Breast Cancer Biomarkers: S100 beta and HOXC11

Introduction

Every year approximately 1.2 million worldwide, are diagnosed with breast cancer (International

Agency for Research). Currently women diagnosed with breast cancer generally undergo

surgery to remove the tumour. Many will also receive either chemo or radiotherapy or a

combination of both. Approximately two thirds of all breast cancers are estrogen receptor

positive and it is these patients who will then receive endocrine treatment for a further 5 years.

Though most patients initially respond to treatment, approximately 40% eventually relapse.

Why these patients develop resistance to the drug treatment is unknown. Currently there is no

method of predicting which patients are likely to recur following initial surgery. Clinical followup

of these women involves routine 6 monthly or annual checkups where they are assessed.

Breast cancer recurrence is an insidious affliction as unlike the primary tumour there is often

very little outward sign that all is not well until the disease has progressed.

The Technology

Translational studies at RCSI have shown that the SRC1 associated proteins HOXC11 and

S100beta are strong predictors of poor disease-free survival in breast cancer patients (n=560).

This translational study identifies a biomolecular interaction network central to the adaptive

response to endocrine therapy with clear clinical applications (Fig.1). Disease recurrence

precipitates cessation of the regime and the initiation of second line therapy, often with tyrosine

kinase inhibitors (TKIs). Early detection of breast disease recurrence with S100beta prior to

clinical manifestation may detect the switch from endocrine to growth factor dependent breast

cancer hence these biomarkers have the potential to provide clinical information regarding the

timely commencement of TKI therapy.

The proposed immunohistochemical test detects the presence of HOXC11 or S100beta in tissues taken at the time of initial surgery, this represents a statistically significantly predictor of disease-free survival independent of treatment (p<0.0001; hazard ratio: 5.79). This association is significantly stronger than any of the currently used clinical makers, including HER2. Monitoring of S100-beta, in patient’s blood could enable evaluation of their response to current therapy and also facilitate improved drug selection if recurrence does occur. Levels of S100beta will be taken preoperatively, postoperatively and every six months during the survival period. S100-beta is a strong predictor of poor disease-free survival on endocrine treatment (hazard ratio: 5.82; p<0.0001) and may be used as a serum marker of tumour progression (hazard ratio: 5.3; p<0.001) (Fig.2) (McIlroy et al Cancer Res 2010; 70;1585–94).

Applications

These biomarkers have the potential to provide clinical information regarding the timely commencement of TKI therapy, providing an opportunity for a partnership between RCSI and a pharmaceutical company or diagnostic test manufacturer to develop a companion diagnostic for the timely use of these drugs for breast cancer.