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Aim Precancer identification of women with hereditary breast and ovarian cancer (HBOC) could prevent 20% of these ovarian cancers. The objective was to determine whether standardized Facing Our Risk of Cancer Empowered (FORCE) materials are acceptable, improve knowledge of HBOC and increase disclosure to family members. Methods A prospective cohort of women with breast or ovarian cancer was identified prior to genetic testing. Subjects completed a baseline knowledge survey and were provided three communication aids. Knowledge, acceptability and communication to family members were reassessed at 6 months and compared to a retrospective cohort who had undergone genetic testing for breast or ovarian cancer prior to the intervention. The primary outcome was increase in HBOC knowledge, requiring 20 pre‐ and postknowledge scores to detect a 10% difference. Results Forty women were enrolled. The median age at cancer diagnosis was 50 years and 55% had a family history of breast or ovarian cancer. Though subjects found the resources acceptable, knowledge scores did not improve after their use. Disclosure rates were of no different between cohorts (83% preintervention vs 77% postintervention, P = 0.26) though there was an increase in deleterious mutation carriers, 0% (0/6) preintervention vs 100% (22/22) postintervention. Rates of subsequent testing in relatives were low in both preintervention and postintervention cohorts (0% vs 4.5%). Conclusion Inclusion of standardized communication tools is acceptable to patients. Knowledge did not improve after their use. In deleterious mutation carriers, disclosure rates increased postintervention.

Lung cancer is the main cause of cancer mortality worldwide. Approximately ∼80% of lung cancer cases are non-small cell lung cancer (NSCLC) in type and >50% of NSCLC are adenocarcinoma in histopathology. A shifting paradigm in the field of pulmonary oncology is the identification of molecular markers that are therapeutic targets and/or provide prognostic information. The recent recognition of the role biomarkers such as EGFR, KRAS, and ALK play in NSCLC adenocarcinoma patients demonstrates this trend. Although these three highly characterized molecular markers make up one-quarter to two-thirds of NSCLC adenocarcinoma patients, the remaining population, termed “Triple-Negative Lung Cancer” (TNLC), has yet to be fully defined. The complete absence of therapeutic targets for triple-negative lung cancer patients undeniably supports the need to identify up-regulated and mutated genes that better define this poor prognostic cohort. Recent genome-wide expression profiles subdivided TNLC patients into a poor prognostic group based on the overexpression of the DEP domain containing 1 gene (DEPDC1) (Okayama et al., 2011). We hypothesized that overexpression of DEPDC1 correlates with a specific sub-population of adenocarcinoma patients. Our initial studies indicate that DEPDC1 is constitutively expressed in both normal lung as well as lung cancer specimens. DEPDC1 transcripts are present as two variants (V1 and V2), with constitutive expression of the V1 variant in normal lung. We hypothesized that expression of the V2 transcript could be unique to NSCLC adenocarcinomas. Screening of FFPE NSCLC adenocarcinoma specimens using a proprietary qPCR approach demonstrated the presence of the DEPDC1 V2 variant but at levels that were not sufficient to serve as a sole biomarker. We therefore investigated whether the ratio of DEPDC1 V2 expression relative to V1 could serve as a biomarker in TNLC. Our preliminary data suggest that the ratio of V2 to V1 expression of DEPDC1 does in fact segregate TNLC into specific sub-populations. These studies have exciting diagnostic as well as therapeutic implications as Phase I/II studies using novel peptide vaccines derived against DEPDC1 have proven tolerable and efficacious for patients with bladder cancer and could potentially be extended to target these newly identified TNLC sub-populations. Citation Format: Brock L. Schweitzer, Kasey D. Lawrence, John Handshoe, Rachel Skelton, Lindsay Chatfield, Liquan Xue, Stephan W. Morris, David R. Hout. The unknown piece of the pie: Molecular markers in triple-negative lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1930. doi:10.1158/1538-7445.AM2013-1930

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Lung cancer is the main cause of cancer mortality worldwide, 80% of which are non-small cell lung cancer (NSCLC) in type and >50% are adenocarcinoma in histology. Lung adenocarcinomas are mainly driven by three oncogenes, KRAS, EGFR, and ALK, leaving the remaining cases placed into a triple-negative adenocarcinoma (TNA) category, driven in part by recently identified oncogenic drivers, chromosomal fusions of ROS1 and RET and overexpression of DEPDC1, in up to ~12% of all TNA cases. The utilization of FISH assays has been predominant in the market for detection of biomarker fusions such as ROS1 and RET, yet the sensitivity of these tests is low, interpretation remains subjective, and genetic anomalies can lead to false-negatives. Herein, we hypothesize that a comprehensive quantitative polymerase chain reaction (qPCR) panel could be developed and used as a broad-based TNA detection assay to classify a previously unidentified, but clinically significant, cohort of TNA patients who are readily treatable with currently available therapeutic agents. Single-plexed qPCR strategies, both conventional and proprietary, were collectively developed to fabricate a TNA diagnostic panel specific for the detection of ROS1 and RET fusions and overexpression of DEPDC1 variants. All novel assay designs were validated according to CLIA guidelines in cell line-based studies and further subjected to feasibility testing in retrospective patient specimens. Extensive validation of each qPCR TNA assay showed analytical limits of detection of 1% or better and clinical applicability in patient FFPEs, thus establishing a feasible strategy for a multiplexed TNA panel. Until now, the ability to develop a commercially available multiplex diagnostic panel to reliably identify ROS1 and RET fusions and DEPDC1 overexpression in TNA patients remained elusive. Use of the comprehensive and easily adaptable qPCR strategy described here would therefore be ideally suited for routine clinical testing of such poorly prognostic NSCLC patients.