Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen

Yue, Wei; Wang, Jiping; Atkins, Kristen A.; Bottalico, Lisa; Mesaros, Clementina; Blair, Ian A.; Santen, Richard J.

doi:10.1002/ijc.31401

Cited by 11 publications

(8 citation statements)

References 52 publications

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“…268 Randomized trials are needed to confirm these findings. Preclinical data suggest that CEE may have lesser effects on occult breast cancer growth than estradiol, 269 but clinical data from observational studies, such as the Collaborative Group study, do not report a difference. 22 Regarding route, both oral and transdermal estrogens appear to have similar effects on number of breast cancers diagnosed, whereas vaginal estrogens have no effect.…”

Section: Role Of Type Of Hormone Use Dose and Route Of Administrationmentioning

confidence: 99%

The 2022 hormone therapy position statement of The North American Menopause Society

2022

Menopause

269

219

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and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women's health and menopause was recruited by NAMS to review the 2017 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Advisory Panel's recommendations were reviewed and approved by the NAMS Board of Trustees.Hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing therapy.For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome VMS and prevention of bone loss. For women who initiate hormone therapy more than 10 years from menopause onset or who are aged older than 60 years, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS, with shared decision-making and periodic reevaluation. For bothersome genitourinary syndrome of menopause symptoms not relieved with over-the-counter therapies in women without indications for use of systemic hormone therapy, low-dose vaginal estrogen therapy or other therapies (eg, vaginal dehydroepiandrosterone or oral ospemifene) are recommended.

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Section: Role Of Type Of Hormone Use Dose and Route Of Administrationmentioning

confidence: 99%

The 2022 hormone therapy position statement of The North American Menopause Society

2022

Menopause

269

219

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“…BZA also inhibited growth of hormone-independent MCF-7 5C cells (10) and tamoxifen-sensitive and -resistant xenografts (11). Conjugated estrogen (CE) rather than estradiol was used to partner with BZA, given its less potent proliferative effect on breast epithelium (12), as well as absence of increase in breast cancer incidence when used without a progestin (13).…”

Section: Introductionmentioning

confidence: 99%

Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study

Fabian

Nye

Powers

et al. 2019

Cancer Prevention Research

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Interventions that relieve vasomotor symptoms while reducing risk for breast cancer would likely improve uptake of chemoprevention for perimenopausal and postmenopausal women. We conducted a pilot study with 6 months of the tissue selective estrogen complex bazedoxifene (20 mg) and conjugated estrogen (0.45 mg; Duavee) to assess feasibility and effects on risk biomarkers for postmenopausal breast cancer. Risk biomarkers included fully automated mammographic volumetric density (Volpara), benign breast tissue Ki-67 (MIB-1 immunochemistry), and serum levels of progesterone, IGF-1, and IGFBP3, bioavailable estradiol and testosterone. Twenty-eight perimenopausal and postmenopausal women at increased risk for breast cancer were enrolled: 13 in cohort A with baseline Ki-67 < 1% and 15 in cohort B with baseline Ki-67 of 1% to 4%. All completed the study with > 85% drug adherence. Significant changes in biomarkers, uncorrected for multiple comparisons, were a decrease in mammographic fibroglandular volume (P ¼ 0.043); decreases in serum progesterone, bioavailable testosterone, and IGF-1 (P < 0.01), an increase in serum bioavailable estradiol (P < 0.001), and for women from cohort B a reduction in Ki-67 (P ¼ 0.017). An improvement in median hot flash score from 15 at baseline to 0 at 6 months, and menopause-specific quality-of-life total, vasomotor, and sexual domain scores were also observed (P < 0.001). Given the favorable effects on risk biomarkers and patient reported outcomes, a placebocontrolled phase IIB trial is warranted.

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“…In both models, estradiol significantly increased tumor incidence and multiplicity of tumors. In striking contrast, CEE did not stimulate growth, even though the estrogenic effects of CEE and estradiol on uterine weight were identical 152 . Mechanistically, E2 blocked apoptosis, whereas CEE stimulated apoptosis.…”

Section: Tissue Selective Estrogen Complex Therapymentioning

confidence: 80%

“…In striking contrast, CEE did not stimulate growth, even though the estrogenic effects of CEE and estradiol on uterine weight were identical. 152 Mechanistically, E2 blocked apoptosis, whereas CEE stimulated apoptosis. As CEE comprised more than 200 different compounds, it is not surprising that E2 and CEE exerted differing effects.…”

Section: In Vivo Studiesmentioning

confidence: 98%

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Mechanistic Effects of Estrogens on Breast Cancer

2022

Self Cite

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Purpose Current concepts regarding estrogen and its mechanistic effects on breast cancer in women are evolving. This article reviews studies that address estrogen-mediated breast cancer development, the prevalence of occult tumors at autopsy, and the natural history of breast cancer as predicted by a newly developed tumor kinetic model. Methods This article reviews previously published studies from the authors and articles pertinent to the data presented. Results We discuss the concepts of adaptive hypersensitivity that develops in response to long-term deprivation of estrogen and results in both increased cell proliferation and apoptosis. The effects of menopausal hormonal therapy on breast cancer in postmenopausal women are interpreted based on the tumor kinetic model. Studies of the administration of a tissue selective estrogen complex in vitro, in vivo, and in patients are described. We review the various clinical studies of breast cancer prevention with selective estrogen receptor modulators and aromatase inhibitors. Finally, the effects of the underlying risk of breast cancer on the effects of menopausal hormone therapy are outlined. Discussion The overall intent of this review is to present data supporting recent concepts, discuss pertinent literature, and critically examine areas of controversy.

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Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen

Cited by 11 publications

References 52 publications

The 2022 hormone therapy position statement of The North American Menopause Society

The 2022 hormone therapy position statement of The North American Menopause Society

Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study

Mechanistic Effects of Estrogens on Breast Cancer

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