FDA approves genetic test for women with breast cancer

BMJ 1998; 316 doi: (Published 17 January 1998) Cite this as: BMJ 1998;316:167
  1. Deborah Josefson
  1. San Francisco

    The Food and Drug Administration in the United States has recently approved a gene based test that may help to predict the recurrence of breast cancer. The test detects levels of Her2/neu, a gene on chromosome 17 which is amplified in a subset of breast cancers.

    The test will be manufactured by Oncor under the name Inform and is expected to be commercially available for a cost of about $200 (£125) within three months. This is the first time a gene based test for cancer has been approved by the Food and Drug Administration. The predictive value of the test, however, is controversial.

    About 180 000 women in the United States are diagnosed with breast cancer annually, and 44 000 die of the disease each year. Two thirds of women with breast cancer have localised disease at the time of diagnosis, and 40 000 a year experience a recurrence despite surgical resection. Women whose lymph nodes are positive for metastatic disease at the time of diagnosis routinely undergo chemotherapy, with or without ancillary treatment with antioestrogens or radiation treatment. Therapeutic decisions for patients with node negative disease are more difficult, and increasingly doctors and patients are turning to molecular markers to help them navigate among the choices.

    Many studies have shown that the Her2/neu gene is amplified in a subset of breast cancers and some have implicated it in metastatic disease. About a third of breast cancers test positive for amplification of the Her2/neu gene.

    In clinical trials sponsored by Oncor 31% of patients with localised breast cancer at the time of diagnosis who had a positive Her2/neu test died within five years of surgery, whereas 97% of those with a negative test were still alive five years after surgical resection of the tumour. Dr Jeffrey Ross, chairman of pathology at the Albany Medical Center, and a participant in Oncor's studies, said: ‘The amplification of the Her2/neu gene predicted which women would have a higher risk of relapse and which women were more likely to die of the disease. The Her2/neu test is designed to provide additional information to the patient and her oncologist.’

    But some are cautious about using the test. Daniel Hayes, chief of breast oncology at Lombardi Cancer Center, said: ‘I think it is dangerous to use Her2 to make clinical decisions because I don’t think we know what we are doing with it.’

    The American Society of Clinical Oncology recently voted against recommending the test for patients with breast cancer because of uncertainty about what to do with the results. Numerous research studies have shown that amplification of Her2/neu does correlate with both earlier relapse and shorter survival in women with node positive breast cancer, but in node negative cancers the prognostic significance is much less clear. It is precisely in the node negative population, however, that the test would be most useful.

    The spokesman for the Food and Drug Administration, Dr Steve Gutman, said: ‘This is an interesting and exciting new test, but it should not be used alone in making treatment decisions in patients with breast cancer.’ The administration also cautioned that the current test has a high false positive rate but is quite accurate in assuring a woman that her tumour is Her2/neu negative.

    Oncor's chief executive, Stephen Turner, said that the next step is studying whether the Inform test can help to improve breast cancer survival by helping to risk stratify women into different therapies.

    In a related development many medical research centres have already started clinical trials of monoclonal antibodies directed against the Her2/neu gene product in women whose breast cancers carry the amplification.


    A third of breast cancers carry the Her2/neu gene amplification US NATIONAL CANCER INSTITUTE/SPL

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