The Oncotype DX recurrence-score test is introduced

A dated milestone. This page describes work published in 2004 and what came after it. It is not breaking news.

The question the test was built to answer

For decades, the decision about chemotherapy after breast cancer surgery rested on things a pathologist could see: how big the tumor was, how many lymph nodes were involved, how abnormal the cells looked, the patient's age.

Those measures are blunt. Many women given chemotherapy would never have had their cancer come back. They took the side effects for nothing. Nobody could tell which ones.

In December 2004, Soonmyung Paik, Steven Shak, and colleagues published a possible answer in the New England Journal of Medicine.

What the 2004 paper showed

They measured the activity of 21 genes in tumor tissue that had already been fixed in paraffin — 16 cancer-related genes and 5 reference genes — and fed the results into a fixed formula. Out came a single number, the recurrence score, and a risk group.

They ran it on 668 tumor samples from women in the NSABP B-14 trial. All had node-negative, estrogen-receptor-positive breast cancer and had been treated with tamoxifen.

The split was 51% low risk, 22% intermediate, and 27% high. Distant recurrence at 10 years was 6.8% in the low group, 14.3% in the intermediate group, and 30.5% in the high group.

Crucially, the score added information that age and tumor size did not already carry. That is what made it more than a repackaging of what doctors already knew. Our page on breast cancer stages covers the older measures the score sits alongside.

The gap the paper left open

Look again at that middle group. An intermediate score meant a 14.3% chance of distant recurrence, which is neither reassuring nor alarming. The 2004 paper could not say whether those women should have chemotherapy.

That was not a small gap. It covered nearly a quarter of patients.

TAILORx settled most of it

The answer took 14 years. TAILORx enrolled 10,273 women with hormone-receptor-positive, HER2-negative, node-negative breast cancer. Of the 9,719 with follow-up, 6,711 had a midrange score of 11 to 25. Those women were randomly assigned to endocrine therapy alone or endocrine therapy plus chemotherapy.

At nine years, invasive disease-free survival was 83.3% with endocrine therapy alone and 84.3% with both. Freedom from distant recurrence was 94.5% and 95.0%. Overall survival was 93.9% and 93.8%. Endocrine therapy alone was not worse.

There was one exception, and it matters. The benefit of chemotherapy varied with score and age together. Some women aged 50 or younger with a score of 16 to 25 did gain from it.

So for most women in that middle band, chemotherapy could be left out. For younger women at the top of the band, it could not. Our page on chemotherapy covers what the treatment involves.

RxPONDER took on positive nodes

The 2004 study only covered women with no cancer in the lymph nodes. RxPONDER asked what the score meant when one to three nodes were involved.

It randomly assigned 5,083 women with hormone-receptor-positive, HER2-negative disease and a score of 25 or lower to endocrine therapy alone or chemotherapy plus endocrine therapy. The answer split by menopausal status.

Among women past menopause, five-year invasive disease-free survival was 91.9% without chemotherapy and 91.3% with it. No benefit.

Among women before menopause, it was 89.0% without and 93.9% with. A clear benefit. And the size of that benefit did not grow as the score rose, which suggests the gain came from something other than the score itself.

What to keep in perspective

• The 2004 validation applied only to node-negative, estrogen-receptor-positive breast cancer treated with tamoxifen. It said nothing about other groups.
• The recurrence score is not a diagnosis or a stage. It estimates the chance of distant recurrence, and in later trials the chance of gaining from chemotherapy.
• TAILORx and RxPONDER both found that age or menopausal status changes what a given score means. One number is never read alone.
• These are trial averages. They describe groups, not the person reading them.
• This page summarizes published trials. It is not advice about anyone's own treatment.

When to get checked

None of this replaces finding the cancer in the first place. The US Preventive Services Task Force recommends a screening mammogram every two years for women aged 40 to 74. Our guide to mammograms covers the practical side.

Between screenings, ask a clinician about:

• A new lump in the breast or under the arm, or a thickened area
• A change in the size or shape of one breast
• Dimpling or puckering of the skin, or swelling with no lump
• A nipple that flattens or turns inward, or discharge that is not breast milk
• Skin on the breast or nipple that is red, darker, scaly, or swollen

Most breast changes are not cancer. They still need a cause found.

Sources

• Paik S et al., A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer, N Engl J Med 2004 — https://pubmed.ncbi.nlm.nih.gov/15591335/
• Sparano JA et al., Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer (TAILORx), N Engl J Med 2018 — https://pubmed.ncbi.nlm.nih.gov/29860917/
• Kalinsky K et al., 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer (RxPONDER), N Engl J Med 2021 — https://pubmed.ncbi.nlm.nih.gov/34914339/
• NCI, Breast Cancer Signs and Symptoms — https://www.cancer.gov/types/breast/symptoms
• US Preventive Services Task Force, Breast Cancer: Screening — https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-screening

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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