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Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the multiple outcomes of raloxifene evaluation study participants.
J Clin Oncol 2001; 19(12):3111-6JC

Abstract

PURPOSE

To test the hypothesis that risk factors related to lifetime estrogen exposure predict breast cancer incidence and to test if any subgroups experience enhanced benefit from raloxifene.

PATIENTS AND METHODS

Postmenopausal women with osteoporosis (N = 7,705), enrolled onto the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, were randomly assigned to receive placebo, raloxifene 60 mg/d, or raloxifene 120 mg/d for 4 years. Breast cancer risk was analyzed by the following baseline characteristics indicative of estrogen exposure: previous hormone replacement therapy, prevalent vertebral fractures, family history of breast cancer, estradiol level, bone mineral density (BMD), body mass index, and age at menopause. Therapy-by-subgroup interactions were assessed using a logistic regression model.

RESULTS

Overall, women with the highest one-third estradiol levels (> or = 12 pmol/L) had a 2.07-fold increased invasive breast cancer risk compared with women with lower levels. Raloxifene significantly reduced breast cancer risk in both the low- and high-estrogen subgroups for all risk factors examined (P <.05 for each comparison). The women with the highest BMD and those with a family history of breast cancer experienced a significantly greater therapy benefit with raloxifene, compared with the two thirds of patients with lower BMD or those without a family history, respectively; the subgroup-by-therapy interactions were significant (P =.005 and P =.015, respectively).

CONCLUSION

The MORE trial confirms that increased lifetime estrogen exposure increases breast cancer risk. Raloxifene therapy reduces breast cancer risk in postmenopausal osteoporotic women regardless of lifetime estrogen exposure, but the reduction is greater in those with higher lifetime exposure to estrogen.

Authors+Show Affiliations

Osteoporosis Research Program, Women's College Hospital, Toronto, Ontario, Canada. lippmanm@umich.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

11408508

Citation

Lippman, M E., et al. "Indicators of Lifetime Estrogen Exposure: Effect On Breast Cancer Incidence and Interaction With Raloxifene Therapy in the Multiple Outcomes of Raloxifene Evaluation Study Participants." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 19, no. 12, 2001, pp. 3111-6.
Lippman ME, Krueger KA, Eckert S, et al. Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the multiple outcomes of raloxifene evaluation study participants. J Clin Oncol. 2001;19(12):3111-6.
Lippman, M. E., Krueger, K. A., Eckert, S., Sashegyi, A., Walls, E. L., Jamal, S., ... Cummings, S. R. (2001). Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the multiple outcomes of raloxifene evaluation study participants. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 19(12), pp. 3111-6.
Lippman ME, et al. Indicators of Lifetime Estrogen Exposure: Effect On Breast Cancer Incidence and Interaction With Raloxifene Therapy in the Multiple Outcomes of Raloxifene Evaluation Study Participants. J Clin Oncol. 2001 Jun 15;19(12):3111-6. PubMed PMID: 11408508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the multiple outcomes of raloxifene evaluation study participants. AU - Lippman,M E, AU - Krueger,K A, AU - Eckert,S, AU - Sashegyi,A, AU - Walls,E L, AU - Jamal,S, AU - Cauley,J A, AU - Cummings,S R, PY - 2001/6/16/pubmed PY - 2001/7/6/medline PY - 2001/6/16/entrez SP - 3111 EP - 6 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 19 IS - 12 N2 - PURPOSE: To test the hypothesis that risk factors related to lifetime estrogen exposure predict breast cancer incidence and to test if any subgroups experience enhanced benefit from raloxifene. PATIENTS AND METHODS: Postmenopausal women with osteoporosis (N = 7,705), enrolled onto the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, were randomly assigned to receive placebo, raloxifene 60 mg/d, or raloxifene 120 mg/d for 4 years. Breast cancer risk was analyzed by the following baseline characteristics indicative of estrogen exposure: previous hormone replacement therapy, prevalent vertebral fractures, family history of breast cancer, estradiol level, bone mineral density (BMD), body mass index, and age at menopause. Therapy-by-subgroup interactions were assessed using a logistic regression model. RESULTS: Overall, women with the highest one-third estradiol levels (> or = 12 pmol/L) had a 2.07-fold increased invasive breast cancer risk compared with women with lower levels. Raloxifene significantly reduced breast cancer risk in both the low- and high-estrogen subgroups for all risk factors examined (P <.05 for each comparison). The women with the highest BMD and those with a family history of breast cancer experienced a significantly greater therapy benefit with raloxifene, compared with the two thirds of patients with lower BMD or those without a family history, respectively; the subgroup-by-therapy interactions were significant (P =.005 and P =.015, respectively). CONCLUSION: The MORE trial confirms that increased lifetime estrogen exposure increases breast cancer risk. Raloxifene therapy reduces breast cancer risk in postmenopausal osteoporotic women regardless of lifetime estrogen exposure, but the reduction is greater in those with higher lifetime exposure to estrogen. SN - 0732-183X UR - https://www.unboundmedicine.com/medline/citation/11408508/full_citation L2 - http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3111?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -