Given the heterogeneity of breast cancer, personalisation of treatment is critical. Biomarkers can play an essential role in determining patient prognosis as well as aiding treatment decisions and assessing potential treatment response.
Recent guidelines from the European Group on Tumour Markers offer a series of recommendations around the use of biomarkers in breast cancer (Duffy et al., 2017).
The main application of HR measurement is to identify patients with invasive breast cancer who are likely to benefit from endocrine therapy. As such, they are used in the neoadjuvant, adjuvant and advanced disease setting.
Patients with HR+ tumours tend to have better outcomes than those with HR- tumours. However, for HR+ tumours, the favourable prognosis occurs largely during the first 5–7 years after diagnosis. Thereafter, the risk of recurrence seems to be greater in patients with HR+ tumours than those with HR- tumours. However, the effect of treatment on these prognostic outcomes cannot be excluded with some studies showing that the improved outcomes in HR+ patients was only seen in patients who received endocrine therapy.
Once considered an indicator for poor prognosis, the development of multiple anti-HER2 therapies has greatly improved outcomes (Global Status of Advanced/Metastatic Breast Cancer 2005–2015 Decade Report, 2016). Measurement of HER2 should be principally used to predict response to anti-HER2 therapy in the neoadjuvant, adjuvant and advanced disease setting. However, HER2 gene amplification/overexpression appears to be necessary but not sufficient for response to available anti-HER2 treatments.
Ki67 is a nuclear antigen that is expressed in proliferating cells and elevated levels have been shown to be independently associated with adverse outcomes in patients with breast cancer. Despite intra-tumour heterogeneity in staining and inter- and intra-observer variability in scoring, Ki67 has been shown to be a prognostic and predictive marker in breast cancer (Duffy et al., 2017; Koopman et al., 2018).
While high Ki67 levels have been consistently shown to be associated with poor patient outcomes, high Ki67 levels in the neoadjuvant setting have been frequently, although not always, linked to chemotherapy response. With endocrine therapy, treatment-induced reductions in Ki67 levels have been shown to be predictive of patient response and outcome. However, little data is available in the metastatic setting (Duffy et al., 2017).
In recent years, several commercially available multianalyte tests have been developed to predict outcomes in patients with newly diagnosed invasive breast cancer. The majority have been validated in ER+, HER2-, lymph node-negative patients between 40 and 65 years of age. However, some (Oncotype DX, MammaPrint, Endo-Predict and Prosigna) have been found to be prognostic in lymph node-positive patients as well.
Current recommendations for the use of multianalyte tests include:
Table 3: Recommendations for the use of multianalyte tests in ER+, HER2- breast cancer patients by different expert groups. (Adapted from Duffy et al., 2017).