Group of People Holding Ribbon Breast Cancer. Photo Courtesy: 2019 Fotolia.

A study by researchers at the Johns Hopkins Kimmel Cancer Center and six other medical centers, inlcuding the University of Iowa and Duke University, have identified a set of molecular markers linked to a chemical process called methylation that may help predict the risk of cancer recurrence within five years for patients with triple-negative breast cancers (TNBC).[1]

Triple-negative breast cancer (TNBC), which lacks expression of the estrogen (ER), progesterone (PR), and HER2 receptors, is an aggressive type of breast cancer, accounting for up to 20% of all breast cancers with poorer survival rates than other types of breast cancer. [2] TNBC is diagnosed more frequently in younger and premenopausal women and is highly prevalent in African American and Hispanic women.[3]

Because of the absence of receptors seen in other forms of breast cancer, TNBC is unresponsive to the targeted hormonal and anti-HER2 therapies used to treat patients diagnosed with other breast cancers. Furthermore, one of the features of TNBC is that the most widely used gene expression profiling tests, including 21-gene Oncotype DX, the 70-gene Mammaprint, or the PAM50, have no clinical utility in patients with TNBC.

Overall, about one-quarter of these cancers recur within five years of localized treatment with surgery or radiation. Physicians currently lack accurate tools to identify which patients are at greatest risk of recurrence.

Hypothesis
In the study, the researchers were able to confirm their hypothesis that higher levels of methylation* would be associated with earlier recurrence and worse outcomes for patients.

“The finding did, however, not distinguish specific levels of methylation or specific methylation markers that could be used to personalize patient treatment,” noted  Christopher B. Umbricht, M.D., Ph.D., associate professor of surgery, oncology, and pathology at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center and the study’s author.

In an article published in the January 31, 2020, issue of the journal npg Breast Cancer, Umbricht noted that their results may support physicians’ decisions to manage patients with less aggressive disease more conservatively and trigger earlier treatment for those with more aggressive disease.

Study
Umbricht and his colleagues examined breast cancer tissue from 110 triple-negative breast cancer (TNBC) patients from archival tissue repositories to look for the biological footprints of DNA methylation, an epigenetic process that can chemically silence genes that suppress tumors and has been well-documented across many types of cancer. The researchers observed that high methylation was associated with shorter recurrence-free interval

Based on these results they identified a set of such molecular markers in which higher levels of methylation were associated with a greater risk of a five-year recurrence of TNBC, confirming that their hypermethylation signatures identified increased recurrence risk independent of whether patients received chemotherapy.

Notes
* Methylation refers to the addition of a methyl group (three hydrogen atoms bound to a carbon atom) to a DNA molecule.
** Epigenetic process refers to the process where chemical compounds are added to genes to regulate their activity

Reference
[1] Fackler MJ, Cho S, Cope L, et al. DNA methylation markers predict recurrence-free interval in triple-negative breast cancer. NPJ Breast Cancer. 2020;6:3. Published 2020 Jan 31. doi:10.1038/s41523-020-0145-3 [Article]
[2] Li CH, Karantza V, Aktan G, et al. Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review. Breast Cancer Res. 2019 Dec 16;21(1):143.
[3] Wahba HA, El-Hadaad HA. Current approaches in treatment of triple-negative breast cancer. Cancer Biol Med. 2015 Jun;12(2):106-16.