Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142)

A trial of the eastern cooperative oncology group

Amye J. Tevaarwerk, Molin Wang, Fengmin Zhao, John H. Fetting, David Cella, Lynne I. Wagner, Silvana Martino, James N. Ingle, Joseph A. Sparano, Lawrence J. Solin, William C. Wood, Nicholas J. Robert

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Purpose: The effects of ovarian function suppression (OFS) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were randomly assigned to tamoxifen with or without OFS. Patients and Methods: Premenopausal women with axillary node-negative, hormone receptor-positive breast cancer tumors measuring ≤ 3 cm were randomly assigned to tamoxifen alone versus tamoxifen plus OFS; adjuvant chemotherapy was not permitted. Primary end points were disease-free survival (DFS) and overall survival (OS). Secondary end points included toxicity and patient-reported outcomes. Patient-reported outcome data included health-related quality of life, menopausal symptoms, and sexual function. These were evaluated at baseline, 6 months, 12 months, and then annually for up to 5 years after registration. Results: In all, 345 premenopausal women were enrolled: 171 on tamoxifen alone and 174 on tamoxifen plus OFS. With a median follow-up of 9.9 years, there was no significant difference between arms for DFS (5-year rate: 87.9% v 89.7%; log-rank P = .62) or OS (5-year rate: 95.2% v 97.6%; log-rank P = .67). Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm (22.4% v 12.3%; P = .004). Patients treated with tamoxifen plus OFS had more menopausal symptoms, lower sexual activity, and inferior health-related quality of life at 3-year follow-up (P < .01 for all). Differences diminished with further follow-up. Conclusion: When added to tamoxifen, OFS results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen.

Original languageEnglish (US)
Pages (from-to)3948-3958
Number of pages11
JournalJournal of Clinical Oncology
Volume32
Issue number35
DOIs
StatePublished - Dec 10 2014

Fingerprint

Tamoxifen
Hormones
Breast Neoplasms
Survival
Quality of Life
Disease-Free Survival
iodonitrotetrazolium
Adjuvant Chemotherapy
Sexual Behavior

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142) : A trial of the eastern cooperative oncology group. / Tevaarwerk, Amye J.; Wang, Molin; Zhao, Fengmin; Fetting, John H.; Cella, David; Wagner, Lynne I.; Martino, Silvana; Ingle, James N.; Sparano, Joseph A.; Solin, Lawrence J.; Wood, William C.; Robert, Nicholas J.

In: Journal of Clinical Oncology, Vol. 32, No. 35, 10.12.2014, p. 3948-3958.

Research output: Contribution to journalArticle

Tevaarwerk, Amye J. ; Wang, Molin ; Zhao, Fengmin ; Fetting, John H. ; Cella, David ; Wagner, Lynne I. ; Martino, Silvana ; Ingle, James N. ; Sparano, Joseph A. ; Solin, Lawrence J. ; Wood, William C. ; Robert, Nicholas J. / Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142) : A trial of the eastern cooperative oncology group. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 35. pp. 3948-3958.
@article{a5605adc91824021b67485d8610d9712,
title = "Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): A trial of the eastern cooperative oncology group",
abstract = "Purpose: The effects of ovarian function suppression (OFS) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were randomly assigned to tamoxifen with or without OFS. Patients and Methods: Premenopausal women with axillary node-negative, hormone receptor-positive breast cancer tumors measuring ≤ 3 cm were randomly assigned to tamoxifen alone versus tamoxifen plus OFS; adjuvant chemotherapy was not permitted. Primary end points were disease-free survival (DFS) and overall survival (OS). Secondary end points included toxicity and patient-reported outcomes. Patient-reported outcome data included health-related quality of life, menopausal symptoms, and sexual function. These were evaluated at baseline, 6 months, 12 months, and then annually for up to 5 years after registration. Results: In all, 345 premenopausal women were enrolled: 171 on tamoxifen alone and 174 on tamoxifen plus OFS. With a median follow-up of 9.9 years, there was no significant difference between arms for DFS (5-year rate: 87.9{\%} v 89.7{\%}; log-rank P = .62) or OS (5-year rate: 95.2{\%} v 97.6{\%}; log-rank P = .67). Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm (22.4{\%} v 12.3{\%}; P = .004). Patients treated with tamoxifen plus OFS had more menopausal symptoms, lower sexual activity, and inferior health-related quality of life at 3-year follow-up (P < .01 for all). Differences diminished with further follow-up. Conclusion: When added to tamoxifen, OFS results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen.",
author = "Tevaarwerk, {Amye J.} and Molin Wang and Fengmin Zhao and Fetting, {John H.} and David Cella and Wagner, {Lynne I.} and Silvana Martino and Ingle, {James N.} and Sparano, {Joseph A.} and Solin, {Lawrence J.} and Wood, {William C.} and Robert, {Nicholas J.}",
year = "2014",
month = "12",
day = "10",
doi = "10.1200/JCO.2014.55.6993",
language = "English (US)",
volume = "32",
pages = "3948--3958",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "35",

}

TY - JOUR

T1 - Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142)

T2 - A trial of the eastern cooperative oncology group

AU - Tevaarwerk, Amye J.

AU - Wang, Molin

AU - Zhao, Fengmin

AU - Fetting, John H.

AU - Cella, David

AU - Wagner, Lynne I.

AU - Martino, Silvana

AU - Ingle, James N.

AU - Sparano, Joseph A.

AU - Solin, Lawrence J.

AU - Wood, William C.

AU - Robert, Nicholas J.

PY - 2014/12/10

Y1 - 2014/12/10

N2 - Purpose: The effects of ovarian function suppression (OFS) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were randomly assigned to tamoxifen with or without OFS. Patients and Methods: Premenopausal women with axillary node-negative, hormone receptor-positive breast cancer tumors measuring ≤ 3 cm were randomly assigned to tamoxifen alone versus tamoxifen plus OFS; adjuvant chemotherapy was not permitted. Primary end points were disease-free survival (DFS) and overall survival (OS). Secondary end points included toxicity and patient-reported outcomes. Patient-reported outcome data included health-related quality of life, menopausal symptoms, and sexual function. These were evaluated at baseline, 6 months, 12 months, and then annually for up to 5 years after registration. Results: In all, 345 premenopausal women were enrolled: 171 on tamoxifen alone and 174 on tamoxifen plus OFS. With a median follow-up of 9.9 years, there was no significant difference between arms for DFS (5-year rate: 87.9% v 89.7%; log-rank P = .62) or OS (5-year rate: 95.2% v 97.6%; log-rank P = .67). Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm (22.4% v 12.3%; P = .004). Patients treated with tamoxifen plus OFS had more menopausal symptoms, lower sexual activity, and inferior health-related quality of life at 3-year follow-up (P < .01 for all). Differences diminished with further follow-up. Conclusion: When added to tamoxifen, OFS results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen.

AB - Purpose: The effects of ovarian function suppression (OFS) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were randomly assigned to tamoxifen with or without OFS. Patients and Methods: Premenopausal women with axillary node-negative, hormone receptor-positive breast cancer tumors measuring ≤ 3 cm were randomly assigned to tamoxifen alone versus tamoxifen plus OFS; adjuvant chemotherapy was not permitted. Primary end points were disease-free survival (DFS) and overall survival (OS). Secondary end points included toxicity and patient-reported outcomes. Patient-reported outcome data included health-related quality of life, menopausal symptoms, and sexual function. These were evaluated at baseline, 6 months, 12 months, and then annually for up to 5 years after registration. Results: In all, 345 premenopausal women were enrolled: 171 on tamoxifen alone and 174 on tamoxifen plus OFS. With a median follow-up of 9.9 years, there was no significant difference between arms for DFS (5-year rate: 87.9% v 89.7%; log-rank P = .62) or OS (5-year rate: 95.2% v 97.6%; log-rank P = .67). Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm (22.4% v 12.3%; P = .004). Patients treated with tamoxifen plus OFS had more menopausal symptoms, lower sexual activity, and inferior health-related quality of life at 3-year follow-up (P < .01 for all). Differences diminished with further follow-up. Conclusion: When added to tamoxifen, OFS results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen.

UR - http://www.scopus.com/inward/record.url?scp=84918571561&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918571561&partnerID=8YFLogxK

U2 - 10.1200/JCO.2014.55.6993

DO - 10.1200/JCO.2014.55.6993

M3 - Article

VL - 32

SP - 3948

EP - 3958

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 35

ER -