Patients with HER2-positive Early Breast Cancer Receiving Adjuvant Trastuzumab: Clinicopathological Features, Efficacy, and Factors Affecting Survival

Abstract

Background: The aim of the present study was to evaluate clinicopathological characteristics of our early stage breast cancer patients who are epidermal growth factor receptor 2 (HER2) overexpressed/ amplified (HER2+), the efficacy of trastuzumab treatment and survival results. Materials and Methods: Patients with HER2-positive early stage breast cancer receiving adjuvant trastuzumab were investigated retrospectively. Clinicopathological features of 210 patients and treatment outcome were analysed. To evaluate survival rates, the Kaplan-Meier method was used. Univariate and multivariate analyses were conducted with the Cox regression model. Results: Mean age of the patients was 51.8, 71.9% being postmenopausal. Some 37.6% of patients were node negative, and 31% had T1 tumor size and 52.4% were positive for estrogen receptor. Of 210 patients, 89.5% completed planned 52 weeks adjuvant trastuzumab treatment. The median follow up was 27.5 months (6.0-86.0 ). Relapse free survival (RFS) was 68.0 months (95% CI: 62.1-74.0) and overall survival (OS) was 74.8 months (95% CI: 69.5-80.1). The 3 year OS for all patients was 92.0% and RFS was 79.6%. During follow up, relapse was detected at the rate of 14.3%. Trastuzumab associated cardiotoxicity was found at the rate of 3.3%. In univariate analyses, larger tumor size and grade III were significantly associated (p<0.05) with RFS. Multivariate analyses of covariates displaying p<0.05 identified grade III as an independent prognostic factor. Conclusions: In the present study, it was established that trastuzumab had a satisfactory safety profile and treatment efficacy as in other clinical studies and that among clinicopathological factors evaluated, only being grade 3 had a significant effect on RFS. The occurrence of relapse with adjuvant trastuzumab makes it necessary to identify molecular predictors, which will define this group better and help explain resistance to anti HER2 based therapies.

Efetividade do Trastuzumabe adjuvante em mulheres com câncer de mama HER-2+ no SUS

“…Como esperado, houve maior número de recidivas documentadas no estudo que seguiu as pacientes por maior período de tempo (11 anos) 5 . Em outros estudos avaliados, que incluíram pacientes com características clínicas semelhantes das incluídas neste estudo, foram descritos taxa de sobrevida livre de recorrência variando de 66% a 94% 4,[11][12][13][14][15][16][17][18] . Essa variação também dependeu do estágio de doença no momento do diagnóstico, onde pacientes com doença em estágios mais avançados no momento do diagnóstico tiveram maior índice de recidiva, e do período de seguimento de cada estudo (de três a 10 anos), onde aqueles que avaliaram períodos menores tiveram menos eventos de recidiva comparados com os estudos que avaliaram as pacientes durante um período maior [18][19][20][21][22] .…”

“…Em outros estudos avaliados, que incluíram pacientes com características clínicas semelhantes das incluídas neste estudo, foram descritos taxa de sobrevida livre de recorrência variando de 66% a 94% 4,[11][12][13][14][15][16][17][18] . Essa variação também dependeu do estágio de doença no momento do diagnóstico, onde pacientes com doença em estágios mais avançados no momento do diagnóstico tiveram maior índice de recidiva, e do período de seguimento de cada estudo (de três a 10 anos), onde aqueles que avaliaram períodos menores tiveram menos eventos de recidiva comparados com os estudos que avaliaram as pacientes durante um período maior [18][19][20][21][22] . No presente estudo, observa-se que a variável estágio III no momento do diagnóstico, mostrou-se como fator de risco isolado para maior chance de recidiva o que corrobora com os estudos relatados acima.…”

Human epithelial growth factor receptor 2 in human salivary carcinoma ex pleomorphic adenoma: a potential therapeutic target

“…HER2 overexpression and amplification are an important factor to be considered in the selection of targeted therapy. 12 , 13 It has been reported that the targeting therapeutic antibody herceptin could downregulate protein expression by targeting HER2 and thus reduce the activation of the PI3K/AKT and MAPK/ERK signaling pathways. 14 , 15 …”

The possibility of using magnetic nanoparticles to increase the therapeutic efficiency of Herceptin antibody

“…Herceptin-modified MNPs were prepared as described previously [17,20]. Briefly, 1,6-diaminohexane-derivatized iron oxide nanoparticles (10 mg Fe/ml) were reacted with 0.2 ml aqueous glutaraldehyde for 1.5 h at 23°C.…”

“…HER2 is overexpressed in 20-30% of early-stage breast cancers. Patients with HER2-overexpressing breast cancer may be candidates for Herceptin treatment [5,17,20]. However, due to the cardiotoxicity of Herceptin, some patients cannot tolerate the treatment due to preexisting heart conditions [22].…”