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1.  Trends and Novel Approaches in Neoadjuvant Treatment of Breast Cancer 
Breast Care  2011;6(6):427-433.
Breast cancer is the most prevalent malignant disease in women worldwide. Traditionally, surgical tumour resection was the primary step within the treatment algorithm of early stage disease; systemic therapy in order to reduce the rate of systemic recurrences followed. National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-18 found that pre- and postoperative administration of chemotherapy was equally effective. This study therefore established neoadjuvant chemotherapy as a valid treatment option, as the breast conservation rate is increased. Modern neoadjuvant regimens encompassing anthracyclines and taxanes yield pathological complete response (pCR) rates of around 20%, with higher efficacy observed in triple-negative tumours. The antibody trastuzumab is the first targeted agent established in neoadjuvant regimens for the treatment of Her2-positive breast cancer, as it raised pCR rates up to 50%. Novel approaches are aiming to increase the efficacy of neoadjuvant therapy. Inclusion of capecitabine might further increase pCR rates in selected patients, although data are not unanimous throughout the respective clinical trials. In patients harbouring BRCA-1 germline mutations, platinum derivatives are apparently promising. Novel Her2-targeted agents such as lapatinib and pertuzumab are currently under investigation in several clinical trials, while the role of bevacizumab, a monoclonal antibody inhibiting angiogenesis, awaits future clarification.
doi:10.1159/000335331
PMCID: PMC3290012  PMID: 22419895
Breast cancer; Chemotherapy; Neoadjuvant therapy; Targeted therapy
2.  Opinions on the ASCO 2011 Annual Meeting 
Breast Care  2011;6(4):315-319.
doi:10.1159/000331171
PMCID: PMC3225217  PMID: 22164128
3.  Breast Cancer: Rank Ligand Inhibition 
Breast Care  2010;5(5):320-325.
Summary
Breast cancer and bone health are closely linked. Early menopause induced by gonadotropin-releasing hormone analogues or chemotherapy as well as aromatase inhibitors reduce oestrogen levels, thereby causing cancer treatment-induced bone loss (CTIBL). Furthermore, bone metastases are commonly found in advanced disease. Current treatment options for bone lesions comprise systemic anti-tumour therapy, irradiation, surgery and bisphosphonates. The main mechanism of osteolysis, osteoclast activation, is induced by the RANK ligand and suppressed by osteoprotegerin (OPG). A human antibody targeting the RANK ligand, denosumab, had superior activity compared to OPG and was therefore further developed in the clinical setting. This article reviews clinical data on denosumab. Data were obtained by searching the Medline database and abstracts from the ASCO annual meeting, ASCO breast meeting, ECCO, ESMO, and the San Antonio Breast Cancer Symposium. Clinical trials have demonstrated that denosumab reduces markers of bone turnover, and suggest equal efficacy to bisphosphonates in reducing the rate of skeletal-related events. While overall fewer side effects were observed, a numerically increased rate of osteonecrosis of the jaw was reported. Denosumab was well tolerated, and clinical activity was similar to bisphosphonates in metastatic disease. Trials of denosumab in the prevention of CTIBL are ongoing.
doi:10.1159/000321122
PMCID: PMC3132956  PMID: 21779214
Bisphosphonates; Bone metastases; Denosumab; Osteoporosis; Cancer treatment-induced bone loss
4.  Capecitabine and Vinorelbine as an All-Oral Chemotherapy in HER2-Negative Locally Advanced and Metastatic Breast Cancer 
Breast Care  2010;5(3):158-162.
Summary
Background
The oral formulation of vinorelbine together with capecitabine allows for an all-oral combination chemotherapy which promises to raise quality of life of patients with advanced breast cancer.
Patients and Methods
Patients with HER2-negative, locally advanced, inoperable or metastatic breast cancer were included in this prospective observational trial (treatment schedule: capecitabine 500 mg/m2 twice daily, days 1-14; vinorelbine 60 mg/m2, days 1+8; repeated in 3-week cycles).
Results
All 32 patients (median age 50 years) were evaluable for toxicity, and 30 patients for response. Twentyfour patients received therapy as first-line treatment, and 8 patients as beyond first-line treatment. Median time to progression was 8 months, and median overall survival was 32 months. Complete response was observed in 1 patient (3%), partial response in 10 patients (33%), and disease stabilization for more than 6 months (SD > 6) in 10 patients (33%). This results in an overall response rate (ORR) of 37% and a clinical benefit rate (ORR + SD > 6) of 70%. The only grade 3/4 toxicities were neutropenia (19%) and hand-foot syndrome (9%).
Conclusions
The all-oral combination of capecitabine/vinorelbine at this schedule appears to be an effective, well-tolerated regimen for treatment of advanced breast cancer, and offers a promising alternative to single-agent capecitabine and vinorelbine as well as intravenous polychemotherapy.
doi:10.1159/000314214
PMCID: PMC2931054  PMID: 21048830
Capecitabine; Vinorelbine; Combination therapy; Breast cancer, advanced
5.  The Role of Supportive Therapy in the Era of Modern Adjuvant Treatment – Current and Future Tools 
Breast Care  2009;4(3):167-176.
Summary
Recent advances in adjuvant treatment of breast cancer have improved progression-free and overall survival. Optimal management of treatment-induced side effects has therefore gained further importance. This review cannot provide a comprehensive overview of treatment-related toxicity and its management, but focuses on important new developments in the field of supportive therapy. Erythropoietins, while highly effective in treating chemotherapy-induced anaemia, may have detrimental effects on outcome, and should only be used with the aim to reduce the number of whole blood transfusions. Granulocyte colony-stimulating factors were a prerequisite for development of dose-dense regimens, and are also necessary in many anthracycline/taxane combination regimens. A potential tumour-stimulating effect was not proven in solid cancers. For side effects of conventional chemotherapy, such as mucositis, nausea, or diarrhoea, regularly updated guidelines may improve symptom control. Overall, modern supportive treatment tools will further reduce treatment-related mortality and help increase quality of life.
doi:10.1159/000223360
PMCID: PMC2931004  PMID: 20847876
Adjuvant treatment; Breast cancer; Growth factors; Side effects; Supportive care

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