In the October 4 issue of Nature, investigator participants in the Cancer Genome Atlas Network described “Comprehensive molecular portraits of human breast tumors.”
While breast cancer has been categorized into four main types, these are based on whether the tumors express the estrogen receptor (ER positive) or the progesterone receptor (PR positive), overexpress one of the members of the epidermal-growth-factor receptor family (Her2 positive) or none of these, an extremely difficult to treat classification known as triple-negative breast cancer.
And although tumor morphology is often associated with the pattern of molecular aberrations in breast cancers, tumors of the same histological subtype display “remarkably different” clinical behavior.
The researchers, using data generated as part of The Cancer Genome Atlas (TCGA), based their studies of the four standard molecular subtypes on a comprehensive characterization of samples from 825 breast cancer patients.
The investigators combined data from five different platforms, including genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing, and reverse-phase protein arrays, to provide insights into previously defined gene expression subtypes, each of which shows significant molecular heterogeneity.
They also confirmed many “molecular commonalities” between basal-like breast tumors, or highly aggressive triple-negative tumors indicating a related etiology and similar therapeutic opportunities. This data suggests that patients with triple-negative breast cancer might benefit from therapies used to treat ovarian cancer.
“The molecular similarity of one of the principal subtypes of breast cancer to that found in ovarian cancer gives us additional leverage to compare treatments and outcomes across these two cancers,” commented Harold Varmus, NCI director. “This treasure trove of genetic information will need to be examined in great detail to identify how we can use it functionally and clinically.”
As molecular analysis of cancer goes beyond genomics to include a detailed molecular understanding of cancer, this knowledge will advance our understanding of the disease and improve the ability to diagnose, treat, and prevent it, according to the TCGA. But to recapitulate the American Society of Pathology’s report, the potential impact on the diagnostic process and clinical correlations will become more “extraordinary and clinical interpretation will be challenging.”