NEW ORLEANS — A huge European trial has shown that the 70-gene assay MammaPrint can identify patients with early breast cancer who can safely skip adjuvant chemotherapy, even if they have clinical characteristics suggesting they are at high risk.
Results from this academic trial have been eagerly awaited since the trial began in 2007.
Known as MINDACT (Microarray for Node-Negative Disease May Avoid Chemotherapy Trial), the study involved 6693 patients across nine European countries.
It cost around €47 million (US$53 million), with funding provided by the European Organisation for Research and Treatment of Cancer (EORTC) Charitable Trust.
Outcome data, with a median follow-up of 5 years, were reported for the first time here at the American Association for Cancer Research 2016 Annual Meeting.
The women taking part in this trial had early-stage breast cancer and had undergone surgery. For the total trial population, the results show that using the genomic assay resulted in a 14% reduction in chemotherapy use versus assessment by clinical features of disease.
But the results were even more striking for a subgroup of patients, who were classed as high risk on clinical assessment. In these patients, use of the genomic assay is associated with a 46% reduction in chemotherapy prescription.
"The MINDACT trial results provide level 1A evidence that using MammaPrint could change clinical practice by substantially de-escalating the use of adjuvant chemotherapy and sparing many patients an aggressive treatment they will not benefit from," said principal investigator Martine Piccart, MD, PhD, head of the Department of Medicine at the Jules Bordet Institute in Brussels, and cofounder and chair of the Breast International Group (BIG).
Congratulating Dr Piccart and colleagues on their "heroic research enterprise," discussant Harold Burstein, MD, PhD, from the Dana-Farber Cancer Institute in Boston, said the new data make a "seminal contribution" to the field. "If you integrate this genomic assay into clinical practice, you can identify patients who can skip chemotherapy," he said.
However, Dr Burstein also noted that the results "bear mostly on the heterogeneity within ER-positive and HER2-negative cancers, which are familiar terrains for other genomic profiles/assays."
It is unclear where MammaPrint will fit in alongside the other gene-expression signature assays that are already available, and in particular Oncotype Dx, which is widely used in the United States and dominates the market. One clinician estimated that MammaPrint has only 10% of the market share.
Dr Piccart hopes that the new data will encourage clinicians to use MammaPrint, but she also acknowledged that there are other genomic tests available that "are quite good."
"What is important is for women to have access to one of these genomic tests," she said.
She noted that in the past (and in the trial), the MammaPrint test was carried out on frozen tissue samples, which had to be transported under liquid nitrogen to the testing laboratory. This has been cited as a major drawback of the test for regular use in clinical practice. But a new version of MammaPrint has been available now for about 2 years that is carried out on fixed paraffin tissue samples — the most common way that samples are stored.
Results Relevant for the United States
Approached for comment, Clifford Hudis, MD, chief of the breast medicine service at the Memorial Sloan Kettering Cancer Center in New York City, told Medscape Medical News that the new data from Europe "are relevant for the United States."
"One of the drivers of the use of another test, the Oncotype Dx, was the availability of data suggesting that it could be used to select for or against the addition of chemotherapy to endocrine adjuvant treatment in hormone-receptor-positive disease," he said. With the new data, the MammaPrint test "may be able to fulfill a similar role in helping guide clinicians to a better treatment decision for each individual patient."
"A key aspect of this new result is that it may provide additional evidence that genomic tests really can play a role in everyday practice for patients with early-stage breast cancer," Dr Hudis said.
Details of the Results
When the MINDACT trial began in 2007, it recruited patients with early-stage breast cancer and negative lymph nodes, but the protocol was changed in 2009 to also allow patients with one to three positive nodes, Dr Piccart noted. In the overall trial population, about one in five patients had node-positive disease, she noted, and about 10% of tumors were HER2-positive, which are biologically aggressive.
The genomic test was compared with clinical assessment using Adjuvant! Online, and women were classed into one of four categories.
Women who were assessed as low risk by both genomic and clinical tests — i.e., G-low, C-Low (n = 2743; 41%) — did not received chemotherapy, and the results show that they had the best outcomes, with a distant-metastasis-free survival at 5 years of 97.6%.
Women who were assessed as high risk by both measures — i.e., G-high and C-high (n = 1807; 27%) — were strongly encouraged to have chemotherapy, but despite this, they had the worst outcomes, with a distant-metastasis-free survival rate at 5 years of 90.6%.
The main part of the trial focused on the women in which the results were discordant, having been assessed as high risk by one measure but low risk by the other, and these patients were randomized to receive chemotherapy or not (anthracycline or taxane regimens). Patients also received endocrine therapy (tamoxifen for 2 years followed by letrozole for 5 years or letrozole for 7 years).
The outcomes in these two discordant groups were similar, with a distant-metastasis-free survival rate at 5 years of 94.8% in women assessed as C-high, G low (n = 1550; 23%), and a rate of 95.1% in women assessed as C-low, G-high (n = 592; 9%).
The curves for patients who did receive chemotherapy were almost superimposable on those who did not, Dr Piccart said, suggesting that there was no benefit from the chemotherapy.
"We know that not all patients who currently receive adjuvant chemotherapy need the treatment, and they endure significant adverse side effects without gaining clinical benefits," Dr Piccart commented. These new results show that use of this genomic assay helps to identify those patients that can skip chemotherapy, even if they are assessed clinically as being high risk.
In his discussion, Dr Burstein said the implications from MINDACT and other recent related trials are that "most ER-positive HER2-negative stage I and II cancers, including N1, warrant tumor genomic profiling for optimal decision making, in particular choosing whether to receive chemotherapy."
Dr Piccart reports serving as a consultant for several pharmaceutical companies, but said the disclosures are not relevant to this academic trial. Dr Burstein has disclosed no relevant financial relationships.
American Association for Cancer Research (AACR) 2016 Annual Meeting: Abstract CT-039. Presented April 18, 2016.
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Cite this: MammaPrint Shows Which Breast Cancer Patients Can Skip Chemo - Medscape - Apr 19, 2016.