Preoperative Therapy with Pegylated Liposomal Doxorubicin, Cisplatin and Infusional Fluoruracil + Trastuzumab (±Endocrine Therapy) in Locally Advanced HER2 Positive Breast Cancer.
Authors: Torrisi R. , Dellapasqua S. , Cancello G. , Balduzzi A. , Montagna E. , Ghisini R. , Iorfida M. , Veronesi P. , Viale G. , Goldhirsch A. , Colleoni M. 
Published: December 2010

Background: Preoperative trastuzumab (T) and anthracyclines increase either pathological complete remission (pCR) and long term outcome in pts with locally advanced HER2 positive breast cancer. Pegylated liposomal doxorubicin (PLD) has been shown as active as conventional anthracyclines in advanced breast cancer albeit less toxic. Little is known about PLD activity as primary therapy in combination with T.Patients and methods: We tested a combination of PLD with cisplatin and infusional fluorouracil (CCF) and T in patients (pts) with HER2 positive T2-T4a-d N0-3 M0 breast cancer. PLD (25 mg/sqm), cisplatin (60 mg/sqm) and infusional fluorouracil (200 mg/sqm/day c.i.) q21 days for 8 courses. T was administered i.v. 6 mg/kg (after a loading dose of 8 mg/kg) every q21 days. Patients with ER and/or PgR≥10% tumors received endocrine therapy with letrozole (+ triptorelin q28 days if premenopausal). The endpoints were the rate of clinical response (CR) and of pCR defined as the absence of invasive or measurable tumor in the breast and in the axillary nodes and the tolerability of the combination.Results: Thirty-two pts entered the study and all are evaluable for pCR, CR and toxicity. Median age was 47 yrs (range 28-69). One pt had recurrent and 1 pt had bilateral cancer. Fifteen pts had hormone receptor positive (HR+ve), 15 had HR absent (HR-ve) tumors and 2 pts had ER 1-9% (HR poor) tumors. Thirteen pts (41%) had T4d cancer and 2 pts had T4b cancer. Twenty-six pts (86%) had clinically positive nodes.Overall 4 pts (13%) and 26 pts (81%) obtained a complete and a partial response, respectively with an overall CR rate of 94% [95%CI, 85%-100%]; no pt progressed. Thirteen pts [41% 95%CI, 24%-58%] obtained a pCR; in addition 1 pt had only isolated tumor cells and 2 pts had pT1a residual tumor. The pCR rate was 33% and 47% in patients with HR+ve and HR-ve tumors, respectively. Seventy-four percent [95%CI, 59%-90%]of pts had negative nodes at surgery.Among the 13 T4d cancers 7 pts obtained a pCR [54%, 95%CI, 27%-81%]. In particular 2/6 HR+ve (33%), 4/6 HR-ve (66%) and 1/1 HR poor T4d tumors achieved a pCR Treatment was completed in 21 pts, 11 pts discontinued treatment before completion of 8 cycles, although only 7 grade &gt; 2 non haematological toxicity were observed, 3 of them in the same pt.No decrease of LVEF &lt; 50% was observed.Conclusions: Our results indicate that CCF + T were active in a population of very locally advanced breast cancer yielding a pCR rate comparable to that observed with the combination of T + standard anthracyclines. Most interestingly, an impressive rate of pCR was observed in T4d tumors, suggesting an enhanced local delivery and increased activity of PLD. This result merits further investigations in larger series.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1097.