Preliminary results of a randomized phase iib double-blind 2x2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention

B. Bonanni, A. Guerrieri-Gonzaga, C. Robertson, D. Serrano, M. Cazzaniga, S. Mora, M. Gulisano, H. Johansson

Research output: Contribution to journalArticle

Abstract

Background and Purpose: Low-dose tamoxifen and fenretinide, a vitamin A derivative, have both shown to modulate biomarkers of breast cancerogenesis in premenopausal women. In the present study we are investigating whether the combination of the two drugs have a synergistic effect on putative surrogate biomarkers of breast cancerogenesis in premenopausal women at increased risk for breast cancer. Additionally, we are interested in studying the safety and the endometrial effects of the drug combination. Patients and Methods: Between October 1998 and April 2002, 235 women were randomly assigned in a double-blind 4-arm trial to tamoxifen 5 mg/day, fenretinide 200 mg/day, both agents, or placebo for 2 years. All subjects are being followed for three additional years. The primary endpoints were the changes in circulating insulin-like growth factor-I (IGF-I) and computerized mammographic percent density. Results: Subjects were included because of a previously excised DCIS (57%), LCIS (13%), micro-invasive breast cancer (7%), or a 5-year Gail risk ≥1.3% (23%). There was a 15% reduction on IGF-I levels on tamoxifen, as early as after 6 months of treatment, while the reduction on fenretinide was about 2%. Recruitment was stopped earlier, based on the lack of a synergistic interaction of the two drugs on plasma IGF-I levels. After a median follow-up of 40 months, 35 subjects dropped the study for refusal (n=19) or adverse events (n=16). So far, 24 primary or recurrent breast cancers have been observed, with no difference among arms. Of the three serious adverse events, one stage-I endometrial cancer occurred in the fenretinide arm, one optic nerve ischemia and one deep venous thrombosis occurred in the tamoxifen arm. There was no increased endometrial thickness and no difference in endometrial polyps among the four arms. Conclusions: The combination of low-dose tamoxifen and fenretinide is safe and well tolerated, but is not synergistic in lowering circulating IGF-I levels. Low-dose tamoxifen does significantly reduces IGF-I levels and does not affect endometrial proliferation. Mammographic percent density is currently under evaluation and updated results will be presented at the conference.
Original languageEnglish
Pages (from-to)S168-S169
JournalBreast cancer research and treatment
Volume94
Issue numberSupplement 1
DOIs
Publication statusPublished - Dec 2005

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Fenretinide
Tamoxifen
Insulin-Like Growth Factor I
Breast Neoplasms
Arm
Drug Combinations
Breast
Biomarkers
Ischemic Optic Neuropathy
Carcinoma, Intraductal, Noninfiltrating
Endometrial Neoplasms
Polyps
Vitamin A
Drug Interactions
Venous Thrombosis
Placebos
Safety

Keywords

  • tamoxifen
  • fenretinide
  • vitamin A
  • breast cancerogenesis
  • premenopausal women
  • surrogate biomarkers
  • breast cancer
  • endometrial effects

Cite this

Bonanni, B. ; Guerrieri-Gonzaga, A. ; Robertson, C. ; Serrano, D. ; Cazzaniga, M. ; Mora, S. ; Gulisano, M. ; Johansson, H. / Preliminary results of a randomized phase iib double-blind 2x2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention. In: Breast cancer research and treatment. 2005 ; Vol. 94, No. Supplement 1. pp. S168-S169.
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Preliminary results of a randomized phase iib double-blind 2x2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention. / Bonanni, B.; Guerrieri-Gonzaga, A.; Robertson, C.; Serrano, D.; Cazzaniga, M.; Mora, S.; Gulisano, M.; Johansson, H.

In: Breast cancer research and treatment, Vol. 94, No. Supplement 1, 12.2005, p. S168-S169.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Preliminary results of a randomized phase iib double-blind 2x2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention

AU - Bonanni, B.

AU - Guerrieri-Gonzaga, A.

AU - Robertson, C.

AU - Serrano, D.

AU - Cazzaniga, M.

AU - Mora, S.

AU - Gulisano, M.

AU - Johansson, H.

N1 - Strathprints' policy is to record up to 8 authors per publication, plus any additional authors based at the University of Strathclyde. More authors may be listed on the official publication than appear in the Strathprints' record.

PY - 2005/12

Y1 - 2005/12

N2 - Background and Purpose: Low-dose tamoxifen and fenretinide, a vitamin A derivative, have both shown to modulate biomarkers of breast cancerogenesis in premenopausal women. In the present study we are investigating whether the combination of the two drugs have a synergistic effect on putative surrogate biomarkers of breast cancerogenesis in premenopausal women at increased risk for breast cancer. Additionally, we are interested in studying the safety and the endometrial effects of the drug combination. Patients and Methods: Between October 1998 and April 2002, 235 women were randomly assigned in a double-blind 4-arm trial to tamoxifen 5 mg/day, fenretinide 200 mg/day, both agents, or placebo for 2 years. All subjects are being followed for three additional years. The primary endpoints were the changes in circulating insulin-like growth factor-I (IGF-I) and computerized mammographic percent density. Results: Subjects were included because of a previously excised DCIS (57%), LCIS (13%), micro-invasive breast cancer (7%), or a 5-year Gail risk ≥1.3% (23%). There was a 15% reduction on IGF-I levels on tamoxifen, as early as after 6 months of treatment, while the reduction on fenretinide was about 2%. Recruitment was stopped earlier, based on the lack of a synergistic interaction of the two drugs on plasma IGF-I levels. After a median follow-up of 40 months, 35 subjects dropped the study for refusal (n=19) or adverse events (n=16). So far, 24 primary or recurrent breast cancers have been observed, with no difference among arms. Of the three serious adverse events, one stage-I endometrial cancer occurred in the fenretinide arm, one optic nerve ischemia and one deep venous thrombosis occurred in the tamoxifen arm. There was no increased endometrial thickness and no difference in endometrial polyps among the four arms. Conclusions: The combination of low-dose tamoxifen and fenretinide is safe and well tolerated, but is not synergistic in lowering circulating IGF-I levels. Low-dose tamoxifen does significantly reduces IGF-I levels and does not affect endometrial proliferation. Mammographic percent density is currently under evaluation and updated results will be presented at the conference.

AB - Background and Purpose: Low-dose tamoxifen and fenretinide, a vitamin A derivative, have both shown to modulate biomarkers of breast cancerogenesis in premenopausal women. In the present study we are investigating whether the combination of the two drugs have a synergistic effect on putative surrogate biomarkers of breast cancerogenesis in premenopausal women at increased risk for breast cancer. Additionally, we are interested in studying the safety and the endometrial effects of the drug combination. Patients and Methods: Between October 1998 and April 2002, 235 women were randomly assigned in a double-blind 4-arm trial to tamoxifen 5 mg/day, fenretinide 200 mg/day, both agents, or placebo for 2 years. All subjects are being followed for three additional years. The primary endpoints were the changes in circulating insulin-like growth factor-I (IGF-I) and computerized mammographic percent density. Results: Subjects were included because of a previously excised DCIS (57%), LCIS (13%), micro-invasive breast cancer (7%), or a 5-year Gail risk ≥1.3% (23%). There was a 15% reduction on IGF-I levels on tamoxifen, as early as after 6 months of treatment, while the reduction on fenretinide was about 2%. Recruitment was stopped earlier, based on the lack of a synergistic interaction of the two drugs on plasma IGF-I levels. After a median follow-up of 40 months, 35 subjects dropped the study for refusal (n=19) or adverse events (n=16). So far, 24 primary or recurrent breast cancers have been observed, with no difference among arms. Of the three serious adverse events, one stage-I endometrial cancer occurred in the fenretinide arm, one optic nerve ischemia and one deep venous thrombosis occurred in the tamoxifen arm. There was no increased endometrial thickness and no difference in endometrial polyps among the four arms. Conclusions: The combination of low-dose tamoxifen and fenretinide is safe and well tolerated, but is not synergistic in lowering circulating IGF-I levels. Low-dose tamoxifen does significantly reduces IGF-I levels and does not affect endometrial proliferation. Mammographic percent density is currently under evaluation and updated results will be presented at the conference.

KW - tamoxifen

KW - fenretinide

KW - vitamin A

KW - breast cancerogenesis

KW - premenopausal women

KW - surrogate biomarkers

KW - breast cancer

KW - endometrial effects

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