The management of early-stage, hormone-receptor-positive, and HER2-negative breast cancer presents a common challenge for patients and oncologists. After surgery, the main decision revolves around whether to add adjuvant chemotherapy to standard hormone therapy to prevent recurrence. Chemotherapy carries significant side effects, making it undesirable for patients who will not benefit. Physicians employ genomic testing to analyze the tumor’s biology, providing a personalized prediction of recurrence risk and potential effectiveness of chemotherapy. These tests analyze the expression patterns of specific genes within the tumor tissue to determine the likelihood of the cancer spreading.
The Oncotype DX Recurrence Score
The Oncotype DX Breast Recurrence Score test is a genomic assay that quantifies the expression of 21 specific genes. This panel includes 16 genes related to cancer processes like cell proliferation and invasion, along with five reference genes used for normalization. The test is performed on a small tumor sample, typically from tissue removed during the initial biopsy or surgery, using reverse transcription-polymerase chain reaction (RT-PCR).
The result is the Recurrence Score (RS), a continuous number from 0 to 100. This score predicts the 10-year risk of distant recurrence if the patient is treated only with hormone therapy. The RS is categorized into Low, Intermediate, and High risk groups. For women over 50 with node-negative disease, a score of 0 to 25 indicates a low risk and little benefit from chemotherapy. Scores of 26 and above indicate a higher risk and potential benefit from adding chemotherapy.
The MammaPrint Risk Assessment
The MammaPrint test uses a 70-gene signature, a much broader panel than Oncotype DX. This assay examines genes associated with tumor progression and metastasis to determine the biological aggressiveness of the cancer cells. Its primary focus is on prognosis, predicting the likelihood of the cancer spreading to distant sites.
The MammaPrint output provides a binary result: either Low Risk or High Risk. This clear classification minimizes the ambiguity that can arise from intermediate scoring ranges. The test can be applied to a broader group of patients, including those with up to three positive lymph nodes.
Key Differences in Methodology and Scope
The most obvious distinction between the two assays is the number of genes analyzed (21 vs. 70). This difference reflects distinct approaches to measuring tumor biology and recurrence potential. Oncotype DX reports a continuous Recurrence Score (0 to 100), allowing for a granular assessment of risk. In contrast, MammaPrint provides a definitive Low Risk or High Risk result, simplifying interpretation.
Both tests generally utilize formalin-fixed, paraffin-embedded (FFPE) tumor tissue. Their predictive scopes vary: Oncotype DX is validated to be both prognostic (predicting recurrence risk) and predictive (estimating the benefit of chemotherapy). MammaPrint is primarily a prognostic test, but clinical trials have established its utility in guiding chemotherapy decisions.
Applying the Results to Treatment Decisions
The results of these genomic tests are integrated into clinical guidelines, helping oncologists decide when hormone therapy alone is sufficient and when chemotherapy is necessary. The TAILORx trial provided definitive clarity for the Oncotype DX test, particularly for the intermediate Recurrence Score range of 11 to 25 in women with node-negative disease. The trial found that the majority of these patients, including nearly all women over 50, could safely skip chemotherapy and rely on hormone therapy alone. A specific subset of younger women, aged 50 or younger with intermediate scores from 16 to 25, was identified as potentially benefiting from the addition of chemotherapy.
Similarly, the MINDACT trial established the clinical utility of the MammaPrint test for de-escalating treatment. This study focused on patients deemed high risk based on traditional clinical factors but classified as Low Risk by the genomic test. The findings showed that for this “clinical high risk/genomic low risk” group, omitting chemotherapy was safe, resulting in excellent long-term survival outcomes. These landmark trials have transformed treatment by providing quantitative, personalized data, allowing thousands of women to avoid unnecessary toxicities.