Researchers from Caris Life Sciences® and Fox Chase Cancer Center – Temple Health announced the presentation of two studies revealing the potential for exploring new therapeutic options for triple-negative breast cancer (TNBC) at the 2015 San Antonio Breast Cancer Symposium (SABCS).
Researchers used Caris Molecular Intelligence®, Caris's panomic, comprehensive tumor profiling service, to assess biomarker profiles in subsets of patients with TNBC, an aggressive type of breast cancer in which the cancer cells lack estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). In the studies, multiplatform tumor profiling confirmed molecular differences between rare and aggressive subsets of TNBC, which can potentially lead to new treatment options and clinical trial strategies.
"Triple-negative breast cancer remains challenging because of its aggressive and complex nature, its high rate of recurrence and propensity to become a metastatic disease, and the lack of an effective targeted therapy," said Elias Obeid, MD, MPH, assistant professor in the Departments of Clinical Genetics and Medical Oncology at Fox Chase. "With the advancement of comprehensive molecular profiling technology and our partnership with Caris Life Sciences, our understanding of the differences in the subtypes of triple negative breast cancer is unfolding, as well as our understanding of the molecular drivers of the disease that may serve as potential targets for new therapies."
The first study compared the biomarker profiles of patients with quadruple-negative breast cancer (QNBC) – a subgroup of TNBC that lacks androgen receptor (AR) expression – against those of patients with TNBC who are AR-positive (AR+), confirming the molecular heterogeneity of TNBC. In the second study, researchers identified differences in the molecular profiles of BRCA1/2-mutated and BRCA1/2-non-mutated TNBCs, providing insights into potential targeted treatment strategies for these tumor subtypes.
Both studies utilized Caris Molecular Intelligence's multi-technology approach, which included protein expression analysis (immunohistochemistry [IHC]), gene copy number analysis (chromogenic or fluorescence in situ hybridization [CISH or FISH]), and gene sequencing (SEQ, using Next-Generation or Sanger sequencing).
QNBC Study Highlights (P3-07-26)
In the QNBC study, Caris and Fox Chase researchers analyzed 2,071 TNBC samples, including 1,952 that underwent AR IHC. The biomarker results suggest that for AR+ TNBC tumors, future clinical trial designs should consider fluoropyrimidines, taxanes, and agents targeting the PI3K/AKT/mTOR pathway, as well as pan-HER inhibitors, and combining those agents with anti-androgen therapies may be a viable treatment strategy. And, clinical trials for immune checkpoint inhibitors, TOPO2A inhibitors, and agents that target cKIT and EGFR should be considered for patients with QNBC.
"Our findings highlight the molecular differences that should be considered in the design of future clinical trials involving patients with TNBC," said lead investigator Joanne Xiu, PhD, a research scientist and molecular science liaison at Caris Life Sciences. "In particular, patterns of biomarker expression in both QNBC and AR-positive TNBC warrant further investigation for improving targeted therapy and outcomes in TNBC."
BRCA1/2 Mutation Study Highlights (P3-07-30)
In the second study, a team of Caris and Fox Chase researchers led by David Arguello, MD, a research scientist at Caris Life Sciences, compared BRCA1/2-mutated and BRCA1/2-non-mutated TNBC specimens to identify molecular differences between these tumor subtypes, and to shed light on potential therapeutic options for each subtype. Of the 386 specimens analyzed, 63 (16.3 percent) harbored mutations in BRCA1 or BRCA2, and 323 (83.7 percent) had no detectable BRCA1/2 alterations.
[P3-07-26] Biomarker comparison between androgen receptor – Positive-triple-negative breast cancer (AR+ TNBC) and quadruple-negative breast cancer (QNBC), Xiu J, Obeid E, Gatalica Z, Reddy S, Goldstein LJ, Link J, Waisman J, Thursday, December 10, 2015 at 5:00 PM, Poster Session 3: Prognostic and Predictive Factors: Response Predictions -- Biomarkers and Other Factors (5:00 PM-7:00 PM).
[P3-07-30] Molecular profiling comparison of BRCA1/2-mutated and BRCA1/2 non-mutated triple-negative breast cancer (TNBC), Arguello D, Abbott B, Reddy S, Gatalica Z, Obeid E, Goldstein L, Thursday, December 10, 2015 at 5:00 PM, Poster Session 3: Prognostic and Predictive Factors: Response Predictions -- Biomarkers and Other Factors (5:00 PM-7:00 PM).