Bone Metastasis – Breast cancer
Over one million new cases of breast cancer are diagnosed each year (GLOBOCAN 2012). Metastases are secondary malignant growths that develop through interactions between tumor cells and normal tissue in vital organs. It is responsible for 90% of deaths in cancer patients with solid tumors.
Bone is one of the most common locations for metastasis. It is characterized by severe pain and disabling bone damage that causes a drastic reduction in the patient's quality of life. It is the only type of metastasis that can be managed, but not cured, by metastasis specific drugs. Treatment is only given once the metastasis has been identified, which is often too late. Identifying bone metastasis at an early stage is crucial to improving the patient's quality of life.
Current preventive treatment for bone metastasis is expensive and comes with undesirable side effects. In addition, significant differences in treatment responses (according to menopausal status) in the rates of recurrence outside bone has been reported in clinical trials (Coleman et al NEJM 2013). With only 15-20% of cancer patients likely to develop metastasis, identifying these patients at an early stage is crucial, as indiscriminate administration of medications is not a cost-effective option.
Thousands of high-risk patients have been involved in clinical trials for preventative bone metastasis drugs (Coleman et al NEJM 2013, Paterson et al Lancet Oncol 2012, EBCTCG group Lancet 2015). The somewhat inconclusive results of these trials have not yet influenced routine clinical practice. This highlights an urgent medical need for an early stage diagnostic test that more selectively identifies patients that would benefit of such treatments (Dhesy-Thind et al JCO 2017, and Hadji et al Annals of Oncol 2016).
Predictive Biomarker - MAF Test
Inbiomotion has discovered a single biomarker to predict the risk of metastasis relapse, in particular to the bone, in breast cancer primary tumors, and most importantly such biomarker has the potential to identify those early stage breast cancer patients that will benefit from bisphosphonate adjuvant treatment.
The MAF test was initially extensively studied in retrospective series of breast cancer patients (>900), demonstrating that it can identify patients with the highest risk of tumor metastasis specific to the bone (Pavlovic et al JNCI 2015).
More recently, Inbiomotion has been collaborating with Prof. Rob Coleman in the retrospective analysis of the AZURE (ISRCTN79831382) clinical trial using the MAF test as biomarker. MAF gain in primary tumors from women included in the AZURE trial was used to determine the prognostic value of MAF and its potential to predict the effects of adjuvant zoledronic acid (ZOL) on disease outcomes. The AZURE trial was a registrational, prospective, open label, randomized phase III multicenter, parallel-group trial, performed in 3360 women with stage II/III breast cancer to receive standard adjuvant systemic therapy alone or with ZOL every 3-4 weeks for 6 doses, then 3-6 monthly thereafter to complete 5 years treatment. Multivariate analyses of disease outcomes by MAF Test status were performed in control and ZOL patients separately on an intention to treat basis according to a pre-specified statistical analysis plan.
The results suggest that MAF Test may allow better and more precise selection of patients for adjuvant treatment with ZOL. MAF test negative patients are likely to represent almost 80% of breast cancers who could benefit from the use of adjuvant ZOL (outcompeting the initial registration HR required) (Coleman et al Lancet Oncol 2017). On the other hand, the MAF Test allows to segregate those patients that may be harmed by the treatment because the presence of MAF test positive tumors appears to be associated with adverse disease outcomes when patients are treated with bisphosphonates - especially if treatment is initiated before menopause is complete (Coleman et al Lancet Oncol 2017).
The MAF Test biomarker could be the first companion diagnostic used in treatment strategies for metastasis prevention.
Since the MAF Test has the ability to select patients at a higher risk of metastasis, in particular to the bone, it may also support clinical studies for the validation of preventive drugs and hence has the potential to increase the probability of success of current and future clinical trials by identifying those patients that are likely to respond.
- One single gene/protein level in stage I, II and III primary tumor biopsies has the potential to predict bone metastasis at the first site of relapse
- Proprietary metastasis biomarker is independent of any known clinical-pathological parameter known for metastasis prediction
- Multivariate statistical analysis confirmed the clinical significance of independence of our biomarker from any other clinical-pathological parameter currently applied in the standard of care
- Biomarker predicts breast cancer patients that benefit from bisphosphonate treatment in the adjuvant setting (80% of the breast cancer patients)
- Biomarker predicts the subset of early stage breast cancer patients that may be harmed by bisphosphonate treatment in the adjuvant setting
- Biomarker has a causal role in cancer to bone metastasis. Loss-and-gain-of-function experiments in experimental mouse models of metastasis suggest a driver role in bone metastasis processes
- Inbiomotion has aggressively protected MAF Test and currently owns or has worldwide exclusive control of 10 patent families with over 80 pending applications and 7 granted patents (not including European validation countries)