OncotypeDX™ Effectively Guides Early Stage Breast Cancer Treatment

TAILORx trial reveals how OncotypeDX™ Effectively guides breast cancer treatment and improves patient decision making

by Dr. C.H. Weaver M.D. updated 5/2019

About the Oncotype DX Test:

The Oncotype DX Breast Recurrence Score test provides a genomic-based, individualized risk assessment for invasive breast cancer that individuals can use to personalize a treatment plan. The Breast Recurrence Score test can predict the likely benefit of chemotherapy as well as the risk of distant recurrence. The test measures the expression of 21 genes: 16 cancer-related genes and five reference genes - in a tumor sample after it has been removed by surgery or biopsy.

Oncotype DX calculates a “recurrence score” between 0 and 100. The higher the score, the greater the chance the cancer will come back. Previous studies have found that women with node negative ESBC and scores of 10 or lower did not need chemotherapy, while women with scores higher than 25 did benefit from chemotherapy. But for the large group of women with intermediate scores (11 to 25) the need for chemotherapy has been less clear.

Oncotype DX™ Influences Breast Cancer Treatment Choices

  • In roughly 31% of women evaluated, the Oncotype DX test result changed the oncologist’s choice of treatment.
  • The most common change in treatment plan involved a shift away from chemotherapy.
  • 27% of patients changed their treatment decision based on the Recurrence Score.
  • Patient anxiety was lower after receipt of the Recurrence Score results.

Recurrence Score results can influence treatment recommendations and treatment decisions for women with early breast cancer, and can help relieve anxiety.

Low Oncotype® Recurrence Score® Identifies ESBC Patients That can Avoid Chemotherapy

The results from a group of 1,626 patients with a Recurrence Score between 0 and 10 demonstrated that 99.3 percent of node-negative, estrogen receptor-positive, HER2-negative patients who met accepted guidelines for recommending chemotherapy in addition to hormonal therapy had no distant recurrence at five years after treatment with hormonal therapy alone. Outcomes were excellent irrespective of patient age, tumor size, and tumor grade.(1)

Oncotype DX in Node Negative Early Stage Breast Cancer

Many women with the most common type of early stage breast cancer (ESBC) likely do not need chemotherapy after surgery according to the results of the Trial Assigning IndividuaLized Options for Treatment (TAILORx) study involving more than 10,000 women with hormone receptor (HR) positive, HER2-negative that had not spread to lymph nodes. The study was presented the 2018 American Society of Clinical Oncology meeting and published in the New England Journal of Medicine.(3)

Historically only 1 in 10 women with ESBC treated with chemotherapy benefited from that treatment. Physicians however had no way to determine which patient benefited, therefore 9 women received chemotherapy unnecessarily. The results of the current study suggest that chemotherapy can be avoided in about 70% of patients with node negative ESBC.

In the TAILORx study women’s tumors were tested with Oncotype DX, the brand-name of genomic that looks at a set of 21 genes in cancer cells from tumor biopsy samples to get a “recurrence score” between 0 and 100. The higher the score, the greater the chance the cancer will come back. Previous studies have found that women with scores of 10 or lower did not need chemotherapy, while women with scores higher than 25 did benefit from chemotherapy. But for the large group of women with intermediate scores (11 to 25) the need for chemotherapy has been less clear.

A total of 6,711 women from the trial with a mid-range Oncotype DX score of 11 to 25 were randomly assigned to receive hormone therapy with or without adjuvant chemotherapy following surgery.

  • Five years after treatment, the rate of invasive disease-free survival was 93.1% for those who had chemo and 92.8% for those who did not.
  • Nine years after treatment, the rate of invasive disease-free survival was 84.3% for those who had chemo and 83.3% for those who did not.
  • Five years after treatment, the rate of overall survival was 98.1% for those who had chemo and 98.0% for those who did not.
  • Nine years after treatment, the rate of overall survival was 93.8% for those who had chemo and 93.9% for those who did not.

Age as a factor

Chemotherapy did appear to have some benefit in women who were age 50 or younger with a recurrence score of 16 to 25. For this age group, there were 2% fewer cases of cancer returning for recurrence scores between 16 to 20, and 7% fewer cases for scores between 21 to 25.

The authors conclude that the new findings suggest chemotherapy may be avoided in about 70% of women with HR-positive, HER2-negative, node-negative breast cancer. They say this applies to women who are:

  • older than age 50 and with a recurrence score of 11–25
  • any age with a recurrence score of 0–10
  • age 50 years or younger with a recurrence score of 11–15

The findings suggest that chemotherapy may be considered for the remaining 30% of women with HR-positive, HER2-negative, node-negative breast cancer – those who are:

  • any age with a recurrence score of 26–100
  • age 50 years or younger with a recurrence score of 16–25
  • Adding chemotherapy to hormone therapy was beneficial for women 50 years or younger.

Oncotype DX® in Node-Positive ESBC Treated with Tamoxifen or Arimidex

The TAILORx clinical trial did not include women with node positive ESBC who are at significantly higher risk of cancer recurrence than women with cancer that does not involve the lymph nodes.

Among postmenopausal women with early, hormone receptor-positive ESBC treated with either Nolvadex® or Arimidex® the Oncotype DX test can predict the risk of distant cancer recurrence in node-positive patients.(4)

Researchers collected information from 1,231 women who participated in the ATAC (Arimidex, Tamoxifen, Alone or in Combination) clinical trial of postmenopausal women with hormone receptor-positive ESBC.

  • The nine-year risk of distant cancer recurrence was 17% among women with a low Recurrence Score, 28% among women with an intermediate Recurrence Score, and 49% among women with a high Recurrence Score.

To further explore use of the Oncotype DX test among women with node-positive breast cancer, researchers assessed more than 1000 women who had participated in a clinical trial known as NSABP B-28. All of the women had ER-positive ESBC that was treated with chemotherapy and hormone therapy.(5)

  • Disease-free survival (survival without a recurrence or new cancer) varied significantly depending on a woman’s recurrence score. Ten-year disease-free survival was 76% among women with a low recurrence score, 57% among women with an intermediate recurrence score, and 48% among women with a high recurrence score.

These results indicate that the Oncotype DX recurrence score predicts risk of recurrence and survival outcomes among women with ER-positive, node-positive breast cancer treated with chemotherapy and hormone therapy. High-risk women may benefit from more extensive treatment or enrollment in a clinical trial.

Oncotype Dx® Predicts Chemotherapy Benefit in Node-positive Breast Cancer

Among women with node-positive, hormone receptor-positive breast cancer, use of the Oncotype DX test identifies a subset of women who do not appear to benefit from adjuvant (post-surgery) anthracycline-based chemotherapy.(6)

To assess the test among women with node-positive, hormone receptor-positive breast cancer, researchers evaluated information from 367 patients. Some patients received adjuvant therapy with tamoxifen [Nolvadex®] alone, and some received tamoxifen plus anthracycline-based chemotherapy.

  • The addition of chemotherapy to tamoxifen significantly improved breast cancer survival among women with a high Recurrence Score (RS>31).
  • The addition of chemotherapy did not improve breast cancer survival among women with a low Recurrence Score.
  • Women with an intermediate or high Recurrence Score had a two- to threefold increase in recurrence risk compared to women with a low Recurrence Score.

Oncotype DX® Predicts Local and Regional Breast Cancer Recurrence

In addition to providing information about risk of distant breast cancer recurrence, the Oncotype DX® Recurrence Score also provides information about risk of local or regional breast cancer recurrence.

To evaluate the Recurrence Score in relation to risk of local and regional breast cancer recurrence, researchers evaluated information from 895 women treated with tamoxifen [Nolvadex®], 355 women treated with placebo, and 424 patients treated with chemotherapy plus tamoxifen. All of the women had node-negative, estrogen receptor-positive breast cancer.

  • Among women treated with tamoxifen, 10-year risk of local or regional cancer recurrence was 4.3% among women with a low Recurrence Score, 7.2% among women with an intermediate Recurrence Score, and 15.8% among those with a high Recurrence Score. The Recurrence Score also predicted risk of local or regional recurrence among women treated with placebo and women treated with chemotherapy and tamoxifen.

These results indicate that in addition to predicting the risk of distant cancer recurrence, the Recurrence Score also predicts the risk of local or regional cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer.

Genomic Testing with Oncotype DX Provides Prognostic Information in Stage IV Breast Cancer

Among women with Stage IV, estrogen receptor-positive breast cancer, the Oncotype DX® breast cancer test provided information about cancer prognosis; this may help guide treatment decisions. To assess the Oncotype DX test among women with advanced breast cancer, researchers evaluated 102 women with Stage IV breast cancer.(8)

  • 23% of the women had a low Recurrence Score (<18), 28% had an intermediate Recurrence Score (18-30), and 49% had a high Recurrence Score (31 or higher).
  • Among women with estrogen receptor-positive cancer, those with a higher Recurrence Score experienced a quicker worsening of their cancer (shorter time to cancer progression).
  • Among women with cancer that was both estrogen receptor-positive and HER2-negative, a higher Recurrence Score was linked with shorter overall survival.

These results suggest that the Oncotype DX breast cancer test provides information about the prognosis of Stage IV, estrogen receptor-positive breast cancer. Additional research would help to determine whether women who have a particularly poor prognosis based on the test benefit from more aggressive treatment.

Ductal Carcinoma In Situ

Results from a study of the DCIS score involving 327 women with DCIS who had been treated with lumpectomy but had not received radiation therapy have been published.(4)

Three-quarters of the patients had a low risk of recurrence based on the DCIS score. For these women the likelihood of any kind of local recurrence (either DCIS or invasive breast cancer) was 12 percent, and likelihood of a recurrence that involved invasive breast cancer was 5 percent. By comparison, among women with a high risk of recurrence based on the DCIS score, the likelihood of any kind of local recurrence was 27 percent, and the likelihood of a recurrence that involved invasive breast cancer was 19 percent.

These results suggest that the Oncotype DX DCIS score provides information about the risk of recurrence after breast-conserving surgery for DCIS. This information could help guide decisions about the need for postoperative radiation therapy following treatment with lumpectomy. Research in genomics is expanding at a rapid rate and will have a profound effect on many aspects of disease prevention, diagnosis, and treatment. Diseases such as cancer are remarkably complex; genomics provides researchers and physicians with tools to explore and address these complexities and help individualize treatment decisions.

References:

  1. Mamounas EP, Tang G, Fisher B et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. Journal of Clinical Oncology. [early online publication] January 11, 2010.
  2. Albain KS, Barlow WE, Shak S et al. Prediction of 10-year chemotherapy benefit and breast cancer-specific survival by the 21-gene Recurrence Score (RS) assay in node-positive, ER-positive breast cancer—An update of SWOG-8814 (INT0100). Presented at the 32nd CTRC-AACR San Antonio Breast Cancer Symposium. December 9-13, 2009. San Antonio, TX. Abstract 112.
  3. https://www.nejm.org/doi/10.1056/NEJMoa1804710
  4. Dowsett M, Cuzick J, Wales C et al. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. Journal of Clinical Oncology [early online publication]. March 8, 2010.
  5. Mamounas EP, Tang G, Paik S et al. Prognostic impact of the 21-gene recurrence score (RS) on disease-free and overall survival of node-positive, ER-positive breast cancer patients (pts) treated with adjuvant chemotherapy: Results from NSABP B-28. Presented at the 2012 Breast Cancer Symposium. September 13-15, 2012.San Francisco,CA. Abstract 1.
  6. Albain KS, Barlow WE, Shak S et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, estrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomized clinical trial. Lancet Oncology [early online publication]. December 10, 2009.
  7. Mamounas EP, Tang G, Fisher B et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. Journal of Clinical Oncology. [early online publication] January 11, 2010.
  8. King TA, Lyman JP, Gonen M et al. prognostic impact of the 21-gene recurrence score in patients presenting with stage IV breast cancer. Presented at the 49th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract 507.
  9. Solin LJ, Gray R, Baehner FL et al. A quantitative multigene RT-PCR assay for predicting recurrence risk after surgical excision alone without irradiation for ductal carcinoma in situ (DCIS): a prospective validation study of the DCIS Score from ECOG E5194. Paper presented at: 34th Annual CTRC-AACR San Antonio Breast Cancer Symposium. December 6-10, 2011; San Antonio, TX. Abstract S4-6.

Other References:

  1. https://www.cancer.net/blog/2018-06/asco-annual-meeting-2018-less-treatment-needed-some-patients-with-breast-cancer-and-kidney-cancer
  2. Paik S, Tang G, Shak S et al. Gene Expression and Benefit of Chemotherapy in Women with Node-Negative, Estrogen Receptor-Positive Breast Cancer. Journal of Clinical Oncology. Early online publication May 23, 2006.
  3. Lo SS, Mumby PB, Norton J et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. Journal of Clinical Oncology [early online publication]. January 11, 2009.
  4. Lyman GH, Cosler LE, Kuderer NM, Hornberger J. Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies. Cancer. 2007;109:1011-8.

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