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Poster Display session

52P - RNA Sequencing-Based Single Sample Predictors of Molecular Subtype and Risk of Recurrence for Clinical Assessment of Early-Stage Breast Cancer

Date

04 May 2022

Session

Poster Display session

Presenters

Johan Vallon-Christersson

Citation

Annals of Oncology (2022) 33 (suppl_3): S123-S147. 10.1016/annonc/annonc888

Authors

J. Vallon-Christersson1, J. Staaf2, J. Häkkinen1, C. Hegardt1, L. Saal1, A. Ehinger1, C. Larsson1, N. Loman1, L. Rydén1, M. Malmberg3, Å. Borg1

Author affiliations

  • 1 Lund University, Lund/SE
  • 2 Lund University, 223 81 - Lund/SE
  • 3 Skåne University Hospital, Lund/SE
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Abstract 52P

Background

Multigene expression assays for molecular subtypes and biomarkers can aid clinical management of early invasive breast cancer. Based on RNA-sequencing we aimed to develop single-sample predictor (SSP) models for conventional clinical markers, molecular intrinsic subtype and risk of recurrence (ROR).

Methods

A uniformly accrued breast cancer cohort of 7743 patients with RNA-sequencing data from fresh tissue was divided into a training set and a reserved test set. We trained SSPs for PAM50 molecular subtypes and ROR assigned by nearest-centroid (NC) and SSPs for conventional clinical markers from histopathology data. Additionally, SSP classifications were compared with Prosigna® in two external cohorts. Prognostic value was assessed using distant recurrence-free interval.

Results

In the test set, agreement between SSP and NC classifications for PAM50 (five subtypes) and Subtype (four subtypes) was high (85%, Kappa=0.78) and very high (90%, Kappa=0.84) respectively. Accuracy for ROR risk category was high (84%, Kappa=0.75, weighted Kappa=0.90). The prognostic value for SSP and NC was assessed as equivalent. Agreement for SSP and histopathology was very high or high for receptor status, while moderate and poor for Ki67 status and Nottingham histological grade, respectively. SSP concordance with Prosigna® was high for subtype and moderate and high for ROR risk category. In pooled analysis, concordance between SSP and Prosigna® for emulated treatment recommendation for chemotherapy (yes vs. no) was high (85%, Kappa=0.66). In postmenopausal ER+/HER2-/N0 patients SSP application suggested changed treatment recommendations for up to 17% of patients, with nearly balanced escalation and de-escalation of chemotherapy.

Conclusions

SSP models for histopathological variables, PAM50, and ROR classifications can be derived from RNA-sequencing that closely matches clinical tests. Agreement and outcome analyses suggest that NC and SSP models are interchangeable on a group-level and nearly so on a patient level. Retrospective evaluation in postmenopausal ER+/HER2-/N0 patients suggested that molecular testing could lead to a changed therapy recommendation for almost one-fifth of patients.

Legal entity responsible for the study

Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.

Funding

Swedish Cancer Society, Swedish Research Council, Mrs Berta Kamprad Foundation, Lund-Lausanne L2-Bridge/Biltema Foundation, Mats Paulsson Foundation, Swedish governmental funding ALF grant, Bröstcancerförbundet, Norwegian Cancer Society, South-Eastern Norway Regional Health Authority, Oslo University Hospital.

Disclosure

All authors have declared no conflicts of interest.

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