Human Reproduction Update Advance Access originally published online on September 8, 2005
Human Reproduction Update 2005 11(6):545-560; doi:10.1093/humupd/dmi028
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Breast cancer risk with postmenopausal hormonal treatment
1 Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, 2 Department of Obstetrics and Gynaecology, Dalhousie University, Halifax, Nova Scotia, 3 Department of Obstetrics and Gynecology, University of Toronto at Sunnybrook-Women’s Hospital, Toronto, Ontario, Canada and 4 Department of Obstetrics and Gynecology, University of Milan, Milan, Italy
5 To whom correspondence should be addressed at: 400 Mader’s Cove Road, RRI, Mahone Bay, NS BOJ 2EO, Canada. E-mail: collinsj{at}auracom.com
Submitted on April 30, 2005; revised on June 27, 2005; accepted on July 16, 2005.
This review was designed to determine from the best evidence whether there is an association between postmenopausal hormonal treatment and breast cancer risk. Also, if there is an association, does it vary according to duration and cessation of use, type of regimen, type of hormonal product or route of administration; whether there is a differential effect on risk of lobular and ductal cancer; and whether hormone treatment is associated with breast cancers that have better prognostic factors? Data sources for the review included Medline, the Cochrane Database of Systematic Reviews (Cochrane Library, 2005) and reference lists in the identified citations. Eligible citations addressed invasive breast cancer risk among postmenopausal women and involved use of the estrogen products with or without progestin that are used as treatment for menopausal symptoms. Abstracted data were demographic groupings, categories of hormone use, categories of breast cancer, two-by-two tables of exposure and outcome and adjusted odds ratios, relative risks (RRs) or hazard rates. Average estimates of risk were weighted by the inverse variance method, or if heterogeneous, using a random effects model. The average risk of invasive breast cancer with estrogen use was 0.79 [95% confidence interval (95% CI) = 0.61–1.02] in four randomized trials involving 12 643 women. The average breast cancer risk with estrogen–progestin use was 1.24 (95% CI = 1.03–1.50) in four randomized trials involving 19 756 women. The average risks reported in recent epidemiological studies were higher: 1.18 (95% CI = 1.01–1.38) with current use of estrogen alone and 1.70 (95% CI = 1.36–2.17) with current use of estrogen–progestin. The association of breast cancer with current use was stronger than the association with ever use, which includes past use. For past use, the increased breast cancer risk diminished soon after discontinuing hormones and normalized within 5 years. Reasonably adequate data do not show that breast cancer risk varies significantly with different types of estrogen or progestin preparations, lower dosages or different routes of administration, although there is a small difference between sequential and continuous progestin regimens. Epidemiological studies indicate that estrogen–progestin use increases risk of lobular more than ductal breast cancer, but the number of studies and cases of lobular cancer remains limited. Among important prognostic factors, the stage and grade in breast cancers associated with hormone do not differ significantly from those in non-users, but breast cancers in estrogen–progestin users are significantly more likely to be estrogen receptor (ER) positive. In conclusion, valid evidence from randomized controlled trials (RCTs) indicates that breast cancer risk is increased with estrogen–progestin use more than with estrogen alone. Epidemiological evidence involving more than 1.5 million women agrees broadly with the trial findings. Although new studies are unlikely to alter the key findings about overall breast cancer risk, research is needed, however, to determine the role of progestin, evaluate the risk of lobular cancer and delineate effects of hormone use on receptor presence, prognosis and mortality in breast cancer.
Key words: breast cancer / duration of use / estrogen / progestin / recency / relative risk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. W. Reding, C. I. Li, N. S. Weiss, C. Chen, C. S. Carlson, D. Duggan, K. E. Thummel, J. R. Daling, and K. E. Malone Genetic Variation in the Progesterone Receptor and Metabolism Pathways and Hormone Therapy in Relation to Breast Cancer Risk Am. J. Epidemiol., November 15, 2009; 170(10): 1241 - 1249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fournier, S. Mesrine, M.-C. Boutron-Ruault, and F. Clavel-Chapelon Estrogen-Progestagen Menopausal Hormone Therapy and Breast Cancer: Does Delay From Menopause Onset to Treatment Initiation Influence Risks? J. Clin. Oncol., November 1, 2009; 27(31): 5138 - 5143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hooper, J. Ryder, M. Kurzer, J. Lampe, W. Phipps, and A. Cassidy Reply: Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis Hum. Reprod. Update, October 8, 2009; (2009) dmp042v1. [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Cline and C. E. Wood The Mammary Glands of Macaques Toxicol Pathol, December 1, 2008; 36(7_suppl): 130S - 141S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Otto, I. Fuchs, H. Altmann, M. Klewer, A. Walter, K. Prelle, R. Vonk, and K.-H. Fritzemeier Comparative Analysis of the Uterine and Mammary Gland Effects of Drospirenone and Medroxyprogesterone Acetate Endocrinology, August 1, 2008; 149(8): 3952 - 3959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. H James Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception J. Endocrinol., July 1, 2008; 198(1): 3 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Goodwin, S. J. Green, C. M. Moinpour, J. D. Bearden III, J. K. Giguere, C. S. Jiang, S. M. Lippman, S. Martino, and K. S. Albain Phase III Randomized Placebo-Controlled Trial of Two Doses of Megestrol Acetate as Treatment for Menopausal Symptoms in Women With Breast Cancer: Southwest Oncology Group Study 9626 J. Clin. Oncol., April 1, 2008; 26(10): 1650 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Rebbeck, A. B. Troxel, S. Norman, G. Bunin, A. DeMichele, R. Schinnar, J. A. Berlin, and B. L. Strom Pharmacogenetic Modulation of Combined Hormone Replacement Therapy by Progesterone-Metabolism Genotypes in Postmenopausal Breast Cancer Risk Am. J. Epidemiol., December 15, 2007; 166(12): 1392 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Birrell, L. M. Butler, J. M. Harris, G. Buchanan, and W. D. Tilley Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer FASEB J, August 1, 2007; 21(10): 2285 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System Endocr. Rev., June 1, 2007; 28(4): 387 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Antoine, F. Liebens, B. Carly, A. Pastijn, S. Neusy, and S. Rozenberg Safety of hormone therapy after breast cancer: a qualitative systematic review Hum. Reprod., February 1, 2007; 22(2): 616 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. I.J. Wildschut, T.J. Peters, and C. P. Weiner Screening in women's health, with emphasis on fetal Down's syndrome, breast cancer and osteoporosis Hum. Reprod. Update, September 1, 2006; 12(5): 499 - 512. [Abstract] [Full Text] [PDF]
|
|