Estrogen

Diagnosis and management of endometriosis

Rowan Hutchins — Sun, 19 Mar 2023 05:00:00 +0000

Date Added:

March 19, 2023

Journal/Publication:

CMAJ

Publisher:

Canadian Medical Association

Publication Date:

March 14, 2023

Issue:

Volume:

195

Pages:

E363-E371

URL:

Diagnosis and management of endometriosis

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1503/cmaj.220637

Keywords

PMID (1):

36918177

MeSH

A concise summary of what we know about endometriosis. James W. Mold, MD, MPH

Free full text

View

Endometriosis is a chronic condition defined by the presence of endometrial-like tissue outside of the uterus, which can lead to estrogen-driven inflammation. The extent of disease can be highly variable, ranging from minimal peritoneal deposits to deep disease that can invade into the bowel, bladder and ureter and, more rarely, spread to extrapelvic (e.g., cutaneous, thoracic) sites. Endometriosis is a complex disease that has considerable impact on the quality of life of those affected and that has no cure. It remains poorly understood. We review the epidemiology, pathophysiology, diagnosis and management of endometriosis, based on the best available evidence and clinical guidelines

Author/s:

Allaire, Catherine, Bedaiwy, Mohamed, Yong, Paul

Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial

John Bayhi — Fri, 10 Jan 2020 16:02:17 +0000

Date Added:

January 10, 2020

Journal/Publication:

Lancet

Publisher:

Elsevier Ltd.

Publication Date:

January 11, 2020

Issue:

10218

Volume:

395

Pages:

117-122

URL:

Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1016/S0140-6736(19)32955-1

Keywords

breast cancer

anastrozole

female

PMID (1):

31839281

MeSH

cardiovascular diseases

Anastrozole (Arimidex) reduced the long term risk of breast cancer by 50% in women at risk with no major adverse side effects. Menopausal symptoms were increased, primarily during the first year of treatment. James W. Mold, MD, MPH.

Free full text

View

BACKGROUND:

Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period.

METHODS:

IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer.

FINDINGS:

3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105-156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39-0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27-0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45-0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33-0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22-0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78-0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69-1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57-0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed.

INTERPRETATION:

This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality.

FUNDING:

Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca.

Author/s:

Cuzick, J, Sestak, I, Forbes, JF, Dowsett, M, Cawthorn, S, Mansel, RE, Loibl, S, Bonanni, B, Evans, DG, Howell, A, IBIS-II Investigators

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence

John Bayhi — Sat, 31 Aug 2019 15:40:18 +0000

Date Added:

August 31, 2019

Journal/Publication:

The Lancet

Publisher:

Elsevier Ltd.

Publication Date:

August 29, 2019

URL:

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/S0140-6736(19)31709-X

Keywords

MeSH

The relevant information for advising individual patients is covered in the Summary Interpretation section and the last two paragraphs of the Discussion (end of paper).

Free full text

View

Summary

Background

Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence.

Methods

Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users.

Findings

During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5–14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40–44, 45–49, 50–54, and 55–59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use.

Interpretation

If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.

Funding

Cancer Research UK and the Medical Research Council.

Author/s:

Collaborative Group on Hormonal Factors in Breast Cancer