Breast cancer risk associated with HRT increases with longer use, finds studyBMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l5332 (Published 30 August 2019) Cite this as: BMJ 2019;366:l5332
All rapid responses
Progesterone increases breast cancers Re: Breast cancer risk associated with HRT increases with longer use, finds study
Progesterone increases breast cancers
Dr Peter Lewis responds that progestogens increase the risk of breast cancer and not "natural" progesterone. In fact, the Collaborative Group on Hormonal Factors in Breast Cancer reviewed all the available relevant randomised evidence and found micronized progesterone and oestrogen significantly nearly doubled the risk of breast cancer (RR 1.93 (1.84-2.01).1 Oral progesterone is micronized to aid alimentary absorption and double its progestogenic potency.
Importantly, in 1896 Colonel Sir George Thomas Beatson discovered that oophorectomy, which stopped the endogenous secretion of oestrogens and progesterone from functioning ovaries, remitted metastatic breast cancer. Beatson is considered the father of anti-hormonal treatment of breast cancer. Oophorectomy became the standard treatment for advanced breast cancer.
Genetic testing by Evans and colleagues revealed that women born after 1940 with BRCA1 and BRCA2 had a cumulative risk of 22% for breast cancer by 40 years of age compared to 8% in women born before 1930 (p =.0005).1 The almost universal use of hormonal contraceptives and consequent use of HRT has been disastrous for women's health.
Evans DG. Shenton A, Woodward E, Lalloo F, Howell A, Mather ER. Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: Risks of breast/ovarian cancer quoted should reflect the cancer burden in the family. BMC Cancer 2008, 8:155
Competing interests: No competing interests
Interestingly, although not mentioned in the main body of the article, the Lancet meta-analysis found that the relative risk for <5 years use of oestrogen + micronized (natural) progesterone was 0.91, i.e. 9% lower than for never-users of MHT (1) , which suggests that that this combination is safe at least for short duration of use, and should therefore be the preferred MHT preparation prescribed for relief of menopausal symptoms.
1. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019. www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31709-X (appendix Figure S15, p. 45)
Competing interests: No competing interests
The HRT - breast cancer data from The Collaborative Group on Hormonal Factors in Breast Cancer reported in The Lancet this week is not surprising.1 What it suggests is that the cumulative exposure to HRT is the predominant risk for increased breast cancer risk. This is at a population level and not taking into account oestrogen receptor sensitivity and family history which increases the risk in individuals with these risks.
What the study or meta-analysis does not consider is the cumulative lifetime exposure to extraneous female hormones. There is great variation in women at 50 years of age from the point of view of hormone exposure to date. Many have taken the contraceptive pill or hormonal contraception for years and others not. In this meta-analysis they all start from baseline at age 50 or thereabouts and their hormone exposure to date is not considered as a confounding factor as regards subsequent cancer risk. Some if not the majority, would have heightened risk to start with from years of hormonal contraception. As the HRT study shows, the risk continues for years after stopping HRT and there is no reason to think that contraceptive hormonal exposure behaves any differently. Thus, those who took hormonal contraception for years are at more risk when they add to the hormonal load by taking HRT later in life. What is required is a comprehensive cumulative index of lifetime hormonal exposure or hormonal load from teens to 60s or 70s to correlate genuine cancer risk versus hormonal cumulative load. This is not even taking into account the behaviour of hormones in young women as compared to older post-menopausal women. Hormones may confer greater risk in reproductive age women for example the vast numbers of young women with invasive breast cancer cannot be understood except by attributing the enormous risk to hormone exposure from contraceptive sources.2 The sooner the real risks associated with hormone use is clarified the better for women of all ages.
1. Collaborative Group on Hormonal factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet: https://doi.org/10.1016/S0140-6736(19)31709-X
2. Breen EG. The Screech Owls of Breast Cancer. Authorhouse 2013.
Competing interests: I wrote a book about hormones and breast cancer "The Screech Owls of Breast Cancer".Authorhouse 2013.