Abstract
There remains controversy about the risk of breast cancer diagnosis and mortality associated with HRT. This fact sheet summarises key findings and conclusions from clinical trials, including the 2019 Collaborative Group for Hormonal Risk Factors (CGHFBC) and 2020 long-term follow-up of the placebo-controlled, randomised Women’s Health Initiative (WHI) Study.
HRT and the risk of being diagnosed with breast cancer
In women with a low underlying risk of breast cancer (i.e. most of the population), the symptomatic benefits of HRT use for up to five years will exceed potential harm Where risk with HRT is estimated to be elevated, the degree conferred is considered small Most women will not be diagnosed with breast cancer as a result of their exposure to HRT In women with premature ovarian insufficiency years of HRT exposure should be counted from the age of 50 and not the age at which HRT is commenced There is insufficient evidence to recommend time from menopause should influence decision-making when commencing HRT Risk is not increased in overweight or obese women who use HRT
Unopposed estrogen
Is associated with little or no change in risk There is no evidence of a dosage effect Risk is not increased with vaginal estrogen Risk may be increased in past users
Combined HRT
Can be associated with a duration-dependent increased risk Although continuous combined HRT confers a greater risk than sequential HRT, the absolute excess risk is small (i.e. 10 additional diagnoses per 1000 women aged 50 to 59 with up to 14 years use). This should also be weighed against the risk of endometrial cancer, which is significantly decreased by long-term, continuous combined HRT Risk may be increased in past users
HRT and other lifestyle risk factors for breast cancer
There is little difference in the risk incurred by lifestyle factors, including current and past use of HRT
aHealthy weight, body mass index (BMI) < 25 kg/m2, overweight BMI 25–29.9 kg/m2, obese BMI ≥ 30 kg/m2.
HRT and mortality
In women at population risk, the overall mortality risk benefit ratio favours both unopposed and combined HRT Unopposed HRT may be associated with a reduction in breast cancer mortality Combined HRT is not associated with an increased risk of breast cancer mortality
HRT and women at increased risk of breast cancer
Most women (∼90% of the female population) have a low lifetime risk of breast cancer Overall, there is no strong evidence for an additive effect of HRT upon risk of diagnosis in women at elevated personal risk due to a family history of breast cancer or personal diagnosis of a high-risk benign breast condition (i.e. lobular carcinoma in situ, atypical hyperplasia). Risk conferred by HRT will be dependent on the baseline risk in these higher risk women It is recommended to avoid HRT in women at high risk, with the exception of BRCA1 and BRCA2 mutation carriers, who have had prophylactic oophorectomy. Here add-back HRT can be used for symptom management until the age of 50 as this has not been associated with an increased risk of breast cancer diagnosis. After 50, lifestyle changes and non-hormonal alternatives should be used High-risk symptomatic women at an elevated risk of breast cancer should be referred to a menopause specialist for advice
Symptomatic women with previous breast cancer
Offer counselling about early menopause risk and symptoms with some breast cancer treatments Refer symptomatic women to a menopause specialist
Vasomotor symptoms
First-line treatment – lifestyle changes and HRT alternatives Avoid paroxetine and fluoxetine in women taking tamoxifen as they may reduce tamoxifen’s efficacy If severe, refractory symptoms, systemic HRT may be offered but this requires informed, documented consent and discussion with the breast cancer team Systemic HRT should not be used in women treated with an aromatase inhibitor
Managing vulvo-vaginal atrophy
Vaginal moisturizers should be first-line management If refractory symptoms, ultra-low-dose topical estrogen can be considered Topical estrogen should be avoided in the presence of an aromatase inhibitor
Footnotes
Declaration of conflicting interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:
Jo Mardsen Conflicts of Interest.
Lectures for Mylan 2015-to date, Member of Council of British Menopause Society, Advisory Board for Novo Nordisk, Chief Investigator of the national UK trial of HRT in symptomatic women with early breast cancer. Hugo Pedder has no declaration of conflict of interest.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.