Chapter One - Biomarkers in Breast Cancer: Where Are We and Where Are We Going?

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Abstract

Biomarkers play an important role in the detection and management of patients with breast cancer. Thus, BRCA1/2 mutation testing is used for risk assessment in families with a high prevalence of breast and ovarian cancer. Following a diagnosis of breast cancer, measurement of multi-analyte profiles such as uPA/PAI-1 or Oncotype DX may be used for determining prognosis and identifying lymph node-negative patients who may be spared from having to receive adjuvant chemotherapy. Other -gene tests such as the PAM50 ROR, Breast Cancer Index, and EndoPredict have been reported to predict the development of late recurrences and thus may be of value in selecting patients for extended hormone therapy. Mandatory assays include estrogen receptors for identification of endocrine-sensitive cancers and HER2 in selecting patients for treatment with anti-HER2 therapy (e.g., trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine). Finally, serum biomarkers such as CA 15-3 or CEA may be used in monitoring therapy in patients with advanced disease receiving systemic therapy. Promising new biomarkers undergoing evaluation include circulating tumor cells and circulating tumor-derived DNA.

Section snippets

Use of Biomarkers in the Identification of Women at Increased Risk of Developing Breast Cancer (Risk Assessment)

Biomarkers are playing an increasingly important role in the detection and management of patients with several different cancer types, including breast cancer [1], [2]. For breast cancer, biomarkers are particularly useful in the identification of individuals at increased risk of developing the malignancy within high-risk families, determining prognosis at the time of initial diagnosis, identifying the most appropriate systemic therapy, postoperative surveillance, and monitoring therapy in

Use of Biomarkers in Determining Prognosis

Following a diagnosis of primary invasive breast cancer, the most urgent questions to be addressed are: what is the prognosis and should adjuvant systemic therapy (e.g., chemotherapy) be administered? Thus, the accurate determination of prognosis at the time of diagnosis of breast cancer is clearly essential for optimum patient management, especially to avoid overtreatment of nonaggressive disease and undertreatment of aggressive forms. Traditionally, pathological and clinical criteria such as

Use of Biomarkers in Guiding Treatment

A wide variety of systemic treatments are available for patients with breast cancer, including chemotherapy drugs, hormone treatments, and anti-HER2 agents (Table 3). With such a broad range of treatment options, it is important that every patient receives the most appropriate regime. Fortunately, predictive biomarkers are available for two of the three main forms of treatment, i.e., ER and progesterone receptor (PR) for selecting for hormone therapy and HER2 gene amplification/overexpression

Use of Biomarkers in the Postoperative Follow-Up of Asymptomatic Patients Following Curative Surgery

Intensive surveillance following treatment with curative-intent surgery is now a common practice in patients with several different cancer types, including breast cancer. This practice is based on the widely held belief that early detection of recurrent/metastatic disease as a result of regular testing, followed by the early commencement of treatment in the event of a biomarker increase, results in a better outcome, compared to starting treatment when disease recurrence is clinically

Use of Biomarkers in Monitoring Therapy in Patients with Metastasis

While therapy predictive biomarkers indicate upfront the likelihood of an initial response to a specific treatment, most patients sooner or later develop resistance and tumor progression. In order to determine real-time response to a systemic treatment, measurement of serial serum biomarker measurements is a low cost and relative minimally invasive approach. The most widely used biomarker for monitoring response to treatment in advanced breast cancer is CA 15-3, although CEA, TPA, and TPS are

Circulating Tumor Cells

Circulating tumor cells (CTCs), like circulating biochemical biomarkers, are released from tumor tissue. Also, similar to circulating biomarkers, CTCs tend to be increased in most patients with advanced disease but rarely in those with localized disease. Although frequently regarded as a homogenous group of tumor cells, CTCs are in fact a highly heterogeneous collection of cells, including epithelial tumor cells, epithelial-to-mesenchymal cells, hybrid epithelial/EMT cells, and cancer stem

Conclusion

Based on the above, it is clear that biomarkers are currently playing an important role in the management of patients with diagnosed breast cancer. New blood-based biomarkers, however, are needed especially in screening for early disease and in aiding early diagnosis. A further urgent need is the identification and validation of biomarkers for predicting response to specific forms of chemotherapy. Up until now most biomarker measurements detected single analytes. Looking to the future, this is

Acknowledgments

The authors wish to thank Science Foundation Ireland, Strategic Research Cluster Award (08/SRC/B1410) to Molecular Therapeutics for Cancer Ireland (MTCI)/National Cancer Research Centre in Ireland (NCRCI), and the BREAST-PREDICT (CCRC13GAL) programme of the Irish Cancer Society for funding this work. The opinions, findings, and conclusions or recommendations expressed in this chapter, however, are those of the relevant authors and do not necessarily reflect the views of the funding

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