Journal of the National Cancer Institute Advance Access originally published online on April 8, 2008
JNCI Journal of the National Cancer Institute 2008 100(8):598-599; doi:10.1093/jnci/djn080
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© The Author 2008. Published by Oxford University Press.
CORRESPONDENCE |
Re: Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population
Affiliation of author: Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
Correspondence to: Jayant S. Vaidya, MBBS, MS, DNB, FRCS, PhD, FRCS (Gen), Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK (e-mail: j.s.vaidya{at}dundee.ac.uk).
A recent article in the Journal (1) indicates that reduced screening mammography is unlikely to explain the recent reduction in breast cancer incidence in the United States, which has been attributed to the general reduction in use of hormone replacement therapy (HRT) (2,3). However, in the United States, both screening mammography and HRT use are individual choice–driven activities, and there could be several confounding factors that influence these analyses.
In Scotland, by contrast, population screening mammography is a state-administered activity and continues to be a part of the routine life of every woman older than 50 years (82% of the eligible population receives screening mammography every 3 years; www.isdscotland.org). Also, almost all the HRT taken by women is through prescriptions issued by the National Health Service. Furthermore, Scotland also has a generally stable population, thus reducing any confounding by population migration. To investigate the relationship between HRT use and breast cancer rates, I obtained information on the yearly number of HRT prescriptions dispensed and breast cancer diagnoses in Scotland from 1997 to 2006 (Figure 1). The number of HRT prescriptions dispensed dropped substantially over this time, from 143096 to 30053 (estrogen + progesterone combination) and from 82708 to 33416 (estrogen only). However, the number of breast cancer cases has not followed this trend, thus challenging the idea that reduction in HRT use was responsible for the observed reduction of breast cancer in the United States.
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A problem with the previous studies (1–3) is the lack of universal coverage by screening mammography and the fact that HRT data were collected by self-reporting (1). One possible explanation for the findings in the most recent US study (1) could be the following: The women who chose to continue having screening mammography may well have adopted other lifestyle changes that reduced their risk, such as increasing physical exercise (4). The association with physical exercise is evident whether it is done at a young age or in the referent year and is especially evident in those women who are recently exposed to HRT (4)—thus benefiting the very women who were risk averse and likely to have started exercise recently. Exercise has dramatic effects on estrogen metabolism (5), and it is possible that endogenous estrogens have a stronger influence on estrogen receptor–positive breast cancer than exogenous estrogens provided by HRT. The full explanation is likely to be much more complex, however.
The findings in Scotland could mean that HRT stimulates the growth of only the clinically significant breast cancer. HRT also increases breast density and reduces the sensitivity of screening mammography (6). In a population that continues to undergo screening mammography, one would therefore expect that a reduction in HRT would move the spectrum of the disease stage to the left, with a higher proportion being detected mammographically, at an earlier stage (albeit some of which may never have crossed the clinical threshold), without a perceptible reduction in the overall number of cancers.
NOTES
I wish to thank Victoria Hepworth and Susan Jensen of Information Services Division Scotland for providing the raw data for the analysis.
REFERENCES
1. Kerlikowske K, Miglioretti DL, Buist DS, Walker R, Carney PA. Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population. J Natl Cancer Inst (2007) 99(17):1335–1339.
2. Ravdin PM, Cronin KA, Howlader N, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med (2007) 356(16):1670–1674.
3. Clarke CA, Glaser SL. Declines in breast cancer after the WHI: apparent impact of hormone therapy. Cancer Causes Control (2007) 18(8):847–852.[CrossRef][Web of Science][Medline]
4. Slattery ML, Edwards S, Murtaugh MA, et al. Physical activity and breast cancer risk among women in the southwestern United States. Ann Epidemiol (2007) 17(5):342–353.[CrossRef][Web of Science][Medline]
5. Matthews CE, Fowke JH, Dai Q, et al. Physical activity, body size, and estrogen metabolism in women. Cancer Causes Control (2004) 15(5):473–481.[CrossRef][Web of Science][Medline]
6. Kavanagh AM, Cawson J, Byrnes GB, et al. Hormone replacement therapy, percent mammographic density, and sensitivity of mammography. Cancer Epidemiol Biomarkers Prev (2005) 14(5):1060–1064.
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J Natl Cancer Inst 2008 100: 599.
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