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Genetic test indicates chemotherapy benefit for early-stage breast cancer

30 August 2016
Appeared in BioNews 866

A new genetic test could predict which patients with early-stage breast cancer patients would benefit from chemotherapy.

The study, published in the New England Journal of Medicine, suggested 46 percent of women judged to be at high risk of recurrence based on traditional screening methods did not require chemotherapy.

Like many cancers, treatment for breast cancer is most effective when it is caught early. As a result, patients often receive chemotherapy after surgery. However, chemotherapy can be physically challenging and expensive for patients to receive, and may not even affect survival outcomes for some patients.

A multi-national team of researchers enrolled 6693 patients across nine European countries, who had undergone surgery for early-stage breast cancer, in the MINDACT trial. The patients were screened for the expression of 70 gene variants associated with the risk of cancer spread (metastasis) and recurrence using a test known as MammaPrint.

Based on the results, patients were categorised into high and low genomic risk groups, where risk is defined as either a 23 percent or 10 percent chance of recurrence, respectively. Patients were also assessed for risk according to traditional clinical criteria, using a modified version of Adjuvant! Online.

Patients with low genomic risk but high risk according to Adjuvant! Online, or vice versa, were classed as 'intermediate risk'. These 2187 patients were randomly assigned chemotherapy to see how this affected survival outcomes.

Ninety-five percent of patients classed as high clinical risk and low genomic risk, who skipped chemotherapy, were free of metastasis five years later. Compared to patients who received chemotherapy, the difference in survival was about 1.5 percent.

The researchers say that their findings indicate around 46 percent of patients classed as high clinical risk are of low genomic risk, and could be spared chemotherapy without significantly compromising survival rate. The test currently costs around £2000, and is available privately.

Dr Maggie Cheang, a senior researcher at the Institute of Cancer Research in London, noted that 'in the group of patients that are clinically high risk but MammaPrint low, the benefit of chemotherapy and the survival beyond five years is still unclear. In this group, longer follow-up and future studies are needed before we decide to forego adjuvant chemotherapy.'

Professor David Hunter from Harvard University wrote an accompanying editorial to the study, noting that the research study raises questions about the use and interpretation of precision medicine, such as genomic risk, in the future. 'The new tools for tailoring treatment will demand a greater tolerance of uncertainty and greater facility for calculating and interpreting probabilities than we have been used to as physicians and patients', he said.

Professor Laura van 'T Veer, a chief research officer and co-founder of Agendia, who created the test, defended the study's focus on five-year results, saying that breast cancer metastasis is most likely to occur in the first two to five years after a woman's initial treatment. 'The small benefit is something to discuss between a woman and her physician, everyone has to reach their own judgement.'  

70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer
The New England Journal of Medicine |  25 August 2016
Breast cancer patients could be spared chemotherapy with new test
The Telegraph |  24 August 2016
MammaPrint Genetic Test Can Reduce Use of Post-surgery Chemotherapy Among Early-stage Breast Cancer Patients
American Association for Cancer Research (press release) |  18 April 2016
Study Of Breast Cancer Treatment Reveals Paradox Of Precision Medicine
npr |  24 August 2016
When DNA and medical tests disagree about breast cancer risk, which to believe?
STAT |  24 August 2016
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