CHEK2, P53, PTEN for breast cancer genetic testing – pro

M Levin, MD — Tue, 28 Aug 2012 18:29:54 +0000

Despite a negative (normal) genetic test for mutations in the BRCA1 and BRCA2 genes, about 12 percent of breast cancer patients from high-risk families carried previously undetected cancer-associated mutations. Risks for young women with inherited BRCA1 or BRCA2 mutations are particularly increased. Among white women in the U.S., 5 percent to 10 percent of breast cancer cases are due to inherited mutations in BRCA1 and BRCA2. Inherited mutations in other genes, including CHEK2, TP53 and PTEN, can also influence risk of breast cancer. BART and PTEN mutationa are reviewed as a separate entry.

There is currently no clear understanding how these other factors can be used in planning therapy or genetic counselling and there are no guidelines to advise physicians.

Tom Walsh, PhD; Silvia Casadei, PhD; Kathryn Hale Coats, BS; Elizabeth Swisher, MD; Sunday M. Stray, BS; Jake Higgins, BS; Kevin C. Roach, BS; Jessica Mandell, MS, CGC; Ming K. Lee, PhD; Sona Ciernikova, PhD; Lenka Foretova, MD, PhD; Pavel Soucek, PhD; Mary-Claire King, PhD Spectrum of Mutations in BRCA1, BRCA2, CHEK2, and TP53 in Families at High Risk of Breast Cancer JAMA. 2006;295:1379-1388

Pilarski R, Burt R, Kohlman W, et al. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013; 105(21):1607-1616.

Pilarski R, Stephens JA, Noss R, et al. Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. J Med Genet. Aug 2011;48(8):505-512

Veristrat: Current Status – pro

M Levin, MD — Wed, 01 Aug 2012 17:25:36 +0000

VeriStrat® is a blood-based predictive and prognostic proteomic test for patients with advanced non-small cell lung cancer who test negative for EGFR mutations (EGFR wild-type) or whose EGFR mutation status is unknown. Veristrat was presented in April 2012.at the 3rd European Lung Cancer Conference in Geneva, Switzerland. The VeriStrat test was validated through a retrospective analysis was performed on serum samples from advanced non-squamous non-small cell lung cancer (NSCLC) patients treated with the combination therapy of Avastin and plus erlotinib. VeriStrat test was able to identify patients likely to have better and worse survival outcomes in these trials.

A similar retrospective analysis of the Phase III trial, EGF30008, were presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. Results showed that the VeriStrat test was able to identify a group of patients who have worse progression free survival (PFS) when treated with Femara alone, independent of Her2 status.

VeriStrat test may be useful for clinical decision-making, about treatment with erlotinib and erlotinib combinations. Prospective trials are ongoing, including a Phase III trial in advanced squamous cell lung cancer, sponsored by the European Thoracic Oncology group. Per the NCCN Guidelines for the treatment of nonsmall cell lung cancer, this testing (VeriStrat proteomic testing) is medically appropriate for patients with a performance status of 0 to 2 who had progression with initial chemotherapy treatment and may be candidates for treatment with erlotinib.

Carbone et al, Prognostic and Predictive Role of the VeriStrat Plasma Test in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Erlotinib or Placebo in the NCIC Clinical Trials Group BR.21 Trial. Journal of Thoracic Oncology November 2012,

Gregorc V, et al.Predictive value of a proteomic signature in patients with non-small cell lung cancer treated with second-line erlotinib or chemotherapy (PROSE): a biomarker stratified, randomised phase 3 trial. The Lancet Oncology. 2014..

Taguchi F, Solomon B, Gregorc V, et al. Mass spectrometry to classify non-small-cell lung cancer patients for clinical outcome after treatment with epidermal growth factor receptor tyrosine kinase inhibitors: a multicohort cross-institutional study. J Natl Cancer Inst. 2007;99:838-846.

NCCN, Non-small cell Lung Cancer, 2016

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Cancer Treatment Today » Breast Cancer

CHEK2, P53, PTEN for breast cancer genetic testing – pro

Veristrat: Current Status – pro