A significant piece of research was published recently in the British Journal of Cancer.^1. The Breakthrough Generations Study comprised observational, cohort research on 113,693 women from the UK, using questionnaire information and NHS data to observe breast cancer epidemiology. This is a prospective study, and in the conclusion the authors state that previous studies may have underestimated the risk of breast cancer associated with combined hormone replacement therapy, also called menopausal hormone therapy (MHT).

The study concludes that the risk of post-menopausal breast cancer is increased with current use of menopausal hormone therapy MHT (HRT), as in previous studies. However, the researchers say this risk increases in duration with use of combined MHT up to 15 years or more, and relative risks quoted in most of the published literature are likely to be substantially underestimated because of lack of updating MHT status through follow-up in cohort studies.

Royal College of Obstetricians and Gynaecologists/British Menopause Society response to British Journal of Cancer Study

The RCOG and BMS have said the findings of this latest study reconfirm that some previous studies may have underestimated the risk of breast cancer associated with combined oestrogen-progestogen HRT use: 

“Similar to the evidence base considered with the recent NICE guidelines on menopause, women using combined HRT are at an increased risk of developing breast cancer depending on duration of use, although this reduces once HRT use stops. 

“Further clarity around the effects of different types and routes or progestogens in combined HRT is needed. In women using oestrogen-only HRT, there was no overall increase in breast cancer risk compared with women who had never used HRT.

“HRT is an effective treatment for menopausal symptoms, particularly with the management of hot flushes. However, the risks and benefits are different for each woman, depending on her own medical history, her family history and her menopausal symptoms. To take or not to take HRT or other treatments for menopausal symptoms is an individual choice.

“Women need clear, evidence-based information to break through the conflicts of opinion and confusion about the menopause. For many women, any change in breast cancer risk is outweighed by the benefit on their quality of life, bearing in mind that there are many other factors that increase the risk of breast cancer; for example, lifestyle factors.”

Breast cancer trends

In monitoring breast cancer trends among the participants there was a group of approximately 4,000 women who used or still use HRT. Interestingly, many of these women were using the controversial Women’s Health Initiative study² products; Prempack C and Premique. 

The data in the new study confirms what is already known. Supplementing oestrogen alone doesn’t seem to increase the risk of developing breast cancer. The additional risk appears to come from one of the other female hormone components of standard HRT – progestogen. Oestrogen cannot be used alone as it can cause dysplasia of the endometrium and malignancies have occurred. The only women who may take oestrogen alone are women who have had a hysterectomy or those who are wearing a Mirena coil that has been in for less than five years. 

What’s new in the study is the amount of increased relative risk. To date, the relative risk has been quoted as about 1.7, whereas the British Journal of Cancer study has placed the increased relative risk closer to 2.7 after the first five years and up to 3.3 after 15 years.

The new study is not a randomised controlled trial and should not in itself change the clinical management of menopause. It is important work but should be viewed in context. 

Over the past decade GPs are much more cautious with HRT prescribing. The Women’s Health Initiative study from the early 2000s showed us that taking combined HRT (ie. oestrogen plus progestogen hormone) is associated with a small but significant increase in the risk of developing breast cancer, but this evidence applies only to women using HRT who are over 50 years of age and women who choose to remain on HRT beyond five years. 

This association is equivalent to approximately three more breast cancer diagnoses per 1,000 users. That is, if 1,000 women aged between 50 to 59 use combined HRT for more than five years, it is estimated an extra three breast cancers will be diagnosed. The increase in risk associated with combined HRT falls after it is stopped and there is no evidence that the risk of dying from breast cancer is increased in women with a history of using it. 

This associated risk increase is similar to that seen with  being overweight (BMI > 25); drinking two or more units of alcohol per day; having your first baby after 30 years of age; and starting your periods before 11 years of age, among other factors. 

Important message

The message for patients is that while many women derive enormous symptom relief and quality of life improvement from HRT, they need to know that remaining on it beyond their mid-50s could have an impact on the risk of GPs finding a breast cancer, but this risk is relatively low (three extra cases per 1,000 ) and similar to that seen with factors such as alcohol consumption and excess body weight.

Unlike being overweight, delaying your first pregnancy and drinking alcohol, HRT offers many advantages to the user. It does not increase your risk of dying from breast cancer. Prescribers should be carrying out physical examination of the breasts at least once a year in HRT users.

Advantages of HRT

Advantages of HRT go beyond symptom relief. It certainly has beneficial effects on bone density while using it and it may also have a preventative impact on the risk of developing cardiovascular diseases. 

Quantifying and qualifying the risks/benefits ratio will be different for each woman. Individualisation of care is the key. HRT is clearly not necessary for all women but for those who need it, it should be made available and they should feel supported by us while using it. They should be no more or less ‘afraid’ of using HRT than they are afraid of being overweight or drinking if their symptoms demand treatment. As always, the choice is theirs. 

See www.icgp.ie/women’s health.

References

1. British Journal of Cancer (2016),1-9, doi:1-.1038/bjc.2016.231
2. www.bjcancer.com
3. Women’s Health Initiative Trial (2002) JAMA 288(3):321-333