domingo, 6 de octubre de 2019

---Comprehensive transcriptomic profiling identifies breast cancer patients who may be spared adjuvant systemic therapy. - PubMed - NCBI

2019 Sep 26. pii: clincanres.1038.2019. doi: 10.1158/1078-0432.CCR-19-1038. [Epub ahead of print]

---Comprehensive transcriptomic profiling identifies breast cancer patients who may be spared adjuvant systemic therapy.

Sjöström M1, Chang SL2, Fishbane N3, Davicioni E4, Hartman L5, Holmberg E6, Feng FY7, Speers C8, Pierce LJ8, Malmström P9, Fernö M10, Karlsson P11.

Author information

1: Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University Martin.Sjostrom@med.lu.se.
2: PFS Genomics.
3: Biostatistics, Decipher Biosciences.
4: Clinical Laboratory, Decipher Biosciences Inc.
5: Oncology, Lund University.
6: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at Univerity of Gothenburg.
7: Radiation Oncology, Helen Diller Comprehensive Cancer Center, University of California, San Francisco.
8: Radiation Oncology, University of Michigan-Ann Arbor.
9: Departrment of Oncology and Pathology, Clinical Sciences Lund, Lund University.
10: Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University.
11: Department of Oncology, Institute of Clinical Sciences, Department of Oncology, Sahlgrenska Academy, University of Gothenburg.

Abstract

PURPOSE:

There is currently no molecular signature in clinical use for adjuvant endocrine therapy omission in breast cancer. Given the unique trial design of SweBCG91-RT, where adjuvant endocrine and chemotherapy were largely unadministered, we sought to evaluate the potential of transcriptomic profiling for identifying patients who may be spared adjuvant endocrine therapy.

EXPERIMENTAL DESIGN:

We performed a whole transcriptome analysis of SweBCG91-RT, a randomized phase III trial of +/- radiotherapy after breast-conserving surgery for node-negative stage I-IIA breast cancer. 92% of patients were untreated by both adjuvant endocrine therapy and chemotherapy. We calculated 15 transcriptomic signatures from the literature and combined them into an Average Genomic Risk, which was further used to derive a novel 141-gene signature (MET141). All signatures were then independently examined in SweBCG91-RT, and in the publicly-available METABRIC cohort.

RESULTS:

In SweBCG91-RT, 454 patients were node-negative, post-menopausal and systemically untreated with ER-positive, HER2-negative cancers, which constitutes a low-risk subgroup and potential candidates for therapy omission. Most transcriptomic signatures were highly prognostic for distant metastasis, but considerable discordance was observed on the individual patient level. Within the MET141 low-risk subgroup (lowest 25th percentile of scores), 95% of patients were free of metastasis at 15 years even in the absence of adjuvant endocrine therapy. In a clinically low-risk subgroup of the METABRIC cohort not treated with systemic therapy, no breast cancer death occurred among the MET141 low-risk patients.

CONCLUSION:

Transcriptomic profiling identifies patients with an excellent outcome without any systemic adjuvant therapy in clinically low-risk patients of the SweBCG91-RT and METABRIC cohorts.