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.
EDITORIAL
Breast cancer: Challenges, controversies, breakthroughs
Lisa Hutchinson
doi:10.1038/nrclinonc.2010.192
Nature Reviews Clinical Oncology 7, 669-670 (2010)
RESEARCH HIGHLIGHTS
Breast cancer: High-dose fulvestrant is a safe and effective therapy for breast cancer
Rebecca Kirk
doi:10.1038/nrclinonc.2010.181
Nature Reviews Clinical Oncology 7, 673 (2010)
Breast cancer: SLN surgery alone is best for node-negative breast cancer
Lisa Hutchinson
doi:10.1038/nrclinonc.2010.179
Nature Reviews Clinical Oncology 7, 674 (2010)
NEWS & VIEWS
Ultra-targeted APBI using TARGIT—a cautionary note
Rajiv Sarin
doi:10.1038/nrclinonc.2010.187
Nature Reviews Clinical Oncology 7, 675-676 (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, TA RGIT APBI should remain an experimental approach.
Optimizing dose-dense regimens for early-stage breast cancer
Patrick G. Morris & Clifford A. Hudis
doi:10.1038/nrclinonc.2010.188
Nature Reviews Clinical Oncology 7, 678-679 (2010)
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.
REVIEWS
Triple-negative breast cancer: disease entity or title of convenience?
Lisa Carey, Eric Winer, Giuseppe Viale, David Cameron & Luca Gianni
doi:10.1038/nrclinonc.2010.154
Nature Reviews Clinical Oncology 7, 683-692 (2010)
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.
Molecular mechanisms of metastasis in breast cancer—clinical applications
Michal Mego, Sendurai A. Mani & Massimo Cristofanilli
doi:10.1038/nrclinonc.2010.171
Nature Reviews Clinical Oncology 7, 693-701 (2010)
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.
BRCA mutations in the management of breast cancer: the state of the art
Steven A. Narod
doi:10.1038/nrclinonc.2010.166
Nature Reviews Clinical Oncology 7, 702-707 (2010)
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 a BRCA1 or BRCA2 mutation may be different from that of non-carriers. Thus, identifying the BRCA mutation status in patients could assist appropriate decision making for individualized cancer prevention, screening and treatment.
The role of BRCA mutation testing in determining breast cancer therapy
Alison H. Trainer, Craig R. Lewis, Kathy Tucker, Bettina Meiser, Michael Friedlander & Robyn L. Ward
doi:10.1038/nrclinonc.2010.175
Nature Reviews Clinical Oncology 7, 708-717 (2010)
BRCA mutation 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 as BRCA status can influence treatment decisions. The authors of this Review discuss the assessment of familial cancer risk and the criteria for targeting BRCA mutation testing in women with breast cancer. They also examine how this genetic knowledge impacts on optimal patient management.
Synthetic lethal approaches to breast cancer therapy
Farah L. Rehman, Christopher J. Lord & Alan Ashworth
doi:10.1038/nrclinonc.2010.172
Nature Reviews Clinical Oncology 7, 718-724 (2010)
Synthetic lethality has emerged as a novel approach to treat cancer. Inhibitors of poly (ADP-ribose) polymerase, a target that has synthetic lethality with BRCA mutations, 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.
Breast cancer assessment tools and optimizing adjuvant therapy
Catherine Oakman, Libero Santarpia & Angelo Di Leo
doi:10.1038/nrclinonc.2010.170
Nature Reviews Clinical Oncology 7, 725-732 (2010)
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.
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