What You Need to Know: Patients with triple negative breast cancer tend to fall into two categories: those that succumb to their disease within 3 to 5 years, regardless of treatment; and those that remain disease-free for longer than the average patient whose breast cancer is not triple-negative type (at least 8 years postdiagnosis). When the breast cancer DNA methylome was compared with that of healthy persons, distinct methylation patterns were revealed in the primary biopsy breast cancer cells. These patterns indicated a better or worse prognosis, according to an intriguing new study.
Background: The methylome provides a new picture of the genome and shows how it is epigenetically decorated with methyl groups, a process known as DNA methylation.
- Triple negative breast cancers, which make up 15% to 20% of all breast cancers, lack any of the three receptors (estrogen, progesterone, or HER2) that would make them responsive to targeted drugs. Overall, patients have a higher risk of disease recurrence and shorter survival than those with other breast cancers.
- Patients with triple negative breast cancer tend to fall into two categories: those that succumb to their disease within 3 to 5 years, regardless of treatment; and those that remain disease-free for longer than the average patient whose breast cancer is not triple-negative type (at least 8 years postdiagnosis).
- At present, there is no reliable way to stratify triple negative cancers into these two subgroups. Clinicians use tumor size, degree of spread, and infiltration of lymph nodes to determine whether a patient falls into a high-risk or low-risk category. Ironically, the outcome of triple negative breast cancers is far less associated with cancer stage than other breast cancers.
Basic Science: DNA contains combinations of four nucleotides which include cytosine, guanine, thymine and adenine. DNA methylation refers to the addition of a methyl (CH3) group to the cytosine or guanine nucleotides. This modification of the DNA alters the genes expressed in cells when they divide and differentiate from embryonic stem cells into cells of a particular tissue. The change in gene expression is stable and the cell does not revert back to a stem cell or another type of cell.
Professor Susan Clark, PhD (Sydney’s Garvan Institute of Medical Research, in Australia) led the current investigation. Her team performed whole genome methylation capture sequencing on archival tissue samples from patients with triple negative breast cancer and matched normal samples, followed by next generation sequencing to determine cancer-specific changes in DNA methylation.
My Take: This is the first study looking at the methylome of triple negative breast cancer and its relationship with disease outcomes. Triple negative breast cancer is not a uniform disease/ By stratifying cancers epigenetically, we should be better able to ultimately more individualize cancer management. These results point to the need for more investigation among much larger groups of patients with breast cancer. I’m Dr. Michael Hunter.
The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.
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- Nature Communications (2015; doi:10.1038/ncomms6899).