Approximately 15% of women diagnosed with a hormone receptor positive, HER2-negative, lymph node negative invasive breast cancer will have the cancer come back within 10 years after treatment with adjuvant endocrine therapy alone. The risk could be reduced by adding chemotherapy to the treatment of some of these women.

Different multigene tests have been developed to stratify patients with early breast cancer into different risk groups by analysing the activity of various genes. 

The goal of these tests is to identify patients who might benefit from the addition of chemotherapy and patients who gain little or nothing from it and may safely avoid toxicities of chemotherapy.


If you have been diagnosed with hormone receptor positive, HER2-negative, lymph node negative or up to three lymph nodes positive invasive breast cancer, should multigene tests be used to guide the use of chemotherapy?

The ECIBC's Guidelines Development Group (GDG) suggests:

Who is this recommendation for?

  • You have been diagnosed with breast cancer, and you may have been told the tumour is hormone receptor positive, HER2-negative and has not spread to the lymph nodes or has spread only to three or fewer lymph nodes
  • Your healthcare professional may have advised multigene tests to decide the best treatment for you

What would following this recommendation mean for you?

It might be important to speak with your healthcare professional about your clinical risk of the cancer coming back after treatment.

You may also wish to speak with your healthcare professional about:

  • availability of the multigene tests, and how these are performed
  • what the test results mean
  • treatment for invasive breast cancer and the benefits and harms of chemotherapy.

Additional considerations

The use of the 21 gene recurrence score may result in a significant reduction in the administration of chemotherapy to women who are unlikely to benefit from it. The utility of the test (or changes in treatment decisions) would probably be larger in women with high clinical risk. However, the evidence is very uncertain.

In women with a high clinical risk, the use of the 70 gene signature test may result in a reduction in the administration of chemotherapy to women who are considered unlikely to benefit from it. However, this may be associated with a slight increase in the risk of the cancer spreading to other parts of the body (distant metastasis) and the cancer recurring after treatment.

The evidence suggests that women with low clinical risk of cancer recurrence will have no or little benefit from chemotherapy. Therefore, the GDG judged that they would not benefit, in terms of treatment recommendations, from having either test (21 gene recurrence score or 70 gene signature test) performed. 

The GDG noted that the costs of providing the tests would be high, but in women with high clinical risk of recurrence there would be a net saving if chemotherapy is not needed.


In breast cancer, hormone receptors are proteins located in and around breast cells that signal cells to grow.

HER2 is a protein located around breast cells that promote growth. When a breast cancer is HER2-negative it means that the cancer cells do not contain high levels of this protein on their surface and may grow more slowly.

Clinical risk of cancer recurrence uses clinical risk factors, such as tumour size and grade, to estimate the possibility of the cancer coming back after a period of time.

Adjuvant endocrine therapy is a type of treatment given after surgery to women who have a positive hormone receptor test. It lowers or stops oestrogen/progesterone from acting on breast cancer cells and keeps cancer from growing and spreading.

Chemotherapy is a type of treatment that uses drugs to stop the growth of cancer cells.  Because it also damages some other body cells, the side effects can be very unpleasant (e.g. skin rashes, hair loss, nerve damage, nose bleeds).  In deciding whether to undertake it, the benefits of cancer control must be balanced against the harms of these side effects.

Documentation for professionals