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The 21-Gene Recurrence Score and Locoregional Recurrence in Breast Cancer Patients

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Although the 21-gene recurrence score (RS) assay has been validated to assess the risk of distant recurrence in hormone receptor-positive breast cancer patients, the relationship between RS and the risk of locoregional recurrence (LRR) remains unclear. The purpose of this study was to determine if RS is associated with LRR in breast cancer patients and whether this relationship varies based on the type of local treatment [mastectomy or breast-conserving therapy (BCT)].

Methods

163 consecutive estrogen receptor-positive breast cancer patients at our institution had an RS generated from the primary breast tumor between August 2006 and October 2009. Patients were treated with lumpectomy and radiation (BCT) (n = 110) or mastectomy alone (n = 53). Patients were stratified using a pre-determined RS of 25 and then grouped according to local therapy type.

Results

Median follow-up was 68.2 months. Patients who developed an LRR had stage I or IIA disease, >2 mm surgical margins, and received chemotherapy as directed by RS. While an RS > 25 did not predict for a higher rate of LRR, an RS > 24 was associated with LRR in our subjects. Among mastectomy patients, the 5-year LRR rate was 27.3 % in patients with an RS > 24 versus 10.7 % (p = 0.04) in those whose RS was ≤24. RS was not associated with LRR in patients who received BCT.

Conclusions

Breast cancer patients treated with mastectomy for tumors that have an RS > 24 are at high risk of LRR and may benefit from post-mastectomy radiation.

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References

  1. 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(27):2817–26.

    Article  CAS  PubMed  Google Scholar 

  2. 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. J Clin Oncol. 2010;28(10):1671–6.

    Article  PubMed  Google Scholar 

  3. 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(23):3726–34.

    Article  CAS  PubMed  Google Scholar 

  4. Nuyten DS, Kreike B, Hart AA, et al. Predicting a local recurrence after breast-conserving therapy by gene expression profiling. Breast Cancer Res. 2006;8(5):R62.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Kreike B, Halfwerk H, Armstrong N, et al. Local recurrence after breast-conserving therapy in relation to gene expression patterns in a large series of patients. Clin Cancer Res. 2009;15(12):4181–90.

    Article  CAS  PubMed  Google Scholar 

  6. Connor CS, Touijer AK, Krishnan L, Mayo MS. Local recurrence following breast conservation therapy in African-American women with invasive breast cancer. Am J Surg. 2000;179(1):22–6.

    Article  CAS  PubMed  Google Scholar 

  7. Taghian A, Jeong J-H, Mamounas E, et al. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004;22(21):4247–54.

    Article  PubMed  Google Scholar 

  8. Jones HA, Antonini N, Hart AA, et al. Impact of pathological characteristics on local relapse after breast-conserving therapy: a subgroup analysis of the EORTC boost versus no boost trial. J Clin Oncol. 2009;27(30):4939–47.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Wallgren A, Bonetti M, Gelber RD, et al. Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII. J Clin Oncol. 2003;21(7):1205–13.

    Article  CAS  PubMed  Google Scholar 

  10. Abdulkarim BS, Cuartero J, Hanson J, Deschenes J, Lesniak D, Sabri S. Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. J Clin Oncol. 2011;29(21):2852–8.

    Article  PubMed  Google Scholar 

  11. Selz J, Stevens D, Jouanneau L, Labib A, Le Scodan R. Prognostic value of molecular subtypes, ki67 expression and impact of postmastectomy radiation therapy in breast cancer patients with negative lymph nodes after mastectomy. Int J Radiat Oncol Biol Phys. 2012;84(5):1123–32.

    Article  CAS  PubMed  Google Scholar 

  12. Sparano JA, Paik S. Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol. 2008;26(5):721–8.

    Article  PubMed  Google Scholar 

  13. 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. J Clin Oncol. 2010;28(10):1677–83.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Fisher B, Costantino J, Redmond C, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989;320(8):479–84.

    Article  CAS  PubMed  Google Scholar 

  15. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1997;89(22):1673–82.

    Article  CAS  PubMed  Google Scholar 

  16. Solin LJ, Gray R, Goldstein LJ, et al. Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early stage breast carcinoma: results from the Eastern Cooperative Oncology Group E2197 study. Breast Cancer Res Treat. 2012;134(2):683–92.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Gonzalez-Angulo A, Barlow W, Gralow J, et al. OT1-03-01: a randomized phase III clinical trial of standard adjuvant endocrine therapy ± chemotherapy in patients (pts) with 1–3 positive nodes, hormone receptor (HR)-positive and HER2–negative breast cancer with recurrence score (RS) of 25 or less: SWOG S1007. Cancer Res. 2011;71(24 Suppl 3).

  18. Edge SB, American Joint Committee on Cancer. AJCC cancer staging manual, 7th ed. New York: Springer; 2010.

  19. Mandrekar J, Mandrekar S, Cha S. Cutpoint determination methods in survival analysis using SAS®. Proceedings of the 28th SAS Users Group International Conference (SUGI) 2003.

  20. Therneau TM, Grambsch PM, Fleming TR. Martingale-based residuals for survival models. Biometrika. 1990;77(1):147–60.

    Article  Google Scholar 

  21. Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data, vol. 360. New York: Wiley; 2011.

    Google Scholar 

  22. Cox DR. Regression models and life tables. J R Stat Soc Series B Stat Methodol. 1972;34(2):187–220.

    Google Scholar 

  23. Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.

    Article  CAS  PubMed  Google Scholar 

  24. Cheng SH, Horng CF, West M, et al. Genomic prediction of locoregional recurrence after mastectomy in breast cancer. J Clin Oncol. 2006;24(28):4594–602.

    Article  CAS  PubMed  Google Scholar 

  25. Nimeus-Malmstrom E, Krogh M, Malmstrom P, et al. Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy. Breast Cancer Res. 2008;10(2):R34.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Sabatier R, Finetti P, Cervera N, et al. Gene expression profiling and its utility in prediction of local relapse after breast-conserving therapy in early breast cancer. Cancer Genomics Proteomics. 2011;8(4):199–209.

    CAS  PubMed  Google Scholar 

  27. Belletti B, Vaidya JS, D’Andrea S, et al. Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res. 2008;14(5):1325–32.

    Article  CAS  PubMed  Google Scholar 

  28. Fisher B, Costantino J, Redmond C, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor–positive tumors. N Engl J Med. 1989;320(8):479–84.

    Article  CAS  PubMed  Google Scholar 

  29. Fisher B, Dignam J, Emir B, et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1997;89(22):1673–82.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of the Winship Cancer Institute of Emory University and National Institutes of Health/National Cancer Institute under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    Naresh K. Jegadeesh MD, Roshan S. Prabhu MD, David S. Yu MD, PhD, Karen G. Godette MD, Donna Mister MS & Mylin A. Torres MD

  2. Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Sunjin Kim MS & Jeffrey M. Switchenko PhD

  3. Department of Pathology and Laboratory Medicine, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Gabriela M. Oprea MD

  4. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Sunjin Kim MS, Amelia B. Zelnak MD & Jeffrey M. Switchenko PhD

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  1. Naresh K. Jegadeesh MD
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  2. Sunjin Kim MS
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  3. Roshan S. Prabhu MD
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Correspondence to Mylin A. Torres MD.

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Jegadeesh, N.K., Kim, S., Prabhu, R.S. et al. The 21-Gene Recurrence Score and Locoregional Recurrence in Breast Cancer Patients. Ann Surg Oncol 22, 1088–1094 (2015). https://doi.org/10.1245/s10434-014-4252-y

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  • DOI: https://doi.org/10.1245/s10434-014-4252-y

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