The MammaTyper (BioNTech Diagnostics GmbH) test is a molecular in vitro diagnostic test for the relative gene expression quantification of the genes ERBB2, ESR1, PGR and MKI67 in human breast cancer tissue. It is used as a diagnostic test on biopsy samples of invasive breast cancer tissue from surgical resection or pre-operative core needle biopsies. The test is based on reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). MammaTyper classifies breast cancer into 4 subtypes that have different treatments according to St Gallen (2017) guidelines:
Luminal A-like (oestrogen receptor [ER]-positive and generally human epidermal growth receptor 2 [HER2]-negative); treated with endocrine therapy.
Luminal B-like subdivided according to the ERBB2 expression into:
luminal B-like (ER-negative and HER2-positive); treated with anti-HER2 therapy and chemotherapy
luminal B-like (ER-positive and generally HER2-negative); treated with endocrine therapy.
HER2-positive (non-luminal); treated with anti-HER2 therapy and chemotherapy.
Triple-negative (generally ER, progesterone receptor [PR]- and HER2-negative); treated with chemotherapy.
Luminal B-like tumour subtypes are associated with different prognoses and therapy recommendations. Knowing the luminal B-like subtype is designed to enable treatment to be optimised, which may avoid over- or under-treatment. Information about hormone-receptor status and ERBB2 expression can also be used to identify people for whom further multigene testing is not needed. This may avoid the unnecessary use of expensive multigene tests.
The MammaTyper test uses a standard formalin-fixed paraffin-embedded (FFPE) biopsy sample, which is processed using RNXtract to extract ribonucleic acid (RNA). The sample is then run through a RT-qPCR machine with the MammaTyper test and controls supplied with the test.
MammaTyper measures ER and HER2 status on routinely collected FFPE material. It offers an objective, sensitive, and precise test, based on measuring the upregulation of genes on standard RT-qPCR equipment. It would be an alternative to IHC, which is a subjective test that has no defined cut off and may have inter-observer and inter-laboratory variability for some measures, such as those relating to MKI67. It would also provide additional information on luminal B-like tumour subtypes that cannot be assessed using IHC.
Results of the MammaTyper test would be used to guide treatment decisions (based on established St Gallen guidelines).
NICE's guideline on diagnosing and treating early and locally advanced breast cancer recommends people with invasive breast cancer should have postoperative assessment of ER status using IHC with a standardised and qualitatively assured methodology, and report the results quantitatively. HER2 status of all invasive breast cancers should also be assessed using a standardised and qualitatively assured methodology. The results of ER and HER2 assessments can be used to guide systemic treatment.
Using chemotherapy in ER-positive tumours is influenced by assessing MKI67. IHC cannot reliably assess this and so luminal B-like tumours cannot be subdivided by ER status. This means that for people with luminal B-like disease, those who have ER-positive disease may inappropriately have chemotherapy, and those with ER-negative disease may not be offered this potentially beneficial treatment. NICE's guideline on diagnosing and treating early and locally advanced breast cancer also recommends that all people with early invasive breast cancer should be considered for adjuvant treatment after surgery. The choice of treatment should be made by assessing prognostic and predictive factors and the potential benefits and side effects of the treatment. Decisions should be made after discussing these factors with the person and using online prognostic tools such as PREDICT to estimate individual prognosis and the absolute benefit of a treatment.
NICE guidance on gene expression profiling and expanded IHC tests in early breast cancer management is being updated but does not include MammaTyper as it does not provide a result that describes the risk of cancer recurrence.
MammaTyper would be used in place of IHC to identify breast cancer subtype, and further subdivide people with luminal B-like disease by ER status to guide adjuvant treatment based on established methods (St Gallen guidelines).
NICE is aware of the following CE-marked device that appears to fulfil a similar function as MammaTyper:
IHC4 AQUA (Genoptix Inc) – assesses risk (low, intermediate, high) and subtype.
MammaTyper would be used to guide treatment decisions in people with breast cancer. The test would be done in secondary care on a surgical resection of the breast cancer tissue (or the initial diagnostic core biopsy) so results are available to guide post-surgical chemotherapy or initial treatment. It would be used in the same place in the care pathway as IHC, to identify people likely to have a low-risk subgroup of ER-positive luminal A-like or B-like disease and to avoid using chemotherapy in these groups.
The test uses industry-standard RT-PCR machines (including Roche LightCycler, Versant kPCR Cycler, cobas z480 Analyzer and others) and is done on routine clinical samples such as FFPE material, so additional training is not needed.
The company state the price per patient of MammaTyper is £400, including RNXtract to extract RNA. It states that there is potential for preferential NHS pricing. The test can be run on a range of industry-standard RT-PCR devices and needs 45 minutes of technician time (about £16).
The MammaTyper test would add costs compared with the standard IHC test in initial testing and treatment of breast cancer. It has the potential to make resource savings in avoiding unnecessary chemotherapy, optimising treatment regimens and potentially avoiding the need for more expensive multigene testing. As MammaTyper is an objective test, it does not need expert histopathology clinicians to read the result, and so can release staff time.
The test runs on a range of standard PCR devices and would need no changes to infrastructure beyond buying the relevant technology.