The 21-gene RS test analyses 21 genes that can influence the development of cancer and how it responds to treatment.
This is according to the latest results of the West German Study Group (WSG) phase III PlanB trial, presented at the 10th European Breast Cancer Conference (EBCC-10) in Amsterdam, the Netherlands, March 9-11, 2016.
The investigators found that 94% of early breast cancer patients whose score on the 21-gene Recurrence Score (RS) test showed them to be at low risk of disease recurrence, were disease-free after 5 years.
The trial is the first to use the multi-gene test to report 5-year survival in patients whose breast cancer meets the following conditions:
- Cancer has not spread to lymph nodes (node negative), or has only spread to 1-3 lymph nodes (node positive early stage)
- Cancer is HR+ or HER2 negative.
HR+ means the breast cancer is hormone receptor positive, indicating the cancer cells have high numbers of receptors for estrogen (ER) or progesterone (PR) on their surfaces, allowing the hormones to drive cancer growth.
HER2 negative means the breast cancer cells do not have high numbers of epidermal growth factor receptors and so will not respond to treatment with trastuzumab (Herceptin) and other therapies that target HER2.
The 21-gene RS test analyzes 21 genes that can influence the development of cancer and how it responds to treatment. The test result is a number from 0-100.
94% of low gene-risk patients alive and disease-free at 5 years
For the trial, the investigators defined a 21-gene RS score of 11 and under as indicating the cancer was at low risk of recurrence. This decision was made despite other clinical indicators - such as lymph node status, tumor size, grade and patient age - suggesting otherwise.
In 2009-2011, the trial enrolled 3,198 patients of median age 56, all of whom underwent the gene test. 348 of the patients (15.3%) had a 21-gene RS score of 11 and under - they underwent treatment with anti-hormonal therapy only; they did not receive chemotherapy as well.
All the other patients underwent treatment that did include chemotherapy. These patients were classed as either medium or high risk (RS score over 25) and were randomized to receive one of two types of chemotherapy: six cycles of docetaxel/cyclophosphamide or four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel.
After a median follow-up of 55 months, the investigators found that 94% of patients in the hormonal-therapy only group (the ones whose gene test predicted they had a low risk of recurrence), were still alive and disease-free 5 years after diagnosis.
Of the higher risk patients who received chemotherapy as well as hormonal therapy, those classed as medium-risk patients also showed a 94% disease-free survival 5 years after diagnosis, while for the high-risk patients, this figure was 84%.
One of the study coordinators, Dr. Oleg Gluz, who is based in Mönchengladbach in Germany, says:
"In this prospective trial for patients who had a clinically-determined intermediate or high risk of recurrence and who had 0-3 lymph nodes involved, we have been able to identify about 15% who were assessed by the 21-gene RS as being at low genomic risk.
We were thus able to treat them by anti-hormonal therapy alone and to spare them chemotherapy. The 94% disease-free survival rate that we observe after 5 years without adjuvant chemotherapy is an excellent result."
The team found the 21-gene RS test was a better predictor of breast cancer recurrence than other more traditional clinical prognostic measures - such as node status, tumor size, grade and presence of Ki67 protein (an indicator of cell proliferation).
'Strong prognostic impact'
The 21-gene RS test takes 8-10 days, as the tumor sample has to be sent to a central lab for analysis. Dr. Gluz says the test is easy to perform, but the costs are not covered in all countries. However, he notes that several studies suggest it saves money because it enables therapy to be tailored to individuals and cuts down use of chemotherapy.
Dr. Gluz says the RS test offered "additional and independent prognostic information beyond that of established and important clinical prognostic markers," and concludes:
"Our data clearly reveal a stronger prognostic impact of RS compared to immunohistochemical tools, such as Ki67 and hormone receptor expression, and thus support the incorporation of the RS test, in combination with nodal status, grade and tumor size, into routine clinical practice for making treatment decisions for these patients."
The trial will continue to follow patients for up to 10 years. A follow-up trial - WSG-ADAPT - has already enrolled over 4,000 patients to investigate use of the RS test with the assessment of early response to short-term pre-surgery anti-hormone therapy.
Dr. Gluz anticipates combining both tools could spare around 50-60% of early breast cancer patients the need to undergo chemotherapy. He and his colleagues expect final survival results from this study to be released in 2021.
Meanwhile, from a study published in the Science Signaling journal, Medical News Today recently learned it may be possible to stop breast cancer spreading via the bloodstream by disrupting the signals cancer cells exchange with cells in the lining of blood vessels.