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Oncotype DX Study Underscores Challenges for Patients, Doctors in Interpreting Genomic Test Results

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Originally published March 9.

By Turna Ray

Further highlighting the complexity of physician-patient discussions in communicating genomic test results, a new study published in Cancer this week reports that some women who had their breast tumors analyzed by Genomic Health's Oncotype DX breast cancer recurrence test did not understand their test results.

In the study, titled "Women's Experiences With Genomic Testing for Breast Cancer Recurrence Risk," researchers led by University of North Carolina-Chapel Hill's Noel Brewer surveyed 77 women previously treated for early-stage breast cancer at the university's Breast Center who had received testing on Oncotype DX between 2004 and 2009, and found that one-third of participants did not fully understand discussions surrounding their genomic test results.

While most of the women in the study (95 percent) said the Oncotype DX test helped improve their understanding of whether they would benefit from chemotherapy, around 25 women, or 32 percent, said they comprehended "a moderate amount or less" of the discussion of their test results with their physician. Approximately 25 percent of participants said they felt "distressed" when receiving their test results.

Genomic Health's Oncotype DX, which has been on the market since 2004, assesses the expression of 21 genes in a patient's tumor sample and yields a recurrence score between 0 and 100 that translates into high risk, low risk, or intermediate risk for patients. Previous studies have shown that a low 21-gene recurrence score identifies patients with estrogen receptor-positive breast cancer who do not appear to benefit from CAF plus tamoxifen treatment despite positive axillary lymph nodes.

Brewer suggested a number of possible reasons for why some women understood their genetic risk information less than others, including the complexity of the information in the Oncotype DX test report, and the type of communication the patient had with their doctor.

"The output from Oncotype DX that's provided from Genomic Health presents a lot of information," Brewer told Pharmacogenomics Reporter last week. The report is "pretty hard to follow," he added. "It gives you your recurrence score, then it gives you your recurrence risk; it gives you a 95 percent confidence interval, which I think is a sophisticated notion for most people."

Additionally, the way doctors presented genetic risk information seemed to impact patients' grasp of the information in the study. Researchers found that women who reported that they understood less were more likely to not have received printed materials about Oncotype DX.

"Our findings suggest that a way to help women achieve greater perceived understanding may be to provide printed materials about the test," the researchers said in the paper.

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Brewer discussed the study findings with the caveat that Oncotype DX testing is performed during an already stressful period in a woman's life, making her more prone to anxiety. Oncotype DX is only performed to guide treatment decisions for women who have been newly diagnosed with early-stage breast cancer with either node-negative, estrogen-receptor positive or postmenopausal, node-positive, hormone-receptor-positive disease.

"Making decisions about breast cancer treatment is very complicated," Brewer said. "They have to make decisions about treatment as they go and chemotherapy is just one more decision. So it's a time during which most women are pretty anxious about what their future holds. Then there is all this relatively sophisticated information coming at them.

"The length and complexity of the conversation makes this hard," Brewer explained. "Then on top of that the communication tools that Genomic Health provides are not ideal."

According to Genomic Health's Chief Medical Officer Steve Shak, the company developed the format for the test report with input and guidance from patients, physicians, and advocacy groups. "The current version of the report does reflect their best advice and guidance on how to make the key information available," Shak said.

In Shak's view, while Oncotype DX provides important information about breast cancer patients' treatment choices, the ultimate decision is made between the patient and the doctor after factoring in things that are outside the scope of the test, such as patient choice, medical history, and tumor characteristics.

"The recurrence score by itself, as an individual number, doesn't tell you to treat or not to treat. Therefore, the discussion about the recurrence score and what it means for an individual patient does need to involve a discussion about the patient's preference, other factors such as age, and tumor size," Shak noted. "Those aspects that are key to decision-making are not actually on the report. That's the role of the physician.

"We can do what we do … but that communication that occurs in the doctor's office is the key to getting to the best decision," he added.

Genomic Health depends mainly on its educational websites, the numerous published studies in peer-reviewed journals on Oncotype DX, and its 88-person sales team to educate physicians and patients. The company runs a website dedicated to educating breast cancer patients about Oncoytype DX, called mytreatmentdecisions.com, which includes an automated questionnaire to help determine if genetic testing is appropriate for patients, testimonials from women who have been tested on Oncotype DX, and guidelines for what to ask physicians about testing.

According to Genomic Health spokesperson Emily Faucette, the company is continuously updating and improving the test report. She pointed out that a section on Genomic Health's site dedicated to physician education explains every portion of the Oncotype DX report, and noted that this could be a resource for physicians in helping guide conversations with their patients.

Genomic Health officials highlighted another study published in January in the Journal of Clinical Oncology that evaluated 89 patients prospectively to determine if the Oncotype DX recurrence score impacts doctor-patient decisions about adjuvant treatment selection and affects their level of satisfaction. This study, led by researchers from Loyola University, concluded that test-related anxiety among patients was highest before receiving test results, but decreased after results were received, and further lessened over a 12-month period.

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The researchers in the JCO study concluded that Oncotype DX test results impact physician and patient adjuvant treatment decision-making, physician confidence in making treatment recommendations, and patient satisfaction, and ultimately decrease patient anxiety.

Likewise, the findings of the Cancer study are generally positive about women's perceptions of the Oncotype DX test. Researchers found that most participants recalled their recurrence risk accurately, and two-thirds said they understood most of what they discussed with their doctors.

"On the basis of these two findings, it seems that physicians are successfully incorporating genomic test results and promoting informed decision making about adjuvant treatment options," the study authors found.

However, researchers noted that test-related distress and perceived recurrence risk increased with higher patients' recurrence risk scores. A woman's risk of recurrence is considered "low" if Oncotype DX yields a score under 18. A recurrence score of between 18 and 30 percent is considered "intermediate" and a score higher than or equal to 31 means a woman is at "high" risk of having their cancer recur.

In the study, 13 percent of women received a "high" recurrence score, 50 percent received a "low" score, and 37 percent were in the "intermediate" category. "The intermediate risk group had mean levels of test-related distress, and perceived recurrence risk that were between the low and the high recurrence risk groups," the researchers reported.

The National Cancer Institute is currently evaluating the effect of chemotherapy on women who fall in the "intermediate" recurrence score category after getting tested on Oncotype DX. The Trial Assigning Individualized Options for Treatment, or TAILORx, study is studying 10,000 patients from multiple sites in the US, Canada, Ireland and Peru.

Last year, the St. Gallen International Expert Consensus panel recommended the use of multi-gene assays to guide treatment decisions in early breast cancer patients. However, experts found that intermediate scores from such multi-gene tests provide "little guidance in reaching a decision to use chemotherapy" [see PGx Reporter 07-08-2009].

"Results from the TAILORx trial may further refine the identification of women with intermediate recurrence risk who will benefit from chemotherapy and those who can go without," Brewer and his colleagues point out in their paper.

In Brewer's view, Agendia's MammaPrint, which gives a binary result (low risk or high risk), may remove some of the uncertainty and distress experienced by patients deemed "intermediate" by Oncotype DX.

Still, in terms of communicating genetic risk information to patients, its seems neither test report has gotten it just right, yet. Conversations with patients tested on MammaPrint and Oncotype DX suggest that patients want a little more information than the MammaPrint report provides, but not as much as the Oncotype DX report gives, according to Brewer.

Limitations of the study conducted by Brewer and colleagues include a small sample size, and its retrospective cross-sectional design. The study authors did not provide any recommendations for how to improve the conversation between doctors and patients about genetic risk data.

Improving physician knowledge of pharmacogenomics and genomic testing in general has been emphasized by regulatory officials and industry observers alike. The FDA and the American Medical Association offer a free online educational course to improve doctors' basic understanding of pharmacogenomics [see PGx Reporter 06-20-2007]. The American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend the use of Oncotype Dx to guide decisions about adjuvant chemotherapy treatment in early stage breast cancer patients.

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