What Does Oncotype DX Score Mean?

The Oncotype DX Recurrence Score is not a staging test and not a screening test. It exists to answer a single question: will adding chemotherapy to hormone therapy lower your risk of the cancer coming back?

The lab measures how strongly 21 genes are switched on in your tumor tissue. That pattern is turned into one number. The National Cancer Institute calls the 21-gene assay the most fully validated gene profile test so far.

It applies to one situation. The cancer must be hormone receptor-positive and HER2-negative. Hormone receptor-positive means the cells carry receptors for estrogen or progesterone. HER2-negative means the cells do not make too much of the HER2 protein. If your report differs on either point, this score is the wrong tool.

The number runs from 0 to 100. The thresholds are not arbitrary. They come out of two large trials, and the trial you fall under depends on your lymph nodes.

For node-negative disease, NCI's professional summary sets the bands this way:

• Score 11 or lower: low risk. Chemotherapy is not indicated.
• Score above 11 and up to 25: intermediate risk.
• Score above 25: high risk. Chemotherapy is indicated.

TAILORx enrolled 10,273 women with hormone receptor-positive, HER2-negative, node-negative breast cancer, at 1,182 sites.

Women with a score of 0 to 10 got hormone therapy alone. Women with a score of 26 or higher got hormone therapy plus chemotherapy. The real question sat in the middle. Women scoring 11 to 25 were randomly assigned to hormone therapy alone or hormone therapy plus chemotherapy.

The middle group produced the headline result. Invasive disease-free survival at 5 years was 92.8 percent with hormone therapy alone and 93.1 percent with chemotherapy added. At 9 years the figures were 83.3 percent and 84.3 percent.

Overall survival barely moved. At 5 years it was 98.0 percent without chemotherapy and 98.1 percent with it. At 9 years, 93.9 percent and 93.8 percent.

In other words, for most women in that intermediate band, months of chemotherapy bought a difference too small to measure reliably.

One subgroup did not follow the pattern. Among women aged 50 or younger with scores of 16 to 25, researchers saw what may be a small benefit from chemotherapy.

The reason is unsettled. It may be a direct effect on the cancer. Or chemotherapy may shut down the ovaries, which lowers estrogen and acts like extra hormone therapy. That difference matters. Drugs can shut down the ovaries without chemotherapy. If you are premenopausal with a score in the high teens or low twenties, this is the conversation to have.

TAILORx also followed 1,389 women with scores of 26 to 100, all of whom received chemotherapy plus hormone therapy. The drug regimens varied. A taxane with cyclophosphamide was used in 42 percent. An anthracycline without a taxane was used in 24 percent. An anthracycline with a taxane was used in 18 percent.

About 96 percent were alive at 5 years, and more than 90 percent had no recurrence at the original site or elsewhere. Researchers then modeled the other path. Only 78.8 percent would have been free of recurrence at 5 years on hormone therapy alone.

That gap is the argument for chemotherapy when the score is high. Note the caveat NCI includes: this was a model, not a randomized comparison.

A positive node used to mean chemotherapy almost automatically. RxPONDER tested that.

The trial screened 9,383 women and randomized 5,083, with 5,015 analyzed. All had hormone receptor-positive, HER2-negative disease. All had one to three positive lymph nodes. All had a score of 25 or lower. Each got hormone therapy alone, or hormone therapy plus several months of chemotherapy by vein.

Menopausal status split the answer cleanly.

Postmenopausal women: invasive disease-free survival at 5 years was 91.6 percent with chemotherapy and 91.9 percent without it. No benefit, at any score in that range.

Premenopausal women: 94.2 percent with chemotherapy and 89.0 percent without it. That is a real and statistically significant difference.

NCI's summary turns that into a rule for node-positive disease after menopause. A score of 25 or lower: chemotherapy is not indicated. A score above 25: it is.

It does not tell you whether you have cancer, how large the tumor is, or what stage you are. Those come from surgery and pathology.

It does not apply to HER2-positive or triple-negative breast cancer. Those cancers have their own standard treatments, whatever a gene score says.

It is not the only genomic assay. MammaPrint uses a different 70-gene panel. It was tested in the MINDACT trial, which also enrolled hormone receptor-negative patients. TAILORx did not. The two tests are not interchangeable, and their scales do not line up.

Pull the surgical pathology report and the assay report side by side, and confirm these:

• Estrogen receptor and progesterone receptor status, with percentages
• HER2 result, and whether it came from immunohistochemistry or FISH
• Number of lymph nodes examined and number positive
• Your Recurrence Score, and which risk band your report assigns it to
• Whether you are premenopausal or postmenopausal, which flips the node-positive answer

Then ask three things. Which trial applies to me, TAILORx or RxPONDER? In my case, how many percentage points does chemotherapy add? Ask for the absolute number, not relative risk. If ovary shutdown is why chemotherapy might help, could ovarian suppression plus an aromatase inhibitor do the same job?

• NCI — Breast Cancer Treatment (PDQ), Health Professional Version
• NCI — TAILORx: chemotherapy adds no benefit for most women with early breast cancer
• NCI Cancer Currents — TAILORx, high recurrence scores and chemotherapy
• NCI — Some postmenopausal women with breast cancer may forgo chemotherapy (RxPONDER)