Cancer drugs, survival, and ethics

BMJ 2016; 355 doi: (Published 09 November 2016) Cite this as: BMJ 2016;355:i5792

Decreased hormone use lowers breast cancer mortality Re: Cancer drugs, survival, and ethics

Dr Peter Wise does not mention that breast cancer survival also depends on rises or falls in hormone use (BMJ 2016;355:i5792). Professor Michael Baum reminds us of Sir George Beatson's publication of three cases of metastatic breast cancer being treated successfully by bilateral oophorectomy.1 The most important consequences of this discovery are, not only endocrine ablation in cancer management, but more importantly, that widespread use of progestogens and oestrogens has caused a predictable and therefore preventable breast cancer epidemic.
The rises and falls in the percentage increases in breast cancer registrations since 1962 in England and Wales have matched the increases and smaller falls in hormone use for contraception or hormone “therapy” with extra increases in diagnosis due to the introduction of screening for middle age women. Figure attached
The Womens’ Health Initiative (WHI) trials found “remarkably similar” increased risks of HT-associated breast cancer to the Million Women Study (MWS) and the worldwide Collaborative Group’s study (in which 80% of HT users had used oestrogen-only preparations). The estimated excess incidence of breast cancer with oestrogens increased from 2 to 6 per 1000 users in the Collaborative Group study and from 1.5 to 5 per 1000 users in the MWS for 5 and 10 years of use. The excess incidence for progestogen/oestrogen HT increased from 6 to 18 per 1000 users in for 5 and 7 years’ use in the WHI trial and from 6 to 19 per 1000 for 5 to 10 years of use in the MWS. Progestogen containing HT caused 4 times more breast cancer than oestrogen HT in both the WHI trial and the MWS. Longer use of oestrogen HT or combination HT for up to 10 years trebled breast cancer risks compared with use for up to 5 years.2

After the premature terminations of the WHI randomized trial of combined HT in 2002 and oestrogen only HT trial in 2004, the fall in HT use in hormone taking countries matched declines in breast cancer mortality.3   Professor Graham Colditz described the decline in breast cancer incidence as due to the removal of the promoter.4  Oestrogen positive breast cancers particularly decreased perhaps because women who had hysterectomies and oophorectomies may have taken oestrogens for longer than users of combined HT.

1 Beatson G.  On Treatment of Inoperable Cases of Carcinoma of the Mamma: Suggestions for a New Method of Treatment, with Illustrative Cases Lancet 1896, ii:104-107
2 Beral V. Banks E, Reeves G, Bull D, on behalf of the Million Women Study collaborators. Breast cancer and hormone replacement therapy: the Million Women Study. Lancet 2003;362:1330-1331.
3 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.
4 Colditz GA. Decline in breast cancer incidence due to removal of promoter: combination estrogen plus progestin. Breast Cancer Res. 2007;9:108.
5 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. Vol. 356, No.16. April 19, 2007

Competing interests: No competing interests

17 November 2016
Ellen C G Grant
Physician and medical gynaecologist
Kingston-upon-Thames. KT2 7JU. UK