Healthy Skepticism International News
July 2001
Hormone Replacement Therapy: Breast Cancer
Results:
41% of 1152 respondents indicated that the impact of HRT on increasing or decreasing the risk of breast cancer was very certain.
79% of 1148 respondents indicated that regarding breast cancer, HRT was likely to be mildly harmful.
There was a significant negative correlation between respondent’s level of certainty and their estimate of benefit. (Spearman’s rho = -0.36 p
<0.0001) Those who felt more certain were more likely to believe that HRT had a harmful effect on breast cancer rates.
Our comment:
The impact of HRT on breast cancer is very uncertain but could be very harmful.
Explanation:
In the HERS trial the rate of breast cancer was 1.8% in the placebo group vs 2.3% in the HRT group. (p = 0.33 ie not significant). Results from ERA are consistent with that but in both studies the numbers were too small to have the power to show statistical significance.
A reanalysis of 90% of the relevant observational studies found that the risk of having breast cancer diagnosed is increased in women using HRT and increases with increasing duration of use. (Relative risk for women who used HRT for 5 years or more: 1.35, 95% confidence intervals 1.21-1.49) This effect is reduced after cessation of use of HRT and largely, if not completely, disappears after about 5 years.[1] The relationship between increased risk per year of HRT and per year of delayed menopause is very similar. [2] On the other hand some observational studies have suggested that breast cancer mortality is unchanged or lower in women using HRT.[3],[4] The authors of the reanalysis mentioned above concluded that the impact of HRT on breast cancer mortality is unknown. For all these studies the general rule that any observational finding could be due to confounding also applies here.
To avoid doing more harm than good it is necessary to take more notice of weak evidence of rare but serious adverse effects than we would of equally weak evidence of benefit.
In our clinical experience women are more concerned about getting breast cancer in their 50s than fractures in their 70s and 80s. Ann has indicated that she may be particularly concerned about this risk because of her family history. Having a mother or sister who had breast cancer doubles the lifetime absolute risk from the normal average of 8% to 16%. However, having a cousin with breast cancer would only increase Ann’s risk by 1.5 times normal ie: 12%.[5],[6] In fact her risk of breast cancer is even less because her history of a myocardial infarct leads to a higher risk of premature death from heart disease. Many women who have a second degree relative with breast cancer fear that their own risk of breast cancer is higher than it really is. Consequently, Ann may feel reassured by being told that her absolute risk is less than 12% and mammography is beneficial.[7] Whether or not Ann’s family history of breast cancer would make HRT more dangerous for her than for women without such a family history is not known.
Next: Gallbladder disease
[1] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet. 1997 Oct 11; 350(9084): 1047-59.
[2] Willett WC et al. Postmenopausal estrogens: opposed, unopposed, or none of the above. JAMA. 2000 Jan 26;283(4):534-5
[3] Yuen J et al. Hormone replacement therapy and breast cancer mortality in Swedish women: results after adjustment for ‘healthy drug-user’ effect. Cancer Causes Control 1993 Jul;4(4):369-74
[4] Jernstrom H etal. Hormone replacement therapy before breast cancer diagnosis significantly reduces the overall death rate compared with never-use among 984 breast cancer patients. Br J Cancer. 1999 Jul;80(9):1453-8.
[5] Taylor R et al. Absolute risk of breast cancer for Australian women with a family history. Aust N Z J Surg 2000 Oct;70(10):725-31
[6] Pharoah PD et al. Family history and the risk of breast cancer: a systematic review and meta-analysis. Int J Cancer 1997 May 29;71(5):800-9.
[7] Larsson LG et al. The Swedish randomised mammography screening trials: analysis of their effect on the breast cancer related excess mortality. J Med Screen 1996;3(3):129-32
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