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Aim For early-stage breast cancer, four cycles of docetaxel and cyclophosphamide (TC) was proven superior to doxorubicin plus cyclophosphamide in the US Oncology 9375 trial. Given primary prophylactic antibiotics, 5% febrile neutropenia was recorded in a population comprising 75.5% Caucasians. Smaller trials and retrospective studies reviewing TC use in Asian patients did not produce similar incidence rates. This study aims to discover the variable hematological toxicities with TC use in Caucasian and Asian patients. Methods Breast cancer data was retrospectively reviewed for patients receiving adjuvant docetaxel 60-75 mg/m2 plus cyclophosphamide 600 mg/m2 from six countries (China, Hong Kong, Japan, Taiwan, Italy, and United States). Similar number of patients with relatively balanced baseline characteristics were chosen for analysis of hematological and nonhematological toxicities and survival data. Results From March 2004 to July 2013, data of 227 patients (127 Asians and 100 Caucasian) patients were analyzed for treatment-related toxicities. During the four cycles of TC, Asians had a significantly higher rate of grade ≥2 neutropenia than Caucasians (45.7% vs 6.0%; P <0.001) and significantly more grade ≥3 neutropenia events were documented (respectively 30.7% vs 4.0%, P <0.001). The prophylactic use of G-CSF was similar; 26.0% in Asians and 28.0% in Caucasian ( P = 0.764). There were no differences in nonhematological toxicities. No significant difference in disease-free survival was observed between Asians and Caucasians (log-rank P = 0.910). Conclusions Ethnic differences in toxicity profile exist between Asian and Caucasian patients given adjuvant TC. Over 30% Asians but less than 5% Caucasians experienced grade ≥3 neutropenia. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include acute chemotherapy-related toxicity in BRCA1 and BRCA2 mutation carriers treated for breast cancer in Great Britain, neoadjuvant endocrine therapy for locally advanced breast cancer, and human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer.

C-erbB-2/HER-2 (designated HER-2) is overexpressed in both primary and metastatic breast cancer and predicts poor prognosis. We investigated the expression of HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) with autologous blood stem cell (ABSC) support and correlated the presence (positive) or absence (negative) of HER-2 overexpression in these patients with response to treatment, progression-free survival (PFS) and overall survival (OS). The level of HER-2 expression was analyzed in 57 patients with metastatic breast cancer undergoing HDCT with ABSC support. Plasma from peripheral blood was taken at three different time points during the course of treatment and was analyzed using an enzyme immunoassay (EIA) to detect circulating levels of the extracellular portion of HER-2. HER-2 levels were elevated (>0.2 U/mg protein) in 27/57 (47.4%) patients at one or more time points during treatment. The level of HER-2 varied during the course of treatment. Following induction chemotherapy (ICT), five patients who were negative initially, showed overexpression of HER-2. Three patients overexpressed HER-2 only after HDCT/ABSC. Response to treatment was similar in patients independent of plasma HER-2 levels. Overexpression of HER-2 was associated with a significantly shorter PFS (P = 0.004, log rank) and OS (P = 0.003, log rank) after HDCT/ABSC. HER-2 overexpression, patient age, estrogen receptor status, progesterone receptor status, and previous hormone treatment were assessed by univariate and multivariate analysis. Univariate analysis determined that only HER-2 overexpression correlated significantly with decreases in progression free survival (P = 0.005, Cox regression). Decreased overall survival correlated significantly with HER-2 overexpression (P = 0.004) and decreased expression of both estrogen receptor (P = 0.032) and progesterone receptor (P = 0.039). In multivariate analysis of these variables, only HER-2 expression... [ABSTRACT FROM AUTHOR]

Background.--Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. Methods.--In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block random!sat!on to receive FEC (fluorouracil 600 mg/m², epirubicin 60 mg/m², cyclophosphamide 600 mg/m² at 3-weekly intervals) for four cycles followed by docetaxel (100mg/m² at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m² at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m², methotrexate 40mg/m², and fluorouracil 600 mg/m² at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. Findings.--All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0-85-1.08; p=0-44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74-3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0-0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and lethargy (456 vs 272). Interpretation.--This study did not show any overall gain from the addition of docetaxel to standard anthracycline chemotherapy. Exploration of predictive biomarker-defined subgroups might have the potential to better target the use of taxane-based therapy (Fig 3). [ABSTRACT FROM AUTHOR]

The article discusses research being done on the use of neoadjuvant docetaxel, vinorelbine and trastuzumab in treating primary breast cancer. It references a study by S. A. Limentani and colleagues, published in the 2007 issue of the "Journal of Clinical Oncology." The study included women with human epidermal growth factor receptor 2-overexpressing locally advanced breast cancer. It noted that more chemotherapy that do not increase toxicity is needed. A comment on the study is also offered.

Abstract: The introduction of third generation aromatase inhibitors [anastrozole, letrozole, and exemestane] has certainly improved outcomes in patients with early breast cancer. Although survival benefit has not been identified (except in the subpopulation of patients with lymph node positive breast cancer on the MA17 study), the primary endpoints in all studies reached statistical significance in favor of Al. The strategy can include: replacing TAM outright after diagnosis; switching from TAM to one of the aromatase inhibitors after 2–3 years; or to add an AI after 5 years of TAM. DFS, recurrence, and the incidence of contra lateral breast cancer is influenced favorably with such an approach. The following issues remained unanswered: Will the OS be improved as well? Is the incidence of serious long-term side effects acceptable to our patients [osteoporosis, fractures, cognitive function and lipid profile changes]? What is the influence of chemotherapy on the effect of aromatase inhibitors? We still do not know the true role of AI in HER2 positive disease. Which effect do AI have in pre-menopausal women (with the use of LHRH agonists)? How long should patients after TAM be receiving AI? Several of these questions will be certainly answered with the new generation of studies, but many of these questions have just been generated with these new results. [Copyright &y& Elsevier]