Genetic testing
Credit: Darryl Leja, NHGRI
This article was last reviewed on
This article waslast modified on 19 June 2018.

Genetic testing of tumour tissue removed during surgery has been shown to help identify women with early breast cancer who do not need chemotherapy. Chemotherapy can have many unpleasant side effects including tiredness, feeling sick, loss of appetite, sore mouth, anaemia and hair loss.

About half of all women with newly diagnosed breast cancer have a low risk of recurrence after surgery. They have tumours which are hormone receptor (HR) positive and human epidermal growth factor receptor-2 (HER-2) negative with no spread to lymph glands in the axilla (armpit). A randomised trial involving 651 such women published in 2006 used a genetic test, Oncotype DX that examined the activity of 21 genes in RNA extracted from samples of breast tumour. Samples were allocated a score between 0 and 100 to help predict the likelihood of the tumour recurring.

The trial found that those women who had low Oncotype DX test scores were highly unlikely to benefit from the addition of chemotherapy to hormone treatment, while those with higher scores may benefit. However, the majority of women had mid-range test scores, and due to the uncertainty of this score, chemotherapy could not be excluded.

To resolve this uncertainty a much larger prospective randomised controlled trial was carried out with collaboration between researchers from many organisations in North and South America and Canada, funded by the US National Cancer Institute and others. Nearly ten thousand women aged 18 to 75 with early breast cancer who were HR positive, HER-2 negative and axillary node negative agreed to take part and had follow-up information collected. All women whose early tumours had Oncotype DX test scores less than 10 (17% of the total of 9,719) received only endocrine treatment while all those with scores greater than 26 (14%) received both endocrine treatment and chemotherapy. The ‘uncertain’ group with mid-range scores of 11-25 (76%) were randomly allocated to receive either combined treatment or hormone treatment alone.

The results, published in The New England Journal of Medicine on 3 June 2018, showed that the two treatments were similarly effective. Similar proportions of women were free from recurrence of cancer during 9 years follow-up (84.3% after combined treatment, 83.3% after endocrine treatment alone) and 94% in each group had survived. However, an effect of age was noted, there being some benefit from chemotherapy in women of 50 or younger who had upper mid-range test scores of 16 to 25. It was concluded that women over 50 with scores between 0 and 25 could be spared the addition of chemotherapy to hormone treatment, as could those under 50 with scores between 0 and 15.

The lead author of the study, Joseph Sparano of the Montefiore Medical Center, Albert Einstein College of Medicine, New York said “Half of all breast cancers are hormone receptor positive, HER2 negative, and axillary node negative. Our study shows that chemotherapy may be avoided in about 70% of these women when its use is guided by the 21 gene recurrence score, so limiting chemotherapy to the 30% who we can predict will benefit from it”.

The UK National Institute for Health and Care Excellence (NICE) is currently updating its 2013 guidance about the NHS use of the Oncotype DX test in helping to make decisions about chemotherapy in patients after surgery for early breast cancer.