Test Pinpoints Which Breast Cancer Patients Can Avoid Chemotherapy

By using a multi-gene test, researchers have found they can determine which patients with early breast cancer can be spared chemotherapy and still survive 5 years after diagnosis.

The results of a West German Study Group (WSG) phase 3 plan B trial showed that 94% of women who with low risk of breast cancer recurrence were disease free after 5 years. This assessment was done by the 21-gene Recurrence Score (RS) (Oncotype DX) test.

The RS test analyzes a group of 21 genes that have the ability to affect how cancer will most likely respond to treatment. For the current study, those who scored an 11 or less were categorized as low risk of recurrence, despite other factors like tumor size, age, grade, and nodal status that suggests patients could be at high risk.

The study enrolled 3198 patients with a median age of 56-years between 2009 and 2011. Of these patients, 248 with an RS score of 11 or less were treated with anti-hormonal therapy alone, while adjuvant chemotherapy was omitted from their treatments altogether.

Patients who had an RS greater than 11 and had more than 4 lymph nodes or hormone-receptor negative disease were categorized at intermediate or high risk. The participants were randomized to receive 1 of 2 types of chemotherapy: either 6 cycles of docetaxel/cyclophosphamide or 4 cycles of epirubicin/cyclophosphamide, followed by 4 cycles of docetaxel.

The results of the study presented at the 10th European Breast Cancer Conference showed that after a median follow-up of 55 months, 94% of low-risk patients administered anti-hormonal therapy were alive and disease free at 5 years, matching the number of patients disease free at 5 years with adjuvant chemotherapy. Meanwhile, 84% of high risk patients who received chemotherapy were disease free at 5 years.

“In this prospective trial for patients who had a clinically determined intermediate or high risk of recurrence and who had 0 to 3 lymph nodes involved, we have been able identify about 15% who were assessed by the 21-gene RS as being at low genomic risk,” said scientific coordinator of the WSG, Oleg Gluz. “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.”

When analyzing additional clinical factors like tumor size, nodal status, grade, and Ki67 protein, the 21-gene RS was a superior independent predictor of disease recurrence than Ki67 or clinical factors alone, according to the study.

“The RS provided additional and independent prognostic information beyond that of established and important clinical prognostic markers such as nodal status, tumor grade and size,” Gluz said. “These are the first 5 year data for a prospectively planned comparison between an independent review of the tumor pathology, including Ki67, versus 21-gene RS. 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.”

Once the RS test is completed, which takes about 8 to 10 days, the tumor tissue is sent to a central laboratory for analysis.

“Based on our results, we now have stronger evidence for the use of the 21-gene RS test and its implementation into clinical guidelines,” added scientific lead of WSG, Nadia Harbeck. “We are also awaiting further long-term data for another test (i.e. Mammaprint) from a prospective trial in the next few months. We would hope that reimbursement for prospectively evaluated genomic assays would now be possible in most, if not all, European countries.”

The follow up for the clinical trial patients will be extended for up to 10 years. Additionally, WSG-ADAPT has enrolled more than 4000 participants to study the combination of RS with the assessment of early response to short-term preoperative and anti-hormonal therapy after a decrease in Ki67. This has the potential to help omit adjuvant chemotherapy in approximately 50% to 60% of early breast cancer patients.

“This very important trial adds to the evidence from the low-risk arm of the TAILORx study, and to a wealth of other retrospective studies, supporting the use of genomic testing to help accurately select early breast cancer patients who can safely be spared chemotherapy,” said Chair of EBCC-10, Fatima Cardoso. “Many cost-effectiveness studies have provided additional support for this strategy. Hopefully, very soon these type of tests will become reimbursed and hence accessible to breast cancer patients in Europe.”