Benefit–Risk Data Aid Adjuvant Ovarian Suppression Decision In Young Breast Cancer Patients

Age-specific efficacy and safety data from the SOFT and TEXT trials inform clinicians on the use of ovarian function suppression in addition to tamoxifen or exemestane for younger women with breast cancer

medwireNews: An analysis of the phase III SOFT and TEXT trials focusing on women younger than 35 years of age suggests adjuvant ovarian function suppression (OFS) may benefit some women in this patient population.

In the SOFT study, women with early-stage breast cancer who remained premenopausal after surgery with or without chemotherapy were randomly assigned to receive tamoxifen alone or with OFS, or exemestane plus OFS for 5 years. And in TEXT, all participants received OFS alongside either tamoxifen or exemestane for a period of 5 years; chemotherapy was optional and given concomitantly with OFS.

Previous analyses of these trials have shown a breast cancer-free interval (BCFI) benefit with OFS plus exemestane for women with hormone receptor-positive breast cancer with high-risk features. But in view of age-related differences in breast cancer outcomes, Gini Fleming, from The University of Chicago Medical Center in Illinois, USA, and co-researchers focused on the group of women younger than 35 years.

Among 240 participants of the SOFT trial who were younger than 35 years and had received prior chemotherapy for human epidermal growth factor receptor (HER)2-negative disease, 67.1% in the tamoxifen alone group remained breast cancer-free at 5 years, compared with 75.9% in the tamoxifen plus OFS trial arm and 83.2% in the exemestane plus OFS group.

The 5-year BCFI rates for the 145 women with the same characteristics in the TEXT trial were 79.2% for tamoxifen plus OFS and 81.6% for exemestane plus OFS.

In an editorial published alongside the research in the Journal of Clinical Oncology, Philip Poorvu and Ann Partridge, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, write: “Such large absolute differences are compelling, although results were not powered to demonstrate statistical significance, and whether they will ultimately translate into future survival advantage is unclear as we await long-term follow-up.”

The study authors also investigated adverse events and quality of life (QoL), finding that vasomotor symptoms – including hot flushes and sweats – had the greatest impact on QoL, worsening it by around 30–40 points among women given OFS in the SOFT trial.

Gynaecological symptoms, such as loss of sexual interest and difficulties in becoming aroused, also contributed to worsening QoL for the OFS groups, and although the difference was not as large as for vasomotor symptoms, it was clinically meaningful (≥8-point change). There was little improvement in the scores for loss of sexual interest up to the 60-month mark, but women in the exemestane plus OFS group reported less difficulties in becoming aroused at this timepoint.

Despite the substantial toxicities associated with the combined regimens, the symptom-specific QoL changes were largely independent of age, notes the research team.

But women younger than 35 years were more likely to be nonadherent to assigned oral therapy than their older counterparts. At the 4-year mark, for instance, the cumulative incidence of nonadherence was 25% in the younger group and 21% among women aged 35 years or older.

Gini Fleming et al conclude: “Availability of these age-specific data regarding risks and benefits of combined endocrine therapy will support shared decision making regarding OFS among young women at high risk for recurrence and death from breast cancer and, it is hoped, improve adherence among those who select OFS.”

The editorial authors agree that the analysis “provides important new data to support informed decision making for the youngest women with hormone receptor–positive early breast cancer.”

They add: “[The] judicious use of OFS represents an opportunity to improve breast cancer outcomes for our youngest patients, but we must select patients carefully, actively manage the consequences, and adapt to the individual patient’s experience and preferences.”


Saha P, Regan MM, Pagani O, et al. 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. J Clin Oncol; Advance online publication 27 June 2017. doi:10.1200/JCO.2016.72.0946

Poorvu PD, Partridge AH. Ovarian suppression for women younger than 35 years: new data to support informed decision making. J Clin Oncol; Advance online publication 30 June 2017. doi:10.1200/JCO.2017.73.5662

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