21-Gene Recurrence Score Assay Defining Characteristics

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Estrogen receptor positive (ER+) tumors:
    • Can be very sensitive to endocrine therapy:
      • Which may allow some patients to safely avoid chemotherapy
      • However, the presence of ER receptors on immunohistochemistry:
        • Does not necessarily mean that the tumor’s growth is being driven by ER-related pathways
  • Additionally, other molecular features may influence the tumor cells’ sensitivity to hormonal therapy
  • The development of predictive molecular assays:
    • Has been a major advancement in the field
  • The assay (Oncotype Dx) measures mRNA expression of 21 genes:
    • Using reverse transcriptase-polymerase chain reaction techniques
    • It can be performed on formalin-fixed paraffin-embedded tumor specimens obtained by core biopsy or surgery
    • It has been validated in:
      • ER+, node-negative women who have not received any prior therapy
    • This assay is more reliable in predicting cancer recurrence than such clinical parameters as size, hormone receptor status, nuclear grade, or Ki-67 alone
  • The assay measures downstream ER-regulated genes:
    • To assess the functionality of the ER receptor
  • Patients with low scores (< 18):
    • Are considered at low risk for disease recurrence and may not receive any benefit from adjuvant chemotherapy
    • These patients are now treated with hormonal therapy alone without cytotoxic chemotherapy
    • In fact, the published subset analysis of the prospective validation of the 21-gene expression assay in breast cancer:
      • Confirmed that 98.7% of women with 21-gene signature scores of less than 10 managed with endocrine therapy alone had no evidence of local, regional, or distant recurrence at 5 years
  • Patients with a high score (> 31):
    • Have been shown to gain a large benefit from the addition of chemotherapy
  • While the assay is not performed on HER2-overexpressing tumors:
    • It does measure HER2 and other proliferative genes
  • It was only validated for node-negative patients:
    • The RxPONDER (SWOG 1007) trial:
      • Evaluated women with 1 to 3 positive lymph nodes and an 21-gene signature score of less than 25
      • These patients were randomized to receive chemotherapy and endocrine therapy to endocrine therapy alone
      • Results:
        • Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease–free survival and distant relapse–free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy
  • References:
    • Paik S. Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen. Oncologist. 2007;12(6):631-635.
    • 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):2817-2826.
    • 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):3726-3734.
    • Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. New Engl J Med. 2015;373(21):2005-2014.
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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