The Cancer Journal, May/June 2022: Special edition on hormone therapy and breast cancer
Hormone Replacement Therapy After Breast Cancer: It Is Time – Avrum Zvi Bluming, MD.
In this article, Dr Sarah Ball, a menopause specialist with an interest in breast cancer reviews an article by Dr Avrum Bluming in the latest issue of The Cancer Journal.
Dr Avrum Bluming, who sits on the Advisory Board of the NHMS, is a medical oncologist who has been studying the role of HRT for breast cancer survivors for over 30 years. He is the co-author of Oestrogen Matters (1), a book written to empower those with a history of breast cancer (and even those without) to make decisions about their own treatments for menopause, based on a detailed evaluation of the scientific evidence.
In this latest publication of The Cancer Journal, Dr Bluming presents a summary (2) of the totality of the evidence he has been dissecting since the early 1990s. We are reminded of the irrefutable evidence of HRT’s benefits, namely effective control of menopausal symptoms, significant reductions in cardiovascular disease, hip fractures, cognitive decline as well as an improvement in life expectancy. We are similarly reminded that the doubling of risk of thromboembolic events can be entirely avoided with the use of transdermal (rather than oral) oestrogen replacement.
Just prior to the highly injurious and misleading reports which came out of the Women’s Health Initiative study in 2002, medical research was beginning to explore the possible role of HRT in those with a history of breast cancer. Sadly, the misinterpretation and exaggeration of breast cancer risk in relation to HRT users in general, ever since the WHI trial reported its initial findings, has halted this exploration for breast cancer survivors in its tracks.
Thankfully, surviving breast cancer is increasingly commonplace. This article reminds us of the other pathological processes which remain prevalent for all females, including those post breast cancer, for example, heart disease – which causes seven times as many deaths as those from breast cancer and from which a sufferer is more likely to die from than her breast cancer. Death in the 12 months post hip fracture is as common as dying from breast cancer whilst Alzheimer’s disease affects twice as many women than breast cancer does. Preventing heart disease and fractures with HRT use is very well established and there is increasing evidence demonstrating the brain-protecting effects of oestrogen and a reduction in cognitive decline with HRT used around the time of menopause. HRT also reduces the risk of bowel cancer and developing type 2 diabetes. Using HRT reduces all-cause mortality in those with a history of breast cancer.
With all this evidence now available, we therefore need to consider very carefully whether it is appropriate to continue to deny women these potential and hugely significant health benefits in addition to the benefits of HRT for improving menopausal symptoms, based purely on a history of breast cancer.
Between 1980 and 2013 a total of 25 studies have examined the effects of HRT on breast cancer recurrence and mortality rates. Five of these studies show a decreased recurrence rate and four show a reduced mortality rate. Only one of the 25 studies, HABITS, reported an increase in tumour recurrence (local and contralateral, but not distant metastases or increased mortality rates) of breast cancer with HRT use. However, this study’s results should be interpreted with caution. This study had only recruited one third of its intended subjects and was terminated early after a median follow up of 2 years, and was also analysed on an ‘intention to treat’ basis. Use of oestrogen-only HRT was not associated with any adverse outcomes. Presence of lymph node involvement was not associated with adverse outcomes and only concomitant use of tamoxifen with HRT seemed to relate to the increased rate of recurrence – a finding not seen in other studies. Longer term follow up showed no increased mortality with HRT use.
In addition to the 25 studies which have examined this highly controversial subject, there are also 20 review articles (1994-2021) of all of them, including the HABITs study, but the significant limitations of the HABITs study are not recognised. The most recent review of this subject by Poggio et al (3), is highly skewed, for example, by the inclusion of 78% of their study subjects being on tibolone (which is not oestrogen).
Essentially, the HABITs study has led to the apparent excess of just 22 women who used HRT after breast cancer (having local or contralateral, but not distant, recurrence AND no increase in death rate) and this has dictated the perceived thinking regarding menopause therapy for millions of women around the world i.e., to not offer HRT.
Although the question ‘Should women be offered HRT after breast cancer?’ is far from having been answered, conclusions have thus far only been drawn from highly questionable and insufficient evidence.
A closely related question is the extent to which suppression of ovarian function post breast cancer is justified. Reduction in risk of cancer recurrence with for example, Tamoxifen or an aromatase inhibitor, needs to be interpreted in the context of overall survival and quality of life, given the potential toxicities of suppressing oestrogen. On a related point, we are also reminded that pregnancy occurring post breast cancer is not associated with an adverse prognosis.
To provide a much-needed answer to the question will not be straightforward. Conducting RCTs of HRT after breast cancer is unlikely to be forthcoming for multiple reasons. Dr Bluming suggests the crucial need for use of national cancer registries and/or individual responsible clinicians keeping data for those patients in whom HRT is offered post breast cancer following an individualised consultation involving shared care decision making.
We are reminded how challenging it can be to change minds in the face of long held medical beliefs, even where those beliefs are not founded in science. Hopefully this article and many of the parallel conversations that likeminded clinicians, researchers and now patients are having will further our understanding and improve health for all those who have had breast cancer.
References:
- ‘Oestrogen Matters’ by Avrum Bluming and Carole Tavris. Published by Piatkus 2018.
- Bluming, A (2022) Hormone Replacement Therapy After Breast Cancer: It Is Time. The Cancer Journal 2022;28: 183-190
- Poggio F, Del Mastro L, Bruzzone M et al (2021) Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis. Breast Cancer Res Treat. https://doi.org/10.1007/s10549-021-06436-9