Gene expression profiling

Breast cancer

Gene expression profiling


Pathologists use tests to determine the size, stage, grade, lymph node involvement, and receptor status of a tumour.

These diagnostic tests include histopathology (microscopic examination of tissue which has been sliced and preserved on glass slides) and immunohistochemistry (IHC), which is a process using antibodies to detect specific proteins in tissue. This allows clinicians to decide which treatments will work best for each individual patient.

For example, high-risk tumours benefit more from chemotherapy to reduce the risk of recurrence, but in low-risk tumours the side effects of chemotherapy would most likely outweigh the benefits.

However, in some tumours this risk distinction is not clear and additional tests are needed to help make a decision about whether chemotherapy would add extra benefit compared to hormone therapy alone.

This is where gene expression profiling can be helpful.

Gene expression profiling is a relatively new technology that assesses the tumour at a genetic level to further understand its biological behaviour and help oncologists decide whether chemotherapy is needed or could safely be avoided.

Many tests have been developed over the last five to 10 years and research around the use and effectiveness of gene expression profiling is ongoing.

Even though none of these tests are publicly funded in New Zealand yet, tumour samples can be sent overseas for testing. If you are interested, do discuss these tests with your specialist team.

All of these tests are performed on tissue that has been used for diagnostic purposes, so no additional biopsies are needed.


This is one of the first developed tests. It analyses 70 genes from within the tumour and can be used on breast cancer that’s stage 1 or 2, oestrogen receptor positive or negative, HER2 negative and with 0 – 3 positive lymph nodes.

The Mammaprint test calculates a score to indicate the risk of distant recurrence – either low (10%) or high (29%) after hormonal therapy. This helps to determine whether a patient would benefit from the addition of chemotherapy.

Oncotype DX

This is a molecular diagnostic test that predicts the likelihood of a patient's tumour recurring over a ten-year period and whether any benefit is gained by adding chemotherapy to the patient's hormone therapy. It analyses 21 genes in the tumour and develops a three tier recurrence score between 0 and 100.

If the recurrence score is:

  • lower than 18: There is a low risk of recurrence. The benefit of chemotherapy treatment is likely to be small and outweighed by the risk of side effects.
  • 18 up to and including 30: There is an intermediate risk of recurrence and it's not clear whether the chemotherapy benefits are greater than the risks of side effects.
  • greater than or equal to 31: There is a high risk of recurrence and the benefits of chemotherapy are likely to be greater than the risks of side effects.

The test is used for stage 1 or 2, oestrogen receptor positive, lymph node negative or 0-3 positive, HER2 negative breast cancer that will be treated with hormone therapy.

Initial results from the TAILORx trial, published in 2015, showed that women with a recurrence score of 10 or lower could safely be treated with hormone therapy and omit chemotherapy. However, it wasn't clear what was the best treatment for women with an intermediate score.

New results from this trial, presented at the 2018 ASCO (American Society of Clinical Oncology) meeting, show that about 70% of women in this group, with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer, may also be able to avoid chemotherapy.

ProSigna (PAM50)

This test combines two types of results. It divides tumours into their molecular subtypes – Luminal A, Luminal B, HER2 enriched and Triple Negative. It then looks at 50 genes and combines these results to provide a risk of recurrence score – either low, medium or high.

The test is suitable for use in postmenopausal women with hormone receptor-positive, early-stage (stages I, II and IIIA), node negative or positive breast cancer that will be treated with hormone therapy.

Molecular subtypes

Conventional classifications of breast cancer, along with size, stage, grade and receptor status are used to try and predict the likely outcome of a cancer and the likelihood that it will respond to a particular treatment. However, it is now known that there are also intrinsic molecular subtypes of tumours, which explain why seemingly identical tumours can have differing outcomes.

Five main intrinsic or molecular subtypes have been identified, based on the particular genes expressed in a tumour.

  • Luminal A - Hormone receptor positive ( ER and/or PR positive) HER2 negative,and low levels of Ki67( a marker of proliferation). Luminal A cancers tend to be low grade and have the best prognosis of all the subtypes.
  • Luminal B - Hormone receptor positive HER2 positive or negative and high levels of Ki67. These cancers have a slightly worse prognosis than Luminal A cancers.
  • Triple negative/basal-like - Hormone receptor negative and HER2 negative. More common in women with BRCA1 mutations and younger women.
  • HER2 enriched - Hormone receptor negative and HER2 positive. These cancers grow faster than luminal cancers and can have a worse prognosis but treatment with therapies that specifically target the HER2 protein have markedly improved outcomes.
  • Normal-like - Hormone receptor positive, HER2 negative and low levels of Ki67. Similar to Luminal A but has a slightly worse prognosis.

Researchers are continuing to develop methods of accurately identifying the molecular types so that treatments can be better targeted. The next step is to develop genetic profiling to better predict whether a particular tumour will respond to a specific treatment and research in this area is ongoing.

We’re here to help

If you’ve got questions about your breast health, get in touch.