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Background PST with taxanes, anthracycline-containing regimens and T showed a high percentage of pathologic complete response (pCR); T administered concurrently with chemotherapy is more effective, but the combination with anthracyclines may be at risk of cardiotoxicity. The present study evaluates efficacy and toxicity of T administered concurrently with a sequential regimen of D followed by EC in neoadjuvant setting. Materials and methods This phase II single stage trial is enrolling pts with cT2-T4, N0-2, M0, Her-2 positive (IHC 3+ or 2+ amplified) breast cancer. A core biopsy is required prior treatment start to evaluate hormonal receptors, Ki67, topoisomerase II, Her-2, with re-evaluation of these parameters, whenever possible, at definite surgery. LVEF is evaluated before and during treatment. Blood samples are collected at baseline for evaluation of 9 genetic polymorphisms related to higher risk of developing cardiac toxicity. We are quantitatively evaluating gene copy number by multiple ligand probe amplification (MLPA), PTEN, p-Akt, p-MAPK, and PIK3CA mutations. Pts receive 4 cycles of D (100mg/m2) plus T (loading dose 8mg/kg followed by 6mg/kg), followed by 4 cycles of EC (120/600mg/m2) plus T, every 3 weeks. Definite surgery is planned at the end of PST, and standard radiotherapy and hormonal adjuvant treatment in case of positive hormonal receptors are given; adjuvant T is given for 6 months. The primary objective of the trial is pCR (absence of invasive tumor cells in the breast and axilla); secondary objectives are cardiac safety, toxicity, disease-free survival. The planned sample size is 42 pts. Results To date, 29 pts have been enrolled; median age is 45 years, pre/postmenopausal 22/7, ER and/or PgR positive in 16 pts. 27 pts are evaluable for pathological response: we observed 20 pCR (74%, 95%C.I, 57.5-90.6). Grade 3-4 neutropenia was the most frequent toxicity, encountered in 75% of the pts, other toxicities were mild to moderate. No clinical cardiotoxicity was observed. Conclusions At preliminary analysis, PST with sequential administration of D followed by EC, given concurrently with T, appears to be very active and safe in stage II-III breast cancer pts. Disclosure All authors have declared no conflicts of interest. |
