Volume 7 Issue 12, December 2010

One of the seven ongoing trials of accelerated partial breast irradiation (APBI) has concluded that single-dose intraoperative radiotherapy should be considered as an alternative to protracted whole-breast irradiation. With a median follow up of 2 years, such conclusions seem premature. Until the risk and pattern of breast recurrence is reported at longer follow up, TARGIT APBI should remain an experimental approach.

Rituximab has become the mainstay of systemic therapy for patients with follicular lymphoma and is associated with an improved outcome at both diagnosis and relapse, either as induction or maintenance therapy. The challenge lies in maximizing the benefit of this drug in a condition characterized by multiple relapses.

Survival of patients with high-risk early-stage breast cancer has been improved by chemotherapy administration at shorter dose intervals: 'dose-dense' therapy. Validation for this approach is provided by the AGO trial, which demonstrated the biggest survival advantage of any study of dose-dense chemotherapy to date.

Microscopic deposits of tumor cells in regional lymph nodes can be detected using immunohistochemical techniques in patients without conventional histopathological evidence of lymph-node involvement. In the case of bile duct cancer, these micrometastases have an intermediate prognostic significance between that of positive and negative conventional pathology.

Triple-negative breast cancer tumors relapse more frequently in spite of good initial response to chemotherapy, and have a worse prognosis than hormone receptor-positive, luminal subtypes. New systemic therapies are urgently needed because hormonal therapies and HER2-targeted agents are ineffective in this group of tumors. Poly (ADP-ribose) polymerase inhibitors, angiogenesis inhibitors, EGFR-targeted agents, and src kinase and mTOR inhibitors are among the therapeutic agents being actively investigated in clinical trials in these patients.

Circulating tumor cells (CTCs) have a crucial role in the metastatic cascade, tumor dissemination and progression. Furthermore, CTCs are involved in treatment failure, therapy resistance and disease progression. New therapeutic possibilities are offered by the established clinical prognostic and predictive value of CTCs with the additional possibility of using them for the real-time monitoring of systemic-therapy efficacy. This Review discusses the future clinical applications of CTCs in breast cancer including the incorporation of CTCs as end points in clinical trials and the blockade of tumor dissemination and self seeding via the therapeutic targeting of CTCs.

Genetic testing for breast cancer susceptibility is widely available in North America and in Europe. The optimum treatment of women with breast (or ovarian) cancer and aBRCA1 or BRCA2 mutation may be different from that of non-carriers. Thus, identifying the BRCAmutation status in patients could assist appropriate decision making for individualized cancer prevention, screening and treatment.

BRCAmutation carriers have an increased risk of developing breast cancer. Modern technology has made it possible to move genetic screening into the mainstream setting, which is important asBRCA status can influence treatment decisions. The authors of this Review discuss the assessment of familial cancer risk and the criteria for targeting BRCAmutation testing in women with breast cancer. They also examine how this genetic knowledge impacts on optimal patient management.

Synthetic lethality has emerged as a novel approach to treat cancer. Inhibitors of poly (ADP-ribose) polymerase, a target that has synthetic lethality withBRCAmutations, have already shown promise in clinical trials. The authors of this Review describe the clinical application of synthetic lethality for patients with breast cancer, and discuss biomarkers that can be used to select patients who will respond to this therapy. Other potential genes that could be involved in synthetic lethality, and are thus new targets, are also explored.

Adjuvant assessment tools for prognosis and prediction of treatment benefit in breast cancer aid clinical decision making; however, all these tools have limitations. For an individual diagnosed with early-stage breast cancer, recommendation of systemic therapy and selecting the most appropriate agent remains a challenge. The authors highlight the issues in choosing the most appropriate adjuvant therapy and provide some suggestions for how current assessment tools can be used to tailor treatment.

This Focus issue on breast cancer contains specially commissioned Reviews that translate the latest pathogenesis and management insights into clinical practice. The challenges in defining and treating triple-negative tumors are highlighted. Synthetic lethality provides a novel approach to identify new targets, and advances in the treatment of BRCA mutation carriers using PARP inhibitors are described. Genetic testing for patients with BRCA mutations and the implications for incorporating such testing into mainstream cancer settings is discussed, together with the role of circulating tumor cells in metastasis development and how genetic profiling of these cells can help improve patient management.