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Breast Cancer Res. 2017 Nov 14;19(1):120. doi: 10.1186/s13058-017-0911-9.

Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up.

Author information

1
Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Postbox 4953 Nydalen, 0424, Oslo, Norway. Hege.Oma.Ohnstad@ous-hf.no.
2
Division of Laboratory Medicine, Department of Pathology, Oslo University Hospital, Oslo, Norway.
3
Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
4
Department of Cancer Genetics, Institute of Cancer Research, Oslo University Hospital, Oslo, Norway.
5
Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Postbox 4953 Nydalen, 0424, Oslo, Norway.
6
Division of Medicine, Department of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway.
7
Breast and Endocrine Surgery Unit, Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Oslo, Norway.
8
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

BACKGROUND:

The aim of this study was to investigate the prognostic value of the PAM50 intrinsic subtypes and risk of recurrence (ROR) score in patients with early breast cancer and long-term follow-up. A special focus was placed on hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) pN0 patients not treated with chemotherapy.

METHODS:

Patients with early breast cancer (n = 653) enrolled in the observational Oslo1 study (1995-1998) were followed for distant recurrence and breast cancer death. Clinicopathological parameters were collected from hospital records. The primary tumors were analyzed using the Prosigna® PAM50 assay to determine the prognostic value of the intrinsic subtypes and ROR score in comparison with pathological characteristics. The primary endpoints were distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS).

RESULTS:

Of 653 tumors, 52.2% were classified as luminal A, 26.5% as luminal B, 10.6% as HER2-enriched, and 10.7% as basal-like. Among the HR+/HER2- patients (n = 476), 37.8% were categorized as low risk by ROR score, 22.7% as intermediate risk, and 39.5% as high risk. Median follow-up durations for BCSS and DDFS were 16.6 and 7.1 years, respectively. Multivariate analysis showed that intrinsic subtypes (all patients) and ROR risk classification (HR+/HER2- patients) yielded strong prognostic information. Among the HR+/HER2- pN0 patients with no adjuvant treatment (n = 231), 53.7% of patients had a low ROR, and their prognosis at 15 years was excellent (15-year BCSS 96.3%). Patients with intermediate risk had reduced survival compared with those with low risk (p = 0.005). In contrast, no difference in survival between the low- and intermediate-risk groups was seen for HR+/HER2- pN0 patients who received tamoxifen only. Ki-67 protein, grade, and ROR score were analyzed in the unselected, untreated pT1pN0 HR+/HER2- population (n = 171). In multivariate analysis, ROR score outperformed both Ki-67 and grade. Furthermore, 55% of patients who according to the PREDICT tool ( http://www.predict.nhs.uk/ ) would be considered chemotherapy candidates were ROR low risk (33%) or luminal A ROR intermediate risk (22%).

CONCLUSIONS:

The PAM50 intrinsic subtype classification and ROR score improve classification of patients with breast cancer into prognostic groups, allowing for a more precise identification of future recurrence risk and providing an improved basis for adjuvant treatment decisions. Node-negative patients with low ROR scores had an excellent outcome at 15 years even in the absence of adjuvant therapy.

KEYWORDS:

Breast cancer; Follow-up; PAM50; Patient stratification; Risk of recurrence

PMID:
29137653
PMCID:
PMC5686844
DOI:
10.1186/s13058-017-0911-9
[Indexed for MEDLINE]
Free PMC Article

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