title: Gene expression profiling to predict the risk of locoregional recurrence in breast cancer: a pooled analysis.
abstract: The 70-gene signature (MammaPrint) has been developed to predict the risk of distant metastases in breast cancer and select those patients who may benefit from adjuvant treatment. Given the strong association between locoregional and distant recurrence, we hypothesize that the 70-gene signature will also be able to predict the risk of locoregional recurrence (LRR). 1,053 breast cancer patients primarily treated with breast-conserving treatment or mastectomy at the Netherlands Cancer Institute between 1984 and 2006 were included. Adjuvant treatment consisted of radiotherapy, chemotherapy, and/or endocrine therapy as indicated by guidelines used at the time. All patients were included in various 70-gene signature validation studies. After a median follow-up of 8.96 years with 87 LRRs, patients with a high-risk 70-gene signature (n = 492) had an LRR risk of 12.6% (95% CI 9.7-15.8) at 10 years, compared to 6.1% (95% CI 4.1-8.5) for low-risk patients (n = 561; P < 0.001). Adjusting the 70-gene signature in a competing risk model for the clinicopathological factors such as age, tumour size, grade, hormone receptor status, LVI, axillary lymph node involvement, surgical treatment, endocrine treatment, and chemotherapy resulted in a multivariable HR of 1.73 (95% CI 1.02-2.93; P = 0.042). Adding the signature to the model based on clinicopathological factors improved the discrimination, albeit non-significantly [C-index through 10 years changed from 0.731 (95% CI 0.682-0.782) to 0.741 (95% CI 0.693-0.790)]. Calibration of the prognostic models was excellent. The 70-gene signature is an independent prognostic factor for LRR. A significantly lower local recurrence risk was seen in patients with a low-risk 70-gene signature compared to those with high-risk 70-gene signature.
authors.affiliation: Department of Surgical Oncology, Netherlands Cancer Institute, Postbus 90203, 1006 BE, Amsterdam, The Netherlands.
authors.forename: C A
authors.initials: CA
authors.lastname: Drukker
authors.forename: S G
authors.initials: SG
authors.lastname: Elias
authors.forename: M V
authors.initials: MV
authors.lastname: Nijenhuis
authors.forename: J
authors.initials: J
authors.lastname: Wesseling
authors.forename: H
authors.initials: H
authors.lastname: Bartelink
authors.forename: P
authors.initials: P
authors.lastname: Elkhuizen
authors.forename: B
authors.initials: B
authors.lastname: Fowble
authors.forename: P W
authors.initials: PW
authors.lastname: Whitworth
authors.forename: R R
authors.initials: RR
authors.lastname: Patel
authors.forename: F A
authors.initials: FA
authors.lastname: de Snoo
authors.forename: L J
authors.initials: LJ
authors.lastname: van 't Veer
authors.forename: P D
authors.initials: PD
authors.lastname: Beitsch
authors.forename: E J Th
authors.initials: EJ
authors.lastname: Rutgers
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D009367:Neoplasm Staging; D009426:Netherlands; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors
chemical_list: D009363:Neoplasm Proteins