HRT and breast cancer.
When considering the use of Hormone Replacement Therapy for treating menopausal symptoms, many women and healthcare professionals have been strongly influenced by the risk of breast cancer thought to be associated with the use of HRT. Previous publications have strongly emphasised the risk and headlines such as “HRT doubles risk of breast cancer” has understandably had an impact. In many cases, this concern has led to women choosing to tolerate menopausal symptoms, which, at times, can be severe, and to healthcare professionals refusing to prescribe HRT or advising women to stop HRT unnecessarily. While no medication is entirely without risk, it is essential that risk is kept in perspective and that there is a clear understanding of the balance between benefits and risks.
Breast cancer is the most common cancer affecting women in the UK with just over 50,000 diagnoses in 2011, equating to around 155 per 100,000 women per year. However it is not the leading cause of death in women, many more women dying each year from cardiovascular disease and dementia. The baseline risk for breast cancer for women around the age of menopause in the UK is around 23 cases per 1000 women, but each woman’s risk will vary according to her history, family history, and in relation to some modifiable risk factors. While the association between HRT and risk of breast cancer is well known and often exaggerated and misunderstood, the risk from other modifiable factors is often unknown and ignored.
The recent NICE guideline on diagnosis and management of menopause included a section on breast cancer as part of the section on Long-term benefits and risks of hormone replacement therapy. Over the years many individual publications have shown varying levels of risk, with some showing no increase in breast cancer and others showing an alarming increase. Each publication has received varying levels of publicity leading to widespread confusion. The NICE guideline development group have closely examined all publications not only for their findings but also for the quality of the study. The result is an unquestionable authoritative document which supports both women and healthcare professionals to make informed choices about menopause management and use of HRT.
So what does NICE say? The first important point is that the levels of risk were reported as absolute figures rather than percentage or relative risk. This may seem an academic point but in fact how risk is reported can have a huge impact on how risk is perceived. For example, a risk being reported as “doubled” or “100% increase” sounds much more alarming than if the absolute rise was an increase from 1 case per 1000 to 2 cases per 1000. Sadly alarmist headlines rarely report absolute figures. The reporting of the Women’s Health Initiative trial in 2002 was an example of the use of percentage increases which led to dramatic loss of confidence in the use of HRT despite the fact that absolute risks were very small.
Secondly, NICE clearly describes different effect from different types of HRT. The purpose of HRT is to replace estrogen since it is the declining and low level of estrogen that is believed to cause the consequences of the menopause in terms of menopausal symptoms and later health effects. Women who have had a hysterectomy can generally take estrogen only HRT while women who have an intact uterus need to take progestogen along with the estrogen (combined HRT) to prevent estrogenic stimulation of the uterine lining. It has been suggested for some time that estrogen only is not associated with the same level of risk of breast cancer as combined HRT but there has been a lack of awareness of this difference, many young women who have had a hysterectomy stopping estrogen early or being advised to do so. NICE confirms that HRT with estrogen alone is associated with little or no change in the incidence of breast cancer. The absolute figure given is for 4 fewer cases of breast cancer in women taking estrogen only HRT per 1000 menopausal women over 7.5 years, based on baseline risk for that group being 22.48 per 1000.
For women who take combined HRT, NICE confirms that this can be associated with an increase in the incidence of breast cancer. The absolute figure given is 5 more cases of breast cancer in women taking combined HRT per 1000 menopausal women over 7.5 years, baseline risk as noted. This increase in risk appears to be associated with the length of time that HRT is taken, the risk being higher when combined HRT is used for more than 4 years. However, the risk reduces and returns to each woman’s baseline risk after HRT is stopped. Another important point highlighted is that the mortality from breast cancer does not appear to be increased compared to women who develop breast cancer and are not taking HRT. The conclusion from these two points is that combined HRT may, in a small number of women, stimulate the growth of cancer cells which are already present, rather than cause breast cells to turn into cancer, and the natural history of disease for each woman is not altered.
The NICE group did examine whether different types or routes of HRT affect risk. With the knowledge that estrogen only seems to be less likely to affect risk than combined HRT, it has been suggested that certain types of progestogen may also differ in association with risk. NICE concluded that the evidence was not yet strong enough to recommend that certain types of progestogen were better than others. It has been recommended that further research be carried out to determine if there are differences in risk between different types of progestogen within combined HRT so that preparations can be offered which maximise benefits and minimise risk.
While any diagnosis of breast cancer is devastating, it is really important to fully understand the role of HRT, that any risk is small, the risk returns to baseline when HRT is stopped, that each woman’s risk of dying from breast cancer is not affected by the use of HRT and that each woman should take this into consideration along with the benefits of HRT for her.
It has been known for some time that there are other factors which affect breast cancer risk and the table shows that being overweight, having first birth after age 31, and regular alcohol are all associated with higher level of extra cases of breast cancer than the use of combined HRT. Further, regular physical activity is associated with reduced risk. Therefore, the decision around use of HRT and consideration around health benefits and risk should also take into account other factors, particularly weight, which can be addressed.
Finally, concern and confusion often arises around the options for treatment of menopausal symptoms in women who have had breast cancer, or who may be thought to be at high risk for breast cancer, for example due to strong family history. Menopause may occur as part of the treatment for breast cancer when it may lead to premature menopause, or may occur naturally regardless of treatment. The NICE guideline recommends that women should be given information about all available treatment options. These include non-hormonal treatments such as the antidepressants, Selective serotonin reuptake inhibitors (SSRIs) which have often been used in this situation to reduce hot flushes and sweats due to the serotonin action. However the guideline emphasises that paroxetine and fluoxetine should not be offered to women who are taking tamoxifen for breast cancer treatment since interactions with medication may occur leading to the tamoxifen being less effective.
NICE also reviewed the role of Alternative therapies for women in this situation and concluded that while there is some evidence that St John’s Wort may be helpful for reducing menopausal symptoms, women should be aware that there is lack of clarity about appropriate doses, there may be variation in preparations and that it may interact with other medications including tamoxifen. Further research has been called for to examine the effectiveness and safety for treatments for menopausal symptoms in women who have had breast cancer.
Referral to a healthcare professional who is a menopause specialist is often required for women who have had, or are at high risk for breast cancer.
Overall, the association of breast cancer risk with use of HRT does cause concern to many women and healthcare professionals but the NICE guideline provides clear information and goes a long way in putting the small risk in perspective. Work is still required to understand which treatments can be safely offered to women who have had breast cancer.