Study Finds Effect of Combined Hormone Replacement Therapy on Breast Cancer Risk Likely to Have Been Underestimated
The effect of combined hormone replacement therapy (HRT) in increasing a woman’s risk of breast cancer is likely to have been underestimated by a number of previous studies, according to a new prospective study published by Jones et al in the British Journal of Cancer.
HRT is used to treat uncomfortable symptoms of the menopause—such as hot flashes, migraines, disrupted sleep, mood changes, and depression—by increasing the decreased levels of estrogen being produced by the body. Around one in ten women use HRT during their fifties, with use lessening in older age groups as menopausal symptoms reduce.
There are two main types of HRT, one containing just estrogen (estrogen-only HRT), and the other a combination of estrogen and a progestogen (combined HRT). It can be taken in four ways: through tablets, skin patches, a cream, or a gel. A third, less commonly used type of HRT known as tibolone contains a steroid that acts like estrogen and progestogen.
The Generations Study
The new research was part of the Breast Cancer Now Generations Study—a major prospective study led by scientists at The Institute of Cancer Research, London, following more than 100,000 women for 40 years to investigate the causes of breast cancer.
Some 39,000 women with a known age at menopause were identified and monitored for 6 years, with follow-up questionnaires gathering comprehensive data on any HRT use (type and duration) as well as their general health and lifestyle.
During this time, 775 of these women developed breast cancer, with the researchers finding that women using combined HRT (for a median duration of 5.4 years) were 2.7 times more likely to develop breast cancer during the period of HRT use than women who had never used HRT.
This risk increased with duration of use, with women who had used combined HRT for over 15 years being 3.3 times more likely to develop breast cancer than nonusers. However, in women using estrogen-only HRT, there was no overall increase seen in breast cancer risk compared with women who had never used HRT.
Importantly, this increased risk level has been found to return to about normal once HRT use ends: after a year or two had gone by since women stopped taking combined HRT, the scientists did not find a significantly increased risk of breast cancer, confirming the findings of previous studies.
A More Accurate Estimate of Breast Cancer Risk
It is widely acknowledged that combined HRT is linked to an increased risk of breast cancer, and this could be explained by an increased exposure to hormones affecting the development and growth of some breast cancers; however, scientists have debated exactly how great this increase in risk is.
Unlike many studies in this area, the researchers updated information on women’s use of HRT over time through follow-up questionnaires. This avoids the biases created when women who have stopped using HRT after entering a study are still counted as “current users”, or women who have started using HRT after entering the study are still counted as “never users”. In the Generations Study, 65% of women who were using HRT when they entered the study later stopped.
The study also updated menopausal status through follow-up, ensuring the study could accurately identify postmenopausal women and did not include as postmenopausal those who had undergone a hysterectomy (without ovary removal) before the natural menopause, who have been included in past studies and can introduce further bias in risk estimates.
By adjusting for actual age at menopause and updating information on HRT use, the study authors believe the findings provide a more accurate estimate of the increased risk of breast cancer for HRT users and that several previously published estimates of risk for combined HRT use are likely to underestimate the risk.
To test this hypothesis, the researchers also analyzed their data without adjusting for changes in HRT use or women’s known menopause age. This led to an estimate of a 1.7-fold increase in risk for combined HRT use compared with non-users, meaning this method underestimated the more accurate (2.7-fold) risk estimate by about 60%.
Allowing Women to Make Informed Decisions
Study leader Anthony Swerdlow, PhD, MPH, Professor of Epidemiology at the ICR, said: “Our research shows that some previous studies are likely to have underestimated the risk of breast cancer with combined estrogen-progestogen HRT. We found that current use of combined HRT increases the risk of breast cancer by up to three fold, depending on how long HRT has been used. Our findings provide further information to allow women to make informed decisions about the potential risks and benefits of HRT use. This research was only possible because of the detailed information provided over many years by the dedicated participants in the Generations Study.”
Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, said, “Whether to use HRT is an entirely personal choice, which is why it’s so important that women fully understand the risks and benefits and discuss them with their GP. We hope these findings will help anyone considering the treatment to make an even more informed decision.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
