Breast Cancer Gene Expression Tests

Gene expression tests are a form of personalized medicine - a way to learn more about your cancer and tailor your treatment.

These tests are done on breast cancer cells after surgery or biopsy to look at the patterns of a number of different genes. This process or test is sometimes called gene expression profiling.

What do the test results mean?

The patterns found can help predict if certain early-stage breast cancers are likely to come back after initial treatment.

Some gene expression testing/profiling can help predict which women will most likely benefit from chemotherapy after breast surgery (adjuvant chemotherapy.) Hormone therapy is a standard treatment for hormone receptor-positive breast cancers, but it’s not always clear when to use chemotherapy. These tests can help guide that decision. Still, these tests cannot tell any one woman for certain if her cancer will come back with or without chemotherapy.

These tests continue to be studied in large clinical trials to better understand how and when to best use them. In the meantime, ask your doctor if these tests might be useful for you. 

Testing options

The Oncotype DX, MammaPrint, and Prosigna are examples of tests that look at different sets of breast cancer genes to see if chemotherapy is needed to help reduce the risk of cancer coming back (recurrence). More tests are in development. The type of test that's used will depend on your situation. Keep in mind that these tests are used for early-stage cancers, and testing isn’t needed in all cases. For example, if breast cancer is advanced, it might be clear that chemotherapy is needed, even without gene expression testing.

Oncotype DX

The Oncotype DX test is used for stage I, II or IIIa hormone receptor-positive tumors that have not spread to more than 3 lymph nodes and are HER2 negative. It can also be used for DCIS (ductal carcinoma in situ or stage 0 breast cancer).

This test looks at a set of 21 genes in cancer cells from tumor biopsy or surgery samples to get a “recurrence score,” which is a number between 0 and 100. The score reflects the risk of the breast cancer coming back (recurring) in the next 9 years if you are treated with hormone therapy alone and how likely you are to benefit from getting chemo after surgery.

For women who are older than 50 years and have no lymph nodes with cancer:

  • A low score (0-25) means a low risk of recurrence. Most women with low-recurrence scores do not benefit from chemotherapy and have good outcomes when treated with hormone therapy.
  • A high score (26-100) means a higher risk of recurrence. Women with high-recurrence scores are more likely to benefit from the addition of chemotherapy to hormone therapy to help lower the chance of the cancer coming back.

For women age 50 or younger and have no lymph nodes with cancer:

  • A low score (0-15) means a low risk of recurrence. Most of these women with low-recurrence scores do not benefit from chemotherapy and have good outcomes when treated with hormone therapy.
  • An intermediate score (16-25) means that some women in this group might have a small benefit from adding chemotherapy to hormone therapy to lower the risk of the cancer coming back. Talk to your doctor about options.
  • A high score (26-100) means a higher risk of recurrence. Women with high-recurrence scores are more likely to benefit from the addition of chemotherapy to hormone therapy to help lower the chance of the cancer coming back.

For women age 50 or younger that have cancer in the lymph nodes:

  • A low score (0-25) means a lower risk of recurrence, but women in this group might have a benefit from adding chemotherapy to hormone therapy. Another option might be ovarian suppression along with tamoxifen or an aromatase inhibitor
  • A high score (26-100) means a higher risk of recurrence. Women in this group are more likely to benefit from the addition of chemotherapy to hormone therapy to help lower the chance of the cancer coming back.

MammaPrint

The MammaPrint test can be used to help determine how likely breast cancers are to recur in a distant part of the body after treatment. It can be used for any type of invasive breast cancer that’s 5cm (about 2 inches) or smaller and has spread to no more than 3 lymph nodes. This test can be done regardless of a woman's age or the cancer's hormone or HER2 status.

The test looks at 70 different genes to determine if the cancer is at low risk or high risk of coming back (recurring) in the next 10 years. The test results come back as either “low risk” or “high risk.” This test is also being studied as a way to determine whether certain women might benefit from chemotherapy. 

Prosigna

The Prosigna test can be used to predict the risk of recurrence in the next 10 years in women who have gone through menopause (postmenopausal) and whose invasive breast cancers are hormone receptor-positive and HER2-negative. It can be used to test early-stage cancers that have not spread to the lymph nodes, or early-stage cancers with no more than 3 positive lymph nodes.

The test looks at 50 genes and classifies the results as low, intermediate, or high risk.  

Breast Cancer Index

The Breast Cancer Index test is done on your tumor sample from when you are first diagnosed. It can be used to predict the risk of recurrence in the 5 to 10 years after diagnosis in women whose invasive breast cancers are hormone receptor-positive and have not spread to nearby lymph nodes or have not spread to more than 3 lymph nodes. It can also help predict who might benefit from hormone therapy for longer than 5 years.

The test looks at 11 genes and classifies the results as low or high risk.  

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Cardoso F, van't Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med. 2016;375(8):717-29.

Foukakis T, and Bergh J, and Hurvitz SA. Deciding when to use adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer. In Vora SR, ed. UpToDate. Waltham, Mass.: UpToDate, 2021. https://www.uptodate.com. Last updated August 17, 2021. Accessed September 14, 2021.

Gnant M, Filipits M, Dubsky P, et al. Predicting risk for late metastasis: The PAM50 risk of recurrence (ROR) score after 5 years of endocrine therapy in postmenopausal women with HR+ early breast cancer: A study on 1,478 patients for the ABCSG-8 trial. Ann Oncol. 2013; 24(Suppl 3): iii29-iii37.

Harris LN, Ismaila N, McShane LM, et al. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34(10):1134–1150.

Knauer M, Mook S, Rutgers EJ, Bender RA, Hauptmann M, van de Vijver MJ et al. The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer. Breast Cancer Res Treat. 2010 Apr;120(3):655-61.

Krop I, Ismaila N, Andre F, et al. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update. J Clin Oncol. 2017;35(24):2838–2847.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Breast Cancer. Version 8.2021. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf on Sept. 14, 2021.

Paik, S. Development and Clinical Utility of a 21-Gene Recurrence Score Prognostic Assay in Patients with Early Breast Cancer Treated with Tamoxifen. The Oncologist. 2007;12(6): 631-635.

Sparano JA, Gray RJ, Makower KI, Pritchard KS, Albain DF, Hayes CE, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121.

Sparano JA, Gray RJ, Ravdin PM, Makower DF, Pritchard KI, Albain KS et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. N Engl J Med. 2019;380(25):2395-2405.

Wallden B, Storhoff J, Nielsen T, et al. Development and verification of the PAM50-based Prosigna breast cancer gene signature assay. BMC Med Genomics. 2015;8:54. 

References

Cardoso F, van't Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med. 2016;375(8):717-29.

Foukakis T, and Bergh J, and Hurvitz SA. Deciding when to use adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer. In Vora SR, ed. UpToDate. Waltham, Mass.: UpToDate, 2021. https://www.uptodate.com. Last updated August 17, 2021. Accessed September 14, 2021.

Gnant M, Filipits M, Dubsky P, et al. Predicting risk for late metastasis: The PAM50 risk of recurrence (ROR) score after 5 years of endocrine therapy in postmenopausal women with HR+ early breast cancer: A study on 1,478 patients for the ABCSG-8 trial. Ann Oncol. 2013; 24(Suppl 3): iii29-iii37.

Harris LN, Ismaila N, McShane LM, et al. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34(10):1134–1150.

Knauer M, Mook S, Rutgers EJ, Bender RA, Hauptmann M, van de Vijver MJ et al. The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer. Breast Cancer Res Treat. 2010 Apr;120(3):655-61.

Krop I, Ismaila N, Andre F, et al. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update. J Clin Oncol. 2017;35(24):2838–2847.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Breast Cancer. Version 8.2021. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf on Sept. 14, 2021.

Paik, S. Development and Clinical Utility of a 21-Gene Recurrence Score Prognostic Assay in Patients with Early Breast Cancer Treated with Tamoxifen. The Oncologist. 2007;12(6): 631-635.

Sparano JA, Gray RJ, Makower KI, Pritchard KS, Albain DF, Hayes CE, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121.

Sparano JA, Gray RJ, Ravdin PM, Makower DF, Pritchard KI, Albain KS et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. N Engl J Med. 2019;380(25):2395-2405.

Wallden B, Storhoff J, Nielsen T, et al. Development and verification of the PAM50-based Prosigna breast cancer gene signature assay. BMC Med Genomics. 2015;8:54. 

Last Revised: November 8, 2021

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