The Oncotype-DX test

My journey started as usual, with the lump that can kill, in April 2010. My cancer was of a bad kind, “pleomorphic, lobular, and multicentric” – in other words, it had many foci in addition to the lump I had felt. My head was bursting. 

My oncologist said my chances of being cured were between 60% and 90%, but as anyone who has lived through cancer can tell you, that is not good enough. You just cannot live with such uncertainty.  For me, the rigors of three operations and six cycles of very aggressive chemotherapy were nothing compared to not knowing: ‘even if I do everything, will I see my kids grow up?’  In this situation, any scrap of information that can narrow this range is precious. Doctors often tell us to “think positive” and “not worry”, but how can you “not worry” when you know you have something so life-threatening? We have cancer, not Alzheimer’s, we haven’t lost it… This is where, for me at least, the importance of the “Oncotype-DX” (Oncotype) test comes in.

The Oncotype test is being used extensively since the mid-2000’s in the US and later in Canada.  The test examines the levels of expression of 21 genes in the tumor that has been operated out. It can be done if the tumor cells have estrogen receptors (ER+) and generally if fewer than 4 lymph nodes are involved. Based on these levels, it can predict the chances of  recurrence in the next 10 years. The “recurrence score” indicates chances of recurrence with or without chemotherapy for the next 10 years (together with the ER inhibitor tamoxifen or aromatase inhibitor). That is, it can predict with reasonable certainty whether chemotherapy will be beneficial or not. It turns out that in 25% of node-negative, ER+ breast cancers, the chances of recurrence are low enough that chemotherapy is not worth the risk of the side-effects. 

However the Oncotype cannot be used for all breast cancers. Sometimes chemo is given before surgery to shrink the tumors, and in such cases this test cannot give reliable results. Also, it cannot estimate the chances of survival after treatment with Herceptin (for Her2-positive cancers) or other drugs, for the simple reason that Herceptin is a relatively new drug and we do not have enough 10-year relapse data yet. More studies are underway to refine the Oncotype scores regarding histological types of the tumor, and Herceptin treatment. And while the Oncotype test is only for ER+ tumors, another test (mamaPrint) is being developed for ER- cancers.

The Oncotype test is now widely used. In Ontario, if it is conducted before chemotherapy, OHIP may cover the cost ($4,000), and it may save the cost of chemotherapy (~$20,000). 

From the patient’s perspective, it is no small thing to be spared the risks of chemotherapy and its discomforts, including nausea and extreme fatigue.  But for me, having a more accurate prognosis was equally important. Oncotype results are based not simply on the morphology of the cells under the microscope as done by the Pathologists, but upon the actual levels of the various gene products that would be doing the metastasizing, i.e., the spreading of the cancer to new sites. And the recurrence score is considered to be very reliable – so much so, that a low Oncotype score may be trusted to justify foregoing chemotherapy even when the cancer looks nasty according to classical criteria, e.g., when the cells appear highly malignant under the microscope! 

I did not know about Oncotype testing at the time of my diagnosis in 2010, so I had it done after chemotherapy. As it happened, the test affirmed that chemotherapy would substantially reduce my chances of recurrence – just as my oncologist and Pathologist had predicted.  Still, just having the prognosis – just knowing that my chances of recurrence in the next 10 years are only ~10% – has been priceless!  I went from getting ready to die, preparing my will and talking to my kids, to getting ready to go back to work… 

Update,  June 2018

A long awaited landmark study has finally come out. It was funded mostly by the US National Cancer Institute and called TAYLORx. It is the largest ever performed looking at breast cancer treatment.

            Based on the original data published in 2005, the “recurrence score” of the Oncotype test could predict that there will be a benefit of chemotherapy if it is over 25, while there will be no benefit if it is less than 11.  However, the majority of patients fall in the midrange of 11 to 25, and in these cases the prediction was not clear.  Chemotherapy was often given “just in case it helps” stave off a relapse.    

            In the new trial over 10,000 women with ER+, Her2-, node negative breast cancer were examined and 6,700 were in the range of 11-25.  They were assigned at random to receive chemotherapy plus endocrine therapy (drugs stopping the action of estrogens, ie tamoxifen or an aromatase inhibitor eg Letrozole), or endocrine therapy alone. 

The results were stunning!  Nine years later the group that did not receive chemotherapy did just as well as the group that did. The rates of survival free of invasive disease (83.3% in the endocrine-therapy group and 84.3% in the chemotherapy + endocrine therapy group), rates of freedom from cancer recurrence at a distant site (94.5% and 95.0%) or overall survival (93.9% and 93.8%) were very similar!  There was only a small benefit of chemotherapy for women under 50 and with a score of 16-25.

            This is great news for women with cancer that is ER+, Her2- and has not spread to the axillary lymph nodes. This is a common type of breast cancer and almost 70% of women in this category will be spared the chemotherapy and its harsh side-effects, some of which may be irreversible.    

            The next question is, whether he Oncotype test will be covered by the Provincial insurance. As with all drugs and diagnostics, Health Canada approves their use in Canada but it is the Provinces that pay for them. Or not.

Health Quality Ontario (HQO) is an agency of the Ontario government, tasked to decide what tests to cover. It consists of a health economist and an epidemiologist but there are no Molecular Biologists, oncologists etc and no survivors on board. The agency is trying to find out women’s preferences on doing the Oncotype (or other tests), or not.

            The issue is, if women are made aware of the power of this test, since it has no side effects of any kind (it is done on a piece of the cancer that is removed anyway), nobody would say no. Besides, most women would like to have it even for  prognosis alone, not to decide on having chemotherapy or not.

            Therefore, our recommendation to HQO would be to negotiate better prices with Genomic Health, the company doing it.  It might also be possible to develop a similar test using different genes, to develop our own test, not affected by the Oncotype patent. Whatever it is, to give it to all women.

            The Oncotype test is now covered by OHIP if it is done before chemotherapy and if there is no lymph node involvement. However, the test is useful even if up to three lymph nodes are involved.  If the tumor has proven itself able to invade the lymph nodes, the chances of the score being low enough as to forgo chemotherapy are rather low, but significant. You may want to do the test even for prognosis, but then OHIP does not cover it.  If the score is low but close to the line you may still want to have chemo, unless you have other health issues that might be aggravated by the chemo.

            A clinical trial is running now at Sunnybrook Hospital in Toronto: They are trying to find out whether the results of the Oncotype test affect the physician’s treatment recommendations for the treatment of women with 1-3 positive lymph nodes who are potential candidates for chemotherapy, but for whom the benefits of chemotherapy may be uncertain. The information is in the next article.

Leda Raptis, Ph.D.,

professor, Queen’s University

July 2018

The original paper is below: 

Sparano et al, New England Journal of Medicine June 3, 2018. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer



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