Skip chemotherapy? Jury still out on genomic test for breast cancer

An independent scientific institute says there’s insufficient evidence that a common diagnostic test, the MammaPrint, is actually helping breast cancer patients as it is claimed to do.

The MammaPrint is supposed to determine whether cancer survivors are likely to benefit from chemotherapy to prevent a breast cancer recurrence. The genomic test analyses so-called biomarkers – in this case the activity of 70 telltale genes in the cancer tumour.
“The actual ‘added value’ of the biomarker test for women affected can only be judged when further results of ongoing studies become available,” says Daniel Fleer, from the Department of Non-Drug Interventions at the Germany-based Institute for Quality and Efficiency in Health Care (IQWiG), in a press release.
The comment came after the IQWiG evaluated preliminary results – covering only a five-year period – of the recently published Mindact study, a randomized controlled trial involving nearly 7,000 women with early-stage breast cancer who had undergone surgery.
Chemotherapy after successful tumour surgery aims to kill any cancer cells that might remain in the body, thereby preventing new tumours from forming. Even without it, most patients don’t experience a recurrence of the disease.
To determine which women would likely benefit from chemotherapy, however, doctors consider clinical factors such as age, the number of affected lymph nodes, tumour size and cancer grade. But sometimes a determination remains difficult, in which case doctors may turn to genomic testing.
Some 70,000 women in Germany alone are diagnosed with breast cancer every year, about 80 per cent of whom have no recurrence of cancer after removal of the tumour, according to the IQWiG.
For roughly 20,000 it’s unclear whether a recurrence is likely or whether their cancer would respond to chemotherapy.
If not, chemotherapy, whose numerous common side effects can include serious long-term complications, would be “an unnecessary burden,” the IQWiG said.
Currently four different biomarker tests are used in Germany to help predict the risk of cancer’s recurrence.
Although the IQWiG looked at several studies of the tests to see how accurately they identify women who could do without chemotherapy, insufficient data quality led it to evaluate just one: the Mindact study of the MammaPrint test.
The Mindact study allows the conclusion that the MammaPrint test is essentially effective, the IQWiG says, adding, however, that a few women figuring in the study should have had chemotherapy, but didn’t.
Such occasional miscalculations, it says, are only acceptable if omitting chemotherapy has very substantial health benefits.
Unfortunately, data on chemotherapy’s downside are quite vague, it notes, saying there are only estimates that about 2 to 3 per cent of chemotherapies cause damage – sometimes fatal – to the heart, kidneys or other internal organs.
Overall, the IQWiG concluded, “At the moment one cannot in good faith advise a woman with a high clinical risk and low genomic risk to omit chemotherapy.”
The accuracy of genomic testing can be properly assessed only when data from a longer time frame is available, it says, because metastases – secondary malignant growths – often appear in other organs many years later.
The IQWiG’s standpoint seems reasonable, says Stefan Weimann, head of the Division of Molecular Genome Analysis at the German Cancer Research Centre. Weimann, who didn’t participate in the genomic test evaluation, points out that relapses and metastases after breast cancer frequently don’t occur until 10 to 15 years later.
“It’s also reasonable to criticise the fact that the MammaPrint test doesn’t identify all high-risk tumour patients,” he remarked.
While the test may lead to misdecisions not to administer chemotherapy, Weimann said, “it’s a matter of personal survival for each individual patient, who usually accepts the adverse side effects of chemotherapy over the chance of dying on account of not having it.”