Caris Life Sciences® Presents Two Studies Demonstrating Utility of Tumor Profiling: Likelihood of Response to Immunotherapeutics in HER2-Positive Breast Cancer and the Largest Case Series Comparing Male Breast Cancer to Female Breast Cancer Patients

Studies Using Caris Molecular IntelligenceTM Identify Standard as well as Novel Therapeutic Options Based on Molecular Characterization of Individual Patients’ Tumors

Irving, TX, Dec. 11, 2014 – Caris Life Sciences® today announced the presentation of two studies in which Caris Molecular Intelligence™, the company’s panomic, comprehensive tumor profiling service, was used to assess different types of breast cancer. The first study showed that only a very small portion of human epidermal growth factor receptor 2 (HER2) positive luminal breast cancers express programmed death ligand 1 (PD-L1), a biomarker of immune evasion. These results suggest that patients with HER2-positive luminal breast cancer are less likely to benefit from anti-PD-L1 therapy. The second study, the largest case series ever performed comparing the molecular profile of male breast cancer (MBC) to female breast cancer (FBC), revealed significant differences. These results indicate that MBC could be considered a distinct disease from FBC.

The two data sets, presented at the 2014 San Antonio Breast Cancer Symposium (SABCS), point toward potential treatment options for both patient populations, based on the molecular characterization of individual patients’ tumors. Both studies utilized Caris Molecular Intelligence’s multi-technology approach, which included gene sequencing, protein expression analysis (immunohistochemistry [IHC]), gene copy number analysis (chromogenic or fluorescence in situ hybridization [CISH or FISH]), and microarray analysis.

“While patients with luminal breast cancers and male breast cancer represent very different populations, comprehensive molecular profiling has much to teach us about treatment strategies that are likely to be effective in each of these disease subtypes,” commented Zoran Gatalica, M.D., D.Sc., executive medical director of Caris Life Sciences, and a co-investigator in the MBC study. “Together, the studies presented at SABCS reflect an expanding range of potential treatment options for patients with specific subtypes of breast cancer, whether rare or relatively common.”

Luminal Breast Cancer Study Highlights
In the luminal breast cancer study, researchers analyzed 1,311 breast cancer samples using a multiplatform approach (whole genome messenger RNA [mRNA] expression, protein expression [IHC], gene copy number changes [ISH], and gene sequencing) and tested an additional 732 samples for PD-L1 and its receptor, PD-1, via IHC. Luminal breast cancer subtypes are both estrogen receptor-positive (ER+) and low-grade. Based on expression of ER, progesterone receptor (PR), and HER2 by IHC and FISH/CISH, the researchers subdivided the data into sub-cohorts.

Elevated mRNA expression of immune markers such as PD-L1, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), B7H-3, and IDO1 was noted in the ER+HER2- luminal population, which included the ER+PR- and ER+PR+ cohorts. In patients with hormone receptor-positive (HR+) disease, IHC revealed PD-L1 expression in 6% of cases and PD-1 expression in 43%. PD-L1 expression was the lowest in the HR+HER2+ cohort (2.3%), followed by the HR+HER2- (6.4%) and HR-HER2+ (9.8%) cohorts, and was the highest in the triple-negative breast cancer (TNBC; i.e., negative for ER, PR, and HER2) cohort (19%). On the other hand, expression of PD-1 was present throughout the different cohorts, ranging from 59% in the TNBC cohort, to 43% in the HR+HER2- cohort, to 44% in the HR+HER2+ cohort.

“The relative lack of PD-L1 and PD-1 expression in the HER2-positive cohort indicates a lesser likelihood of benefit from immune checkpoint therapy in this sub-population, compared to patients with triple-negative breast cancer,” noted Sandeep K. Reddy, M.D., chief medical officer of Caris Life Sciences, and a co-investigator in the luminal breast cancer study. “The expression of immune regulatory targets in the studied population suggests that targeted therapies that inhibit immune checkpoints such as PD-1, PD-L1, CTLA4, B7-H3, and IDO1 may be especially effective in patients with luminal breast cancers, particularly those with ER-positive and HER2-negative disease.”

Male Breast Cancer Study Highlights
In the male breast cancer study, researchers evaluated 60 male (ages 37-84) and 5,000 female (ages 27-98) breast cancer samples for common gene mutations, protein expression, microarray, and/or gene amplification/rearrangement. The researchers analyzed the samples for patterns within the MBC cohort and for similarities with or differences from FBC subtypes, which included TNBC, non-TNBC, HER2+, and ER+.

Although few genetic mutations were identified in the samples, multiplatform evaluation of the MBC tumors’ molecular profiles identified changes in protein expression that may lead to novel treatment options for patients with MBC. In 98% of MBC cases, investigators identified treatment options based on changes in protein expression or gene copy number. By contrast, treatment options were identified based on gene mutations in only 17% of MBC cases.

Androgen receptor (AR) was overexpressed in 70% of MBC patients, similar to ER+ and PR+ FBC patients. According to the investigators, the high incidence of AR overexpression in MBC warrants continued investigation of anti-androgen therapies in this population, especially in combination with other hormone replacement therapies, due to the coincidence of ER, PR, and AR in 50% of cases.

HER2 overexpression (8.8% vs. 11%) and amplification (5% vs. 14.9%) were lower in MBC samples than in FBC. However, the investigators noted that when HER2 aberrations are identified in MBC patients, use of HER2-targeted therapies may be efficacious.

The investigators reported that the PI3 kinase pathway (PIK3CA mutation or loss of PTEN) was aberrated in 50% of MBC samples, suggesting that anti-hormonal therapies may be warranted, especially in combination with PI3 kinase pathway inhibitors. Additionally, 80% of MBC cases tested for Ki67, a protein associated with aggressive disease, were high. Similar to FBC, 83% of MBC cases that were high for Ki67 also overexpressed AR.

“The data from this rare cancer population underscore the importance of examining the individual molecular profile of a patient’s cancerous tissue to more clearly delineate the most appropriate therapy for that patient, which may incorporate standard or investigational treatment options,” said Sherri Z. Millis, M.S., Ph.D., molecular science liaison at Caris Life Sciences, and a co-investigator in the MBC study. “The differences we observed in gene mutation, amplification, and protein expression profiles suggest that the standard of care in female breast cancer patients may not necessarily be the best treatment option for male breast cancer patients.”

About Caris Life Sciences and Caris Molecular Intelligence™
Caris Life Sciences is a leading biosciences company focused on fulfilling the promise of precision medicine through quality and innovation. Caris Molecular Intelligence™, the industry’s leading tumor profiling service with more than 65,000 patients profiled, provides oncologists with the most potentially clinically actionable treatment options available to personalize cancer care today. Using a variety of advanced and validated technologies, which assess relevant biological changes in each patient’s tumor, Caris Molecular Intelligence correlates biomarker data generated from a tumor with biomarker-drug associations supported by evidence in the relevant clinical literature. The company is also developing a series of tests based on its proprietary Carisome® TOP™ platform, a revolutionary blood-based testing technology for diagnosis, prognosis, and theranosis of cancer and other complex diseases. Headquartered in Irving, Texas, Caris Life Sciences offers services throughout Europe, the U.S., Australia and other international markets. To learn more, please visit www.carislifesciences.com.

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