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A third of breast cancer diagnoses are made in women aged 70 years or over. Historically, older women have been regarded as presenting with tumors that are low grade and hormone sensitive and that are likely to have a good prognosis. However, in those older women whose tumors overexpress the HER2 oncogene, the prognosis is likely to be worse. Under these circumstances, due consideration should be given to adjuvant systemic therapy, including chemotherapy and targeted treatments, in order to minimize risks of disease recurrence. In this article we discuss the evidence base for the role of adjuvant systemic therapy in older women with HER2-positive early breast cancer.

Despite advances with adjuvant endocrine treatment for hormone receptor-positive tumors and with trastuzumab for HER2-positive disease, overall, over 50% of women with early-stage breast cancer experience recurrence and die of the disease. Biomarkers for tailoring systemic adjuvant treatment to responder patients are needed. The multigene assays, 21-gene recurrence score (Oncotype DX [Genomic Health, CA, USA]) and 70-gene signature (MammaPrint [Agendia, CA, USA]), and the isolated tumor cells in sentinel lymph node(s) represent the latest advances for improving adjuvant chemotherapy decisions. This article evaluates how these new markers, added to current standard factors (age, tumor size, grade, hormone receptor status and HER2 status), could improve early breast cancer treatment decisions. Moreover, emerging evidence from the latest large-scale studies using next-generation DNA-sequencing technology reveals a high heterogeneity and complexity of breast cancer. This assessment now shapes a new research strategy towards completion of a breast cancer causal (driver) mutations catalog and understanding complex genetic interactions and signaling pathway networks. Despite multiple challenges, advances in cancer genomes and systems biology approaches promise the future development of robust biomarkers.

There have been significant advances in the use of chemotherapy in the treatment of colorectal cancer patients over the last 20 years. Initial improvements in treatment were made with increased understanding of the pharmacology of 5-fluorouracil and the discovery of modulators of its activity (e.g., leucovorin). However, in the last few years the discovery of new cytotoxic drugs with efficacy in large bowel cancer (e.g., oxaliplatin and irinotecan) and monoclonal antibodies (e.g., bevacizumab and cetuximab) have significantly improved patient outcome and prognosis. Systemic chemotherapy in the metastatic setting has been shown to prolong survival and improve quality of life. Chemotherapy now also has a clear role as an adjunct to surgery to improve survival in stage III and certain 'high-risk' stage II colorectal cancer patients. The evolution of chemotherapy use, current practice in the metastatic and adjuvant setting and possible future directions are discussed.

Radical surgical resection currently represents the most effective therapy for patients with retroperitoneal sarcoma. Unfortunately, margin-negative resection often mandates extirpation of multiple retroperitoneal viscera, and such operations are nonetheless fraught with high rates of locoregional recurrence. In an attempt to improve local control and ultimately survival, adjuvant strategies of radiation and chemotherapy have been increasingly employed, with promising results. To date, however, the rarity of the disease has limited large, prospective studies investigating the efficacy of these adjuvant modalities. In this article, we review the current literature pertaining to the diagnosis, staging and treatment of retroperitoneal sarcoma and demonstrate the critical need for future large, multi-institutional studies to advance our knowledge of this uncommon disease.

Bladder cancer is the fifth most common cancer in adult patients. Two-thirds of patients have superficial tumors and their treatment is conservative. Nevertheless, 30% of superficial tumors become infiltrative and represent a third of tumors at initial diagnosis. Overall mortality from bladder cancer is 30%. Important molecular events may explain the carcinogenesis and evolution of these tumors. Infiltrating bladder cancers are currently treated by radical cystectomy. Neoadjuvant chemotherapy has demonstrated a positive impact on patients' outcomes before cystectomy. Adjuvant chemotherapy after cystectomy is currently being studied in an international randomized trial. Patients with advanced disease are treated by chemotherapy with palliative intentions. Two regimens are standard: the combination of methotrexate, vinblastine, adriamycin and cisplatin, and the combination of gemcitabine and cisplatin. The addition of paclitaxel to the latter regimen is the subject of ongoing study. Only a few patients have long-term nonevolutive disease. Research must be focused on the combination of chemotherapy and targeted drugs directed through gene methylation, cytokine-receptor activation and signaling pathways.

High-dose interferon is the only treatment approved by the FDA for adjuvant therapy of melanoma. However, its efficacy in this setting is questionable and its administration is associated with considerable toxicity. Many new agents are being tested clinically that hold the promise of greater efficacy and less toxicity but none of these have yet shown efficacy in controlled trials. These include biologics such as vaccines, cytokines, monoclonal antibodies, gene transfer, cellular therapies and angiogenesis inhibitors as well as chemotherapy combinations.