Association between pathologic complete response and survival in patients treated with sequential anthracyclines and concomitant taxanes and trastuzumab in HER2-positive breast cancer.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #3141 Background: We reported high pathologic complete response (pCR) rates in patients with AC-sensitive and AC-resistant breast cancer (BC) who received trastuzumab-based chemotherapy regimens (SABCS 2004-2007). Following standard chemotherapy, pCR in 33% patients with HER2-positive breast cancer (BC) predicts 5-year DFS of 94% compared to 69% in 67% of patients with residual disease (RD)-a 25% difference (MD Anderson data). However, a similar association of DFS with pCR following trastuzumab has yet to be demonstrated. Material and Methods: A retrospective analysis of 40 patients with stage I-IIIC (6T4a-c, 9T4d, 8T3, 11T2, 6TX-1, 7 LN-negative, 33 LN-positive) HER2-positive (IHC2+ and FISH+ or IHC3+) BC treated preoperatively on and off institutional trials with trastuzumab-based regimens between 11/2002 and 10/2007 was conducted. Generally, patients received in vivo chemosensitivity-adjusted dose-dense doxorubicin and cyclophosphamide (2-4 cycles) followed by paclitaxel (cremophor or albumin-bound), carboplatin and trastuzumab for 12-16 weeks. Median age was 51 (range 26-71), and 16 (40%) had HR-positive BC. Postoperative treatment included radiation based on pretreatment stage, hormonal modulation for HR-positive BC, and additional trastuzumab was optional. Results: Twenty-six (65%, 95% CI 48-79%) patients achieved pCR in breast and axilla. pCR rate was 30%, 67% and 90% (p=0.02) with increasing HER2 FISH ratio of 1-4 (n=10), >4 (n=18), and >7 (n=10), respectively. pCR was demonstrated in 50% HR-positive and in 75% HR-negative BC (p=0.17). DFS and OS of 40 patients at a median follow-up of 28 months (range 2-56) of live patients is 88% (95% CI: 73-96) and 93% (95% CI: 80-98). DFS was 95% for patients who achieved pCR and 69% for patients with RD (Hazard ratio 0.12; 95% CI: 0.02 to 0.72, p=0.022). Age, grade, tumor size, preoperative lymph node and hormone receptor status were not prognostically significant in this small series. DFS was 94% for HER2+/HR+ and 83% for HER2+/HR- BC. Of the 5 relapses, 3 patients had inflammatory (2 had brain relapse as first site), one IIIB and one IIB BC. Discussion: This is the first demonstration of statistically significant difference in DFS of 95% in 65% achieving pCR versus 69% in 35% with RD treated preoperatively with trastuzumab-taxanes following anthracyclines. The strength of association between pCR and DFS is same as that following non-trastuzumab chemotherapy. In contrast, the 2-3 times higher pCR following trastuzumab is associated with a higher DFS of 88% for overall HER+ BC despite inclusion of inflammatory and locally advanced BC, and compares favorably with adjuvant trastuzumab studies of operable BC. The association between pCR and longer-term outcome also underscores the adequacy of in vivo chemosensitivity-adjusted 12-16 weeks (short course) of trastuzumab-taxanes combination sequenced following 2-4 cycles of anthracyclines in the neoadjuvant setting. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3141.