Genomic Testing in Breast Cancer (Oncotype DX, Prosigna, MammaPrint)

by Jason Wasserman MD PhD FRCPC
April 16, 2026

Genomic testing in breast cancer refers to a group of laboratory tests that analyze the activity of specific genes inside a tumor to estimate the risk of the cancer returning and to help decide whether chemotherapy is needed. Unlike standard pathology tests that look at what a cancer looks like under the microscope, genomic tests measure how cancer’s genes behave — which genes are switched on and how actively they are expressed. These tests are most useful in early-stage, hormone receptor-positive, HER2-negative breast cancer, where it is often difficult to know from routine pathology findings alone whether chemotherapy will provide a meaningful benefit on top of hormone-blocking therapy.

This article explains what genomic tests are, how they work, which tests are currently available, how results are reported, and what a result means for your treatment plan.

Why genomic testing is done

In early-stage, hormone receptor-positive, HER2-negative breast cancer, the standard treatment includes surgery, radiation (if appropriate), and hormone-blocking therapy — drugs such as tamoxifen or an aromatase inhibitor that block estrogen from fueling the cancer. For many patients, hormone-blocking therapy alone is sufficient. However, for some patients, adding chemotherapy reduces the chance of the cancer returning.

The challenge is that standard pathology features — tumor size, Nottingham grade, lymph node status, and Ki-67 — do not always reliably identify which patients fall into which group. Chemotherapy carries significant side effects, and giving it to patients who would do equally well without it means exposing them to those side effects unnecessarily. Conversely, withholding chemotherapy from patients who would truly benefit means undertreating their cancer.

Genomic tests were developed to answer this question more precisely. By analyzing how tens of genes in the tumor are actually behaving, these tests generate a score or classification that reflects the tumor’s underlying biology more deeply than microscopic appearance alone.

How genomic tests work

Genomic tests for breast cancer do not look for DNA mutations — they measure gene expression. Gene expression refers to how actively a gene is working: some genes in a cancer cell are switched on at high levels, while others are switched off or running at low levels. The combination of which genes are active and to what degree tells the test’s algorithm something important about how the tumor is likely to behave over time.

These tests use RNA — the molecule that carries instructions from DNA to produce proteins — extracted from the tumor tissue. The tissue comes from the biopsy or surgical specimen that your pathologist already examined. The genomic test lab receives a small portion of that preserved tissue, extracts and measures the RNA from the relevant genes, and feeds the results into a validated algorithm to generate a score or risk category.

The result is reported separately from your main pathology report — it typically comes from a specialized reference laboratory — but it is directly connected to the tumor your pathologist described.

Which patients are candidates for genomic testing

Current clinical guidelines recommend genomic testing for patients with all of the following features:

Invasive breast cancer — genomic testing is not performed for ductal carcinoma in situ (DCIS), which has not yet become invasive.
Hormone receptor-positive (ER-positive and/or PR-positive) — the tests were developed and validated in hormone receptor-positive tumors and have not been shown to be useful in hormone receptor-negative cancers.
HER2-negative — patients with HER2-positive cancers receive HER2-targeted therapy regardless of genomic score, so genomic testing rarely changes their management.
Early-stage disease — typically Stage I or II, with either no lymph node involvement (node-negative) or limited involvement (1–3 positive lymph nodes, depending on the specific test and guideline).

Genomic testing is generally not recommended for patients who are already clearly high-risk (for example, those with many positive lymph nodes) or clearly low-risk (for example, very small, low-grade, node-negative tumors in older patients) because the result is unlikely to change the clinical decision. Your oncologist will determine whether your specific situation is one where genomic testing would provide meaningful guidance.

The available tests

Oncotype DX (21-gene recurrence score)

Oncotype DX is the most widely used genomic test in breast cancer and has the most extensive clinical evidence base. It is performed by Exact Sciences (formerly Genomic Health) on formalin-fixed, paraffin-embedded tumor tissue — the same kind of preserved tissue block your pathologist used for diagnosis.

The test measures the expression of 21 genes: 16 cancer-related genes and 5 reference genes used to normalize the results. The cancer-related genes include those involved in proliferation (how fast cells are dividing), hormone receptor signaling, HER2 signaling, and invasion. The results are combined in a proprietary algorithm to generate a single number called the Recurrence Score, which ranges from 0 to 100.

Low Recurrence Score (0–25 in postmenopausal patients; 0–15 in premenopausal patients) — The cancer has a low risk of returning, and chemotherapy is unlikely to provide meaningful benefit beyond hormone-blocking therapy alone. Hormone therapy alone is the recommended approach.
Intermediate Recurrence Score (16–25 in premenopausal patients) — The benefit of chemotherapy is uncertain and depends on other factors, including the patient’s age and menopausal status. In premenopausal patients with a score in this range, the TAILORx trial showed that chemotherapy significantly reduced recurrence risk, and it is generally recommended.
High Recurrence Score (26–100) — The cancer has a higher risk of returning, and chemotherapy is expected to provide meaningful additional benefit. Chemotherapy followed by hormone-blocking therapy is recommended.

The Recurrence Score thresholds described above reflect current North American guideline recommendations (ASCO 2019) and apply to node-negative cancers. For patients with 1–3 positive lymph nodes, the RxPONDER trial demonstrated that postmenopausal patients with a score of 0–25 can safely omit chemotherapy, while premenopausal patients in this group still benefit from chemotherapy. Your oncologist will explain how the score applies to your specific nodal status and menopausal status.

The key clinical trial supporting Oncotype DX is TAILORx (Trial Assigning IndividuaLized Options for Treatment), which enrolled over 10,000 patients with node-negative, hormone receptor-positive, HER2-negative breast cancer. The trial demonstrated that patients with a Recurrence Score of 0–25 had excellent outcomes with hormone therapy alone, and that chemotherapy provided no significant benefit in this group, except in premenopausal patients with scores of 16–25, where it did reduce recurrence risk meaningfully.

Prosigna (PAM50)

Prosigna is a genomic test based on the PAM50 gene expression algorithm that measures the activity of 50 genes to classify a tumor into one of four intrinsic molecular subtypes and to generate a Risk of Recurrence (ROR) score.

The four intrinsic subtypes identified by PAM50 are:

Luminal A — Hormone receptor-positive, low-proliferation, slow-growing. Associated with a low risk of distant recurrence and a low likelihood of chemotherapy benefit.
Luminal B — Hormone receptor-positive, higher-proliferation. Associated with a higher risk of recurrence compared to Luminal A and a greater likelihood of chemotherapy benefit.
HER2-enriched — Biologically driven by HER2 signaling. Can occur even in IHC-HER2-negative tumors.
Basal-like — Typically corresponds to triple-negative breast cancer biologically.

The ROR score is expressed as a number from 0 to 100 and is interpreted as the risk of developing distant metastasis — cancer spreading to other organs — within 10 years when treated with hormone-blocking therapy alone. Results are also categorized as Low Risk, Intermediate Risk, or High Risk. The Intermediate Risk category is often handled similarly to a high-risk result in clinical practice, though guidelines vary.

Prosigna is performed on tumor tissue in a certified local laboratory using the NanoString nCounter platform, which means it can be run closer to where the patient is being treated rather than being sent to a central reference laboratory. The supporting evidence for Prosigna includes the ABCSG-8, ATAC, and SOFT trials, which demonstrated its ability to predict 10-year distant recurrence risk in postmenopausal patients with hormone receptor-positive, node-negative or node-positive early breast cancer.

MammaPrint (70-gene signature)

MammaPrint measures the expression of 70 genes and classifies a tumor into one of two categories: Low Risk or High Risk for distant recurrence within 10 years. Unlike Oncotype DX, MammaPrint uses fresh or fresh-frozen tumor tissue for optimal results, although an FFPE (formalin-fixed, paraffin-embedded) version is also available. The test is performed by Agendia, a specialized molecular diagnostics company.

MammaPrint also offers a further refinement of the Low Risk category called Ultra Low Risk, which identifies patients with an especially favorable prognosis. In the High Risk category, an additional measure called the Molecular Subtype (using the Blueprint gene expression panel, which runs alongside MammaPrint) can further classify the tumor.

The key clinical evidence for MammaPrint comes from the MINDACT trial, which enrolled over 6,000 patients and compared MammaPrint genomic risk with clinical risk (estimated from traditional factors such as tumor size, grade, and lymph node status). The trial showed that patients who were classified as clinically high-risk but genomically low-risk by MammaPrint had a 5-year distant metastasis-free survival rate of approximately 94.7% with hormone therapy alone — demonstrating that chemotherapy could safely be omitted in a substantial portion of patients who would otherwise have received it based on clinical features alone.

Comparing the tests

All three tests are validated tools for helping to decide whether chemotherapy is needed in early-stage, hormone receptor-positive, HER2-negative breast cancer. They are not interchangeable — they measure different genes, use different algorithms, and report results differently — but they address the same underlying clinical question.

In practice, the test your oncologist recommends will depend on several factors: which tests are covered by your provincial health plan or insurance, which test has the strongest evidence base for your specific situation (node-negative vs. node-positive, pre- vs. postmenopausal), and which test is routinely used at your treating center. In Canada, both Oncotype DX and Prosigna are publicly funded through provincial programs in several provinces for qualifying patients.

Your oncologist is the right person to discuss which test, if any, is appropriate for your situation and what the result would mean for your care.

How results are reported

Genomic test results are typically reported in a separate document from your pathology report — they come from a specialized reference laboratory and may arrive days to weeks after the main pathology results. However, your oncologist will receive the result and discuss it with you, usually at a follow-up appointment.

Oncotype DX — Reports a numeric Recurrence Score from 0 to 100, along with an interpretation (low, intermediate, or high risk), the estimated 10-year distant recurrence risk at that score, and a statement of whether chemotherapy is likely to provide additional benefit.
Prosigna — Reports a numeric Risk of Recurrence (ROR) score from 0 to 100, a risk category (Low, Intermediate, or High), the intrinsic molecular subtype (Luminal A, Luminal B, HER2-enriched, or Basal-like), and the estimated 10-year risk of distant recurrence.
MammaPrint — Reports a binary result (Low Risk or High Risk), along with a numeric index value. Low Risk results may be further categorized as Ultra Low Risk. If Blueprint is run alongside MammaPrint, the molecular subtype is also reported.

What the result means for treatment

Genomic test results are used alongside — not instead of — the other features in your pathology report. Your oncologist will consider the genomic result together with your tumor size, grade, nodal status, Ki-67, menopausal status, overall health, and personal preferences when making a chemotherapy recommendation.

Low-risk genomic result — Indicates that the cancer is unlikely to spread to distant sites within 10 years when treated with hormone-blocking therapy alone. Chemotherapy is generally not recommended in this group, as the added benefit is small and the side effects are not justified. Hormone-blocking therapy (tamoxifen or an aromatase inhibitor, typically for 5–10 years) remains the cornerstone of treatment.
High-risk genomic result — Indicates a meaningful risk of distant recurrence and a clinically significant benefit from adding chemotherapy to hormone-blocking therapy. Most guidelines recommend chemotherapy in this setting, followed by hormone-blocking therapy.
Intermediate-risk genomic result (Oncotype DX) — The decision is nuanced and depends on menopausal status and other clinical factors. Premenopausal patients with an intermediate Recurrence Score (16–25) benefit from chemotherapy based on TAILORx data. Postmenopausal patients in this score range generally do not. Your oncologist will walk through the considerations specific to your situation.

It is important to understand that genomic test results predict average outcomes across groups of patients with similar scores — they cannot tell any individual patient with certainty what will happen. A low-risk result means a low probability of recurrence, not zero probability. A high-risk result means a meaningful risk exists, but it does not mean recurrence is inevitable. These results are tools to help guide decisions, not definitive predictions.

Genomic testing and extended endocrine therapy

Beyond the question of chemotherapy, genomic test results — particularly the Oncotype DX Recurrence Score and the Prosigna ROR score — are also used to help decide whether extending hormone-blocking therapy from 5 years to 10 years provides meaningful benefit. Patients with higher recurrence scores who have completed 5 years of hormone-blocking therapy and remain free of recurrence may benefit from continuing treatment for an additional 5 years. This decision involves weighing the risk of late recurrence against the side effects of extended therapy, and your oncologist will discuss whether it applies to your situation.

Questions to ask your doctor

Is my cancer hormone receptor-positive and HER2-negative — the type where genomic testing is most useful?
Would genomic testing apply to my situation, or is my risk already clear enough from standard pathology findings?
Which genomic test would you recommend, and is it covered by my provincial health plan or insurance?
If I receive a Recurrence Score (Oncotype DX), what number would lead you to recommend chemotherapy, and what number would support hormone therapy alone?
How does my lymph node status affect how the genomic score is interpreted?
Does my menopausal status change how you would use the genomic test result?
If the result is intermediate risk (for Oncotype DX), what would you recommend and why?
How long will it take to get the genomic test result, and will it delay starting treatment?
If my genomic result is low risk and I skip chemotherapy, what does my treatment plan look like?
After 5 years of hormone-blocking therapy, would my genomic test result affect the decision about continuing for another 5 years?
Are there clinical trials studying new ways to use genomic testing in breast cancer that I might qualify for?