Breast cancer: Treatment decisions on the basis of a biomarker-based test can also be harmful

The German Institute for Quality and Efficiency in Health Care (IQWiG) examined the pros and cons of biomarker-based tests to inform decisions about adjuvant chemotherapy for patients with a certain type of breast cancer, i.e., first-time, hormone receptor-positive and HER2/neu-negative breast cancer.

According to the findings, women with breast cancer aged up to 50 or premenopausal should not decide against adjuvant chemotherapy on the basis of the "MammaPrint" or "Oncotype DX" biomarker-based tests. This is because, regardless of whether their lymph nodes are already affected by cancer or not, they may then forego treatment that could prevent a recurrence.

Biomarkers should indicate who will benefit from chemotherapy

Biomarker-based tests determine whether the risk of a tumour recurring after surgical removal is low or high. These tests are primarily used when the individual risk of recurrence cannot be reliably determined by means of clinical factors such as certain tumour characteristics. If the risk of recurrence is low, chemotherapy would be an unnecessary burden.

For primary breast cancer, the German statutory health insurance funds currently reimburse four biomarker-based tests: MammaPrint, Oncotype DX, EndoPredict and Prosigna. Doctors can currently use these tests in outpatient care if the patient's lymph nodes have not yet been affected by the cancer.

Results depend on menopausal status

Meaningful data from randomized controlled trials (RCTs) are only available for MammaPrint (MINDACT study) and Oncotype DX (RxPONDER and TAILORx studies).

IQWiG draws the following main conclusions from these three studies:

• In premenopausal patients (up to 50 years of age), RCT evidence does not support the use of a biomarker-based test to guide breast cancer therapy.
• In postmenopausal patients (over 50 years of age), RCT evidence supports the use of a biomarker-based test (Oncotype DX) to guide breast cancer therapy.

It is not possible to verify whether this evaluation also applies to other biomarker-based tests, such as EndoPredict or Prosigna, as no suitable data are available.

Summarizing the results of the IQWiG report, Daniel Fleer, Deputy Head of IQWiG's Non-Drug Interventions Department, says: "The risk of mistakenly foregoing chemotherapy on the basis of a biomarker-based test is therefore substantially higher in premenopausal than in postmenopausal breast cancer patients."

Procedure of report production

In May 2023 the Federal Joint Committee (G-BA) commissioned IQWiG to assess the use of biomarker-based tests to inform decisions about adjuvant systemic chemotherapy for primary breast cancer involving one to three lymph nodes. In September 2023, the G-BA also commissioned the Institute to assess the same question for premenopausal patients with primary breast cancer without lymph node involvement. IQWiG published the preliminary results, the preliminary report, in June 2024 and invited comments. Following the commenting procedure, the report was revised and sent as a final report to the G-BA, the contracting agency, in October 2024. The written comments submitted on the preliminary report were published in a separate document at the same time as the final report in November 2024. An English translation was published in July 2025.