Impact of neoadjuvant chemotherapy plus HER2-targeting on breast conservation rates: Surgical results from CALGB 40601 (Alliance).

Abstract

501 Background: Neoadjuvant systemic therapy improves breast conserving therapy (BCT) rates, but the magnitude of this benefit is unknown in operable breast cancer. We sought to quantify this benefit in CALGB 40601, a phase III trial of paclitaxel (T) + HER2 blockade with either trastuzumab (TH), lapatinib (TL), or both (THL), by requiring the treating breast surgeon to determine BCT eligibility before and after neoadjuvant therapy and examining surgical results. Methods: Eligible patients (pts) had operable, newly diagnosed, noninflammatory stage II-III HER2+ breast cancer randomized to receive TH, TL or THL. Prior to, and again after neoadjuvant therapy, the treating breast surgeon determined whether the patient was a BCT candidate based on clinical and radiographic criteria, but the subsequent breast cancer operation was at the discretion of the surgeon and patient. Two endpoints examined were: (1) the conversion rate from BCT-ineligible to BCT-eligible and (2) the rate of successful BCT as determined by tumor-free surgical margins. Results: Of 305 pts randomized (118 THL, 120 TH, 67 TL), 294 were evaluable. Prior to neoadjuvant therapy, 136 (46%) patients were candidates and 158 (54%) were non-candidates for BCT. 107/136 (79%) remained BCT candidates following neoadjuvant therapy and 78 chose BCT, of whom 69 (88%) were successful. 29 pts (21%) initially thought to be BCT candidates became non-candidates after neoadjuvant therapy. Conversely, 76/158 (48%) pts considered non-BCT candidates prior to neoadjuvant therapy down-sized sufficiently to be considered BCT candidates; 40 of these opted for BCT with a 75% (30/40) BCT success rate. In total, 183 pts were deemed BCT candidates after neoadjuvant therapy, yet 65 (36%) proceeded directly to mastectomy. Conclusions: This is the first neoadjuvant trial to prospectively quantify a nearly 50% conversion rate from BCT-ineligible to BCT-eligible in HER2+ breast cancer pts treated with modern systemic therapy. Neoadjuvant chemotherapy combined with targeted anti-HER2 treatment permits potential BCT in approximately 80% of properly selected patients. Clinical trial information: NCT00770809.