Medline ® Abstract for Reference 101
of 'Prognostic and predictive factors in early, nonmetastatic breast cancer'
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Perez EA, Olson JA Jr, Zujewski J, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin P, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge GW
N Engl J Med. 2015;373(21):2005. Epub 2015 Sep 27.
BACKGROUND: Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker.
METHODS: We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence).
RESULTS: Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6).
CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).
From the Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (J.A.S., D.F.M.); Dana-Farber Cancer Institute, Boston (R.J.G.); Sunnybrook Research Institute, Toronto (K.I.P.) and Juravinski Cancer Center, Hamilton, ON (T.J.W.) - both in Canada; Loyola University Medical Center, Maywood (K.S.A.), and Northwestern University, Chicago (L.I.W., V.G.K.) - both in Illinois; University of Michigan, Ann Arbor (D.F.H.); Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond (C.E.G.); University of North Carolina, Chapel Hill (E.C.D.), Duke University Medical Center, Durham (J.A.O.), Wake Forest University Health Service, Winston-Salem (L.I.W.), and Southeast Clinical Oncology Research Consortium, Goldsboro (J.N.A.) - all in North Carolina; Mayo Clinic, Jacksonville, FL (E.A.P.); University of Maryland School of Medicine, Baltimore (J.A.O.), and National Institutes of Health, Bethesda (J.Z., T.L.) - both in Maryland; Indiana University Sch