Feasibility and toxicity of EC-T dose-dense adjuvant chemotherapy: A real world study in Chinese early-stage breast cancer patients with high recurrence risk / 中华肿瘤杂志

Objective@#We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk.@*Methods@#370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed.@*Results@#370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282).@*Conclusions@#EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m2 is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

Genetic polymorphisms of autophagy-related gene 5 (ATG5) rs473543 predict different disease-free survivals of triple-negative breast cancer patients receiving anthracycline- and/or taxane-based adjuvant chemotherapy / 癌症

BACKGROUND@#Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC). Hence, autophagy-related gene 5 (ATG5), an essential molecule involved in autophagy regulation, is presumably associated with recurrence of TNBC. This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival (DFS) of early-stage TNBC patients treated with anthracycline- and/or taxane-based chemotherapy.@*METHODS@#We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline- and/or taxane-based chemotherapy using the sequenom's MassARRAY system. Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.@*RESULTS@#Three genotypes, AA, GA, and GG, were detected in the rs473543 of ATG5 gene. The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence (P = 0.024). Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543 (P = 0.034). In addition, after adjusting for clinical factors, multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS (hazard risk [HR], 1.73; 95% confidence interval [CI], 1.04-2.87; P = 0.034). In addition, DFS was shorter in node-negative patients with the presence of A allele (AA/GA) than in those with the absence of A allele (P = 0.027).@*CONCLUSION@#ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.

Efficacy and toxicity of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.</p><p><b>METHODS</b>Clinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX).</p><p><b>RESULTS</b>After 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively.</p><p><b>CONCLUSIONS</b>NVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III clinical trial in larger cohort.</p>

Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment.</p><p><b>METHODS</b>Twenty-nine metastatic TNBC patients were prospectively enrolled to receive capecitabine (1, 000 mg/m(2) twice daily on days 1-14) and cisplatin (75 mg/m(2) on day 1) , repeated every 3 weeks.</p><p><b>RESULTS</b>With a median of 6 cycles of XP, all 29 patients were evaluable for response, including 18 PR (62.1%), 6 SD (20.7%), 5 PD (17.2%) and no CR. The response rate was 62.1%. Patients with earlier stage at diagnosis (stage I to IIIA), longer post-operative disease free survival (>2 years) and less metastatic sites (≤ 3) obtained significantly higher response rate than patients with later stage at diagnosis (stage IIIB to IV), shorter post-operative disease free survival (≤ 2 years) and more metastatic sites (>3). The leading side effects were grade 1/2 gastrointestinal and hematological toxicities. Grade 3/4 toxicities included neutropenia (34.5%), leukocytopenia (31.0%), anemia (6.9%), thrombocytopenia (3.4%), nausea/vomiting (20.7%), stomatitis (3.4%), and hand-foot syndrome (3.4%).</p><p><b>CONCLUSION</b>Cisplatin and capecitabine combination therapy is an active and well-tolerated doublet treatment in metastatic TNBC patients progressing after anthracycline and taxane treatments.</p>

Clinicopathological features and prognosis of metastases to the breast from extramammary solid tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To discuss the clinicopathological features and prognosis of metastases to the breast from extramammary solid tumors.</p><p><b>METHODS</b>The databases of Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2012 were reviewed. 24 patients were identified with a diagnosis of metastasis to the breast from extramammary solid tumors and their clinical data were collected and analyzed. All the primary solid tumors and breast lesions were confirmed by pathology or cytology.</p><p><b>RESULTS</b>Of the 24 patients, 22 were women and two were men. The median age was 54 years. The primary malignancies included non-small cell lung cancer (n = 10), small cell lung cancer (n = 4), rhabdomyosarcoma (n = 3), olfactory neuroblastoma (n = 3), ovarian cancer (n = 2), malignant melanoma (n = 1) and gastric cancer (n = 1). 15 patients (62.5%) complainted self-palpable breast nodules, two patients manifested as diffuse swollen and red of the whole breast, 7 patients (29.2%) were identified as well-defined nodules in the breast on CT images. The majority of metastases to breast presented as a solitary nodule with rapid growth, sometimes associated with axillary lymph node enlargement and occasionally with micro-calcification. Cytopathological examination could be used to differentiate the metastatic lesions from primary breast tumors. 83.3% (20/24) of the patients were concurrently accompanied with metastases in other organs and/or lymph nodes. The metastases to the breast from extramammy solid tumors were associated with a poor prognosis and the median overall survival was only 9.2 months.</p><p><b>CONCLUSIONS</b>Metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. An accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment.</p>

Comparison of the effectiveness of platinum-based chemotherapy versus non-platinum-based chemotherapy for triple-negative breast cancer with metastases confined to the lungs / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the effect of first-line treatment with platinum-based chemotherapy and non-platinum-based chemotherapy in patients with lung metastases from triple negative breast cancer (TNBC).</p><p><b>METHODS</b>Sixty-five eligible patients were divided into platinum-treated group and non-platinum-treated group according to the first-line therapy. Factors predicting the chemotherapeutic efficacy included overall survival (OS), progression-free survival (PFS) and objective response (OR).</p><p><b>RESULTS</b>In the platinum-treated group of 32 patients, 2 cases (6.3%) achieved CR, 16 cases (50.0%) achieved PR, 11 (34.4%) cases achieved SD, and 3 patients (9.4%) achieved PD. In the non-platinum-treated group of 33 patients, 2 cases (6.1%) achieved CR, 6 cases (18.2%) achieved PR, 16 cases (48.5%) achieved SD, and 9 cases (27.3%) achieved PD. Median PFS was significantly longer in the platinum-treated group than in the non-platinum-treated group (10 months vs. 6.0 months, P = 0.012), and OS was also improved (32 months vs. 22 months, P = 0.006). Multivariate analysis of several factors including local-regional lymph node involvement, lung metastasis-related symptoms, first-line platinum-based chemotherapy, disease-free interval, size and number of lung lesions, showed that first-line platinum-based chemotherapy was an independent prognostic factor for TNBC patients with lung metastases.</p><p><b>CONCLUSIONS</b>Compared with non-platinum-based chemotherapy, the first-line platinum-based chemotherapy can improve PFS and OS in TNBC patients with metastases confined to the lungs.</p>

Efficacy and safety of trastuzumab plus different chemotherapy regimens in treatment of the patients with HER-2-positive advanced breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab plus different chemotherapy regimens in treatment of patients with HER-2-positive advanced breast cancer.</p><p><b>METHODS</b>132 patients with advanced HER-2-positive breast cancer were treated with trastuzumab plus different regimens. The clinical characteristics, efficacy and toxicity of the 132 patients were retrospectively analyzed.</p><p><b>RESULTS</b>Five patients had complete response (CR), 61 patients had partial response (PR), 39 patients had stable disease (SD), and 27 patients had progressive disease (PD). The objective response rate was 50.0% and the disease control rate was 79.5%. The median progression-free survival was 9.3 months. The median overall survival time was 46.2 months. The 1-, 2-, 5- year survival rates were 98.3%, 81.9% and 40.2%, respectively. Trastuzumab combined with chemotherapy is superior to trastuzumab monotherapy (51.2% vs. 33.3%). The number of metastatic sites, efficacy, different previous treatment lines were independent prognostic factors of PFS (P = 0.002, P < 0.0001 and P < 0.0001, respectively). Visceral metastases, pathological grade, and PFS were independent prognostic factors of OS (P = 0.041, P = 0.001, P = 0.025, P < 0.001, P < 0.0001 and P < 0.0001, respectively). Regarding the toxicities, one case discontinued treatment due to the decrease of left ventricular ejection fraction to 47%, two cases had heartbeat tachycardia, 6 cases had palpitation, 17 cases had a fever during first input trastuzumab. No other serious cardiac toxicity was observed. The most common toxicities were chemotherapy-related hematological and non-hematological toxicities.</p><p><b>CONCLUSIONS</b>Trastuzumab combined with chemotherapy is superior to trastuzumab monotherapy. Patients may get benefits for early use of trastuzumab. Trastuzumab plus chemotherapy is effective and well tolerated in patients with advanced HER-2 positive breast cancer. No heart failure occurred in this series of patients, and cardiac safety seems better than that in Caucasians because of younger age at the onset in Chinese advanced breast cancer patients.</p>

Safety and tolerance of non-anthracyclin regimen adjuvant chemotherapy in elderly breast cancer patients / 中国癌症杂志

Background and purpose: The incidence of breast cancer increases as patients age, elderly patients account for a large proportion. Due to the insufifcient systemic therapy, more complications and poorly physical condition, the prognosis of elderly patients is often worse than the younger. The aim of this study was to investigate the safety and tolerance with non-anthracyclin regimen as adjuvant chemotherapy in elderly breast cancer patients. Methods:From Nov. 2008 to Jan. 2012, 56 patients (≥65 years) after surgical excision were enrolled into this study. The patients were divided into two groups:TC and PC groups. Each patient received 4 or 6 cycles of chemotherapy of PC (175 and 600 mg/m2, respectively;n=21) or TC (75 and 600 mg/m2, respectively;n=35), administered intravenously every 3 weeks, as adjuvant chemotherapy. Radiation therapy (as indicated) and endocrine therapy, for patients with hormone receptor-positive disease, were administered after completion of chemotherapy. Results: In this study, 50 patients completed chemotherapy as plan, the proportion of two groups were above 90%. After a median follow-up of 33 months, the median disease-free survival(DFS) and overall survival(OS) were not reached. The relapse-free rate and survival rate were 89.5%and 100%in the PC regime group, which were 90.3%and 96.8%in the TC regime group. Major toxicities included:neutropenia, leucopenia, alopecia, nausea, vomiting and various degree of peripheral neuropathy. The incidence of gradeⅢ-Ⅳneutropenia was 76.2%in PC group vs 48.6%in TC group (P=0.044). The most common cause for withdrawing from treatment was to be unable to tolerate the adverse effects. Conclusion:Adjuvant chemotherapy with paclitaxel and cyclophosphamide is safe, tolerable and promising for elderly breast cancer patients.