A genomic test, evaluated in several clinical trials and approved for use in the U.S. and Europe, can effectively tell early stage breast cancer patients what is their risk of cancer returning. The test, called MammaPrint 70-gene Breast Cancer recurrence assay, was developed by Agendia to give patients’ unambiguous low- and high-risk results.
The test analyzes the activity of certain genes in early stage breast cancer and eliminates the uncertainty of other tests. Moreover, it can help clinicians in deciding whether chemotherapy, or other types of treatments aiming to reduce risk after surgery, are required. A prospective, randomized trial — the MINDACT Phase 3 clinical trial — was set up to investigate this exactly.
In this study (NCT00433589), conducted in several European countries, researchers investigated MammaPrint 70-gene test’s clinical utility as an additional approach to the standard criteria in selecting patients for adjuvant chemotherapy.
The trial enrolled 6,693 women with early stage breast cancer and researchers used the 70-gene signature to determine their genomic risk and a modified version of Adjuvant! Online to determine their clinical risk. The latter is a platform that uses clinical data — patient age, tumor size, etc. — to estimate the risk of cancer recurrence.
Trial results showed that while the clinical data categorized approximately 23 percent of women as high risk, supporting them as candidates for chemotherapy, the MammaPrint 70-gene test showed they had low-risk tumors.
Researchers went on to determine the benefits of chemotherapy in such patients, randomly assigning these women to two groups: one that received chemotherapy and one that did not.
In these patients, results showed that chemotherapy had no significant impact, as the five-year survival rate of patients who did not receive chemotherapy was only 1.5 percent lower than those who did — 94.7% versus 96.2%, respectively. No patient in either group developed metastasis (i.e., the spread of cancer to other organs), a deadly event in cancer.
Most importantly, researchers found that 46 percent of women with high clinical risk were found to carry low genetic risk, according to MammaPrint 70-gene test. This means that patients, if evaluated only according the standard clinical risk assessment, may well be being treated with chemotherapy, and suffering its adverse effects, without need.
“The MINDACT trial accurately predicts that there is no meaningful benefit of chemotherapy in MammaPrint Low Risk patients, despite a clinically High Risk assessment. This was the primary endpoint of this positive trial,” Dr. William Audeh, chief medical officer of Agendia, said in an interview with Breast Cancer News. “Since the risk of distant metastasis guides the decision for potentially curative therapy, noting no difference in DMFS [Distant Metastasis Free Survival] in women with a Low Risk MammaPrint test result, randomized to chemotherapy versus no chemotherapy, has given patients and their physicians the confidence to make the decision to forego treatment.”
He added that Dr. Jose Baselga, physician-in-chief of Memorial Sloan Kettering and a past president of the American Association for Cancer Research, called the very large trial a “tour de force” and its results “practice changing” — “in that they provide evidence that nearly half (46%) of women who are currently prescribed chemotherapy following surgery do not need it and can therefore be spared its damaging side effects, including impaired fertility.”
Since the publication of MINDACT trial results, the prognostic test for risk of breast cancer recurrence has been widely adopted in Europe and the U.S. We asked Audeh, a breast medical oncologist with nearly 30 years of clinical practice experience, what has been the feedback from patients and clinicians using MammaPrint 70-gene test.
“We are seeing use of the MammaPrint test increasing worldwide,” he said. “Women are savvier than ever before, advocate on their own behalf, and use the internet and social media to educate themselves. They are requesting the test from their doctors. Additionally, we are working with regions where the test is not readily available to help patients gain access.”
According to Audeh, the MammaPrint test can only analyze the risk of early stage breast cancers. But can be used in patients of all ages, not just post-menopausal women, and cancers with or without lymph node involvement.
“The test is primarily useful for Stage I or II invasive breast carcinoma, LN [lymph node] negative or up to 3 positive LN, ER positive; in the case of HER2 positive or triple negative, those patients with Stage I tumors may also benefit from genomic profiling,” he said.
Trial results also showed that women with clinically high-risk breast cancer may be evaluated as low-risk with the MammaPrint test. This puts the patient in a difficult position, trying to decide whether to go ahead with chemotherapy or not.
When asked how he might counsel a women facing such a decision, Audeh said: “Patients who are clinically High Risk but MammaPrint Low Risk, benefit, as they might safely avoid chemo; those who are clinically Low Risk but MammaPrint High Risk have additional data … to help them and their doctors determine the best course of treatment.
“One of the most important questions, when determining if chemotherapy is the right course of action, is how likely will the cancer come back or spread to other parts of the body, or metastasize,” he said. “If a woman is clinically High Risk and MammaPrint Low Risk, we would point out that the MINDACT data showed a possible reduction of metastasis of 1.5% for patients who had chemotherapy as compared to those who did not receive chemotherapy. This number did not meet statistical significance, and is below the threshold of benefit that most women would accept to justify the toxicity of chemotherapy.”
In the U.S. the test is available for patients with stage 1 or stage 2 cancer, in tumors smaller than 5 centimeters, and either estrogen-receptor-positive or negative.
Audeh points that while MINDACT’s primary endpoint was reached at the five-year data cut-off, a 10-year follow-up is expected to assess the long-term benefits of chemotherapy in genetic low-risk breast cancer patients.
“Based on when the patients enrolled in the trial, some have already been followed for nine years; however, they will be re-evaluated to provide 10-year data.”
To learn more about the MammaPrint test and the MINDACT Phase 3 study results, read the complete interview here.