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NCT00066703 · CITED IN SOURCE DOCUMENTS

Triptorelin With Either Exemestane or Tamoxifen in Treating Premenopausal Women With Hormone-Responsive Breast Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2026-02-06

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using triptorelin, exemestane, and tamoxifen may fight breast cancer by blocking the use of estrogen. It is not yet known whether giving triptorelin together with exemestane is more effective than triptorelin and tamoxifen in treating hormone-responsive breast cancer. PURPOSE: This randomized phase III trial is studying triptorelin and exemestane to see how well they work compared to triptorelin and tamoxifen in treating premenopausal women with hormone-responsive breast cancer.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Disease-free Survival

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outcome · POSTED

Breast Cancer-free Interval

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outcome · POSTED

Distant Recurrence-free Interval

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outcome · POSTED

Overall Survival

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
DISEASE CHARACTERISTICS: * Histologically confirmed breast cancer * Completely resected disease * No clinically detectable residual loco-regional axillary disease * Prior surgery for primary breast cancer of 1 of the following types: * Total mastectomy with or without adjuvant radiotherapy * Breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial mastectomy with margins negative\* for invasive disease and ductal carcinoma in situ) with planned radiotherapy NOTE: \*If all other margins are clear a positive posterior (deep) margin is permitted, provided the excision was performed down to the pectoral fascia and all tumor has been removed OR a positive anterior (superficial; abutting skin) margin is allowed provided all tumor was removed * Tumor confined to the breast and axillary nodes * Tumor detected in internal mammary chain nodes by sentinel node procedure and is not enlarged is allowed * Axillary lymph node dissection or a negative axillary sentinel node biopsy required * Patients with negative or microscopically positive axillary sentinel nodes are eligible * Positive sentinel nodes must have either axillary dissection or radiation of axillary nodes * No distant metastases * No locally advanced inoperable breast cancer, including any of the following: * Inflammatory breast cancer * Supraclavicular node involvement * Enlarged internal mammary nodes (unless pathologically negative) * Bilateral synchronous invasive breast cancer allowed if disease meets all other eligibility criteria * No prior ipsilateral or contralateral invasive breast cancer * Hormone receptor status: * Estrogen and/or progesterone receptor positive * At least 10% of the tumor cells positive by immunohistochemistry * If \> 1 breast tumor, each tumor must be hormone receptor positive PATIENT CHARACTERISTICS: Age * Premenopausal Sex * Female Menopausal status * Premenopausal * Estradiol in the premenopausal range after prior surgery OR meets the following criteria: * Menstruating regularly for the past 6 months * Has not used any form of hormonal treatment (including hormonal contraception) within the past 6 months Performance status * Not specified Life expectancy * Not specified Hematopoietic * Not specified Hepatic * No systemic hepatic disease that would preclude prolonged follow-up Renal * No systemic renal disease that would preclude prolonged follow-up Cardiovascular * No systemic cardiovascular disease that would preclude prolonged follow-up * No prior thrombosis (e.g., deep vein thrombosis) and/or embolism unless patient is medically suitable Pulmonary * No systemic pulmonary disease that would preclude prolonged follow-up Other * Not pregnant or nursing * Fertile patients must use effective nonhormonal contraception * No history of noncompliance to medical regimens * No other nonmalignant systemic disease that would preclude prolonged follow-up * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, nonbreast carcinoma in situ, contralateral or ipsilateral carcinoma in situ of the breast, or other nonrecurrent invasive nonbreast malignancy, including any of the following: * Stage I papillary thyroid cancer * Stage IA carcinoma of the cervix * Stage IA or B endometrioid endometrial cancer * Borderline or stage I ovarian cancer * No psychiatric, addictive, or other disorder that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * Prior or concurrent neoadjuvant or adjuvant trastuzumab allowed Chemotherapy * No prior neoadjuvant or adjuvant chemotherapy Endocrine therapy * No prior tamoxifen, other selective estrogen-receptor modulators (SERMs) (e.g., raloxifene), or hormone replacement therapy for more than 1 year before breast cancer diagnosis * No prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer * No concurrent oral or transdermal hormonal therapy * No other concurrent estrogen, progesterone, or androgens * No other concurrent aromatase inhibitors * No concurrent oral or other hormonal contraceptives (i.e., implants or depot injections) Radiotherapy * See Disease Characteristics * No prior ovarian radiotherapy Surgery * See Disease Characteristics * No prior bilateral oophorectomy Other * No concurrent bisphosphonates, except in the following cases: * Bone density is at least 1.5 standard deviations below the young adult normal mean * Participation in a randomized clinical study testing bisphosphonates in the adjuvant breast cancer setting * No other concurrent investigational agents
healthy Volunteers
false
maximum Age
65 Years
minimum Age
18 Years
sex
FEMALE
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
    intervention Names
    1. Drug: tamoxifen
    2. Drug: triptorelin
    label
    T+OFS
    type
    ACTIVE_COMPARATOR
  2. description
    Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
    intervention Names
    1. Drug: exemestane
    2. Drug: triptorelin
    label
    E+OFS
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. E+OFS
    name
    exemestane
    other Names
    1. Aromasin
    type
    DRUG
  2. arm Group Labels
    1. T+OFS
    name
    tamoxifen
    other Names
    1. Nolvadex
    type
    DRUG
  3. arm Group Labels
    1. E+OFS
    2. T+OFS
    name
    triptorelin
    other Names
    1. GnRH analogue
    2. Trelstar Depot
    3. Decapeptyl Depot
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
2672
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow up.
    measure
    Disease-free Survival
    time Frame
    5-year estimate reported at a median follow-up of 72 months
secondary Outcomes
  1. description
    Estimated percentage of patients alive and disease-free at 5 years from randomization, where breast cancer-free interval is defined as the time from randomization to the invasive breast cancer recurrence at local, regional, or distant site, or invasive contralateral breast cancer; or censored at date of last follow up.
    measure
    Breast Cancer-free Interval
    time Frame
    5-year estimate reported at a median follow-up of 72 months
  2. description
    Estimated percentage of patients alive and disease-free at 5 years from randomization, where distant recurrence-free interval is defined as the time from randomization to breast cancer recurrence at a distant site; or censored at date of last follow-up
    measure
    Distant Recurrence-free Interval
    time Frame
    5-year estimates reported at a median follow-up of 72 months
  3. description
    Estimated percentage of patients alive at 8 years from randomization, where overall survival is defined as the time from randomization to death from any cause; or censored at date last known alive.
    measure
    Overall Survival
    time Frame
    8-year estimates, reported at a median follow-up of 9 years
Full study description
brief Summary
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using triptorelin, exemestane, and tamoxifen may fight breast cancer by blocking the use of estrogen. It is not yet known whether giving triptorelin together with exemestane is more effective than triptorelin and tamoxifen in treating hormone-responsive breast cancer. PURPOSE: This randomized phase III trial is studying triptorelin and exemestane to see how well they work compared to triptorelin and tamoxifen in treating premenopausal women with hormone-responsive breast cancer.
detailed Description
OBJECTIVES: * Compare the disease-free survival, breast cancer-free interval, distant recurrence-free interval and overall survival of premenopausal women with endocrine-responsive breast cancer when treated with triptorelin and exemestane vs triptorelin and tamoxifen. * Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens. OUTLINE: This is a randomized, international, multicenter study. Patients are stratified according to planned use of concurrent adjuvant chemotherapy (yes vs no), and number of positive lymph nodes (0 vs 1 or more). Treatment duration is 5 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. Quality of life is assessed at baseline, every 6 months for 2 years, and annually for 3 years.
Source references
references
  1. citation
    Francis P, Fleming G, Nasi ML, et al.: Tailored treatment investigations for premenopausal women with endocrine responsive (ER+ and/or PGR+) breast cancer: the SOFT, TEXT, and PERCHE trials. [Abstract] The Breast 12 (Suppl 1): A-P104, S44, 2003.
    type
    BACKGROUND
  2. citation
    Regan MM, Pagani O, Walley B, Torrisi R, Perez EA, Francis P, Fleming GF, Price KN, Thurlimann B, Maibach R, Castiglione-Gertsch M, Coates AS, Goldhirsch A, Gelber RD; SOFT/TEXT/PERCHE Steering Committee and the International Breast Cancer Study Group. Premenopausal endocrine-responsive early breast cancer: who receives chemotherapy? Ann Oncol. 2008 Jul;19(7):1231-1241. doi: 10.1093/annonc/mdn037. Epub 2008 Mar 5.
    pmid
    18325918
    type
    BACKGROUND
  3. citation
    Rabaglio M, Ruepp B; Soft/Text/Perche Steering Committee. Death due to liver failure during endocrine therapy for premenopausal breast cancer. Acta Oncol. 2010 Aug;49(6):874-6. doi: 10.3109/0284186X.2010.484813. No abstract available.
    pmid
    20482225
    type
    BACKGROUND
  4. citation
    Regan MM, Pagani O, Fleming GF, Walley BA, Price KN, Rabaglio M, Maibach R, Ruepp B, Coates AS, Goldhirsch A, Colleoni M, Gelber RD, Francis PA; International Breast Cancer Study; GroupSOFT and TEXT Investigators. Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials. Breast. 2013 Dec;22(6):1094-100. doi: 10.1016/j.breast.2013.08.009. Epub 2013 Oct 2.
    pmid
    24095609
    type
    BACKGROUND
  5. citation
    Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. doi: 10.1056/NEJMoa1404037. Epub 2014 Jun 1.
    pmid
    24881463
    type
    RESULT
  6. citation
    Pagani O, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Goetz MP, Ciruelos EM, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Chini C, Puglisi F, Spazzapan S, Ruhstaller T, Winer EP, Ruepp B, Loi S, Coates AS, Gelber RD, Goldhirsch A, Regan MM, Francis PA; SOFT and TEXT Investigators and the International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation). Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials. J Clin Oncol. 2023 Mar 1;41(7):1376-1382. doi: 10.1200/JCO.22.01064. Epub 2022 Dec 15.
    pmid
    36521078
    type
    RESULT
  7. citation
    O'Regan RM, Ren Y, Zhang Y, Fleming GF, Francis PA, Pagani O, Walley BA, Kammler R, Dell'Orto P, Viale G, Loi S, Colleoni M, Treuner K, Regan MM. Identifying premenopausal patients with early-stage hormone receptor-positive breast cancer at minimal risk of distant recurrence by breast cancer index. Breast. 2026 Apr;86:104714. doi: 10.1016/j.breast.2026.104714. Epub 2026 Jan 29.
    pmid
    41637791
    type
    DERIVED
  8. citation
    Ribi K, Cole BF, Fleming GF, Walley BA, Francis PA, Abdi E, Burstein HJ, Cheng KL, Chia SKL, Dakhil SR, Davidson NE, Della-Fiorentina SA, Frith AE, Levine E, Lupichuk S, Pritchard K, Salim M, Stearns V, Stewart J, Valero V, van der Westhuizen A, Pagani O, Loi S, Colleoni M, Gelber RD, Goldhirsch A, Coates AS, Regan MM, Bernhard J. Prognostic value of patient-reported depression in women with hormone-responsive early breast cancer in TEXT and SOFT. Cancer. 2025 Oct 1;131(19):e70094. doi: 10.1002/cncr.70094.
    pmid
    40986647
    type
    DERIVED
  9. citation
    Pagani O, Francis PA, Fleming GF, Walley BA, Viale G, Colleoni M, Lang I, Gomez HL, Tondini C, Pinotti G, Di Leo A, Coates AS, Goldhirsch A, Gelber RD, Regan MM; SOFT and TEXT Investigators and International Breast Cancer Study Group. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol. 2020 Apr 20;38(12):1293-1303. doi: 10.1200/JCO.18.01967. Epub 2019 Oct 16.
    pmid
    31618131
    type
    DERIVED
  10. citation
    Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Lang I, Gomez HL, Tondini C, Ciruelos E, Burstein HJ, Bonnefoi HR, Bellet M, Martino S, Geyer CE Jr, Goetz MP, Stearns V, Pinotti G, Puglisi F, Spazzapan S, Climent MA, Pavesi L, Ruhstaller T, Davidson NE, Coleman R, Debled M, Buchholz S, Ingle JN, Winer EP, Maibach R, Rabaglio-Poretti M, Ruepp B, Di Leo A, Coates AS, Gelber RD, Goldhirsch A, Regan MM; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med. 2018 Jul 12;379(2):122-137. doi: 10.1056/NEJMoa1803164. Epub 2018 Jun 4.
    pmid
    29863451
    type
    DERIVED
  11. citation
    Regan MM, Walley BA, Francis PA, Fleming GF, Lang I, Gomez HL, Colleoni M, Tondini C, Pinotti G, Salim M, Spazzapan S, Parmar V, Ruhstaller T, Abdi EA, Gelber RD, Coates AS, Goldhirsch A, Pagani O. Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT. Ann Oncol. 2017 Sep 1;28(9):2225-2232. doi: 10.1093/annonc/mdx285.
    pmid
    28911092
    type
    DERIVED
  12. citation
    Johansson H, Gray KP, Pagani O, Regan MM, Viale G, Aristarco V, Macis D, Puccio A, Roux S, Maibach R, Colleoni M, Rabaglio M, Price KN, Coates AS, Gelber RD, Goldhirsch A, Kammler R, Bonanni B, Walley BA; the TEXT principal investigators. Impact of CYP19A1 and ESR1 variants on early-onset side effects during combined endocrine therapy in the TEXT trial. Breast Cancer Res. 2016 Nov 8;18(1):110. doi: 10.1186/s13058-016-0771-8.
    pmid
    27825388
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        (HR, 1.75; 95% CI, 1.08&#8211;2.83; <em>P</em> = .02).</li></ul></div></li><li>In two unblinded studies that were analyzed together (<a href="/clinicaltrials/NCT00066703">TEXT</a> [NCT00066703] and <a href="/clinicaltrials/NCT00066690">SOFT</a> [NCT00066690]), exemestane was also compared with tamoxifen in 4,690 premenopausal
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        8&#8211;2.83; <em>P</em> = .02).</li></ul></div></li><li>In two unblinded studies that were analyzed together (<a href="/clinicaltrials/NCT00066703">TEXT</a> [NCT00066703] and <a href="/clinicaltrials/NCT00066690">SOFT</a> [NCT00066690]), exemestane was also compared with tamoxifen in 4,690 premenopausal women who underwent ova
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      1. context
        Updated: April 25, 2025
        datetime
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        display
        April 25, 2025

    Preserved source evidence · Not medical advice