Emerging gene-based prognostic tools in early breast cancer: First steps to personalised medicine

Abstract

Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor (ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer.

A Comparison of the Performance of EndoPredict Clinical and NHS PREDICT in 120 Patients Treated for ER-positive Breast Cancer

“…The next step in cancer prognostication has been the development of genomic assays, such as Oncotype Dx and EndoPredict (46). There is significant evidence suggesting that these assays provide superior prognostication compared to other tools.…”

“…The main limitation of our study relates to the assumption that molecular profiling with EPClin is prognostically superior and that we did not report clinical outcome data to assess which test is superior in stratifying patients for chemotherapy or no chemotherapy interventions. However, the assumption of prognostic superiority of EPClin in this patient population is reasonable and based on level Ib evidence (46).…”

“…It has to be emphasised that as a composite score, EPClin has some advantages over assay-only scores, such as Mammaprint and EndoPredict. Combining clinical information with a molecular score would hopefully provide a more robust prognostic tool (46). Furthermore, an issue common to both genomic assays and online tools is the ambiguity regarding the intermediate-risk group.…”

Are online prediction tools a valid alternative to genomic profiling in the context of systemic treatment of ER-positive breast cancer?

“…Examples of such assays include Blueprint [ 5 ] Mammaprint [ 6 ], Oncotype DX [ 7 ], prediction analysis of microarray 50 (PAM50) [ 8 , 9 ] and EndoPredict (EP) [ 10 ]. The EndoPredict Clinical (EpClin) assay is a composite of standard pathological parameters and molecular profiling scores which has been found to provide superior prognostic information [ 11 ]. These assays have changed the landscape of clinical oncology and allowed clinicians to make therapeutic decisions based on the molecular machinery of the tumour and data derived from randomised controlled trials.…”

“…The use of genomic assays in human breast cancer has been endorsed by the National Institute for Clinical Excellence (NICE) and the American Society of Clinical Oncology (ASCO), among others [ 31 ]. Several histological and molecular markers are used to identify patients with breast cancer at the highest risk of recurrence, which also means tumours with the highest degree of sensitivity to chemotherapy [ 11 ].…”