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Gene test for breast cancer recurrence not cost-effective in real world

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January 10, 2018

Jeanne S. Mandelblatt

Oncotype DX, a common gene expression profile test used to predict recurrence among patients with early-stage, node-negative ER-positive, HER-2-negative breast cancer, may not be cost-effective in a real-world setting, according to a study published in Journal of Clinical Oncology.

Under ideal conditions— in which all patients received the test and all physicians and patients used the results to dictate treatment — the Oncotype DX (Genomic Health) had a cost-effectiveness ratio of $39,496 per quality-adjusted life-years (QALYs). However, test accuracy and adherence to test-recommended treatment contributed to a lack of cost-effectiveness in the real world.

“Under idealized conditions, the test is considered cost-effective,” Jeanne S. Mandelblatt, MD, MPH, professor in the departments of oncology and medicine at Georgetown University School of Medicine and a member of Georgetown Lombardi comprehensive Cancer Center, said in a press release. “But, by looking at national data, our economic analysis found that the likely cost-effectiveness ratio for Oncotype DX testing in community practice was higher than the ratios for the most commonly accepted diagnostic and preventive interventions.”

Gene expression profile testing is used to identify patients at high risk for recurrence who would benefit from chemotherapy, while allowing those with a low risk to forego chemotherapy, thereby offsetting test costs with savings from lower chemotherapy use.

“To date, use of [gene expression profile] testing in community practice remains low, ranging from 22% to 42% of test-eligible patients,” the researchers wrote. “Moreover, chemotherapy use is sometimes discordant with test results, with 17% to 26% of patients with high-recurrence risk scores not receiving chemotherapy, and 8% with low-risk scores receiving chemotherapy.”

Mandelblatt and colleagues used a simulation model to compare costs and QALYs for the use of Oncotype DX in the community from 2005 to 2012 with usual care in the pretesting era from 2000 to 2004. Inputs for the simulation included test use, chemotherapy effectiveness, utilities, survival and recurrence, and Medicare and patient costs.

Twenty-four percent of eligible patients aged 40 to 79 years with stage I or IIa ER-positive, HER-2-negative breast cancer completed the Oncotype DX test. Thirty percent of patients received chemotherapy between 2005 and 2012, which included 75.3% of patients with a high-recurrence risk score and 10.2% of patients with a low-risk score.

Tested patients were younger than untested patients (mean age, 56.2 years vs. 50.7 years).

Tested patients aged younger than age 50 years had lower chemotherapy rates than untested patients of the same age (53% vs. 63.6%). Among older patients, chemotherapy rates appeared higher among tested than untested patients (age 50 to 64 years, 35% vs. 30.8%; age > 65 years, 17.6% vs. 8.2%).


Overall, a larger proportion of tested than untested patients who eventually had a distant recurrence received chemotherapy (55.3% vs. 30.4%).

The investigators conducted one million simulations and accounted for varied costs, patient adherence to test-suggested treatment, and net impact of testing on possible reassurance or worry about distant recurrence.

Researchers determined the cost-effectiveness ratio for the test was $188,125 per QALY compared with usual care.

When adjusting for various scenarios, the simulation resulted in increases of cost-effectiveness:

  • Decreasing Oncotype DX costs from the Medicare reimbursement rate of $3,416 to $2,657 resulted in a cost-effectiveness ratio of $71,250 per QALY;
  • Factoring in the assumption that having information about recurrence risk affected patient worry or reassurance resulted in a cost-effectiveness ratio of $58,431 per QALY;
  • Complete adherence to test-concordant treatment resulted in a cost-effectiveness ratio of $85,490 per QALY; and
  • Assuming ideal circumstances resulted in a cost-effectiveness ratio of $39,496 per QALY.

Under the worst-case scenario simulation, the test would be inferior to usual care.

With perfect accuracy, the test had a cost-effectiveness ratio of $28,947 per QALY; however, Oncotype DX does not consider all genes and factors, so the test has less-than-perfect accuracy, according to researchers.

“However, plausible changes in several factors could change the results and lead to Oncotype testing having a cost-effectiveness ratio similar to other commonly accepted practices,” the researchers wrote. “The substantial differences in conclusions about cost-effectiveness ratios based on community vs. more idealized practice underscores the importance of considering real-world implementation when assessing the costs and survival associated with new diagnostic (or treatment) technology.”

In a statement provided to HemOnc Today, Genomic Health noted limitations of the economic model used in this analysis to define the cost-effectiveness of their gene tests. These limitations included:

  • This model reflects the unique perspective of a particular specialized system of care that is not reflective of community practice;
  • The likelihood of recurrence used in this model is higher than what is evidenced in the clinical literature and does not at all reflect that of patients seen in today’s clinical practice; and
  • The cost of chemotherapy is likely underestimated and does not represent the full cost burden for the majority of patients with early breast cancer.

“Cost-effectiveness analyses are very complex and highly sensitive to the assumptions underlying the economic model,” the statement said.“To truly understand the economics of diagnostic testing, it is important to look for consistency across multiple economic studies. Contrary to this single study, Oncotype DX has been shown to be cost-effective, and often cost-saving, in more than 20 studies across the world, indicating that even with varying assumptions, practice patterns and health care costs, Oncotype DX is cost effective.”

For example, a study by Reed and colleagues, published in 2013 in Genetics in Medicine, calculated the incremental cost-effectiveness of Oncotype DC as $10,788 per QALY. Researchers concluded the assay had economic value for node-negative, ER-positive breast cancer. – by Cassie Homer


Reed SD, et al. Genet Med. 2013;doi:10.1038/gim.2012.119.


Disclosures: Mandelblatt reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.

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Charles L. Shapiro

Charles L. Shapiro

A relatively new buzz phrase in oncology is “value of care.” There are several definitions, including: outcomes achieved minus money spent. A critical aspect of assessing value includes what the individual patient values. Cost-effectiveness analyses also are part of determining value. Chandler and colleagues assess the cost-effectiveness of the Oncotype DX test in the real-world setting of women with stages I to stage IIa and ER-positive, HER-2-negative breast cancers covered by Kaiser Permanente of Northern California. It doesn’t take a sophisticated cost-effectiveness analysis to assess the value of the test to women with breast cancer; about 50% of them will avoid chemotherapy because of a low recurrence score, indicating the benefits of chemotherapy are either nil or very little.

This cost-effectiveness analysis is very well done, but the results are somewhat surprising. The cost-effectiveness for Oncotype DX in this population was over $180,000 per QALY for testing vs. not testing, or usual care, well above the range that is considered cost-effective.

There are several aspects of the study that deserve mention. First, only 24% of eligible women during 2005 to 2012 had the Oncotype DX assay. If a higher percentage of women had the test, the cost per QALY would likely go down. Also, in a scenario analysis, researchers used utility weighting to estimate the reassurance or worry about distant recurrence that women would derive from knowing the recurrence score. In scenario analysis the costs of the test reached about $58,000/QALY, in the range of acceptability.

The scenario analysis illustrates one of the significant limitations of cost-effectiveness analyses. Women with low risk gained 0.05 QALYs, whereas women with high risk lost 0.05 QALYs. The gain or loss of 0.05 QALY is an assumption and, depending on the model assumptions and the empiric weighting of utilities, determines whether a test falls in the range of what is considered cost-effective ($50,000-$60,000/QALY or less). Sensitivity analyses test a variety of assumptions. For example, in sensitivity analysis, the range QALYs would be varied for worry or reassurance, such that one gets a broader range of cost-effectiveness values.

The two most important aspects of Chandler and colleagues’ cost-effectiveness analysis is it reflects real-world experience and the study sponsor wasn’t Genomic Heath, the company that developed and runs the Oncotype DX test. In the case of drugs, pharmaceutical companies sponsor many cost-effectiveness analyses, and invariably the drug that is made by the company is more cost-effective.

We need more independent cost-effectiveness analyses based on real-world experiences. Sometimes, the results of these analyses are contrary expectations, as was the case here. But, if this cost-effectiveness analysis was repeated for years 2012 to 2018, and assuming the uptake among physicians was 75% instead of 24%, it is very likely the cost-effectiveness of Oncotype DX would be much more in the acceptable range of dollars per QALY. The value to women would be high, as well, because the Oncotype DX test identifies who does and doesn't benefit from chemotherapy.

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Schnipper LE, et al. J Clin Oncol. 2015;doi:10.1200/JCO.2015.61.6706.
Shapiro CL, et al. J Clin Oncol. 2017;doi:10.1200/JCO.2017.73.7437.

Charles L. Shapiro, MD, FASCOE

HemOnc Today Editorial Board Member
Icahn School of Medicine, Mt. Sinai

Disclosures: Shapiro reports no relative financial disclosures.