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

Abstract

Purpose To describe benefits and toxicities of adjuvant endocrine therapies in women younger than 35 years with breast cancer (n = 582) enrolled in the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT). Methods In SOFT, women still premenopausal after surgery with or without chemotherapy were randomly assigned to tamoxifen alone, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. In TEXT, all received OFS with or without concomitant chemotherapy and were randomly assigned to exemestane plus OFS or tamoxifen plus OFS. We summarize treatment efficacy, quality of life, and adherence of the cohort of women younger than 35 years in SOFT and TEXT, alongside data from the cohort of older premenopausal women. Results For 240 human epidermal growth factor receptor 2-negative patients younger than 35 years enrolled in SOFT after receiving chemotherapy, the 5-year breast cancer-free interval (BCFI) was 67.1% (95% CI, 54.6% to 76.9%) with tamoxifen alone, 75.9% with tamoxifen plus OFS (95% CI, 64.0% to 84.4%), and 83.2% with exemestane plus OFS (95% CI, 72.7% to 90.0%). For 145 human epidermal growth factor receptor 2-negative patients younger than 35 years in TEXT, 5-year BCFI was 79.2% (95% CI, 66.2% to 87.7%) with tamoxifen plus OFS and 81.6% (95% CI, 69.8% to 89.2%) with exemestane plus OFS. The most prominent quality of life symptom for patients younger than 35 years receiving OFS was vasomotor symptoms, with the greatest worsening from baseline at 6 months (on the order of 30 to 40 points), but loss of sexual interest and difficulties in becoming aroused were also clinically meaningful (≥ 8-point change). The level of symptom burden was similar in older premenopausal women. A total of 19.8% of women younger than 35 years stopped all protocol-assigned endocrine therapy early. Conclusion In women younger than 35 years with hormone receptor-positive breast cancer, adjuvant OFS combined with tamoxifen or exemestane produces large improvements in BCFI compared with tamoxifen alone. Menopausal symptoms are significant but are not worse than those seen in older premenopausal women.

Efficacy of anastrozole after tamoxifen in early breast cancer patients with chemotherapy‐induced ovarian function failure

“…16,21 As this was not observed in patients treated with tamoxifen, this cannot point at an independent prognostic value of age. 22 The incomplete ovarian function suppression by a GnRH agonist was indeed observed in the SOFT-EST trial, 23 where during 12 months of follow-up, 34.2% of the patients had inadequately suppressed (increased) E2 levels, at least once.…”

“…On the contrary, supplementary figure S6 of the TEXT/SOFT analyses regarding the combination of exemestane with a GnRH agonist and the additional analyses in women under 35 years of age show, as illustrated by the HRs, a gradually increasing favorable impact on the disease‐free survival with rising age for the combination AI/GnRH agonist in comparison to tamoxifen/GnRH agonist, possibly due to incomplete ovarian function suppression by GnRH agonists in younger patients . As this was not observed in patients treated with tamoxifen, this cannot point at an independent prognostic value of age . The incomplete ovarian function suppression by a GnRH agonist was indeed observed in the SOFT‐EST trial, where during 12 months of follow‐up, 34.2% of the patients had inadequately suppressed (increased) E2 levels, at least once.…”

Assessment and management of bone health in women with oestrogen receptor‐positive breast cancer receiving endocrine therapy: position statement summary

“…These benefits have been confirmed by a recent 8‐year follow‐up study . In women < 35 years of age, the 5‐year breast cancer‐free interval was 67.1% (95% CI, 54.6–76.9%) with tamoxifen alone, 75.9% with tamoxifen plus ovarian suppression (95% CI, 64.0–84.4%), and 83.2% with exemestane plus ovarian suppression (95% CI, 72.7–90.0%) . After 8 years, the rate of freedom from distant recurrence in this age group was 73.8% with tamoxifen alone, 77.5% with tamoxifen plus ovarian suppression, and 82.4% with exemestane plus ovarian suppression .…”

“…After 8 years, the rate of freedom from distant recurrence in this age group was 73.8% with tamoxifen alone, 77.5% with tamoxifen plus ovarian suppression, and 82.4% with exemestane plus ovarian suppression . These data are expected to increase the number of young, pre‐menopausal women receiving ovarian suppression combined with aromatase inhibitors, which has profound effects on bone health (Box 1).…”

Assessment and management of bone health in women with oestrogen receptor‐positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australasian Menopause Society and the Clinical Oncology Society of Australia

“…In premenopausal women, tamoxifen has traditionally been first‐line treatment, although a combined analysis of 2 large randomized controlled trials (RCT), Tamoxifen and Exemestane Trial (TEXT) and Suppression of Ovarian Function Trial (SOFT), reported improved 5‐year disease‐free survival with ovarian suppression plus the aromatase inhibitor exemestane compared to ovarian suppression plus tamoxifen (91.1% vs 87.3%, hazard ratio [HR] 0.72; 95% CI 0.60‐0.85; P < .001) . The benefit was significant in premenopausal women with high‐risk ER‐positive, HER2‐negative breast cancer, as defined by clinicopathological characteristics and in patients <35 years of age …”