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Clinical Trial
. 2014 Dec 10;32(35):3948-58.
doi: 10.1200/JCO.2014.55.6993. Epub 2014 Oct 27.

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  1 , Molin Wang  2 , Fengmin Zhao  2 , John H Fetting  2 , David Cella  2 , Lynne I Wagner  2 , Silvana Martino  2 , James N Ingle  2 , Joseph A Sparano  2 , Lawrence J Solin  2 , William C Wood  2 , Nicholas J Robert  2
Affiliations
Clinical Trial

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 et al. J Clin Oncol. .

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.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram for Tamoxifen and Ovarian Ablation in Treating Patients With Node-Negative, Receptor-Positive Breast Cancer (E-3193) trial. ER, estrogen receptor; LHRH, luteinizing hormone-releasing hormone; OFS, ovarian function suppression; PgR, progesterone receptor; PO, orally; PRO, patient-reported outcome.
Fig 2.
Fig 2.
Comparison of (A) overall survival (OS) and (B) disease-free survival (DFS) by treatment in analyzable patients. HR, hazard ratio; OFS, ovarian function suppression.
Fig 3.
Fig 3.
Patient-reported outcome scores for (A) Functional Assessment of Cancer Therapy-General (FACT-G), (B) breast cancer subscale, (C) menopause symptom, and (D) sexual function assessments and 95% CIs over time by treatment arm in analyzable patients. Vertical lines represent 95% CIs. lb/ub, lower border/upper border; OFS, ovarian function suppression.
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Comment in

References

    1. Nunn T. On cancer of the breast. London, United Kingdom: J. & A, Churchill; 1882. p. 71.
    1. Beatson GT. On the treatment of inoperable cases of carcinoma of the mamma: Suggestions for a new method of treatment, with illustrative cases. Lancet. 1896;148:162–165. - PMC - PubMed
    1. Thomson A. Analysis of cases in which oophorectomy was performed for inoperable carcinoma of the breast. Br Med J. 1902;2:1538–1541. - PMC - PubMed
    1. [No authors listed] Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: The Scottish trial—Scottish Cancer Trials Breast Group and ICRF Breast Unit, Guy's Hospital, London. Lancet. 1993;341:1293–1298. - PubMed
    1. Jakesz R, Hausmaninger H, Kubista E, et al. Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: Evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer—Austrian Breast and Colorectal Cancer Study Group Trial 5. J Clin Oncol. 2002;20:4621–4627. - PubMed

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