Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin

Garnet L. Anderson, Rowan T. Chlebowski, Jacques E. Rossouw, Rebecca J. Rodabough, Anne McTiernan, Karen L. Margolis, Anita Aggerwal, J. David Curb, Susan L. Hendrix, F. Allan Hubbell, Jamardan Khandekar, Dorothy S. Lane, Norman Lasser, Ana Maria Lopez, JoNell E Potter, Cheryl Ritenbaugh

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Objectives: To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E + P) in the Women's Health Initiative (WHI) randomized trial. Methods: Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E + P over an average 5.6 years of follow-up. Results: Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E + P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E + P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p = 0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p = 0.01) and among never users (p = 0.02) but not among prior users (p = 0.10). The cumulative incidence over time for the E + P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p = 0.08) or recency of prior use (p = 0.17). Prior hormone use significantly increased the E + P hazard ratio for larger, more advanced tumors. Conclusion: A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.

Original languageEnglish
Pages (from-to)103-115
Number of pages13
JournalMaturitas
Volume55
Issue number2
DOIs
StatePublished - Sep 20 2006

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Women's Health
Progestins
Estrogens
Hormones
Breast Neoplasms
Hazards
Placebos
Confidence Intervals
Therapeutics
Incidence
Tumors
Neoplasms

Keywords

  • Breast neoplasms
  • Estrogen
  • Progestin
  • Randomized trials
  • Subgroup analyses

ASJC Scopus subject areas

  • Aging
  • Obstetrics and Gynecology

Cite this

Anderson, G. L., Chlebowski, R. T., Rossouw, J. E., Rodabough, R. J., McTiernan, A., Margolis, K. L., ... Ritenbaugh, C. (2006). Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. Maturitas, 55(2), 103-115. https://doi.org/10.1016/j.maturitas.2006.05.004

Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. / Anderson, Garnet L.; Chlebowski, Rowan T.; Rossouw, Jacques E.; Rodabough, Rebecca J.; McTiernan, Anne; Margolis, Karen L.; Aggerwal, Anita; David Curb, J.; Hendrix, Susan L.; Allan Hubbell, F.; Khandekar, Jamardan; Lane, Dorothy S.; Lasser, Norman; Lopez, Ana Maria; Potter, JoNell E; Ritenbaugh, Cheryl.

In: Maturitas, Vol. 55, No. 2, 20.09.2006, p. 103-115.

Research output: Contribution to journalArticle

Anderson, GL, Chlebowski, RT, Rossouw, JE, Rodabough, RJ, McTiernan, A, Margolis, KL, Aggerwal, A, David Curb, J, Hendrix, SL, Allan Hubbell, F, Khandekar, J, Lane, DS, Lasser, N, Lopez, AM, Potter, JE & Ritenbaugh, C 2006, 'Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin', Maturitas, vol. 55, no. 2, pp. 103-115. https://doi.org/10.1016/j.maturitas.2006.05.004
Anderson, Garnet L. ; Chlebowski, Rowan T. ; Rossouw, Jacques E. ; Rodabough, Rebecca J. ; McTiernan, Anne ; Margolis, Karen L. ; Aggerwal, Anita ; David Curb, J. ; Hendrix, Susan L. ; Allan Hubbell, F. ; Khandekar, Jamardan ; Lane, Dorothy S. ; Lasser, Norman ; Lopez, Ana Maria ; Potter, JoNell E ; Ritenbaugh, Cheryl. / Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. In: Maturitas. 2006 ; Vol. 55, No. 2. pp. 103-115.
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abstract = "Objectives: To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E + P) in the Women's Health Initiative (WHI) randomized trial. Methods: Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E + P over an average 5.6 years of follow-up. Results: Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E + P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E + P versus placebo was 1.96 (95{\%} confidence interval [CI]: 1.17-3.27), significantly different (p = 0.03) from that among 12,297 never users (HR 1.02; 95{\%} CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p = 0.01) and among never users (p = 0.02) but not among prior users (p = 0.10). The cumulative incidence over time for the E + P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p = 0.08) or recency of prior use (p = 0.17). Prior hormone use significantly increased the E + P hazard ratio for larger, more advanced tumors. Conclusion: A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.",
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AU - Anderson, Garnet L.

AU - Chlebowski, Rowan T.

AU - Rossouw, Jacques E.

AU - Rodabough, Rebecca J.

AU - McTiernan, Anne

AU - Margolis, Karen L.

AU - Aggerwal, Anita

AU - David Curb, J.

AU - Hendrix, Susan L.

AU - Allan Hubbell, F.

AU - Khandekar, Jamardan

AU - Lane, Dorothy S.

AU - Lasser, Norman

AU - Lopez, Ana Maria

AU - Potter, JoNell E

AU - Ritenbaugh, Cheryl

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N2 - Objectives: To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E + P) in the Women's Health Initiative (WHI) randomized trial. Methods: Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E + P over an average 5.6 years of follow-up. Results: Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E + P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E + P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p = 0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p = 0.01) and among never users (p = 0.02) but not among prior users (p = 0.10). The cumulative incidence over time for the E + P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p = 0.08) or recency of prior use (p = 0.17). Prior hormone use significantly increased the E + P hazard ratio for larger, more advanced tumors. Conclusion: A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.

AB - Objectives: To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E + P) in the Women's Health Initiative (WHI) randomized trial. Methods: Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E + P over an average 5.6 years of follow-up. Results: Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E + P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E + P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p = 0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p = 0.01) and among never users (p = 0.02) but not among prior users (p = 0.10). The cumulative incidence over time for the E + P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p = 0.08) or recency of prior use (p = 0.17). Prior hormone use significantly increased the E + P hazard ratio for larger, more advanced tumors. Conclusion: A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.

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KW - Estrogen

KW - Progestin

KW - Randomized trials

KW - Subgroup analyses

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