Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women's Health Initiative Randomized Trial
Rowan T. Chlebowski,Susan L. Hendrix,Robert Langer,Marcia L. Stefanick,Margery Gass,Dorothy S. Lane,Rebecca J. Rodabough,Mary Ann Gilligan,Michele G. Cyr,Cynthia A. Thomson,Janardan D. Khandekar,Helen Petrovitch,Anne McTiernan +12 more
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TLDR
Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms, a pattern which continued for the study duration.Abstract:
ContextThe Women's Health Initiative trial of combined estrogen plus progestin
was stopped early when overall health risks, including invasive breast cancer,
exceeded benefits. Outstanding issues not previously addressed include characteristics
of breast cancers observed among women using hormones and whether diagnosis
may be influenced by hormone effects on mammography.ObjectiveTo determine the relationship among estrogen plus progestin use, breast
cancer characteristics, and mammography recommendations.Design, Setting, and ParticipantsFollowing a comprehensive breast cancer risk assessment, 16 608
postmenopausal women aged 50 to 79 years with an intact uterus were randomly
assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus
medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40
clinical centers. Screening mammography and clinical breast examinations were
performed at baseline and yearly thereafter.Main Outcome MeasuresBreast cancer number and characteristics, and frequency of abnormal
mammograms by estrogen plus progestin exposure.ResultsIn intent-to-treat analyses, estrogen plus progestin increased total
(245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001)
and invasive (199 vs 150 cases; HR, 1.24; weighted P =
.003) breast cancers compared with placebo. The invasive breast cancers diagnosed
in the estrogen plus progestin group were similar in histology and grade but
were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P = .04) and were at more advanced stage (regional/metastatic
25.4% vs 16.0%, respectively; P = .04) compared with
those diagnosed in the placebo group. After 1 year, the percentage of women
with abnormal mammograms was substantially greater in the estrogen plus progestin
group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.ConclusionsRelatively short-term combined estrogen plus progestin use increases
incident breast cancers, which are diagnosed at a more advanced stage compared
with placebo use, and also substantially increases the percentage of women
with abnormal mammograms. These results suggest estrogen plus progestin may
stimulate breast cancer growth and hinder breast cancer diagnosis.read more
Citations
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TL;DR: Genotype by environment interaction information may help to define genomic regions relevant to disease risk and raise novel hypotheses concerning the MRPS30 genomic region and the effects of hormonal and dietary exposures on postmenopausal breast cancer risk.
Patent
Sex steroid precursors alone or in combination with a selective estrogen receptor modulator and/or with estrogens and/or a type 5 cgmp phosphodiesterase inhibitor for the prevention and treatment of vaginal dryness and sexual dysfunction in postmenopausal women
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Book ChapterDOI
Estrogens, Progestins, and Risk of Breast Cancer
TL;DR: There is a ceiling to the carcinogenic effect of estrogen on the breast; increases in nonsex hormone-binding globulin-bound estradiol (non-SHBG bound E2) exceeding approximately 10.2 pg/ml have no effect on breast cancer risk; this ceiling is lower than the lowest level seen during the menstrual cycle.
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Estrogen and combined estrogen-progestogen therapy in the menopause and breast cancer
TL;DR: The results recorded in the WHI and the Million Women Study do not confirm the suggestion that breast cancers in women using HT have a more favorable prognosis, and HT has also been related to an increased risk of recurrent breast cancer.
References
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Journal ArticleDOI
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial
Jacques E. Rossouw,Garnet L. Anderson,Ross L. Prentice,Andrea Z. LaCroix,Charles Kooperberg,Marcia L. Stefanick,Rebecca D. Jackson,Shirley A.A. Beresford,Barbara V. Howard,Karen C. Johnson,Jane Morley Kotchen,Judith K. Ockene +11 more
TL;DR: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Journal ArticleDOI
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
Eugenia E. Calle,Clark W. Heath,R. J. Coates,Jonathan M. Liff,Silvia Franceschi,R. Talamini,N. Chantarakul,Suporn Koetsawang,D. Rachawat,A. Morabia,L. Schuman,Walter F. Stewart,Moyses Szklo,Chris Bain,F. Schofield,Victor Siskind,Philip A. Band,Andrew J. Coldman,Richard P. Gallagher,T. G. Hislop,P. Yang,Stephen W. Duffy,L. M. Kolonel,A. M.Y. Nomura,Mark W. Oberle,Howard W. Ory,Herbert B. Peterson,Hoyt G. Wilson,Phyllis A. Wingo,K. Ebeling,D. Kunde,P. Nishan,Graham A. Colditz,Nicholas G. Martin,Tieng Pardthaisong,S. Silpisornkosol,C. Theetranont,B. Boosiri,S. Chutivongse,P. Jimakorn,Pramuan Virutamasen,C. Wongsrichanalai,Anthony J. McMichael,T. Rohan,Marianne Ewertz,Carle Paul,David C. G. Skegg,G. F. S. Spears,P. Boyle,M. Evstifeeva,J. R. Daling,W. B. Hutchinson,Kathi Malone,E. A. Noonan,Janet L. Stanford,David B. Thomas,N. S. Weiss,Emily White,N. Andrieu,A. Bràmond,F Clavel,B. Gairard,J. Lansac,L. Piana,R. Renaud,S. R.P. Fine,H. R. Cuevas,P. Ontiveros,A. Palet,S. B. Salazar,N. Aristizabel,A. Cuadros,A. Bachelot,M. G. Lê,J. Deacon,Julian Peto,C. N. Taylor,E. Alfandary,Baruch Modan,Elaine Ron,Gary D. Friedman,Robert A. Hiatt,T. Bishop,J. Kosmelj,M. Primic-Zakelj,B. Ravnihar,J. Stare,W. L. Beeson,Graeme Fraser,R. D. Bulbrook,Jack Cuzick,I. S. Fentiman,J. L. Hayward,De Yun Wang,R. L. Hanson,M. C. Leske,Martin C. Mahoney,P. C. Nasca,A. O. Varma,A. L. Weinstein,Torgil Möller,Håkan Olsson,Jonas Ranstam,R.A. Goldbohm,P.A. van den Brandt,R. A. Apelo,J. Baens,J. R. de la Cruz,B. Javier,L. B. Lacaya,Corazon A. Ngelangel,C. La Vecchia,E. Negri,Ettore Marubini,Monica Ferraroni,Mariette Gerber,Sylvia Richardson,C. Segala,D. Gatei,P. Kenya,A. Kungu,J. G. Mati,L A Brinton,Robert N. Hoover,Catherine Schairer,Robert Spirtas,H. P. Lee,Matti A. Rookus,F.E. van Leeuwen,J. A. Schoenberg,Marilie D. Gammon,E. A. Clarke,Lee W. Jones,Klim McPherson,A. Neil,M. Vessey,D. Yeates,Valerie Beral,Diana Bull,B. Crossley,C Hermon,Simon Jones,Timothy J. Key,Claire E. Lewis,Gillian K Reeves,Rory Collins,Richard Doll,Richard Peto,P. Hannaford,Kay Cr,Luis Rosero-Bixby,Jian-Min Yuan,H. Y. Wei,T. Yun,C. Zhiheng,G. Berry,J Cooper Booth,T. Jelihovsky,Robert MacLennan,R. Shearman,Q. S. Wang,C. J. Baines,Anthony B. Miller,C. Wall,Eiliv Lund,H. Stalsberg,A. Dabancens,L. Martinez,R. Molina,O. Salas,Freda E. Alexander,B. S. Hulka,C. E. D. Chilvers,Leslie Bernstein,Robert W. Haile,Annlia Paganini-Hill,M. C. Pike,R. K. Ross,Giske Ursin,Mimi C. Yu,M. P. Longnecker,Polly A. Newcomb,T. M.N. Farley,S. Holck,O. Meirik,Hans-Olov Adami,R. Bergkvist,Ingemar Persson,Fabio Levi,Kiyohiko Mabuchi,Dale L. Preston,Klea Katsouyanni,Antonia Trichopoulou,D. Trichopoulos,Leif Bergkvist +194 more
TL;DR: Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast cancer diagnosed in women using HRT and associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body- mass index.
Journal ArticleDOI
Design of the Women's Health Initiative clinical trial and observational study
Garnet L. Anderson,S. Cummings,L. S. Freedman,C. Furberg,Maureen M. Henderson,Susan R. Johnson,L. Kuller,JoAnn E. Manson,A. Oberman,Ross L. Prentice,Jacques E. Rossouw,L. Finnegan,R. Hiatt,L. Pottern,J. McGowan,C. Clifford,B. Caan,V. Kipnis,B. Ettinger,S. Sidney,G. Bailey,Andrea Z. LaCroix,Anne McTiernan,Deborah J. Bowen,C. Chen,Barbara B. Cochrane,Julie R. Hunt,Alan R. Kristal,Brian J. Lund,Ruth E. Patterson,Jeffrey L. Probstfield,Lesley F. Tinker,Nicole Urban,Ching Yun Wang,Emily White,J. M. Kotchen,S. Shumaker,P. Rautaharju,F. Rautaharju,E. Stein,P. Laskarzewski,P. Steiner,K. Sagar,M. Nevitt,M. Dockrell,T. Fuerst,John H. Himes,M. Stevens,F. Cammarata,S. Lindenfelser,Bruce M. Psaty,D. Siscovick,W. Longstreth,S. Heckbert,S. Wassertheil-Smoller,W. Frishman,Judy Wylie-Rosett,D. Barad,R. Freeman,S. Miller,Jennifer Hays,R. Young,C. Crowley,M. A. DePoe,G. Burke,E. Paskett,L. Wagenknecht,R. Crouse,L. Parsons,T. Kotchen,E. Braunwald,J. Buring,C. Hennekens,J. M. Gaziano,Annlouise R. Assaf,R. C. Carleton,M. Miller,C. Wheeler,A. Hume,M. Pedersen,O. Strickland,M. Huber,V. Porter,Shirley A.A. Beresford,V. Taylor,N. Woods,J. Hsia,V. Barnabei,M. Bovun,Rowan T. Chlebowski,R. Detrano,A. Nelson,J. Heiner,S. Pushkin,B. Valanis,V. Stevens,E. Whitlock,N. Karanja,A. Clark +98 more
TL;DR: The rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component is described, including a brief description of the scientific and logistic complexity of the WHI.
Journal ArticleDOI
The use of estrogens and progestins and the risk of breast cancer in postmenopausal women.
Graham A. Colditz,Susan E. Hankinson,David J. Hunter,Walter C. Willett,JoAnn E. Manson,Meir J. Stampfer,Charles H. Hennekens,Bernard Rosner,Frank E. Speizer +8 more
TL;DR: In this paper, the effect of adding progestins to estrogen therapy on the risk of breast cancer in postmenopausal women is investigated. But, the effect on the number of newly diagnosed invasive breast cancer cases was not quantified.
Journal ArticleDOI
Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography.
Patricia A. Carney,Diana L. Miglioretti,Bonnie C. Yankaskas,Karla Kerlikowske,Robert D. Rosenberg,Carolyn M. Rutter,Berta M. Geller,Linn Abraham,Steven H. Taplin,Mark Dignan,Gary Cutter,Rachel Ballard-Barbash +11 more
TL;DR: The accuracy of screening mammography is best in older women and in women with fatty breasts, and the individual and combined effects of age, breast density, and HRT use on mammographic accuracy are examined.
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