Region specific data, presented at the 12th International Breast Cancer Conference at St Gallen, (Switzerland, 16 to 19 March), showed gene expression testing to be readily applicable to European patients with early stage breast cancer. Studies using the Oncotype DX technology were presented for UK, German and Spanish patient populations.

The Oncotype DX breast cancer test, developed by Genomic Health, provides a snap shot of tumour activity at the molecular level by measuring the expression of 21 genes (composed of 16 breast cancer genes and five reference genes). Readouts are then fed into mathematical equations to produce the patient's Recurrence Score^® (RS), giving a numerical figure to the woman's likelihood of benefitting from chemotherapy and experiencing a metastasis over the next 10 years on scales between 0 and 100. Women with scores below 17 are considered at low risk of recurrence, those with scores between 18 and 30 at intermediate risk and those with scores above 31 at high risk. The analysis, which takes place at Genomic Health's headquarters in California, involves using real time PCR on tumour blocks to measure levels of RNA. Together with other laboratory results and clinical findings the score helps doctors develop unique tumour plans for individual patients.

"In the past we've used a one size fits all approach where all women with early stage breast cancer get offered chemotherapy," said Steven Shak, the chief medical officer at Genomic Health. "But in reality only four out of 100 women actual benefit, with the remainder experiencing unnecessary toxicity."

The Oncotype DX test is widely used in the US where it was launched in 2004 and is now routinely offered to women with stage I or II node negative and oestrogen receptor positive disease. It is not offered to women who are oestrogen receptor negative , said Shak, since they are already known to be at high risk of recurrence and to obtain benefit from chemotherapy.

Initial development involved first identifying candidate genes by retrospectively matching the presence of different genes in tumour blocks to patient outcomes; and then in separate studies (involving over 4,000 patients) validating the results.

What has been less clear is whether the Oncotype DX test would be valuable in European health care settings that traditionally use less chemotherapy.

At St Gallen Simon Holt, a surgical oncologist at the Prince Philip Hospital (Llanelli, Wales) presented a prospective analysis of 107 patients who had undergone testing with the South West Wales Breast Cancer Network. In the study the team analyzed how many women initially been evaluated with the Nottingham Prognostic Index (the current evaluation tool) had treatment decisions changed following evaluation with the Oncotype DX technology.

Results showed that overall 33% of patients in the study had their treatment decisions changed. This was composed of 23.6 % who changed from receiving both chemotherapy and hormone therapy to just receiving hormone therapy and 9.4 % who changed from just receiving hormone therapy to receiving hormone therapy plus chemotherapy.

"From the clinical perspective it's probably more important to identify those patients who'll benefit from chemotherapy," said Holt, adding that women were quite happy to undergo treatment once they appreciated its significance. Results of a similar magnitude were also presented from studies undertaken in Germany and Spain.

"In fact the figures for changing treatments proved remarkably similar whether the studies were undertaken in the US or different European countries," said Holt, adding that this demonstrates that women across the world experience similar breast cancers.

In a further abstract John Homberger and colleagues, from Stanford University (California, US), undertook a meta analysis of nine studies involving a total of 1154 patients. The results showed that Oncotype DX testing led to an approximately 35% change in treatment decisions.

Also presented was a cost effective analysis, undertaken by the International Medical Centre in Singapore, showing that the average direct potential savings per patient test were €1,569 for chemotherapy, €90 for management of adverse events , €90 for management of adverse events, and €714 for administration. Additionally, investigators led by Gilberto de Lima Lopes,showed there to be a €249 cost per patient saving from loss of productivity.

Widespread introduction of testing, Holt said, could result in a paradigm shift where more cancers than ever before might be treated with a "watch and wait" strategy.

"You need to know whether the cancer you're dealing with is a tiger or a pussy cat. In future if cancers aren't shown to be aggressive from profiling it may become feasible to leave them alone," he said, adding that such a strategy would be particularly valuable for prostate cancer.

Genomic Health already has an assay in colon cancer, launched in 2010, and another in development in prostate. "Future assays may even be able to show whether anthracyclines or taxanes would be more effective in individual patients," said Shak.

References

S Holt, G Bertelli, D Pudney et al. Results from a prospective clinical study on the impact of Oncotype DX on adjuvant treatment decision and risk classification by Nottingham prognostic index (NPI) and recurrence score (RS) Abstract P196.

G de Lima Lopes, R Chien, J Hornberger Cost-benefit analysis of a 21-gene recurrence score for early stage breast cancer in Singapore Abstract P215A

J Hornberger, R Chien Meta-analysis of the decision impact of the 21-gene breast cancer Recurrence Score® in clinical practice Abstract P201.