Breast cancer and metastasis prevention

Breast cancer is the most commonly diagnosed cancer for women, and still remains the leading cause of cancer death in women worldwide. Most deaths are due to metastatic spread rather than to the primary tumor per se: about 25% of women with breast cancer will have an advanced stage of the disease, with more than 70% of those with bone metastasis. Bone metastasis can be managed but not cured by metastasis-specific drugs; however, diagnosis is often too late for effective management.

A major goal of Inbiomotion is therefore to help prevent metastasis in high-risk patients. As a crucial step, we are working towards early-identification of women with breast cancer who are likely to develop metastasis. In this way, we would help to avoid indiscriminate administration to all patients, which is not only cost-ineffective but also puts not-at-risk women through a needless course of treatment (with all adverse effects/harm involved).

Bisphosphonates, which are bone microenvironment modifying agents, have the theoretical potential to prevent bone metastasis. However, clinical trials studying thousands of high-risk patients have shown inconclusive benefit from their use (Coleman et al., NEJM 2011, Paterson et al., Lancet Oncol 2012, EBCTCG group Lancet 2015). Inbiomotion now is addressing the question: did these trials miss the mark by not pre-selecting the correct women who are at-risk and who would benefit from these treatments?

The MAF biomarker test aims to predict benefit from adjuvant bisphosphonates treatment

Click here to find a detailed summary of MAF biomarker discovery, analytical validation and clinical utility

Role and function of the MAF Test

A predictive biomarker test for response to bisphosphonates; it will allow identification and selection of women with early-stage breast cancer who would benefit from bisphosphonates in adjuvant treatment.

Validation studies and clinical utility

Inbiomotion has generated two large sets of prospective-retrospective data confirming the clinical utility of the MAF Test using patients specimens from:

  1. Hypothesis generating study: AZURE (NCTOOO72020)
    # of patients: 3,360
  2. Confirmatory study: NSABP-B34 (NCT00009945)
    # of patients 3,323

These data are technically, analytically, and clinically validated by Targos Molecular Pathology (now Discovery Life Sciences Biomarker Services GmbH), a leading clinical research organization

The MAF Test has the potential to improve breast cancer outcome using an OPT-IN / OPT-OUT approach:

  • Identify women who will benefit from bisphosphonates in adjuvant treatment of early-stage breast cancer
  • Exclude women who will not benefit from / may be harmed by such treatment

Data from these two studies suggest that the beneficial effects of bisphosphonates are associated with not having the amplified MAF gene in the primary breast tumor (MAF-negative); bisphosphonates do not improve outcome (and may be harmful) for women with MAF-amplified tumors. This underscores the importance of an effective stratification method, such as being developed by the MAF test. Indeed, the MAF Test biomarker could be the first companion diagnostic used in treatment strategies for metastasis prevention, allowing doctors to select breast cancer patients who are MAF-negative for treatment with adjuvant zoledronate or clodronate, and excluding those who are MAF-positive from an ineffective treatment and potential harm.