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. 2016 Jul 1;34(19):2221-31.
doi: 10.1200/JCO.2015.64.3171. Epub 2016 Apr 4.

Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: TEXT and SOFT Trials

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Free PMC article

Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: TEXT and SOFT Trials

Meredith M Regan et al. J Clin Oncol. .
Free PMC article

Abstract

Purpose: Risk of recurrence is the primary consideration in breast cancer adjuvant therapy recommendations. The TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive breast cancer, testing exemestane plus ovarian function suppression (OFS), tamoxifen plus OFS, and tamoxifen alone. We examined absolute treatment effect across a continuum of recurrence risk to individualize endocrine therapy decision making for premenopausal women with human epidermal growth factor receptor 2 (HER2) -negative disease.

Patients and methods: The TEXT and SOFT hormone receptor-positive, HER2-negative analysis population included 4,891 women. The end point was breast cancer-free interval (BCFI), defined as time from random assignment to first occurrence of invasive locoregional, distant, or contralateral breast cancer. A continuous, composite measure of recurrence risk for each patient was determined from a Cox model incorporating age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. Subpopulation treatment effect pattern plot methodology revealed differential treatment effects on 5-year BCFI according to composite risk.

Results: SOFT patients who remained premenopausal after chemotherapy experienced absolute improvement of 5% or more in 5-year BCFI with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone, reaching 10% to 15% at intermediate to high composite risk; the benefit of tamoxifen plus OFS versus tamoxifen alone was apparent at the highest composite risk. The SOFT no-chemotherapy cohort-for whom composite risk was lowest on average-did well with all endocrine therapies. For TEXT patients, the benefit of exemestane plus OFS versus tamoxifen plus OFS in 5-year BCFI ranged from 5% to 15%; patients not receiving chemotherapy and with lowest composite risk did well with both treatments.

Conclusion: Premenopausal women with hormone receptor-positive, HER2-negative disease and high recurrence risk, as defined by clinicopathologic characteristics, may experience improvement of 10% to 15% in 5-year BCFI with exemestane plus OFS versus tamoxifen alone. An improvement of at least 5% may be achieved for women at intermediate risk, and improvement is minimal for those at lowest risk.

Trial registration: ClinicalTrials.gov NCT00066690 NCT00066703.

Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Flow diagram of the 4,891 patients included in the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) hormone receptor–positive, human epidermal growth factor receptor 2 (HER2) –negative analysis population. OFS, ovarian function suppression.
Fig 2.
Fig 2.
Kaplan-Meier estimates of breast cancer–free interval (BCFI) in the overall hormone receptor–positive, human epidermal growth factor receptor 2–negative analysis population according to patient and tumor characteristics. (A) Age at random assignment, (B) nodal status, (C) tumor size, (D) estrogen receptor expression, (E) progesterone expression, (F) tumor grade, and (G) Ki-67 expression.
Fig 3.
Fig 3.
Breast cancer–free interval (BCFI) in the overall hormone receptor–positive, human epidermal growth factor receptor 2 (HER2) –negative population according to composite risk. (A) Kaplan-Meier estimate of BCFI according to quartile of composite risk distribution. (B) Subpopulation treatment effect pattern plot of 5-year BCFI (y-axis) according to composite risk subpopulation (x-axis). (C) distribution of composite risk scores with quartiles of the distribution marked by horizontal lines. The vertical dashed line indicates the median composite risk of 1.59 in the overall hormone receptor–positive, HER2-negative analysis population; the 25th and 75th percentiles are 1.01 and 2.21, respectively. The rug plot along the x-axis illustrates the distribution of composite risk values.
Fig 4.
Fig 4.
Subpopulation treatment effect pattern plot of 5-year breast cancer–free interval (BCFI) in the hormone receptor–positive, human epidermal growth factor receptor 2 (HER2) –negative population according to (A, C, E, G) composite risk subpopulations and (B, D, F, H) distribution of composite risk for each of the four cohorts defined by trial and chemotherapy use. (A, B) SOFT (Suppression of Ovarian Function Trial) no-chemotherapy cohort, (C, D) TEXT (Tamoxifen and Exemestane Trial) no-chemotherapy cohort, (E, F) TEXT chemotherapy cohort, and (G, H) SOFT prior-chemotherapy cohort. The vertical dashed lines indicate the median composite risk of 1.59 in the overall hormone receptor–positive, HER2-negative analysis population. OFS, ovarian function suppression.

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