Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's health initiative randomized trial

Anne McTiernan; Christopher F. Martin; Jennifer D. Peck; Aaron K. Aragaki; Rowan T. Chlebowski; Etta D. Pisano; C. Y. Wang; Robert L. Brunner; Karen C. Johnson; Jo Ann E. Manson; Cora E. Lewis; Jane Morley Kotchen; Barbara S. Hulka; Barbara Alving; Jacques Rossouw; Linda Pottern; Ross Prentice; Garnet Anderson; Andrea LaCroix; Ruth E. Patterson; Sally Shumaker; Pentti Rautaharju; Evan Stein; Steven Cummings; John Himes; Bruce Psaty; Sylvia Wassertheil-Smoller; Jennifer Hays; Annlouise R. Assaf; Lawrence Phillips; Shirley Beresford; Judith Hsia; Cheryl Ritenbaugh; Bette Caan; Barbara V. Howard; Linda Van Horn; Henry Black; Marcia L. Stefanick; Dorothy Lane; Rebecca Jackson; Cora Beth Lewis; Tamsen Bassford; Jean Wactawski-Wende; John Robbins; Allan Hubbell; Howard Judd; Robert D. Langer; Margery Gass; Marian Limacher; David Curb; Robert Wallace; Judith Ockene; Norman Lasse; Mary Jo O'Sullivan; Karen Margolis; Robert Brunner; Gerardo Heiss; Lewis Kuller; Karen C. Johnson; Robert Brzyski; Gloria Sarto; Denise Bonds

doi:10.1093/jnci/dji279

Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's health initiative randomized trial

Anne McTiernan, Christopher F. Martin, Jennifer D. Peck, Aaron K. Aragaki, Rowan T. Chlebowski, Etta D. Pisano, C. Y. Wang, Robert L. Brunner, Karen C. Johnson, Jo Ann E. Manson, Cora E. Lewis, Jane Morley Kotchen, Barbara S. Hulka, Barbara Alving, Jacques Rossouw, Linda Pottern, Ross Prentice, Garnet Anderson, Andrea LaCroix, Ruth E. PattersonSally Shumaker, Pentti Rautaharju, Evan Stein, Steven Cummings, John Himes, Bruce Psaty, Sylvia Wassertheil-Smoller, Jennifer Hays, Annlouise R. Assaf, Lawrence Phillips, Shirley Beresford, Judith Hsia, Cheryl Ritenbaugh, Bette Caan, Barbara V. Howard, Linda Van Horn, Henry Black, Marcia L. Stefanick, Dorothy Lane, Rebecca Jackson, Cora Beth Lewis, Tamsen Bassford, Jean Wactawski-Wende, John Robbins, Allan Hubbell, Howard Judd, Robert D. Langer, Margery Gass, Marian Limacher, David Curb, Robert Wallace, Judith Ockene, Norman Lasse, Mary Jo O'Sullivan, Karen Margolis, Robert Brunner, Gerardo Heiss, Lewis Kuller, Karen C. Johnson, Robert Brzyski, Gloria Sarto, Denise Bonds

Family and Community Medicine

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Abstract

Background: Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density. Methods: In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models. Results: Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P<.001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P<.001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P<.001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density. Conclusions: Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.

Original language	English (US)
Pages (from-to)	1366-1376
Number of pages	11
Journal	Journal of the National Cancer Institute
Volume	97
Issue number	18
DOIs	https://doi.org/10.1093/jnci/dji279
State	Published - Sep 2005

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1093/jnci/dji279

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McTiernan, A., Martin, C. F., Peck, J. D., Aragaki, A. K., Chlebowski, R. T., Pisano, E. D., Wang, C. Y., Brunner, R. L., Johnson, K. C., Manson, J. A. E., Lewis, C. E., Kotchen, J. M., Hulka, B. S., Alving, B., Rossouw, J., Pottern, L., Prentice, R., Anderson, G., LaCroix, A., ... Bonds, D. (2005). Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's health initiative randomized trial. Journal of the National Cancer Institute, 97(18), 1366-1376. https://doi.org/10.1093/jnci/dji279

McTiernan, A, Martin, CF, Peck, JD, Aragaki, AK, Chlebowski, RT, Pisano, ED, Wang, CY, Brunner, RL, Johnson, KC, Manson, JAE, Lewis, CE, Kotchen, JM, Hulka, BS, Alving, B, Rossouw, J, Pottern, L, Prentice, R, Anderson, G, LaCroix, A, Patterson, RE, Shumaker, S, Rautaharju, P, Stein, E, Cummings, S, Himes, J, Psaty, B, Wassertheil-Smoller, S, Hays, J, Assaf, AR, Phillips, L, Beresford, S, Hsia, J, Ritenbaugh, C, Caan, B, Howard, BV, Van Horn, L, Black, H, Stefanick, ML, Lane, D, Jackson, R, Lewis, CB, Bassford, T, Wactawski-Wende, J, Robbins, J, Hubbell, A, Judd, H, Langer, RD, Gass, M, Limacher, M, Curb, D, Wallace, R, Ockene, J, Lasse, N, O'Sullivan, MJ, Margolis, K, Brunner, R, Heiss, G, Kuller, L, Johnson, KC, Brzyski, R, Sarto, G & Bonds, D 2005, 'Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's health initiative randomized trial', Journal of the National Cancer Institute, vol. 97, no. 18, pp. 1366-1376. https://doi.org/10.1093/jnci/dji279

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title = "Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's health initiative randomized trial",

abstract = "Background: Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density. Methods: In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models. Results: Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P<.001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P<.001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P<.001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density. Conclusions: Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.",

author = "Anne McTiernan and Martin, {Christopher F.} and Peck, {Jennifer D.} and Aragaki, {Aaron K.} and Chlebowski, {Rowan T.} and Pisano, {Etta D.} and Wang, {C. Y.} and Brunner, {Robert L.} and Johnson, {Karen C.} and Manson, {Jo Ann E.} and Lewis, {Cora E.} and Kotchen, {Jane Morley} and Hulka, {Barbara S.} and Barbara Alving and Jacques Rossouw and Linda Pottern and Ross Prentice and Garnet Anderson and Andrea LaCroix and Patterson, {Ruth E.} and Sally Shumaker and Pentti Rautaharju and Evan Stein and Steven Cummings and John Himes and Bruce Psaty and Sylvia Wassertheil-Smoller and Jennifer Hays and Assaf, {Annlouise R.} and Lawrence Phillips and Shirley Beresford and Judith Hsia and Cheryl Ritenbaugh and Bette Caan and Howard, {Barbara V.} and {Van Horn}, Linda and Henry Black and Stefanick, {Marcia L.} and Dorothy Lane and Rebecca Jackson and Lewis, {Cora Beth} and Tamsen Bassford and Jean Wactawski-Wende and John Robbins and Allan Hubbell and Howard Judd and Langer, {Robert D.} and Margery Gass and Marian Limacher and David Curb and Robert Wallace and Judith Ockene and Norman Lasse and O'Sullivan, {Mary Jo} and Karen Margolis and Robert Brunner and Gerardo Heiss and Lewis Kuller and Johnson, {Karen C.} and Robert Brzyski and Gloria Sarto and Denise Bonds",

year = "2005",

month = sep,

doi = "10.1093/jnci/dji279",

language = "English (US)",

volume = "97",

pages = "1366--1376",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "18",

}

TY - JOUR

T1 - Estrogen-plus-progestin use and mammographic density in postmenopausal women

T2 - Women's health initiative randomized trial

AU - McTiernan, Anne

AU - Martin, Christopher F.

AU - Peck, Jennifer D.

AU - Aragaki, Aaron K.

AU - Chlebowski, Rowan T.

AU - Pisano, Etta D.

AU - Wang, C. Y.

AU - Brunner, Robert L.

AU - Johnson, Karen C.

AU - Manson, Jo Ann E.

AU - Lewis, Cora E.

AU - Kotchen, Jane Morley

AU - Hulka, Barbara S.

AU - Alving, Barbara

AU - Rossouw, Jacques

AU - Pottern, Linda

AU - Prentice, Ross

AU - Anderson, Garnet

AU - LaCroix, Andrea

AU - Patterson, Ruth E.

AU - Shumaker, Sally

AU - Rautaharju, Pentti

AU - Stein, Evan

AU - Cummings, Steven

AU - Himes, John

AU - Psaty, Bruce

AU - Wassertheil-Smoller, Sylvia

AU - Hays, Jennifer

AU - Assaf, Annlouise R.

AU - Phillips, Lawrence

AU - Beresford, Shirley

AU - Hsia, Judith

AU - Ritenbaugh, Cheryl

AU - Caan, Bette

AU - Howard, Barbara V.

AU - Van Horn, Linda

AU - Black, Henry

AU - Stefanick, Marcia L.

AU - Lane, Dorothy

AU - Jackson, Rebecca

AU - Lewis, Cora Beth

AU - Bassford, Tamsen

AU - Wactawski-Wende, Jean

AU - Robbins, John

AU - Hubbell, Allan

AU - Judd, Howard

AU - Langer, Robert D.

AU - Gass, Margery

AU - Limacher, Marian

AU - Curb, David

AU - Wallace, Robert

AU - Ockene, Judith

AU - Lasse, Norman

AU - O'Sullivan, Mary Jo

AU - Margolis, Karen

AU - Brunner, Robert

AU - Heiss, Gerardo

AU - Kuller, Lewis

AU - Johnson, Karen C.

AU - Brzyski, Robert

AU - Sarto, Gloria

AU - Bonds, Denise

PY - 2005/9

Y1 - 2005/9

N2 - Background: Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density. Methods: In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models. Results: Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P<.001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P<.001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P<.001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density. Conclusions: Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.

AB - Background: Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density. Methods: In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models. Results: Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P<.001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P<.001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P<.001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density. Conclusions: Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.

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Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's health initiative randomized trial

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