title: The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer.
abstract: Multigene assays have been developed and validated to determine the prognosis of breast cancer. In this study, we assessed the additional predictive value of the 70-gene MammaPrint signature for chemotherapy (CT) benefit in addition to endocrine therapy (ET) from pooled study series. For 541 patients who received either ET (n = 315) or ET + CT (n = 226), breast cancer-specific survival (BCSS) and distant disease-free survival (DDFS) at 5 years were assessed separately for the 70-gene high and low risk groups. The 70-gene signature classified 252 patients (47%) as low risk and 289 (53%) as high risk. Within the 70-gene low risk group, BCSS was 97% for the ET group and 99% for the ET + CT group at 5 years with a non-significant univariate hazard ratio (HR) of 0.58 (95% CI 0.07-4.98; P = 0.62). In the 70-gene high risk group, BCSS was 81% (ET group) and 94% (ET + CT group) at 5 years with a significant HR of 0.21 (95% CI 0.07-0.59; P < 0.01). DDFS was 93% (ET) versus 99% (ET + CT), respectively, in the 70-gene low risk group, HR 0.26 (95% CI 0.03-2.02; P = 0.20). In the high risk group DDFS was 76 versus 88%, HR of 0.35 (95% CI 0.17-0.71; P < 0.01). Results were similar in multivariate analysis, showing significant survival benefit by adding CT in the 70-gene high risk group. A significant and clinically meaningful benefit was observed by adding chemotherapy to endocrine treatment in 70-gene high risk patients. This benefit was not significant in low risk patients, who were at such low risk for recurrence and cancer-related death, that adding CT does not appear to be clinically meaningful.
authors.affiliation: Division of Diagnostic Oncology, Netherlands Cancer Institute, Plesmanlaan, Amsterdam, The Netherlands. m.knauer@nki.nl
authors.forename: Michael
authors.initials: M
authors.lastname: Knauer
authors.forename: Stella
authors.initials: S
authors.lastname: Mook
authors.forename: Emiel J T
authors.initials: EJ
authors.lastname: Rutgers
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bender
authors.forename: Michael
authors.initials: M
authors.lastname: Hauptmann
authors.forename: Marc J
authors.initials: MJ
authors.lastname: van de Vijver
authors.forename: Rutger H T
authors.initials: RH
authors.lastname: Koornstra
authors.forename: Jolien M
authors.initials: JM
authors.lastname: Bueno-de-Mesquita
authors.forename: Sabine C
authors.initials: SC
authors.lastname: Linn
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van 't Veer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D043823:Taxoids / Q000008:administration & dosage; D047368:Tumor Burden
chemical_list: D018943:Anthracyclines; D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D043823:Taxoids