A study published this week in the British Journal of Cancer has concluded that the impact of combined hormone replacement therapy (HRT) on a woman’s risk of developing breast cancer has most likely been underestimated in previous studies. The study found that women taking combined HRT can be up to 2.7 times more likely to develop breast cancer during the period of HRT use than women who had never received the therapy.
Statistics suggest that HRT is taken by one in ten women in their fifties in order to alleviate menopausal symptoms. The treatment exists in two forms – estrogen-only HRT or combined HRT consisting of both estrogen and a progestogen.
Combined HRT has been widely recognized as being linked to an increased risk of breast cancer – perhaps owing to the 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.
The study in questions was led by investigators at The Institute of Cancer Research (ICR; London, UK) and was carried out as part of the Breast Cancer Now Generations Study. Powered by the ICR, the Breast Cancer Now Generations Study followed in excess of 100,000 women over a 40 year period in order to investigate the causes of breast cancer.
Of these 100,000 individuals, 39,000 with a known age at menopause were identified and monitored for 6 years. The individuals in questions also completed questionnaires gathering comprehensive data on any HRT use (type and duration) as well as their general health and lifestyle.
Over the follow-up period, 775 of these women were diagnosed with breast cancer. The investigation found 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 received the therapy.
This increase in risk was found to correlate directly with duration of HRT use, with figures demonstrating that women who had used combined HRT for over 15 years were 3.3 times more likely to develop breast cancer than non-users.
However, the team also concluded that this increased risk for the development of breast cancer decreased to normal levels after HRT was ceased. One or 2 years following cessation of combined HRT, the scientists did not find a significantly increased risk of breast cancer, confirming the findings of previous studies.
This study aimed to accurately estimate HRT-related breast cancer risk by updating information on women’s use of HRT over time through follow-up questionnaires, updating menopausal status, not including those who had undergone a hysterectomy and adjusting for actual age at menopause. It is this study design that leads the researchers to believe that several previously published estimates of risk for combined HRT use are likely to be underestimates.
To test this hypothesis, the researchers 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 – underestimating the more accurate (2.7-fold) risk estimate by approximately 60%.
“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,” commented Study leader Anthony Swerdlow (ICR).
The Breast Cancer Now Generations Study participants will continue to complete further questionnaires as the study progresses, enabling the researchers to investigate this link with futher detail and precision.