Postmenopausal hormone therapy and change in mammographic density.

BACKGROUND Mammographic density is an independent risk factor for breast cancer. Postmenopausal hormone use is associated with an increase in mammographic density, but the magnitude of the density increase is unknown. METHODS Baseline and 12-month mammograms were obtained for 571 (65%) of the 875 women, aged 45-64 years, who were enrolled in the Postmenopausal Estrogen/Progestin Interventions Trial and randomly assigned to receive placebo, daily conjugated equine estrogens at 0.625 mg/day (CEE), daily CEE and medroxyprogesterone acetate (MPA) at 10 mg/day on days 1-12 (CEE+MPA-cyclic), daily CEE and MPA at 2.5 mg/day (CEE+MPA-continuous), or daily CEE and micronized progesterone (MP) at 200 mg/day on days 1-12 (CEE+MP). We analyzed digitized mammograms to determine the percentage of the left breast that was composed of dense tissue (i.e., mammographic percent density). Linear regression analysis was used to examine the effects of treatments on the change in mammographic percent density between baseline and 12 months, before and after adjustment for possible confounders. All statistical tests were two-sided. RESULTS The adjusted absolute mean changes in mammographic percent density over 12 months were 4.76% (95% confidence interval [CI] = 3.29% to 6.23%), 4.58% (95% CI = 3.19% to 5.97%), and 3.08% (95% CI = 1.65% to 4.51%) for women in the CEE+MPA-cyclic, CEE+MPA-continuous, and CEE-MP groups, respectively. Each of those absolute mean changes was statistically significantly different from the adjusted absolute mean change in mammographic percent density for women in the placebo group, which was -0.07% (95% CI = -1.50% to 1.38%). CONCLUSION Greater mammographic density was associated with the use of estrogen/progestin combination therapy, regardless of how the progestin was given, but not with the use of estrogen only.

[1]  J. Wolfe.  Breast patterns as an index of risk for developing breast cancer. , 1976, AJR. American journal of roentgenology.

[2]  B. Henderson,et al.  A case-control study of menopausal estrogen therapy and breast cancer. , 1980, JAMA.

[3]  G Block,et al.  A data-based approach to diet questionnaire design and testing. , 1986, American journal of epidemiology.

[4]  M. Szklo,et al.  Mammographic parenchymal patterns and breast cancer risk. , 1987, Epidemiologic reviews.

[5]  J. Wolfe,et al.  Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case-control study. , 1987, AJR. American journal of roentgenology.

[6]  L. Tabár,et al.  Mammographic parenchymal patterns in women receiving noncontraceptive estrogen treatment. , 1989, American journal of epidemiology.

[7]  A. Hossain,et al.  A comparative study on detection of influential observations in linear regression , 1991 .

[8]  R N Hoover,et al.  Mammographic densities and risk of breast cancer , 1991, Cancer.

[9]  N. Boyd,et al.  The risk of breast cancer associated with mammographic parenchymal patterns: a meta-analysis of the published literature to examine the effect of method of classification. , 1992, Cancer detection and prevention.

[10]  A. Oza,et al.  Mammographic parenchymal patterns: a marker of breast cancer risk. , 1993, Epidemiologic reviews.

[11]  M. Pike,et al.  Changes in mammographic densities induced by a hormonal contraceptive designed to reduce breast cancer risk. , 1994, Journal of the National Cancer Institute.

[12]  Susan R. Johnson,et al.  Rationale, design, and conduct of the PEPI trial , 1995 .

[13]  A. Miller,et al.  Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. , 1995, Journal of the National Cancer Institute.

[14]  J. Wolfe,et al.  Mammographic features and breast cancer risk: effects with time, age, and menopause status. , 1995, Journal of the National Cancer Institute.

[15]  Susan R. Johnson,et al.  Effects of Estrogen or Estrogen/ Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial , 1995 .

[16]  T. Bush,et al.  Rationale, design, and conduct of the PEPI Trial. Postmenopausal Estrogen/Progestin Interventions. , 1995, Controlled clinical trials.

[17]  N F Boyd,et al.  Symmetry of projection in the quantitative analysis of mammographic images , 1996, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[18]  S. Ingles,et al.  Leisure, home, and occupational physical activity and cardiovascular risk factors in postmenopausal women. The Postmenopausal Estrogens/Progestins Intervention (PEPI) Study. , 1996, Archives of internal medicine.

[19]  I Persson,et al.  Effect of estrogen and estrogen-progestin replacement regimens on mammographic breast parenchymal density. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  N. Boyd,et al.  Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian Diet and Breast Cancer Prevention Study Group. , 1997, Journal of the National Cancer Institute.

[21]  J Benichou,et al.  An approach to estimating exposure-specific rates of breast cancer from a two-stage case-control study within a cohort. , 1997, Statistics in medicine.

[22]  E. Barrett-Connor,et al.  Can We Measure Prior Postmenopausal Estrogen/Progestin Use? The Postmenopausal Estrogen/Progestin Interventions Trial , 1997 .

[23]  N. Boyd,et al.  Mammographic densities and breast cancer risk. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[24]  M A Astrahan,et al.  The detection of changes in mammographic densities. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[25]  M. Pike,et al.  Problems involved in including women with simple hysterectomy in epidemiologic studies measuring the effects of hormone replacement therapy on breast cancer risk. , 1998, American journal of epidemiology.

[26]  R. Warren,et al.  Mammographic patterns as a predictive biomarker of breast cancer risk: effect of tamoxifen. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[27]  L W Bassett,et al.  Effects of estrogen and estrogen-progestin on mammographic parenchymal density. Postmenopausal Estrogen/Progestin Interventions (PEPI) Investigators. , 1999, Annals of internal medicine.

[28]  N. Boyd,et al.  Macronutrient intake and change in mammographic density at menopause: results from a randomized trial. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[29]  B. V. VON Schoultz,et al.  Mammographic breast density during hormone replacement therapy: differences according to treatment. , 1999, American journal of obstetrics and gynecology.

[30]  D. Venzon,et al.  Effect of tamoxifen on mammographic density. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[31]  Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. , 2000 .

[32]  R. Cook.  Detection of influential observation in linear regression , 2000 .

[33]  P. Langenberg,et al.  Breast Imaging Reporting and Data System: inter- and intraobserver variability in feature analysis and final assessment. , 2000, AJR. American journal of roentgenology.

[34]  G. Colditz,et al.  Bias in breast cancer analyses due to error in age at menopause. , 2000, American journal of epidemiology.

[35]  R. Hoover,et al.  Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. , 2000, JAMA.

[36]  C M Rutter,et al.  Changes in breast density associated with initiation, discontinuation, and continuing use of hormone replacement therapy. , 2001, JAMA.

[37]  M. Freedman,et al.  Digitized mammography: a clinical trial of postmenopausal women randomly assigned to receive raloxifene, estrogen, or placebo. , 2001, Journal of the National Cancer Institute.

[38]  L. Liberman,et al.  Breast imaging reporting and data system (BI-RADS). , 2002, Radiologic clinics of North America.