Circulating hormones and breast cancer risk in premenopausal women: A randomized trial of low-dose tamoxifen and fenretinide

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Abstract

Tamoxifen and fenretinide have been extensively studied and exhibit breast cancer-preventing activity. We aimed to assess their effect on sex hormones, sex hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events. In a double-blind, placebo-controlled trial, premenopausal women at risk for breast cancer were randomized to tamoxifen 5 mg/day, fenretinide, both agents, or placebo for 2 years. We measured MD and circulating concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, testosterone, androstenedione, dehydro-epiandrosteronesulfate, prolactin, SHBG, and retinol at baseline and on yearly intervals. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models. Low-dose tamoxifen markedly and enduringly increased SHBG, whereas the increases in testosterone, estradiol, and prolactin and reduction in LH weakened after 1 year. Fenretinide increased testosterone and androstenedione and decreased retinol. MD correlated directly with SHBG and inversely with retinol. After a median follow-up of 12 years, the 10-year cumulative incidence of breast cancer events was 37 % in women with SHBG ≤ 59.3 nmol/L, 22 % in women with SHBG between 59.3 and 101 nmol/L, and 19 % in women with SHBG > 101 nmol/L (P = 0.018). The difference among SHBG tertiles remained statistically significant at multivariable analysis: HR = 2.26 (95 % CI 1.04, 4.89) for the lowest versus the highest tertile. We conclude that low-dose tamoxifen or fenretinide exhibits favorable hormonal profiles as single agents, further supporting their administration for prevention of breast cancer in premenopause. Notably, SHBG levels were inversely associated with breast neoplastic events.

Original languageEnglish
Pages (from-to)569-578
Number of pages10
JournalBreast Cancer Research and Treatment
Volume142
Issue number3
DOIs
Publication statusPublished - Dec 2013

Fingerprint

Fenretinide
Sex Hormone-Binding Globulin
Tamoxifen
Hormones
Breast Neoplasms
Vitamin A
Testosterone
Androstenedione
Luteinizing Hormone
Prolactin
Estradiol
Premenopause
Placebos
Gonadal Steroid Hormones
Follicle Stimulating Hormone
Progesterone
Breast

Keywords

  • Biomarkers
  • Breast density
  • Brest cancer
  • Chemoprevention
  • Fenretinide
  • Retinol
  • Sex hormones
  • SHBG
  • Tamoxifen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{ecbe3f498d1d4a10a0c6f20cc984d60a,
title = "Circulating hormones and breast cancer risk in premenopausal women: A randomized trial of low-dose tamoxifen and fenretinide",
abstract = "Tamoxifen and fenretinide have been extensively studied and exhibit breast cancer-preventing activity. We aimed to assess their effect on sex hormones, sex hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events. In a double-blind, placebo-controlled trial, premenopausal women at risk for breast cancer were randomized to tamoxifen 5 mg/day, fenretinide, both agents, or placebo for 2 years. We measured MD and circulating concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, testosterone, androstenedione, dehydro-epiandrosteronesulfate, prolactin, SHBG, and retinol at baseline and on yearly intervals. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models. Low-dose tamoxifen markedly and enduringly increased SHBG, whereas the increases in testosterone, estradiol, and prolactin and reduction in LH weakened after 1 year. Fenretinide increased testosterone and androstenedione and decreased retinol. MD correlated directly with SHBG and inversely with retinol. After a median follow-up of 12 years, the 10-year cumulative incidence of breast cancer events was 37 {\%} in women with SHBG ≤ 59.3 nmol/L, 22 {\%} in women with SHBG between 59.3 and 101 nmol/L, and 19 {\%} in women with SHBG > 101 nmol/L (P = 0.018). The difference among SHBG tertiles remained statistically significant at multivariable analysis: HR = 2.26 (95 {\%} CI 1.04, 4.89) for the lowest versus the highest tertile. We conclude that low-dose tamoxifen or fenretinide exhibits favorable hormonal profiles as single agents, further supporting their administration for prevention of breast cancer in premenopause. Notably, SHBG levels were inversely associated with breast neoplastic events.",
keywords = "Biomarkers, Breast density, Brest cancer, Chemoprevention, Fenretinide, Retinol, Sex hormones, SHBG, Tamoxifen",
author = "Harriet Johansson and Bernardo Bonanni and Sara Gandini and Aliana Guerrieri-Gonzaga and Massimiliano Cazzaniga and Davide Serrano and Debora Macis and Antonella Puccio and Sandri, {Maria Teresa} and Marcella Gulisano and Franca Formelli and Andrea Decensi",
year = "2013",
month = "12",
doi = "10.1007/s10549-013-2768-7",
language = "English",
volume = "142",
pages = "569--578",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York LLC",
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T1 - Circulating hormones and breast cancer risk in premenopausal women

T2 - A randomized trial of low-dose tamoxifen and fenretinide

AU - Johansson, Harriet

AU - Bonanni, Bernardo

AU - Gandini, Sara

AU - Guerrieri-Gonzaga, Aliana

AU - Cazzaniga, Massimiliano

AU - Serrano, Davide

AU - Macis, Debora

AU - Puccio, Antonella

AU - Sandri, Maria Teresa

AU - Gulisano, Marcella

AU - Formelli, Franca

AU - Decensi, Andrea

PY - 2013/12

Y1 - 2013/12

N2 - Tamoxifen and fenretinide have been extensively studied and exhibit breast cancer-preventing activity. We aimed to assess their effect on sex hormones, sex hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events. In a double-blind, placebo-controlled trial, premenopausal women at risk for breast cancer were randomized to tamoxifen 5 mg/day, fenretinide, both agents, or placebo for 2 years. We measured MD and circulating concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, testosterone, androstenedione, dehydro-epiandrosteronesulfate, prolactin, SHBG, and retinol at baseline and on yearly intervals. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models. Low-dose tamoxifen markedly and enduringly increased SHBG, whereas the increases in testosterone, estradiol, and prolactin and reduction in LH weakened after 1 year. Fenretinide increased testosterone and androstenedione and decreased retinol. MD correlated directly with SHBG and inversely with retinol. After a median follow-up of 12 years, the 10-year cumulative incidence of breast cancer events was 37 % in women with SHBG ≤ 59.3 nmol/L, 22 % in women with SHBG between 59.3 and 101 nmol/L, and 19 % in women with SHBG > 101 nmol/L (P = 0.018). The difference among SHBG tertiles remained statistically significant at multivariable analysis: HR = 2.26 (95 % CI 1.04, 4.89) for the lowest versus the highest tertile. We conclude that low-dose tamoxifen or fenretinide exhibits favorable hormonal profiles as single agents, further supporting their administration for prevention of breast cancer in premenopause. Notably, SHBG levels were inversely associated with breast neoplastic events.

AB - Tamoxifen and fenretinide have been extensively studied and exhibit breast cancer-preventing activity. We aimed to assess their effect on sex hormones, sex hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events. In a double-blind, placebo-controlled trial, premenopausal women at risk for breast cancer were randomized to tamoxifen 5 mg/day, fenretinide, both agents, or placebo for 2 years. We measured MD and circulating concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, testosterone, androstenedione, dehydro-epiandrosteronesulfate, prolactin, SHBG, and retinol at baseline and on yearly intervals. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models. Low-dose tamoxifen markedly and enduringly increased SHBG, whereas the increases in testosterone, estradiol, and prolactin and reduction in LH weakened after 1 year. Fenretinide increased testosterone and androstenedione and decreased retinol. MD correlated directly with SHBG and inversely with retinol. After a median follow-up of 12 years, the 10-year cumulative incidence of breast cancer events was 37 % in women with SHBG ≤ 59.3 nmol/L, 22 % in women with SHBG between 59.3 and 101 nmol/L, and 19 % in women with SHBG > 101 nmol/L (P = 0.018). The difference among SHBG tertiles remained statistically significant at multivariable analysis: HR = 2.26 (95 % CI 1.04, 4.89) for the lowest versus the highest tertile. We conclude that low-dose tamoxifen or fenretinide exhibits favorable hormonal profiles as single agents, further supporting their administration for prevention of breast cancer in premenopause. Notably, SHBG levels were inversely associated with breast neoplastic events.

KW - Biomarkers

KW - Breast density

KW - Brest cancer

KW - Chemoprevention

KW - Fenretinide

KW - Retinol

KW - Sex hormones

KW - SHBG

KW - Tamoxifen

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DO - 10.1007/s10549-013-2768-7

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