NSABP B-38: Definitive Analysis of a Randomized Adjuvant Trial Comparing Dose-Dense (DD) AC^Paclitaxel (P) Plus Gemcitabine (G) With DD AC->P and With Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) in Women With Operable, Node-Positive Breast Cancer

摘要

The rationale for using trastuzumab in ductal carcinoma in situ (DCIS) is based partly on the ability of anti-HER2 agents to enhance radiation sensitivity. The ongoing NSABP B-43 trial is designed to examine the efficacy of trastuzumab given during whole breast irradiation (WBI) (Abstract TPS657). After lumpectomy for pure DCIS, each patient's lesion will be tested for HER2 status via central IHC analysis. Lesions with a score of HER2 2+ undergo FISH analysis. Patients with HER2 3+ or FISH+ tumors are randomly assigned to WBI alone or to WBI plus 2 doses of trastuzumab (8 mg/kg followed by 6 mg/kg) 3 weeks apart. The primary endpoints are to determine whether trastuzumab decreases ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral DCIS. Secondary endpoints include invasive or DCIS disease-free survival; invasive or DCIS recurrence-free interval; invasive, regional, or distant recurrence; contralateral invasive or DCIS breast cancer; OS; and post-treatment amenorrhea. The trial will accrue 2,000 patients throughout 7.9 years. Definitive analysis of primary end-points will be performed at 163 ipsilateral breast cancer events. As of March 31, 2012, the trial had randomized 878 patients and collected 1,217 (33%) eligible specimens out of 3,647 specimens centrally tested, a rate lower than expected. No trastuzumab safety signals were observed.