Oncotype DX Cost Effective, Challenges Breast Cancer Practice

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.