AMSTERDAM, Netherlands-An "excellent" five-year disease-free survival rate of 94 percent was found in patients with intermediate- or high-risk hormone receptor-positive (HR+) early breast cancer-and up to three involved lymph nodes-who were selected for chemotherapy-free treatment because they had 21-gene recurrence scores (RS) of 11 or below in the prospective phase III Plan B trial reported at the European Breast Cancer Conference (Abstract 8LBA).
"We have been able identify about 15 percent [of patients] who were assessed by the RS as being at low genomic risk. We were thus able to treat them by anti-hormonal therapy alone and spare them chemotherapy," said lead author of the trial Oleg Gluz, MD, Joint Scientific Coordinator of the West German Study Group, and Clinician at the South German Breast Center, Niederrhein Hospital in Monchengladbach.
Gluz said the data show the RS should be incorporated into risk stratification in combination with nodal status, grade, and tumor size for adjuvant treatment decisions in early hormone receptor-positive, HER2-negative breast cancer. "The RS provided additional and independent prognostic information beyond that of established and important clinical prognostic markers such as nodal status, tumour grade and size," he told OT.
In Plan B from among the 3,198 patients recruited with hormone receptor-positive HER2-negative disease, the 348 with RS from 0 to 11 and up to three positive lymph nodes patients were treated by endocrine therapy as their only adjuvant treatment.
Gluz pointed out the excellent event-free survival in patients treated by endocrine therapy alone was irrespective of whether they were node negative or had up to three positive lymph nodes and that all other patients-with intermediate or higher scores, or who had more than four positive lymph nodes-were randomized to anthracycline or anthracycline-free chemotherapy.
The patients with intermediate genomic risk (RS 12-25) had the same event-free survival with chemotherapy as the low-scoring patients without it: 94 percent: "So a significant overtreatment by chemotherapy is likely in this group," Gluz said. And the study found patients with scores over 25 had only 84 percent event-free survival-despite the use of chemotherapy. "In these patients, additional therapy is absolutely needed to improve outcome, he said.
Nadia Harbeck MD, PhD, Scientific Lead of the West German Study Group and Head of the Breast Center and Clinical Trials Unit, University of Munich, Germany, said in a press briefing, "Based on our results, we now have stronger evidence for the use of the 21-gene RS test and its implementation into clinical guidelines."
Harbeck added that further long-term data were expected soon from a prospective trial using the MammaPrint 70-gene test, and that-together with the Oncotype DX findings-these could strengthen the case for incorporating such prospectively evaluated genomic assays into practice in all European countries.
"The use of multi-gene tests also seems reasonable for selecting patients in the future who may benefit from novel-targeted therapies, since patients in the genomic high-risk group do have a relatively poor outcome despite the use of chemotherapy," Harbeck added.
Study Supports Genomic Testing
Chair of the European Breast Cancer Conference, Fatima Cardoso MD, Director of the Breast Unit, Champalimaud Clinical Centre, Lisbon, Portugal, said the data add to the evidence from the low-risk arm of the prospective US-led Trial Assigning IndividuaLized Options for Treatment (TAILORx)-also using Oncotype DX risk stratification.
And Cardoso mentioned a "wealth" of other retrospective studies, supporting the use of genomic testing to help accurately select patients with early breast cancer who can safely do without chemotherapy. "Many cost-effectiveness studies have provided additional support for this strategy," she said.
"[Plan B] is an important study that adds to other information that we already have regarding the use of Oncotype DX," Cardoso added. But she was awaiting confirmation from the forthcoming results due from trials in which the allocation to chemotherapy was randomized.
She highlighted the fact that Plan B did not randomize patients between chemotherapy or not: "They were assigned not to receive chemotherapy for five years. We need to have the 10-year results! [But] at five years, they seem to have a very good prognosis and a very good survival," Cardoso acknowledged.
In an interview for OT, Karen Gelman, MD, Professor of Medicine, University of British Columbia, and Medical Oncologist at the BC Cancer Agency, Vancouver, also mentioned the other large studies on the value of genomic risk assessment. "I think those trials are really going to give us the answers. What the trials do-and what this big cohort Plan B does-is to give us further evidence," she said.
Gelmon added that the benefit of genomic testing is now becoming clear. "We've been looking at the Oncotype recurrence score for a while, and numerous studies have now shown that it does identify a group of women for whom chemotherapy might have been considered but who can be spared chemotherapy," she said. "It gives me further confidence that using these tests will help us make the best decisions for women."
Gluz explained, however, that not all patients need the gene test because at the extremes other markers can discriminate whether to use chemotherapy or not. "We need very good pathological assessment before genomic testing will be done," he said. "For example, based on the Ki67 levels, we will show that patients with very low Ki67, below 10 percent-absolutely very low proliferating tumors-these patients would not need any additional genomic testing."
Similarly, he explained, all patients with Ki67 more than 40 percent-highly proliferating tumors-will have high recurrence scores. "So from a cost perspective for these patients, we could spare the test," he said.
But in the intermediate unclear group such as patients with Ki67 between 15 and 35 percent: "Within this unclear group, I would absolutely recommend to use Onxcotype DX for further chemotherapy decisions and not to give chemotherapy to everybody," he insisted.
"We should use all prognostic markers together to have the best decisions for our patients; central grade, local grade, node status, tumor size, and recurrence score should be put together to have the best adjuvant decisions," Gluz concluded.
Peter M. Goodwin is a contributing editor.