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Papers by Drew Watson

A method for predicting a probability that a human patient with colorectal cancer queexpresa EGFR... more A method for predicting a probability that a human patient with colorectal cancer queexpresa EGFR present a beneficial response to an EGFR inhibitor using a model of four genes basadoen expression levels AREG, EREG, dusp6 and SLC26A3, comprising: measuring, a obtained tumor patient sample, levels of RNA transcripts or their deexpresion products AREG, EREG, dusp6 and SLC26A3, normalize the levels of RNA transcripts or their expression products, of AREG, EREG, dusp6 ySLC26A3 to obtain standardized levels of AREG, EREG, dusp6 and SLC26A3 expression; and use levels normalized expression of AREG, EREG, dusp6 and SLC26A3 determining laprobabilidad that the patient has a beneficial response to an EGFR inhibitor, wherein levels normalized expression enlarged AREG, EREG and SLC26A3 is correlacionanpositivamente with the likelihood that the patient has a beneficial response to EGFR inhibitor; and wherein the normalized expression level increased dusp6 laprobabilidad is negatively correlated w...

Blood, 2021

Background: DNA methyltransferase inhibition (DNMTi) with the hypomethylating agents (HMA) azacit... more Background: DNA methyltransferase inhibition (DNMTi) with the hypomethylating agents (HMA) azacitidine (AZA) or decitabine, remains the mainstay of therapy for the majority of high-risk Myelodysplastic Syndromes (MDS) patients. Nevertheless, only 40-50% of MDS patients achieve clinical improvement with DNMTi. There is a need for a predictive clinical approach that can stratify MDS patients according to their chance of benefit from current therapies and that can identify and predict responses to new treatment options. Ideally, patients predicted to be non-responders (NR) could be offered alternative strategies while being spared protracted treatment with HMA alone that has a low likelihood of efficacy. Recently, an intriguing discovery of immune modulation by HMA has emerged. In addition to the benefits of unsilencing differentiation genes and tumor suppressor genes, HMA's reactivate human endogenous retroviral (HERV) genes leading to viral mimicry and upregulation of the immune ...

Nature Genetics, 1999

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease with highly variable multi... more Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease with highly variable multisystemic manifestations. The mutation underlying DM is an unstable (CTG)n expansion in the 3´ UTR of the myotonic dystrophy protein kinase gene (DMPK). The pathophysiological mechanism(s) of the expanded (CTG)n repeat remains unclear. Various effects have been proposed, most recently a gain of function for mutant DMPK transcripts that results in a generalized RNA metabolism defect, mediated through one or several transacting proteins involved in RNA processing. This would in turn lead to the loss of function of multiple genes by qualitatively or quantitatively affecting post-transcriptional RNA processing, splicing or nuclear export of their transcripts. To test these hypotheses, we examined global mRNA expression changes between DM patients and normal controls by comprehensively and simultaneously profiling more than 6,800 human genes with oligo-based Genechip microarrays (Affymetrix). Total, nuclear and cytoplasmic RNA fractions of DM patient lymphoblastoid cell lines (four adult-onset, one congenital) as well as primary undifferentiated myoblasts and differentiated myotubes (one adult-onset, one congenital) were profiled. DM myoblasts in culture showed a reduced differentiation rate to myotubes and a tendency to dedifferentiate, suggesting a general block in or reprogramming of differentiation. Expression profiles of DM cell lines differed considerably from controls. Between the different DM cell lines profiled, many of the more than 6,800 genes assayed showed dysregulation. Moreover, comparison of nuclear and cytoplasmic fractions suggested a defect in the nuclear export of some processed transcripts. The number of genes dysregulated and the degree of dysregulation correlated with expansion size. Functions of the dysregulated genes were highly varied. In conclusion, DNA microarray expression profiling identified several novel DM phenotype effector candidate genes that may explain the complex pathogenesis of DM.

Cancer Research, 2010

Background: Previous studies have identified differences in the presentation, biology, and behavi... more Background: Previous studies have identified differences in the presentation, biology, and behavior of breast cancer as a function of patient age. To directly study breast cancer tumor profiles as a function of patient age, we examined the Oncotype DX Recurrence Score (RS) and the expression of ER, PR, and proliferation-related genes in a large cohort of invasive breast cancers. Material and Methods: All tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through March 2010 were included. Standard RS testing was performed. Quantitative expression for ER, PR, HER2, and the five proliferation genes, CCNB1, Ki-67, MYBL2, STK15, and Survivin, was measured by quantitative RT-PCR on a scale from 2 to 15 (relative to reference genes), where a one unit increment is associated with an approximate 2-fold increase in expression. The proliferation index (PI), a component of the RS, was calculated as the average of the expression of the five proliferation genes....

BMC Cancer, 2010

Background: The Oncotype DX® Colon Cancer Assay is a new diagnostic test for determining the like... more Background: The Oncotype DX® Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancerrelated genes. By capturing the biology underlying each patient's tumor, the Oncotype DX Colon Cancer Assay provides a Recurrence Score (RS) that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using predetermined performance criteria, which is a critical component of molecular diagnostic test validation. Results: All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log 2 concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 C T s), gene groups (≤0.05 normalized/aggregate C T s) and RS (≤1.38 RS units). Conclusions: Analytical performance characteristics shown here for both individual genes and gene groups in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery.

Blood, 2020

Background. In addition to clinical considerations (e.g., age, de novo vs secondary disease, como... more Background. In addition to clinical considerations (e.g., age, de novo vs secondary disease, comorbidities), therapy selection for AML patients is often based on information considering only cytogenetics and/or molecular aberrations and ignoring other patient-specific omics information that could potentially enable selection of more effective treatments. In turn, despite using cytogenetic and molecular-risk stratification, the current overall outcome of AML patients remains relatively poor. The Cellworks Singula™ report predicts clinical response to physician-prescribed treatments using the novel Cellworks Omics Biology Model (CBM) that simulate in silico downstream molecular effects on cell signaling and survival of drug treatments in patient-specific diseased cells. Methods. The performance of Singula™ was evaluated in a cohort of 474 AML patients aged 2 to 85. The pre-defined Singula™ Classifier utilizes individual patients' next-generation sequencing (NGS) profiles to provid...

Journal of Clinical Oncology

e15527 Background: Multimodal diagnostic classifiers survey signals from multiple biological comp... more e15527 Background: Multimodal diagnostic classifiers survey signals from multiple biological compartments and provide iterative, independent and interactive information. Detection of both CRC and AA is critical for noninvasive colorectal screening to improve overall survival and prevent the 2.5-5% annual transition of AA to CRC. FirstSight integrates clinically validated somatic variants from cfDNA and circulating epithelial cells (CECs) adjusting for age and sex. CECs provide information from both intrinsic factors of the adenoma and extrinsic factors such as adenoma microenvironment which facilitates early systemic entry. We sought to assess differential information from CEC signals for the detection of colorectal cancer and/or advanced adenoma (AA). Methods: Blood samples and colonoscopy pathology results were obtained from 438 asymptomatic screening subjects enriched for CRC/AA obtained from 15 US medical centers. The cohort included 18 CRCs and 64 AAs. Somatic variants from cfD...

Additional file 1: Table S1. Detailed list of clinical samples and cell lines selected for the an... more Additional file 1: Table S1. Detailed list of clinical samples and cell lines selected for the analytical evaluation studies.

Additional file 4: Figure S3. Verification of LoD (top) and LoQ (bottom) across the tested range ... more Additional file 4: Figure S3. Verification of LoD (top) and LoQ (bottom) across the tested range of total input DNA.

Additional file 7: Table S4. Precision of the clonoSEQ Assay in CLL samples.

Additional file 5: Table S2. Precision of the clonoSEQ Assay in MM samples.

Additional file 2: Figure S1. Precision study PCR run execution map.

Additional file 3: Figure S2. Probit model plot to calculate the LoD.

Additional file 9: Table S6. Linearity of the clonoSEQ Assay using clinical specimens from patien... more Additional file 9: Table S6. Linearity of the clonoSEQ Assay using clinical specimens from patients with ALL, CLL, and MM.

Journal of Clinical Oncology, 2021

50 Background: Many of the 50,000 annual colorectal cancer (CRC) deaths can be attributed to 1/3 ... more 50 Background: Many of the 50,000 annual colorectal cancer (CRC) deaths can be attributed to 1/3 eligible Americans not following screening guidelines or approximately 1/2 of the population not adherent to the follow-up post-polypectomy guidelines. The new understanding of the natural history and shared etiology of adenomas and CRC inform integration of clinically relevant biomarkers. The two objectives of CRC screening and surveillance are early detection to improve survival and prevention of CRC through removal of adenomas using colonoscopy. Adenomas account for 98% of actionable colonoscopies. Stool tests have low sensitivity for advanced adenomas (AA, 24-42%). Methods: A prospective, blinded study was conducted at the VA Palo Alto Health Care System. Patients had blood drawn prior to colonoscopy. The test analyzes two biomarkers: circulating gastrointestinal epithelial cells and somatic mutations of cell-free DNA. The probability of advanced neoplasia was obtained by ordinal/nom...

Journal of Clinical Oncology, 2009

549 Background: Because male breast cancer (BC) is rare, there is little known about the disease ... more 549 Background: Because male breast cancer (BC) is rare, there is little known about the disease and treatment is extrapolated from female BC. Newer molecular technologies have not been used to profile male BC. We report here a study of quantitative gene expression by gender status in tumor specimens submitted for Recurrence Score testing. Methods: All estrogen receptor positive tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through December 2008 were included. Quantitative expression for each gene was measured by the 21 gene oncotype DX assay on a scale from 0 to 15 (relative to reference genes), where a one unit increment is associated with a 2-fold change in expression. Results: There were 347 male and 82,434 female BCs. The males were older (mean age 63.8 vs 57.4 yrs). Standard histopathology was similar, although slightly more male BCs were ductal (83% vs 78%). Like female BC, there was a wide variation in gene expression in male BC. The d...

Cancer Research, 2018

Introduction The availability of targeted and immunotherapies has provided NSCLC patients with mo... more Introduction The availability of targeted and immunotherapies has provided NSCLC patients with more effective treatment options. However, this has resulted in an increase in the number and modality of tests required for treatment selection. Given 30-50% of advanced lung cancer patients have insufficient or unavailable tissue for comprehensive genomic profiling, there is a need for a non-invasive assay that can accurately detect all guideline-recommended markers for NSCLC treatment selection. To meet this need, we have developed a blood test that detects six classes of alterations (SNV, Indels, Rearrangements, CNA, Microsatellite Instability and PD-L1 expression) for therapy selection. Methods & Results Three tubes of blood from a routine blood draw were sent to our CLIA-certified and/or CAP accredited lab for analysis. PD-L1 expression was evaluated in circulating tumor cells (CTCs) utilizing two different assays; (i) Immunofluorescence (IF) antibody staining, (ii) mRNA qPCR. CTCs w...

The Journal of Urology, 2018

Journal of Clinical Oncology, 2006

Purpose The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence i... more Purpose The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor–positive, lymph node–negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. Methods The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy–treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. Results A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (≥ 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in...

Journal of Clinical Oncology, 2005

Purpose We sought to identify gene expression markers that predict the likelihood of chemotherapy... more Purpose We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk. Methods Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays. Results Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-r...

A method for predicting a probability that a human patient with colorectal cancer queexpresa EGFR... more A method for predicting a probability that a human patient with colorectal cancer queexpresa EGFR present a beneficial response to an EGFR inhibitor using a model of four genes basadoen expression levels AREG, EREG, dusp6 and SLC26A3, comprising: measuring, a obtained tumor patient sample, levels of RNA transcripts or their deexpresion products AREG, EREG, dusp6 and SLC26A3, normalize the levels of RNA transcripts or their expression products, of AREG, EREG, dusp6 ySLC26A3 to obtain standardized levels of AREG, EREG, dusp6 and SLC26A3 expression; and use levels normalized expression of AREG, EREG, dusp6 and SLC26A3 determining laprobabilidad that the patient has a beneficial response to an EGFR inhibitor, wherein levels normalized expression enlarged AREG, EREG and SLC26A3 is correlacionanpositivamente with the likelihood that the patient has a beneficial response to EGFR inhibitor; and wherein the normalized expression level increased dusp6 laprobabilidad is negatively correlated w...

Blood, 2021

Background: DNA methyltransferase inhibition (DNMTi) with the hypomethylating agents (HMA) azacit... more Background: DNA methyltransferase inhibition (DNMTi) with the hypomethylating agents (HMA) azacitidine (AZA) or decitabine, remains the mainstay of therapy for the majority of high-risk Myelodysplastic Syndromes (MDS) patients. Nevertheless, only 40-50% of MDS patients achieve clinical improvement with DNMTi. There is a need for a predictive clinical approach that can stratify MDS patients according to their chance of benefit from current therapies and that can identify and predict responses to new treatment options. Ideally, patients predicted to be non-responders (NR) could be offered alternative strategies while being spared protracted treatment with HMA alone that has a low likelihood of efficacy. Recently, an intriguing discovery of immune modulation by HMA has emerged. In addition to the benefits of unsilencing differentiation genes and tumor suppressor genes, HMA's reactivate human endogenous retroviral (HERV) genes leading to viral mimicry and upregulation of the immune ...

Nature Genetics, 1999

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease with highly variable multi... more Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease with highly variable multisystemic manifestations. The mutation underlying DM is an unstable (CTG)n expansion in the 3´ UTR of the myotonic dystrophy protein kinase gene (DMPK). The pathophysiological mechanism(s) of the expanded (CTG)n repeat remains unclear. Various effects have been proposed, most recently a gain of function for mutant DMPK transcripts that results in a generalized RNA metabolism defect, mediated through one or several transacting proteins involved in RNA processing. This would in turn lead to the loss of function of multiple genes by qualitatively or quantitatively affecting post-transcriptional RNA processing, splicing or nuclear export of their transcripts. To test these hypotheses, we examined global mRNA expression changes between DM patients and normal controls by comprehensively and simultaneously profiling more than 6,800 human genes with oligo-based Genechip microarrays (Affymetrix). Total, nuclear and cytoplasmic RNA fractions of DM patient lymphoblastoid cell lines (four adult-onset, one congenital) as well as primary undifferentiated myoblasts and differentiated myotubes (one adult-onset, one congenital) were profiled. DM myoblasts in culture showed a reduced differentiation rate to myotubes and a tendency to dedifferentiate, suggesting a general block in or reprogramming of differentiation. Expression profiles of DM cell lines differed considerably from controls. Between the different DM cell lines profiled, many of the more than 6,800 genes assayed showed dysregulation. Moreover, comparison of nuclear and cytoplasmic fractions suggested a defect in the nuclear export of some processed transcripts. The number of genes dysregulated and the degree of dysregulation correlated with expansion size. Functions of the dysregulated genes were highly varied. In conclusion, DNA microarray expression profiling identified several novel DM phenotype effector candidate genes that may explain the complex pathogenesis of DM.

Cancer Research, 2010

Background: Previous studies have identified differences in the presentation, biology, and behavi... more Background: Previous studies have identified differences in the presentation, biology, and behavior of breast cancer as a function of patient age. To directly study breast cancer tumor profiles as a function of patient age, we examined the Oncotype DX Recurrence Score (RS) and the expression of ER, PR, and proliferation-related genes in a large cohort of invasive breast cancers. Material and Methods: All tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through March 2010 were included. Standard RS testing was performed. Quantitative expression for ER, PR, HER2, and the five proliferation genes, CCNB1, Ki-67, MYBL2, STK15, and Survivin, was measured by quantitative RT-PCR on a scale from 2 to 15 (relative to reference genes), where a one unit increment is associated with an approximate 2-fold increase in expression. The proliferation index (PI), a component of the RS, was calculated as the average of the expression of the five proliferation genes....

BMC Cancer, 2010

Background: The Oncotype DX® Colon Cancer Assay is a new diagnostic test for determining the like... more Background: The Oncotype DX® Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancerrelated genes. By capturing the biology underlying each patient's tumor, the Oncotype DX Colon Cancer Assay provides a Recurrence Score (RS) that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using predetermined performance criteria, which is a critical component of molecular diagnostic test validation. Results: All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log 2 concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 C T s), gene groups (≤0.05 normalized/aggregate C T s) and RS (≤1.38 RS units). Conclusions: Analytical performance characteristics shown here for both individual genes and gene groups in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery.

Blood, 2020

Background. In addition to clinical considerations (e.g., age, de novo vs secondary disease, como... more Background. In addition to clinical considerations (e.g., age, de novo vs secondary disease, comorbidities), therapy selection for AML patients is often based on information considering only cytogenetics and/or molecular aberrations and ignoring other patient-specific omics information that could potentially enable selection of more effective treatments. In turn, despite using cytogenetic and molecular-risk stratification, the current overall outcome of AML patients remains relatively poor. The Cellworks Singula™ report predicts clinical response to physician-prescribed treatments using the novel Cellworks Omics Biology Model (CBM) that simulate in silico downstream molecular effects on cell signaling and survival of drug treatments in patient-specific diseased cells. Methods. The performance of Singula™ was evaluated in a cohort of 474 AML patients aged 2 to 85. The pre-defined Singula™ Classifier utilizes individual patients' next-generation sequencing (NGS) profiles to provid...

Journal of Clinical Oncology

e15527 Background: Multimodal diagnostic classifiers survey signals from multiple biological comp... more e15527 Background: Multimodal diagnostic classifiers survey signals from multiple biological compartments and provide iterative, independent and interactive information. Detection of both CRC and AA is critical for noninvasive colorectal screening to improve overall survival and prevent the 2.5-5% annual transition of AA to CRC. FirstSight integrates clinically validated somatic variants from cfDNA and circulating epithelial cells (CECs) adjusting for age and sex. CECs provide information from both intrinsic factors of the adenoma and extrinsic factors such as adenoma microenvironment which facilitates early systemic entry. We sought to assess differential information from CEC signals for the detection of colorectal cancer and/or advanced adenoma (AA). Methods: Blood samples and colonoscopy pathology results were obtained from 438 asymptomatic screening subjects enriched for CRC/AA obtained from 15 US medical centers. The cohort included 18 CRCs and 64 AAs. Somatic variants from cfD...

Additional file 1: Table S1. Detailed list of clinical samples and cell lines selected for the an... more Additional file 1: Table S1. Detailed list of clinical samples and cell lines selected for the analytical evaluation studies.

Additional file 4: Figure S3. Verification of LoD (top) and LoQ (bottom) across the tested range ... more Additional file 4: Figure S3. Verification of LoD (top) and LoQ (bottom) across the tested range of total input DNA.

Additional file 7: Table S4. Precision of the clonoSEQ Assay in CLL samples.

Additional file 5: Table S2. Precision of the clonoSEQ Assay in MM samples.

Additional file 2: Figure S1. Precision study PCR run execution map.

Additional file 3: Figure S2. Probit model plot to calculate the LoD.

Additional file 9: Table S6. Linearity of the clonoSEQ Assay using clinical specimens from patien... more Additional file 9: Table S6. Linearity of the clonoSEQ Assay using clinical specimens from patients with ALL, CLL, and MM.

Journal of Clinical Oncology, 2021

50 Background: Many of the 50,000 annual colorectal cancer (CRC) deaths can be attributed to 1/3 ... more 50 Background: Many of the 50,000 annual colorectal cancer (CRC) deaths can be attributed to 1/3 eligible Americans not following screening guidelines or approximately 1/2 of the population not adherent to the follow-up post-polypectomy guidelines. The new understanding of the natural history and shared etiology of adenomas and CRC inform integration of clinically relevant biomarkers. The two objectives of CRC screening and surveillance are early detection to improve survival and prevention of CRC through removal of adenomas using colonoscopy. Adenomas account for 98% of actionable colonoscopies. Stool tests have low sensitivity for advanced adenomas (AA, 24-42%). Methods: A prospective, blinded study was conducted at the VA Palo Alto Health Care System. Patients had blood drawn prior to colonoscopy. The test analyzes two biomarkers: circulating gastrointestinal epithelial cells and somatic mutations of cell-free DNA. The probability of advanced neoplasia was obtained by ordinal/nom...

Journal of Clinical Oncology, 2009

549 Background: Because male breast cancer (BC) is rare, there is little known about the disease ... more 549 Background: Because male breast cancer (BC) is rare, there is little known about the disease and treatment is extrapolated from female BC. Newer molecular technologies have not been used to profile male BC. We report here a study of quantitative gene expression by gender status in tumor specimens submitted for Recurrence Score testing. Methods: All estrogen receptor positive tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through December 2008 were included. Quantitative expression for each gene was measured by the 21 gene oncotype DX assay on a scale from 0 to 15 (relative to reference genes), where a one unit increment is associated with a 2-fold change in expression. Results: There were 347 male and 82,434 female BCs. The males were older (mean age 63.8 vs 57.4 yrs). Standard histopathology was similar, although slightly more male BCs were ductal (83% vs 78%). Like female BC, there was a wide variation in gene expression in male BC. The d...

Cancer Research, 2018

Introduction The availability of targeted and immunotherapies has provided NSCLC patients with mo... more Introduction The availability of targeted and immunotherapies has provided NSCLC patients with more effective treatment options. However, this has resulted in an increase in the number and modality of tests required for treatment selection. Given 30-50% of advanced lung cancer patients have insufficient or unavailable tissue for comprehensive genomic profiling, there is a need for a non-invasive assay that can accurately detect all guideline-recommended markers for NSCLC treatment selection. To meet this need, we have developed a blood test that detects six classes of alterations (SNV, Indels, Rearrangements, CNA, Microsatellite Instability and PD-L1 expression) for therapy selection. Methods & Results Three tubes of blood from a routine blood draw were sent to our CLIA-certified and/or CAP accredited lab for analysis. PD-L1 expression was evaluated in circulating tumor cells (CTCs) utilizing two different assays; (i) Immunofluorescence (IF) antibody staining, (ii) mRNA qPCR. CTCs w...

The Journal of Urology, 2018

Journal of Clinical Oncology, 2006

Purpose The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence i... more Purpose The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor–positive, lymph node–negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. Methods The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy–treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. Results A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (≥ 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in...

Journal of Clinical Oncology, 2005

Purpose We sought to identify gene expression markers that predict the likelihood of chemotherapy... more Purpose We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk. Methods Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays. Results Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-r...