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Neoadjuvant treatment for HER2 positive early breast cancer – differences between trastuzumab monotherapy and dual anti-HER2 blockade in our clinical practice

Neoadjuvant systemic therapy is standard treatment option for the most of HER2 positive early breast cancer patients. Studies confirm that patients with pathological complete response (pCR) to neoadjuvant therapy have better disease free survival (DFS) and overall survival. It is generally used to downstage the tumor which leads to higher rates of breast-conserving surgery rather than mastectomy. The response to neoadjuvant treatment informs us of the efficacy of the used therapeutic regimen and, therefore, helps us to choose an appropriate treatment strategy. First significant results have been shown in NeoALTTO study, which enrolled women with HER2-positive early breast cancer treated with lapatinib and trastu- zumab and confirmed that patients who achieve pathological complete response after neoadjuvant anti- HER2 therapy have longer event-free and overall survival. Hence, studies with pertuzumab, such as Neo- Sphere trial, show improved efficacy when combined with the established HER2-directed antibody trastu- zumab in breast cancer therapy. According to NeoSphere trial, patients given pertuzumab and trastuzumab plus docetaxel had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel, with favourable safety profile. At University hospital for Tumors, Zagreb, neoadjuvant systemic treatment was officially introduced in May 2015. and during that time, over 400 patients were treated. Our pilot trial analyzed consecutive sample of first 50 HER2 positive patients treated in our Clinic. We’ve analyzed patients characteristics, and compared two cohorts, one treated with anti-HER2 monotherapy (trastuzumab) versus the one treated with dual anti-HER2 therapy (trastuzumab + pertuzumab), from the moment dual anti-HER2 therapy became available. In patient cohort who received only trastuzumab together with chemotherapy, we enrolled 25 patients, consecutively. This cohort included 13 patients with hormone dependent tumors, and 12 patients who had non-luminal tumors. One patient in this cohort had multifocal disease, with both luminal biology tumors. Second cohort of patients which was treated with dual anti-HER2 therapy (pertuzumab+trastuzumab) plus chemotherapy, included 13 patients with luminal disease, 11 patients with non-luminal disease, and again, one of the patients had two primary tumors, both luminal type. In the cohort treated only with trastuzumab, 8 patients achieved pCR (complete pathological response), 3 patients achieved RCB (residual cancer burden) class I response, 5 of them RCB class II response, and two patients RCB class III response. For 6 patients residual cancer burden was not calculated. In the cohort treated with dual anti-HER2 therapy, 10 patients had pCR, 2 patients had RCB class I response, 8 patients had RCB class II response, 3 had RCB class III response, and for 2 patients RCB class was not calculated. In conclusion, there were more patients who achieved com- plete pathological response in cohort treated with both trastuzumab and pertuzumab. Among the patients who achieved pCR with trastuzumab monotherapy, 3 patients had luminal disease, and 4 patients had non-luminal tumor. For comparison, in cohort treated with dual anti-HER2 therapy, 4 of patients who had complete response to neoadjuvant treatment had luminal and 6 had non-luminal disease. Most of the patients in both cohorts who had RCB class II or RCB class III response to treatment had luminal cancers. Statistically significant results were not obtained, likely due to the small number of patients included in this preliminary study. However our data clearly showed a trend of improved response to treatment and higher pCR in patients treated with both trastuzumab and pertuzumab in contrast to trastuzumab mono- therapy, as well as tendency for better response rate to neoadjuvant chemotherapy in patients with HER2 positive non- luminal subtypes, which is consistent with results showed in relevant studies.

neoadjuvant treatment, early breast cancer, HER 2 positive

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