SABCS: Genetic Profiles of TNBC

Research presented today at the 2013 San Antonio Breast Cancer Symposium focused on the genetic makeup of triple-negative breast cancer, which may be the best route to targeted treatment.

SOX4 and P13K

What drives tumor development?  That is especially intriguing in a disease as heterogeneous as triple-negative breast cancer.  Some answers, from an analysis of nearly 500 breast tumor samples from the TCGA project Cancer Genome Atlas Program:

• Basal-like breast cancer tumors have a high level of activity of PI3K, a cellular pathway.

• Basal-like tumors are primarily triple-negative.

• The SOX4 gene amplifies P13K

• Tumors with both PI3K and SOX4 are most likely to be aggressive and to metastasize.

Protein Kinase C

Members of the protein kinase C family are involved in proliferation, cell survival and migration, and have been implicated in the formation and production of tumors.  

• PRKCA, B, I and Q exist in higher levels in TNBC tumors.    

Primary Versus Metastatic Tumors

Does a tumor’s genetic profile change from primary cancer to metastases? In a study of 362 genetic mutations in triple-negative breast cancer, 31 were unique to the metastases—they did not exist in the original tumor.

• TNBC tumors are more likely to contain both P13K and p53.  Tumors with those genes have a less favorable prognosis and are more likely to be resistant to chemo.

• Progression-free survival was less positive with tumors than contained the genes WYNK1, P53, JAK2 and MST1.  

• This profiling can lead to targeted therapy, much of which is already underway.

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

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SOURCES:

[S4-01] An integrated genomics approach identifies novel drivers of oncogenic pathway activity in human breast cancer

Gatza ML, Silva G, Hoadley KA, Fan C, Perou CM. University of North Carolina at Chapel Hill, Chapel Hill, NC

[S4-02] Integrated genomic analyses of members of protein kinase C family identifies subtype specific alterations as novel therapeutic targets

Natrajan RC, Leonidou A, Brough R, Frankum J, Wai PT, Ng CK, Reis-Filho JS, Lord CJ, Ashworth A. The Institute of Cancer Research, London, United Kingdom; Memorial Sloan-Kettering Cancer Center, New York, NY

[S4-03] Exome sequencing reveals clinically actionable mutations in the pathogenesis and metastasis of triple negative breast cancer

Blackwell KL, Hamilton EP, Marcom PK, Peppercorn J, Spector N, Kimmick G, Hopkins J, Favaro J, Rocha G, Parks M, Love C, Scotland P, Dave SS. Duke Cancer Institute, Durham, NC; Forsyth Oncology, Winston-Salem, NC; Novant Oncology Research, Charlotte, NC