| Background:Breast cancer has become the world’s most common malignant tumor, and the second death cause in female cancer related diseases. Breast cancer is one kind of complex heterogeneous disease, which can be divided into five different subtypes, according to the specific gene expression:Luminar A, Luminar B, Her-2positive, Claudin-low and Basal-like. There are approximate20%to65%of breast cancer patients who show over expression of Her-2(Human Epidermal Growth Factor Receptor-2). The abnormal expression of Her-2in breast cancer is closely related to metastasis, poor prognosis, and treatment resistance. Early diagnosis, radiotherapy, chemotherapy and endocrine therapy after operation only decline breast cancer mortality rates, but not reduce breast cancer recurrence and metastasis, especially distant metastasis. After operation, radiotherapy and chemotherapy for tumor therapy, molecular targeted therapy for cancer (MTT) is applied as a new biological treatment. Through specific interference involved in tumorigenesis, development of molecular function, it may target to cancerous cells, reverse the malignant biological behavior, so as to inhibit tumor growth and dissemination at the molecular level. Trastuzumab and bevacizumab, as monoclonal antibodies and molecular targeted drugs, were approved since1998by the United States Food and Drug Administration (FDA) and had entered the Chinese market for the treatment of breast cancer. The studies of Trastuzumab or bevacizumab of combination with chemotherapy drugs applied in the treatment of Her-2 positive metastatic breast cancer with good therapeutic effects are reported. But trastuzumab plus bevacizumab in combination with paclitaxel in treatment of Her-2positive metastatic breast cancer were hardly reported, almost no domestic reports. Related researches came from and related with Europe and the United States population, with treatment patterns referenced to Europe and the United States the scheme but not for the Chinese people. Biological characteristics of breast cancer vary between Europe, the United States population and Chinese population. Therefore, it is necessary to study biological characteristics of trastuzumab plus bevacizumab in combination with paclitaxel in Her-2positive metastatic breast cancer patients in China.Objective:This study aims to retrospectively explore and compare the effect and adverse side effects of trastuzumab and trastuzumab plus bevacizumab in combination with paclitaxel in treatment of Her-2-positive metastatic breast cancer.Methods:From January,2010to May,2011,88cases of Her-2positive metastatic breast cancer female patients in Haikou Municipal Hospital, Hainan, China were retrospectively collected in our study, including42cases of immunohistochemistry (IHC)(++) and fluorescent in situ hybridization (FISH)(+), additionally46cases of IHC(+++).43cases used trastuzumab in combination with paclitaxel were called trastuzumab group. And45cases used of trastuzumab plus bevacizumab in combinmation with paclitaxel were called trastuzumab combined with bevacizumab group. For the trastuzumab group, the first dose of trastuzumab is as4mg/kg, after a dose of2mg/kg,1time per week, for consecutive weeks, from7to14weeks accordingly, paclitaxel175mg/m2, every21days per cycle for at least three consecutive cycles until disease progression or unacceptable toxicity, with antiemetic and antiallergic therapies. Patients who experienced progression on Paclitaxel received other chemotherapy regimens if possible. For the trastuzumab combined with bevacizumab group, trastuzumab and paclitaxel were used as the control group and bevacizumab was administrated10mg/kg, every2weeks,4weeks per cycle, for3consecutive cycles. Patients who experienced progression on Paclitaxel received other chemotherapy regimens if possible. Both groups were reviewed per6weeks. After treatment, all patients were divided as following:complete remission (CR), partial remission (PR), stability disease (SD) and progressive disease (PD). Collection and calculation of overall response rate (ORR), the clinical benefit rate (CBR), time to progression (TTP), progression free survival (PFS) were observed. Evaluations of toxicity of two groups were done.ResuIt:Compared with the trastuzumab group, the age, BMI, performance status score, recurrence and metastatic sites, the number of sites had no significant differences in the trastuzumab combined with bevacizumab group (P>0.05).1patients in the trastuzumab group was complete remission (2.3%), with partial remission in9cases (20%),9cases of remission at a median time of6months, stable period of over6months in13cases (30.2%),13patients with stable a median time of10.5months, stable period of less than6months in12cases (27.9%), the progress of the disease in8patients (18.6%).2patients in the trastuzumab combined with bevacizumab group were complete remission (4.7%), partial remission in19cases (42.2%),19cases of remission at a median time of6.9months, stable period of over6months in15cases (33.3%),15patients with a median time of13.8months, stable period of less than6months in7cases (15.6%), the progress of the disease in2patients (4.4%).Trastuzumab in the the trastuzumab group cycle for a median is of 10weeks (range from7to14weeks), with trastuzumab in the trastuzumab combined with bevacizumab group’s median of11weeks (range from8to14weeks). Compared with the trastuzumab group, trastuzumab treatment time, PR group and SD≥6mo in the trastuzumab combined with bevacizumab group were no significant difference (P>0.05). Partial remission cases in the trastuzumab combined with bevacizumab group were increased significantly (9/43vs.19/45,χ2=4.60, P<0.05) compared with the trastuzumab group, and the progress of the disease were also significantly reduced (8/43vs.2/45, χ2=4.38, P<0.05) in the trastuzumab combined with bevacizumab group.The overall effective rate (ORR) and the clinical benefit rate (CBR) in the trastuzumab group were23.3%(10/43) and53.5%(23/43), respectively The ORR and the CBR in the trastuzumab combined with bevacizumab group were46.7%(21/45) and80.0%(36/45), respectively. Compared with the trastuzumab group, the trastuzumab combined with bevacizumab group’s ORR(10/43vs.21/45,χ2=9.58, P<0.05) and CBR (23/43vs.36/45,χ2=6.99, P<0.05) were increased significantly.Kaplan-Meier survival curve displays the trastuzumab group and the trastuzumab combined with bevacizumab’s median progression-free survival was7.3months (95%confidence ranges from6months to14months) and17.5months (95%confidence ranges from16months to23months), respectively.After the therapy, adverse side effects in the two groups of Her-2positive metastatic breast cancer patients occurred mostly in the first delivery, instead of repeated dosing. Adverse side effects in only3cases had recurred. There was none had the fifth degree adverse side effects, mainly for the2nd-4th. The total incidence of adverse side effects in the trastuzumab group was79.1%(34/43), nausea/vomiting occurred of19 cases (38.8%), with18cases of grade2and3,1case as grade4, Anemia of2cases (4.7%), with2cases were respectively2nd and3rd,2in neutropenia,1in neuropathy, arrhythmia, lower serum albumin, higher alanine aminotransferase/aspartate aminotransferase (ALT/AST), abdominal pain/diarrhea, fatigue, muscle pain, palpitations and shortness of breath, electrocardiogram ST-T change, allergy and fever, respectively were observed. The total incidence of adverse side effects of the trastuzumab combined with trastuzumab group was80%(36/45). Nausea/vomiting occurred of21cases (46.7%), with20cases of grade2-3,1cases as grade4,3cases of anemia(6.6%), with2cases of grade2,1case of grade3, neutrophil cell reduction occurred in2patients (4.4%), neuropathy occurred in2patients (4.4%),1case of arrhythmia, lower serum albumin, higher ALT/AST, abdominal pain/diarrhea, fatigue, muscle pain, palpitations and shortness of breath and electrocardiogram ST-T change, respectively were collected. The adverse side effects in the trastuzumab combined with bevacizumab group was slightly higher than the trastuzumab group, but there were no significant difference (P>0.05) in adverse side effects between the two groups. And most of toxicity can be well tolerated.Conclusion:The trastuzumab plus bevacizumab in combination with paclitaxel group in the treatment of Her-2positive breast carcinoma metastatic showed a better effect than the trastuzumab in combination with paclitaxel group. The adverse side effects can be mostly tolerated. However, the long-term efficacy of the combination treatment group remains to study with enlarging the sample size and prolonging the observation time in the further study. |
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