Tamoxifen therapy for breast cancer and endometrial cancer risk

Leslie Bernstein, Dennis Deapen, James R Cerhan, Stephen M. Schwartz, Jonathan Liff, Erin McGann-Maloney, Jeffrey A. Perlman, Leslie Ford

Research output: Contribution to journalArticle

270 Citations (Scopus)

Abstract

Background: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. Methods: We conducted a case- control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. Results: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1.07-2.17). Risk increased with duration of tamoxifen use (P for trend = .0002). Women with more than 5 years of exposure to tamoxifen had 4.06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P = .10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. Conclusions: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.

Original languageEnglish (US)
Pages (from-to)1654-1662
Number of pages9
JournalJournal of the National Cancer Institute
Volume91
Issue number19
StatePublished - Oct 6 1999

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Tamoxifen
Endometrial Neoplasms
Breast Neoplasms
Estrogen Replacement Therapy
Therapeutics
Confidence Intervals
Medical Records
Case-Control Studies
Estrogens
Body Mass Index
Obesity
Odds Ratio
Interviews
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bernstein, L., Deapen, D., Cerhan, J. R., Schwartz, S. M., Liff, J., McGann-Maloney, E., ... Ford, L. (1999). Tamoxifen therapy for breast cancer and endometrial cancer risk. Journal of the National Cancer Institute, 91(19), 1654-1662.

Tamoxifen therapy for breast cancer and endometrial cancer risk. / Bernstein, Leslie; Deapen, Dennis; Cerhan, James R; Schwartz, Stephen M.; Liff, Jonathan; McGann-Maloney, Erin; Perlman, Jeffrey A.; Ford, Leslie.

In: Journal of the National Cancer Institute, Vol. 91, No. 19, 06.10.1999, p. 1654-1662.

Research output: Contribution to journalArticle

Bernstein, L, Deapen, D, Cerhan, JR, Schwartz, SM, Liff, J, McGann-Maloney, E, Perlman, JA & Ford, L 1999, 'Tamoxifen therapy for breast cancer and endometrial cancer risk', Journal of the National Cancer Institute, vol. 91, no. 19, pp. 1654-1662.
Bernstein L, Deapen D, Cerhan JR, Schwartz SM, Liff J, McGann-Maloney E et al. Tamoxifen therapy for breast cancer and endometrial cancer risk. Journal of the National Cancer Institute. 1999 Oct 6;91(19):1654-1662.
Bernstein, Leslie ; Deapen, Dennis ; Cerhan, James R ; Schwartz, Stephen M. ; Liff, Jonathan ; McGann-Maloney, Erin ; Perlman, Jeffrey A. ; Ford, Leslie. / Tamoxifen therapy for breast cancer and endometrial cancer risk. In: Journal of the National Cancer Institute. 1999 ; Vol. 91, No. 19. pp. 1654-1662.
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abstract = "Background: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. Methods: We conducted a case- control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. Results: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95{\%} confidence interval [CI] = 1.07-2.17). Risk increased with duration of tamoxifen use (P for trend = .0002). Women with more than 5 years of exposure to tamoxifen had 4.06-fold greater odds of developing endometrial cancer than nonusers (95{\%} CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P = .10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. Conclusions: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.",
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AU - Perlman, Jeffrey A.

AU - Ford, Leslie

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N2 - Background: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. Methods: We conducted a case- control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. Results: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1.07-2.17). Risk increased with duration of tamoxifen use (P for trend = .0002). Women with more than 5 years of exposure to tamoxifen had 4.06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P = .10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. Conclusions: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.

AB - Background: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. Methods: We conducted a case- control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. Results: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1.07-2.17). Risk increased with duration of tamoxifen use (P for trend = .0002). Women with more than 5 years of exposure to tamoxifen had 4.06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P = .10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. Conclusions: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.

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