Clinical Summary
Impact on Treatment Decisions
Individualized Recurrence Score results assess the potential benefit of chemotherapy and the likelihood of distant breast cancer recurrence1,2
Treatment decisions were changed even when definitive treatment decisions had already been made for these invasive breast cancer patients*†14
- 33% of the overall population switched from chemotherapy + hormone therapy to hormone therapy alone based on a low Recurrence Score result‡
- 4% of the overall population switched from HT only to CT + HT based on a high Recurrence Score result‡
§ All studies except Henry et al has statistically significant differences in CT recommendation before and after Recurrence Score testing.
Studies have shown that Recurrence Score results reduce chemotherapy use, spare patients the negative health and quality of life impact of unnecessary chemotherapy, and reduce the costs to society and the healthcare system14,23,26,27
Validated in Multiple Clinical Trials
The Oncotype DX® assay has been clinically validated in 13 studies with over 4,000 breast cancer patients.1-13 Oncotype DX reveals the underlying biology that changes treatment decisions 37% of the time.14
Prognostic and Predictive Information for Node-Negative Patients
The Oncotype DX assay provides prognostic information for node-negative patients
Prognostic*:
The Recurrence Score® result is directly correlated with the rate of distant recurrence2
- A low Recurrence Score result correlated with a lower rate of distant recurrence, while a high Recurrence Score result correlated with a higher rate of distant recurrence2
*Prognostic: any measurement available at the time of diagnosis or surgery associated with clinical outcome in the absence of systematic adjuvant therapy or following the standard of care treatment.
NSABP B-14
Prospective analysis of archived tissue from 668 stage I or II patients with ER-positive, node-negative invasive breast cancer treated with tamoxifen. Twenty-nine percent of patients were < 50 years of age and 62% had tumors that were ≤ 2.0 cm in size. The 10-year distant recurrence rate for the overall study population was 15%.
Only the Oncotype DX assay provides predictive information for node-negative patients
Predictive*:
The Recurrence Score result predicts chemotherapy benefits1
*Predictive: any measurement associated with benefit or lack of benefit from a particular therapy.
NSABP B-20
Prospective analysis of archived tissue from 651 patients with ER-positive, node-negative invasive breast cancer treated with tamoxifen or tamoxifen plus CMF/MF. Approximately 45% of the patients were < 50 years of age, two-thirds of tumors were ≤ 2.0 cm in size, and 20% of tumors were PR-negative.
Insight Beyond Traditional Markers
The Oncotype DX Recurrence Score results provide additional insight into underlying tumor biology beyond traditional measures such as patient age, tumor size, tumor grade, and ER status1-3, 15-18
Patient age and tumor size cannot predict the Recurrence Score result
Tumor size cannot predict Recurrence Score result
NSABP B-20
Prospective analysis of archived tissue from 651 patients with ER-positive, node-negative invasive breast cancer treated with tamoxifen or tamoxifen plus CMF/MF. Approximately 45% of the patients were <50 years of age, two-thirds of tumors were ≤2.0 cm in size, and 20% of tumors were PR-negative.
Tumor grade cannot predict the Recurrence Score result
The Oncotype DX assay reveals critical information that changes treatment decisions1
Because high and low Oncotype DX Recurrence Score results reflect different intrinsic tumor biology, physicians can make decisions based on underlying disease.
Combinations of patient age, grade, and tumor size cannot predict the Recurrence Score result1
Study included 1,864 ER-positive, HER2-negative, node-negative patients from the Clalit and Maccabi Health Services in Israel.
Oncotype DX provides an individualized Recurrence Score result that cannot be predicted by traditional clinicopathologic variables alone or in combination1
In a multivariate analysis of clinicopathologic measures from NSABP B-20, the Oncotype DX Recurrence Score result was the strongest predictor of chemotherapy benefit in node-negative patients1
Intrinsic subtypes
Quantitative RT-PCR provides insight beyond traditional measures17,18
*More than 99% of these cases were progesterone receptor–negative; rarely strongly progesterone receptor–positive.
Study included 100,000 invasive breast cancer tumor specimens that were examined in the Genomic Health laboratory from July 2005 through May 2009. Quantitative expression for each gene was measured by the Oncotype DX assay on a scale from 0 to 15, relative to reference genes.
- Quantitative RT-PCR is able to identify a continuum of gene expression18
- Three groups are discernible: HER2-positive, ER-positive/HER2-negative, and a triple-negative group18
- Within each group is a wide distribution of expression and heterogeneity that might not be detected by binary methods
In a multivariate analysis of clinicopathologic measures from NSABP B-20, the Oncotype DX Recurrence Score result was the strongest predictor of chemotherapy benefit in node-negative patients1
Expanded Use of Oncotype DX for Node-positive Patients
The Oncotype DX assay provides recurrence risk information for both node-negative and node-positive patients4
Trans ATAC
Prospective analysis of archived tissue from 1,231 postmenopausal patients with invasive breast cancer treated with tamoxifen or an aromatase inhibitor, of whom 1,178 were ER-positive and either node-negative or node-positive. Of 306 node-positive patients: 79% had 1–3 positive nodes, 21% had 4 or more positive nodes, and 4% had unknown nodal status. The mean age was 64 years and 67% of tumors were ≤ 2.0 cm in size.
The Oncotype DX assay predicts the benefit of chemotherapy in node-positive patients5
SWOG 8814
Prospective analysis of archived tissue from 367 postmenopausal, hormone receptor–positive, node-positive patients with invasive breast cancer treated with tamoxifen or tamoxifen plus CAF. Approximately 62% had 1–3 positive nodes and the remainder had 4 or more. Mean age was 60 years (range 42–81), 20% were PR–negative, and 64% of tumors were 2–5 cm in size.
1. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor–positive breast cancer. J Clin Oncol. 2006;24:3726-3734.
2. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817-2826.
3. Habel L, Shak S, Jacobs M, et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res. 2006;8:R25-R39.
4. Dowsett M, Cuzick J, Wale 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. J Clin Oncol. 2010;28:1829-1834.
5. Albain K, Barlow W, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11:55-65.
6. Paik S, Shak S, Tang G, et al. Expression of the 21 genes in the Recurrence Score assay and tamoxifen clinical benefit in the NSABP study B-14 of node negative, estrogen receptor positive breast cancer. J Clin Oncol. 2005;23(suppl 16S). Abstract 510.
7. Goldstein L, Gray R, Badve S, et al. Prognostic utility of the 21-gene assay in hormone receptor–positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol. 2008;26:4063-4071.
8. Paik S, Shak S, Tang G, et al. Multi-gene RT-PCR assay for predicting recurrence in node negative breast cancer patients—NSABP studies B-20 and B-14. Presented at: 26th Annual San Antonio Breast Cancer Symposium; December 3-6, 2003; San Antonio, TX. Abstract 16.
9. Esteban J, Baker J, Cronin M, et al. Tumor gene expression and prognosis in breast cancer: multi-gene RT-PCR assay of paraffin-embedded tissue. Presented at: 39th Annual Meeting of the American Society of Clinical Oncology; May 31-June 3,2003; Chicago, IL. Abstract 3416.
10. Cobleigh M, Tabesh B, Bitterman P, et al. Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes. Clin Cancer Res. 2005;11:8623-8631.
11. Esteva F, Sahin A, Massimo C, et al. Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy. Clin Cancer Res. 2005;11:3315-3319.
12. Gianni L, Zambetti M, Clark K, et al. Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol. 2005;23:7265-7277.
13. Toi M, Iwata H, Yamanaka T, et al. Clinical significance of the 21-gene signature (Oncotype DX) in hormone receptor-positive early stage primary breast cancer in the Japanese population. Cancer. 2010;116:3112-3118.
14. Hornberger J, Chien R. Meta-analysis of the decision impact of the 21-gene breast cancer Recurrence Score® in clinical practice. Presented at: 33rd Annual San Antonio Breast Cancer Symposium; December 8-12, 2010; San Antonio, TX. Poster P2-09-06.
15. Shak S, Baehner F, Stein M, et al. Quantitative gene expression analysis in a large cohort of estrogen-receptor positive breast cancers: characterization of the tumor profiles in younger patients (≤40 years) and in older patients (≥70 years). Presented at: 33rd Annual San Antonio Breast Cancer Symposium; December 8-12, 2010; San Antonio, TX. Poster P3-10-01.
16. Liebermann N, Baehner FL, Soussan-Gutman L. Evaluation of Recurrence Score® and traditional clinicopathologic assessments in a large estrogen receptor-positive, lymph node-negative patient cohort. [ASCO abstract 632]. J Clin Oncol. 2011;29(suppl).
17. Baehner F, Watson D, Anderson J, et al. Quantitative gene expression by RT-PCR in the special histologic subtypes of estrogen receptor positive invasive breast cancer. Presented at: 99th Annual Meeting of United States & Canadian Academy of Pathology; March 20-26, 2010; Washington, DC. Abstract 150.
18. Shak S, Baehner F, Palmer G, Ballard J, Baker J, Watson D. Subtypes of breast cancer defined by standardized quantitative RT-PCR analysis of 10,618 tumors. Presented at: 29th Annual San Antonio Breast Cancer Symposium; December 14-18, 2006; San Antonio, TX. Abstract 6118.
19. Asad J, Jacobson A, Estabrook A, et al. Does Oncotype DX recurrence score affect the management of patients with early stage breast cancer? Am J Surg. 2008;196:527-529.
20. Henry L, Stojadinovic A, Swain S, et al. The influence of a gene expression profile on breast cancer decisions. J Surg Oncol. 2009;99:319-323.
21. Klang S, Hammerman A, Liebermann N, Efrat N, Doberne J, Hornberger J. Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization. Value Health. 2010;13:381-387.
22. Liang H, Brufsky A, Lembersky B, Rastogi P, Vogel V. A retrospective analysis of the impact of Oncotype DX low recurrence score results on treatment decisions in a single academic breast cancer center. Presented at: 30th Annual San Antonio Breast Cancer Symposium; December 13-16, 2007; San Antonio, TX. Abstract 2062.
23. Lo S, Norton J, Mumby P, 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. J Clin Oncol. 2010;28:1671-1676.
24. Oratz R, Paul D, Cohn A, Sedlacek S. Impact of a commercial reference laboratory test Recurrence Score on decision making in early-stage breast cancer. J Oncol Pract. 2007;3:182-186.
25. Thanasoulis T, Brown A, Frazier T. The role of Oncotype DX™ assay on appropriate treatment for estrogen positive, lymph node negative invasive breast cancer. Presented at: American Society of Breast Surgeons Annual Meeting; April 30-May 4, 2008; New York, NY.
26. Hornberger J, Cosler L, Lyman G. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node–negative, estrogen-receptor–positive, early-stage breast cancer. Am J Manag Care. 2005;11:313-324.
27. Hornberger J, Chien R, Drebs K, Hochheiser L. US insurance program’s experience with a multigene assay for early-stage breast cancer. J Oncol Pract. 2011;7:e38s-e45s.
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