NRG Oncology/NSABP B-47 menstrual history study: impact of adjuvant chemotherapy with and without trastuzumab

Patricia A Ganz,Reena S Cecchini,Patrick J Flynn,John P Crown,Charles E Geyer,Jong-Hyeon Jeong,Jean-Francois Boileau,David M Ellison,Priya Rastogi,Louis Fehrenbacher,Eleftherios P Mamounas,Michael P Thirlwell,Norman Wolmark

doi:10.1038/s41523-021-00264-2

Abstract

The NRG Oncology/NSABP B-47 menstrual history (MH) study examined trastuzumab effects on menstrual status and associated circulating reproductive hormones. MH was evaluated by questions related to hysterectomy, oophorectomy, and reported menstrual changes. Pre/perimenopausal women were assessed at entry, 3, 6, 12, 18, 24, 30, and 36 months. Consenting women had estradiol and FSH measurement at entry, 3, 6, 12, 18, and 24 months. Logistic regression determined predictors of amenorrhea and hormone levels at 12, 24, and 36 months. Between 2/8/2011 and 2/10/2015, 3270 women with node-positive/high-risk node-negative HER2-low breast cancer were enrolled. There were 1,458 women enrolled in the MH study; 1231 consented to baseline blood samples. Trastuzumab did not contribute to a higher amenorrhea rate. Amenorrhea predictors were consistent with earlier studies; however, to our knowledge, this is the largest prospective study to include serial reproductive hormone measurements to 24 months and clinical amenorrhea reports to 36 months. These data can help to counsel patients regarding premature menopause risk.

Highlights

NRG Oncology/NSABP B‐47 is a phase III, multicenter, randomized adjuvant therapy trial designed to evaluate the addition of trastuzumab to adjuvant chemotherapy in patients with HER2-low breast cancer
The primary aims of the menstrual history (MH) sub-study were to assemble an observational cohort of pre- and perimenopausal women to evaluate the effect of chemotherapy with or without trastuzumab on treatment-related amenorrhea (TRA) and the associations between TRA and circulating reproductive hormone levels
AC→WP doxorubicin and cyclophosphamide followed by weekly paclitaxel for 12 weeks, ER estrogen receptor, ET endocrine therapy, HR hormone receptor, IHC immunohistochemistry, PgR progesterone receptor, TC docetaxel plus cyclophosphamide, Trast trastuzumab. aEach characteristic was assessed univariably in separate logistic regression models, all except age group were adjusted for continuous age upon random assignment

Summary

INTRODUCTION

NRG Oncology/NSABP B‐47 is a phase III, multicenter, randomized adjuvant therapy trial designed to evaluate the addition of trastuzumab to adjuvant chemotherapy in patients with HER2-low breast cancer. The primary endpoint was invasive disease‐free survival (IDFS) and clinical results showed no benefit from the addition of trastuzumab to chemotherapy in this population[1]. Because the impact of trastuzumab on menstrual function was unknown at the time of protocol design, a secondary endpoint focused on menstrual health. The primary aims of the menstrual history (MH) sub-study were to assemble an observational cohort of pre- and perimenopausal women to evaluate the effect of chemotherapy with or without trastuzumab on treatment-related amenorrhea (TRA) and the associations between TRA and circulating reproductive hormone levels. Secondary exploratory aims examined associations between chemotherapy regimen, TRA, and IDFS benefit in premenopausal women. We report on these outcomes, as well as medical and demographic predictors of TRA

RESULTS

12 Months

DISCUSSION

METHODS

CODE AVAILABILITY