Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial

Abstract

Background NSABP B-35 is a phase III trial comparing anastrozole (A) to tamoxifen (T) for breast cancer-free interval (BCFI), defined as time from randomization to any breast cancer event: local, regional, distant, or contralateral, invasive or DCIS. Methods Postmenopausal women with hormone-positive DCIS treated by lumpectomy with clear resection margins and whole breast irradiation were randomized to receive either 20mg/day T or 1mg/day A (blinded) for 5 years. Stratification was by <60 versus ≥60 years. Findings From 1/6/2003–6/15/2006, 3,104 patients were entered and randomized. As of 2/28/15, follow-up information was available on 3,083 patients for OS and 3,077 for all other disease-free endpoints, with median follow-up of 9 years. There were 212 BCFI events, 122 in the T group and 90 in the A group (HR, 0.73; 95% CI, 0.56–0.96; p=0.0234). 10-year estimates for BCFI were 89.1% (95% CI, 86.8–91.0) for T and 93.1% (95% CI, 91.5–94.5) for A. A significant time-by-treatment interaction (p=0.0410) became evident later in the study. There was a significant interaction between treatment and age group (p=0.0379); A is superior only in women <60 years. There were 495 DFS events: 260 in the T group, 235 in the A group (HR, 0.89; 95% CI, 0.75–1.07; p=0.21). 10-year DFS estimates were 77.9% (95% CI, 75.0–80.6) for T and 82.7% (95% CI, 80.4–84.7) for A. There were 186 deaths: 88 in the T group, 98 in the A group (HR, 1.11; 95% CI, 0.83–1.48; p=0.48). 10-year OS estimates were 92.1% (95% CI, 90.1–93.7) for T, 92.5% (95% CI, 90.8–93.9) for A. Eight deaths were due to breast cancer in the T group and five in the A. There were 69 cases of invasive breast cancer in the T group and 43 in the A group (HR, 0.62; 95% CI, 0.42–0.90; p=0.0123). A significant reduction in contralateral breast cancers with A (HR, 0.64; 95% CI, 0.43–0.96; p=0.0322) was identified. Interpretation Anastrozole provided a significant improvement compared to tamoxifen for BCFI, primarily in women <60 years. Funding US NCI; AstraZeneca Pharmaceuticals LP.

Is Adjuvant Endocrine Therapy Indicated for DCIS Patients After Complete Surgical Excision?

“…In 2000, tamoxifen, a selective estrogen receptor modulator (SERM), has gained approval by the Food and Drug Administration (FDA) to be used as an adjuvant endocrine therapy in DCIS patients (8). This was based on the first of the several clinical trials that have suggested potential benefits of endocrine therapy in cases of DCIS, the National Surgical Adjuvant Breast and Bowel Project NSABP B-24 trial (8)(9)(10)(11)(12). NSABP B-24 (8) was double-blinded, randomized, controlled trial enrolling 1804 DCIS patients who had previously undergone breast conserving surgery and whole breast radiotherapy.…”

“…Nonetheless, tamoxifen had no apparent benefit among the cohort of patients who received radiotherapy (13). In view of the recent evidence that aromatase inhibitors are superior to tamoxifen in the treatment of postmenopausal women with ER positive invasive breast cancers (14), two large, double-blinded, randomized clinical trials were carried out to compare the performance of anastrozole versus tamoxifen in the adjuvant management of hormone-receptor positive, postmenopausal women with DCIS (11,12). In the NSABP b-35 trial (12), 3104 DCIS patients with established clear surgical margins after breast conserving surgery and radiotherapy were enrolled in this study and randomized into either tamoxifen or anastrozole treatment arms.…”

“…In view of the recent evidence that aromatase inhibitors are superior to tamoxifen in the treatment of postmenopausal women with ER positive invasive breast cancers (14), two large, double-blinded, randomized clinical trials were carried out to compare the performance of anastrozole versus tamoxifen in the adjuvant management of hormone-receptor positive, postmenopausal women with DCIS (11,12). In the NSABP b-35 trial (12), 3104 DCIS patients with established clear surgical margins after breast conserving surgery and radiotherapy were enrolled in this study and randomized into either tamoxifen or anastrozole treatment arms. After a median follow-up of 9 years, there was a significant difference in the breast cancer-free interval in favour of the anastrozole group (HR=0.73, 95%CI=0.56-0.96); however, this was mainly seen in the subgroup of postmenopausal patients younger than 60 years.…”

Diagnosis and Treatment of Breast Cancer in Situ. Russian Association of Oncological Mammology Clinical Guidelines (Project)

“…В исследовании комплексного взаимодействия биомаркеров и визуализации IBIS-II (Integrated Biomarkers and Imaging Study II) [19] и проекте NSABP В-35 [20] оценена роль ингибиторов ароматазы (анастрозола) у постменопаузальных больных DCIS, которым проводили сохранные операции с ЛТ или без нее. Цель исследований -определить проме-жуток времени от момента рандомизации до выявле-ния рака (рецидива или нового случая) и оценить общую выживаемость и качество жизни (см.…”

“…Однако преимущество анастрозола зарегистрировано только у больных в пост-менопаузе моложе 60 лет [20]. Не выявлено существен-ного влияния гормонотерапии на риск развития инвази-вого рака в ипсилатеральной молочной железе, однако зарегистрировано снижение данного риска в контрлате-ральной железе с наибольшей достоверностью в группе анастрозола.…”