COMMENTARY

'Right' Endocrine Therapy Still a Question in Youngest Breast Cancer Patients

Lidia Schapira, MD

Disclosures

July 25, 2017

Treatment Efficacy, Adherence, and Quality of Life Among Women Younger Than 35 Years in the International Breast Cancer Study Group TEXT and SOFT Adjuvant Endocrine Therapy Trials

Saha P, Regan MM, Pagani O, et al; SOFT; TEXT Investigators; International Breast Cancer Study Group
J Clin Oncol. 27 Jun 2017. [Epub ahead of print]

Study Summary

Younger women with endocrine-sensitive (ie, estrogen receptor [ER]-positive or progesterone receptor [PR]-positive and human epidermal growth factor receptor 2-negative) breast cancer benefit from adjuvant endocrine therapy, although the contribution of ovarian function suppression (OFS) to improve outcomes and its inherent toxicities are still being debated.

Investigators enrolled women who remained premenopausal at the completion of chemotherapy and those who did not receive chemotherapy in the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT).[1] In SOFT, women were assigned to receive tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. In TEXT, all women received OFS and were assigned to OFS plus tamoxifen or OFS plus exemestane.

The current analysis of the SOFT and TEXT trials looked at the treatment results in younger women. A total of 240 patients enrolled in SOFT and 145 in TEXT were younger than 35 years. Improved outcomes, defined as a 5-year breast cancer-free interval, were reported for women who received OFS, with the greatest benefit noted for the group treated with OFS plus exemestane. Quality-of-life measurements showed that these women also experienced more profound vasomotor symptoms and sexual dysfunction, and 20% of women stopped all protocol-assigned endocrine therapy early.

OFS combined with tamoxifen or exemestane produces large improvements in breast cancer-free interval, and these gains are accompanied by greater patient-reported sexual dysfunction and vasomotor symptoms that match those reported in older premenopausal women.

Viewpoint

Choosing the "right" endocrine therapy for the youngest women with endocrine-sensitive breast cancer remains a challenge for clinicians, who need to balance the expected benefits of therapy (expressed as decrease in risk for cancer recurrence) with the known burden of toxicities associated with estrogen deprivation therapies. The duration of endocrine therapy is also a factor, because many of these women are still interested in reproductive options, and everybody understands that delaying childbearing will affect their chances of becoming pregnant.

SOFT and TEXT have demonstrated that for premenopausal women with hormone receptor-positive breast cancer and high-risk clinicopathologic factors, treatment with OFS plus exemestane (or any aromatase inhibitor) can produce significant absolute improvement of 10%-15% in the breast cancer-free interval. Not surprisingly, symptom-specific quality of life was reported to be worse in patients who underwent more stringent endocrine therapy that included ovarian ablation. The youngest cohort had a clinically meaningful difference in quality of life (adjusted for endocrine therapy), characterized by worse sweats and hot flushes. This group also had tumors associated with higher risk for cancer recurrence (more women had ER-positive and PR-negative tumors and tumors with clinicopathologic features associated with more aggressive biology).

The investigators conclude that the benefit from OFS needs to be weighed against toxicity and remind readers that longer follow-up is critical in order to clarify potential survival benefits. Meeting the needs of this population remains a challenge, as we strive to minimize the burden of physical symptoms associated with estrogen deprivation.

Abstract

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