancer with long-term use but reduce the risk of endometrial and ovarian cancer’. Some commentators have questioned the breast cancer risk. The UK National Case-Control (UKNCC) study, which looked at oral contraceptive use in women with breast cancer diagnosed before age 36, found a trend for increased risk associated with duration of use.1 ‘The simplest and most plausible explanation’, say the authors of the study, ‘must be that there is a substantial causal relation between prolonged use and breast cancer in young women.’ The increased risk seems to be associated particularly with OC use before the first full-term pregnancy.2 Several studies found no excess risk in OC users aged 45 or over, few of whom had taken the pill before their first pregnancy.3–5 In the UKNCC study the relative risk of breast cancer was 1.43 after 4–8 years’ use and 1.74 after more than 8 years’ use. In broad terms this means that three women in 1000 who use oral contraceptives for 4 or more years might be expected to be under treatment for breast cancer by age 36, compared with two per 1000 non-users.

scholarly journals Antidepressant use during pregnancy and the risk of gestational diabetes mellitus: a nested case–control study

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e025908 ◽  
Author(s):  
Maëlle Dandjinou ◽  
Odile Sheehy ◽  
Anick Bérard
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Index Date ◽  
Case Control Study ◽  
Case Control ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Nested Case Control ◽  
Control Study

ObjectivesThe aim of this study was to determine the association between antidepressant (AD) classes, types and duration of use during pregnancy and the risk of gestational diabetes mellitus (GDM).Design and settingA nested case–control study was conducted within the Quebec Pregnancy Cohort (QPC), a Canadian provincial database which includes data on all pregnancies and children in Quebec from January 1998 to December 2015.Primary outcome measuresGestational diabetes mellitus.ParticipantsCases of GDM were identified after week 20 of pregnancy and randomly matched 1:10 to controls on gestational age at index date (ie, calendar date of GDM) and year of pregnancy. AD exposure was assessed by filled prescriptions between the beginning of pregnancy (first day of last menstrual period) and index date. Conditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR).ResultsAmong 20 905 cases and 209 050 matched controls, 9741 (4.2%) women were exposed to ADs. When adjusting for potential confounders, AD use was associated with an increased risk of GDM (aOR 1.19, 95% CI 1.08 to 1.30); venlafaxine (aOR 1.27, 95% CI 1.09 to 1.49) and amitriptyline (aOR 1.52, 95% CI 1.25 to 1.84) were also associated with an increased risk of GDM. Moreover, the risk of GDM was increased with longer duration of AD use, specifically for serotonin norepinephrine reuptake inhibitors, tricyclic ADs and combined use of two AD classes. No statistically significant association was observed for selective serotonin reuptake inhibitors.ConclusionThe findings suggest that ADs—and specifically venlafaxine and amitriptyline—were associated with an increased risk of GDM.

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