Oncotype DX (Genomic Health), the 21-gene recurrence score (RS) assay that can help predict the risk for metastasis in patients with hormone-receptor-positive breast cancer, was found to have an impact on the use of chemotherapy in a large retrospective study.
The study was published online August 27 in JAMA Oncology.
The team, led by Michaela Ann Dinan, PhD, assistant professor in medicine at the Duke University School of Medicine in Durham, North Carolina, hypothesized that the adoption of this assay would be associated with lower odds of receiving chemotherapy, but this wasn't the case.
In the study of more than 44,000 Medicare beneficiaries, there was no overall association between the receipt of testing and chemotherapy use.
However, for women considered to be at high risk for recurrence, chemotherapy receipt was less frequent when the RS assay was used than when it wasn't (odds ratio [OR], 0.36; 99% confidence interval [CI], 0.26 - 0.50). And for women considered to be at clinically low risk, chemotherapy receipt was more frequent when the RS assay was used (OR, 3.71; 99% CI, 2.30 - 5.98).
In a prespecified subgroup analysis of patients 66 to 70 years of age, there was an overall decrease in the receipt of chemotherapy — from 29% to 24% — but that was limited to patients with high-risk disease and to those tested with the RS assay.
There was also a significant association between use of the assay and the risk categories defined by the National Comprehensive Cancer Network (NCCN); genomic testing appeared to change risk groups.
"Although we can't say for sure, since we did not have the results of the genomic risk score, one hypothesis is that in women with high-risk, node-positive disease, perhaps a low genomic risk score helped them make the decision to forgo chemotherapy," Dr Dinan told Medscape Medical News.
"However," she noted, "an alternative explanation is that genomic testing may have been selectively administered to women at the low end of the high-risk spectrum, in whom doctors were in some way trying to find objective evidence to support forgoing chemotherapy."
For women with very-high-risk disease, when the decision to undergo chemotherapy is obvious, "one would then expect genomic testing to be less likely," she explained.
Crucial Details Missing
Although this is the first investigation to evaluate the association between use of the RS assay and the receipt of chemotherapy in a nationally representative sample of patients in community settings, there were a number of limitations.
Many "crucial details" are missing from this report, write Allison W. Kurian, MD, MSc, from Stanford University School of Medicine in California, and Christopher R. Friese, PhD, RN, from the University of Michigan School of Nursing in Ann Arbor, in an accompany commentary.
The pair notes that the two most critical details are the exclusion of women younger than 65 years, who are the majority of this type of breast cancer patient, and the lack of RS assay results, "which markedly limits evaluation of its impact on chemotherapy decision making."
Another limitation is the absence of both patient and physician perspectives, "without which we cannot fully understand how use of the RS assay informs treatment choices," they write.
Only 14% of the patients in this study actually received chemotherapy, which is much lower than the 40% to 50% seen in studies with wider age ranges. This "substantial difference in systemic therapy use suggests that the RS assay use patterns observed here may not generalize to younger women," Drs Kurian and Friese explain.
This study does offer an "intriguing glimpse" into the role of the RS assay in the examination room, they point out. However, given the gaps in the data available, it is impossible to determine whether RS guidance was followed, despite its discordance from standard tumor prognostic characteristics, or whether physicians "chose to dismiss an RS assay result that was concordant with tumor features in favor of a different treatment path."
"Getting 'under the hood' of such complex medical decision making requires supplementing registry data not only with genomic test results but also with measures of the patient and physician experience," they write.
This study does have gaps in the data; in particular, the RS values are not available for any of the patients in the study, said Steven Shak, MD, cofounder and chief scientific officer of Genomic Health, which markets the assay.
However, the data do appear to indicate that testing affected patient care. "Patients considered low risk were identified who might receive a clear and lifesaving benefit from chemotherapy, while high-risk patients were identified who may not have benefited," he explained.
"These results are consistent with the expectations of recurrence scores, in that they would shift care," Dr Shak told Medscape Medical News.
The hope is that future studies will fill in some of the gaps, such as how the RS assay affects long-term patient outcome. This study only looked at breast cancer diagnosis up to 2009, and Medicare coverage didn't begin for Oncotype DX until 2006, he pointed out. "We will know a lot more about the impact of the assay on care as we look beyond 2009."
Chemotherapy Use Drops After Testing
For their retrospective cohort study, Dr Dinan and colleagues used the Surveillance, Epidemiology, and End Results (SEER)–Medicare dataset to identify 44,044 patients diagnosed with incident breast cancer from 2005 to 2009.
Of this cohort, 24.0% had low-risk disease, 51.3% had intermediate-risk disease, and 24.6% had high-risk disease (lymph-node-positive), as defined by the NCCN guidelines.
Overall, 14.3% of patients received chemotherapy in the 12 months after their diagnosis, and more than 80.0% received it in the 4 months after diagnosis. Most of the patients (90%) who underwent RS testing received chemotherapy in the 3 months after testing.
Overall, chemotherapy use in this population remained relatively stable, at 14.3%, although use varied by NCCN risk factors. But for patients who underwent RS testing from 2005 to 2009, receipt of chemotherapy dropped from 20.0% to 14.6%.
As expected, the use of chemotherapy was substantially higher in patients 70 years and younger, and varied by risk. In the younger population, chemotherapy use declined from 29.1% in 2005 to 24.0% in 2009 (P = .004). This decrease was limited to patients with high-risk disease (67.6% in 2005 vs 56.4% in 2009; P = .002) and patients who underwent RS testing (26.4% in 2005 vs 16.1% in 2009; P = .005).
The study was funded by a grant from the Agency for Healthcare Research and Quality. The study authors, Dr Kurian, and Dr Friese have disclosed no relevant financial relationships.
JAMA Oncol. Published online August 27, 2015. Abstract, Commentary
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Cite this: Oncotype DX Impacts Chemotherapy Decisions in Breast Cancer - Medscape - Aug 28, 2015.