MAF-gene tests to guide adjuvant bisphosphonate treatment in breast cancer
Topic Status Complete
MAF-gene tests to guide adjuvant bisphosphonate treatment in breast cancer
Summary
There is insufficient evidence to support the routine adoption of MAF gene testing to guide adjuvant bisphosphonate treatment in early breast cancer.
The clinical effectiveness of MAF gene testing has been studied in retrospective subgroup analyses of two randomised controlled trials. These trials were designed to evaluate the effectiveness of bisphosphonates, but did not evaluate the prospective use of MAF gene testing to guide treatment. The lack of evidence prospectively comparing MAF gene testing with menopausal status or age as patient stratification methods means the effectiveness of using the test to guide treatment is uncertain.
Economic modelling estimated that using MAF gene testing to guide adjuvant bisphosphonate treatment could be cost effective compared with usual care. However, the uncertainties in the clinical effectiveness evidence also apply to the economic modelling.
Further research is recommended evaluating the use of MAF gene testing to guide bisphosphonate use in prospective studies and real-world clinical practice.
Why was this topic appraised?
Bisphosphonates are a group of drugs that have been shown to reduce recurrence and mortality outcomes in people with breast cancer, but effects are limited to those who are post-menopausal. Bisphosphonates (zoledronic acid or sodium clodronate) can be offered as adjuvant therapy to those who are post-menopausal with node-positive invasive breast cancer and considered for those with node-negative invasive breast cancer and a high risk of recurrence.
Menopause typically occurs over years and defining it can be complex and imprecise. Given this, professional guidelines have highlighted the potential use of biomarkers as an alternative to direct bisphosphonate treatment to those who might benefit most from it. The MAF gene has been suggested as one such biomarker. The MAFTEST (InBiomotion, Barcelona, Spain) is a class IIa tool to detect MAF gene amplification. It is proposed that MAF gene amplification status, as assessed by the MAFTEST, may be used as a patient stratification tool (rather than menopausal status) to direct adjuvant bisphosphonate in early breast cancer.
The topic was proposed to Health Technology Wales (HTW) by the manufacturer, InBiomotion.
Plain language summary
What is breast cancer?
Cancer is a disease in which some of the body’s cells change and grow uncontrollably. Breast cancer is a cancer that starts in breast tissue. Tumours form out of the extra cells that are grown. If left unchecked, these tumours can spread to other parts of the body. Early-stage breast cancer is cancer that is located only to breast tissue and hasn’t yet spread elsewhere.
What is bisphosphonate treatment?
Treatment for early-stage breast cancer is usually surgery to remove the tumour. After surgery, a clinician may prescribe a medication called bisphosphonates. The medication is given to protect bones from thinning because of the breast cancer treatment. This is usually a concern for patients who have gone through menopause. Bisphosphonates are also used to prevent the cancer from returning. This is known as ‘adjuvant’ treatment. However, bisphosphonates can have side effects for some patients. These include mild sickness, indigestion, flu-like symptoms and on occasion, the deterioration of the bones in the jaw, known as osteonecrosis of the jaw. These side effects can have serious implication for some patients.
Deciding if a patient should be prescribed bisphosphonates is usually done by considering a patient’s menopausal status. However, this does not give a clear indication if the bisphosphonates may result in side effects for that patient.
What is the MAF gene test?
The presence of the MAF gene is linked to those patients who experience bone deterioration after bisphosphonate treatment. A test to see if a patient has the MAF gene may be a way of determining if they are an appropriate patient for bisphosphonate treatment.
What did Health Technology Wales do?
Health Technology Wales looked for evidence on the use of MAF gene testing to guide adjuvant bisphosphonate treatment in early breast cancer. There is insufficient evidence to support the routine adoption of MAF gene testing to guide adjuvant bisphosphonate treatment in early breast cancer.
Guidance
EAR072 10.2025
Evidence Appraisal Report
EAR072 10.2025
Topic Exploration Report
TER576 02.2025 (superseded by EAR072 10.2025)
Health Technology Wales Partners
