Risk of breast cancer with HRT depends on therapy type and duration
BMJ 2022; 376 doi: https://doi.org/10.1136/bmj.o485 (Published 08 March 2022) Cite this as: BMJ 2022;376:o485Linked Research
Use of hormone replacement therapy and risk of breast cancer
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Dear Editor
Correction
When the Collaborative Group on Hormonal Factors in Breast Cancer reviewed all the available relevant randomised evidence use of micronized progesterone as HRT doubled the risk of breast cancer ( RR 2.05, 1.38-3.56).
1 Collaborative Group on Hormonal Factors in Breast Cancer. Type and Timing of menopausal therapy and breast cancer risk individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019;394 1159-68. :10.1016/S0140-6736(19)31474332.
Competing interests: No competing interests
Dear Editor
The rapid response from Dr Peter Lewis claims again that only synthetic progestogens increase the risk of breast cancer and not progesterone. In fact, the Collaborative Group on Hormonal Factors in Breast Cancer reviewed all the available relevant randomised evidence and found a significant nearly double increased risk of breast cancer with use of micronized progesterone (RR 1.93 (1.84-2.01).[1]
Colonel Sir George Thomas Beatson was able to remit metastatic breast cancer as early as 1896 by removing functioning ovaries prevent endogenous secretion of oestrogens and progesterone. Oophorectomy became the standard treatment for advanced breast cancer and Beatson is considered the father of anti-hormonal treatment of breast cancer. His results make nonsense of HRT which probably became fashionable because use of progestogenic contraceptives block ovarian function and increase the chance of post-pill amenorrhoea or early menopause.
1 Collaborative Group on Hormonal Factors in Breast Cancer. Type and Timing of menopausal therapy and breast cancer risk individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019;394 1159-68. :10.1016/S0140-6736(19)31474332.
Competing interests: No competing interests
Dear Editor,
The lowest risk of breast cancer in women prescribed HRT/MHT is actually, when progesterone, as opposed to progestins (synthetic progestogens), is used.
A large French study which assessed and compared the association between different HRTs and breast cancer risk, followed up 80,377 women for an average of 8.1 post-menopausal years, and found that compared with HRT never-use, there was no increased risk of breast cancer for oestrogen-progesterone (relative risk 1.00), whereas those using oestrogen plus progestins had a 16-69% increased risk of breast cancer (depending on the progestin used). (1)
Another French study also found that breast cancer risk differed by type of progestogen among current users of oestrogen-progestogen therapies. No increased risk was apparent among users of oestrogen + micronized progesterone (in fact, there was a 20% lower risk for any duration of use, compared with never-users of MHT). (2)
A meta-analysis of studies of postmenopausal women using progesterone vs. synthetic progestins in combination with oestrogen found that progesterone-oestrogen was associated with a 33% lower risk of breast cancer compared with progestins. (3)
The meta-analysis of the worldwide epidemiological evidence published in the Lancet in 2019 found that oestrogen-micronised progesterone combination for <5 years of use had a relative risk of breast cancer of 0.91 compared with women who had never used HRT [although for some reason this data was buried in the supplementary appendix]. (4)
Thus, it seems clear that oestrogen-progesterone carries the lowest risk of breast cancer, and should be the HRT of choice.
1. Breast Cancer Res Treat, 2008;107(1):103-11
2. PLoS ONE, 2013; 8(11): e78016. doi:10.1371/journal.pone.0078016
3. Systematic Reviews, 2016; 5:121; DOI 10.1186/s13643-016-0294-5
4. The Lancet, 2019; Published online August 29: http://dx.doi.org/10.1016/S0140-6736(19)31709-X; appendix p 45
Competing interests: No competing interests
Dear Editor
As most women have taken hormones for contraception and/or menopausal symptoms, observational and randomized trials often lack clean never-ever user controls underestimating large increases in cancers and mortality. In 1989 the UK National Case-control Study Group found breast cancers increased with longer use of OCs before age 36 years. Of cases starting use before age 18, 80% had taken OCs for over four years.[1] The authors mistakenly claimed progestogen-only OCs were protective by adding past combined OC users as never user controls. In fact, taking progestogens for up to 12 months significantly increased breast cancer risks when never ever users were the controls.
After the premature stoppage of WHI randomized trial of CHT in 2002 and EHT study in 2004, HT use in westernised countries fell from 36 million to 12 million matching declines in breast (especially if oestrogen positive) and ovarian cancer incidences and mortality.[2-4]
The menopause is a physiological event protecting women from the carcinogenicity of high levels of sex hormones. Postmenopausal steroid withdrawal vasomotor symptoms have many causes including toxic metal sensitivities and increased bacterial or fungal gut fermentation, increases in blood ethanol levels.[5] Adverse reactions to alcoholic drinks, tobacco , coffee, food and chemicals, and nutritional deficiencies, are increased by use of OCs and HT.[6] Progestogen use can cause micro-thrombi in bone blood vessels. Fracture incidences increased in women in countries using OC and HT hormones. Osteoporosis can increase if HT is discontinued but osteoporosis is mainly due to essential nutrient deficiencies, especially zinc, magnesium and vitamin D. [7]
1 UK National Case-control Study Group. Oral contraceptive use and breast cancer risk in young women.Lancet,1989;i:973-82.
2 Grant ECG. Reduction in mortality from breast cancer: fall in use of hormones could have reduced breast cancer mortality. BMJ. 2005 Apr 30;330(7498):1024.
3 Colditz GA. Decline in breast cancer incidence due to removal of promoter: combination estrogen plus progestin. Breast Cancer Res. 2007;9:108.
4 Ravdin M, Cronin KA, Howlander N, Berg CD, Chlebowski RT, Feuer EJ, Edwards BK, Berry DA. The Decrease in Breast Cancer Incidence in 2003 in the United States. NEJM 356, 16. April 19, 2007.
5 Hunnisett A, Howard J, Davies S. Gut fermentation (or the auto-brewery syndrome): a new clinical test with observations and discussion of clinical and biochemical implications. J Nutr Med 1990:1:33-38.
6 Grant ECG. The pill, hormone replacement therapy, vascular and mood over-reactivity and mineral imbalance. J Nutr Environ Med 1998:8:789-91. DOI:10.1080/13590849862131
7 McLaren-Howard J, Grant ECG, Davies S. Hormone replacement therapy and osteoporosis: bone enzymes and nutrient imbalances. J Nutr Environ Med. 1998;8:129–138.
Competing interests: No competing interests
Risk of breast cancer with HRT depends on therapy type and duration: progesterone vs progestins
Dear Editor,
Dr Ellen Grant, in her reply to my rapid response, claims that ‘the Collaborative Group on Hormonal Factors in Breast Cancer…found a significant nearly double increased risk of breast cancer with use of micronised progesterone (RR 1.93 (1.84-2.01).’ The figure that she quotes does not actually relate to micronised progesterone at all, but instead applies to the relative risk of oestrogen plus intermittent progestogen during 5-14 years of MHT use. As stated in my original rapid response, the relative risk of breast cancer for oestrogen-micronised progesterone combination for <5 years in this meta-analysis was 0.91 [1], suggesting that, at least for up to 5 years MHT use, this combination carries a very low risk.
1. Collaborative Group on Hormonal Factors in Breast Cancer. Type and Timing of menopausal therapy and breast cancer risk individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019;394 1159-68 [Supplementary appendix, page 45, Figure S15]
Competing interests: No competing interests