1. Carlson, Robert H.

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NEW ORLEANS-According to an analysis of the randomized EORTC 10041/BIG 3-04 MINDACT study, a genomic assay can outperform clinical criteria in selecting women for adjuvant chemotherapy for breast cancer by reducing the use of adjuvant chemotherapy without impairing outcome.

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MINDACT evaluated the clinical utility of the 70-gene signature MammaPrint assay in selecting women for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes.


It showed 14 percent of MINDACT patients could have avoided chemotherapy if MammaPrint, combined with common clinical-pathological criteria, were used to assess risk rather than traditional clinical assessment, the researchers reported during a presentation at the American Association for Cancer Research.


"Most oncologists today make recommendations for adjuvant chemotherapy by considering common clinical and biological criteria, but MINDACT trial results provide level 1A evidence that MammaPrint could change clinical practice by substantially de-escalating the use of adjuvant chemotherapy and sparing many patients an aggressive treatment that will not benefit them," said principal investigator Martine Piccart, MD, PhD, Head of the Medicine Department at the Jules Bordet Institute in Brussels, Belgium, and co-founder and Chair of the Breast International Group (BIG).


MammoPrint Assay Utility

American Association for Cancer Research President Nancy E. Davidson, MD, Professor of Oncology and Medicine and Director of the University of Pittsburgh Cancer Institute, was asked to comment on the report after the meeting.


"It is very exciting to see this very large trial come out with this result, though what impact it may have in the U.S. remains to be seen," Davidson told Oncology Times in an interview.


"One of the great things about this trial is that it provides really strong evidence of the clinical utility of the MammoPrint assay," she continued. "We have routinely used the Oncotype DX assay in this country, but doctors are also having discussions about where to use MammaPrint versus Oncotype DX, even at my institution, so this is very much a work in progress."


Patients in MINDACT

MINDACT enrolled 6,693 women in nine countries who had undergone surgery for early-stage breast cancer. They were classified as low or high risk for recurrence by MammaPrint and by a modified version of the Adjuvant! Online tool that uses common clinical and biological criteria, including patient age, tumor stage and grade, as well as hormonal receptor and HER2 status.


Median patient age was 55 years, 79 percent were node negative, 21 percent node positive, 72 percent had T1 tumors (1-2 cm), 88 percent were hormone-receptor positive, and 10 percent were HER2-positive.


Patients were divided into four groups: 2,745 with low risk of recurrence by both genomic and clinical risk-assessment methods; 1,806 with a high risk of recurrence by both risk-assessment methods; 592 with a high risk of recurrence by MammaPrint and low risk of recurrence by a modified version of Adjuvant! Online; and 1,550 with a low risk of recurrence by MammaPrint and high risk of recurrence by Adjuvant! Online.


Patients assessed as having low risk by both genomic and clinical criteria were assigned to no adjuvant chemotherapy, while those assessed as having high risk by both criteria were assigned to adjuvant chemotherapy.


Patients with discordant results-genomic high risk/clinical low risk or genomic low risk/clinical high risk-were randomly assigned adjuvant chemotherapy or no adjuvant chemotherapy.


Low-risk patients were mainly node-negative and hormone-receptor positive with small tumors, while high-risk patients predominantly had larger tumors, were node-positive in 25 percent of the cases, and triple-negative in approximately one-third of cases.


Study Results

Piccart reported a 5-year rate of distant metastasis-free survival of 97.6 percent for women who were low risk by both genomic and clinical criteria who did not receive adjuvant chemotherapy, compared with 90.6 percent among the women who were high risk by both criteria and who did receive adjuvant chemotherapy.


The 5-year rates of distant metastasis-free survival were 94.8 percent in patients who were clinical low risk/genomic high risk, compared with 95.1 percent in those clinical high risk/genomic low risk.


"The MINDACT trial has played a major educational role in Europe, mobilized hundreds of professionals and popularized the concept of biology-driven treatment," Piccart said. "It demonstrated that genomics can provide important information in order to treat patients with early breast cancer, and implemented the logistics to collect and freeze tumor materials in a quality-controlled fashion and built an invaluable biobank for future research in breast cancer."


According to Piccart, the main limitation in clinical practice is that every physician uses his or her own criteria for determining chemotherapy administration, which makes it hard to estimate precisely the true reduction in chemotherapy administration that can be achieved by using MammaPrint.


Robert H. Carlson is a contributing writer.