The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

Abstract

BackgroundOvarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy.MethodsPremenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event.DiscussionThis study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy.Trial registrationClinicalTrials.gov Identifier NCT00912548. Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005. Registered October 26 2009.

Reactivation of cAMP Pathway by PDE4D Inhibition Represents a Novel Druggable Axis for Overcoming Tamoxifen Resistance in ER-positive Breast Cancer

“…Furthermore, fulvestrant has demonstrated clinical efficacy for patients with a second relapse after responding to tamoxifen and AIs (35). Another randomized trail demonstrated an improved median progression-free survival (PFS) in ER-positive, premenopausal metastatic patients when treated with tamoxifen plus ovarian function suppresser (36). Although early-stage disease is manageable owing to use of more potent endocrine agents, resistance inevitably develops in advance, metastatic disease (37).…”

<p>Controversies Regarding Ovarian Suppression and Infertility in Early Stage Breast Cancer</p>

“…(TEXT) and the eight-year follow-up was presentedASCO. 20 The combined analysis of the SOFT and TEXT confirmed statistically significant improvements in disease outcomes with exemestane versus tamoxifen used in combination with ovarian suppression after a median followup of 9 years. Most benefits were seen in women with HER2-negative breast cancer and women who remained premenopausal after receiving chemotherapy before starting ovarian suppression, especially those who also received adjuvant chemotherapy for higher risk of recurrence.…”

Post-chemotherapy serum anti-Müllerian hormone level predicts ovarian function recovery

“…For adjuvant hormone therapy, all patients took tamoxifen regardless of their menstrual status during the study. The study design and enrolment criteria are precisely described in a previous report ( 24 ). However, in this study, unlike in the ASTRRA trial, only the presence of vaginal bleeding was accepted as criteria for resumption of ovarian function.…”