A newly discovered gene known as DEAR1 is mutated in breast cancer and is an independent predictor of local recurrence-free survival in early-onset breast cancer, a research team headed by scientists at The University of Texas M. D. Anderson Cancer Center reports in the journal PLoS Medicine.
"The correlation with local recurrence is significant because so many young women have recurrences in the breast, and cancers that do recur tend to be more aggressive," said senior author Ann McNeill Killary, Ph.D., professor in M. D. Anderson's Department of Genetics. "Young age has been considered a risk factor for local recurrence and metastasis. It is important to understand the genetic mechanisms operating in early-onset breast cancer and to determine whether there is a way to identify young women who might be at a higher risk of recurrence."
After Killary's laboratory research discovered DEAR1 (ductal epithelium-associated ring chromosome 1) and implicated it in breast cancer, the team examined a tumor tissue microarray from 123 women whose breast cancer began between ages 25 and 49, all of whom advanced to invasive disease. Of these, 56 percent lacked DEAR1 expression in their tumors, which was associated with 58 percent local recurrence-free survival 15 years after surgery. For those with DEAR1 expression, local recurrence-free survival was 95 percent at 15 years.
"Immunohistochemical staining for DEAR1 could potentially be performed in any hospital setting, and such an assay might predict which women are at a high risk of recurrence and potentially help guide treatment decisions" Killary said, noting the results will need to be validated in a larger cohort of patients.
Breast cancer that develops before age 50 tends to be more aggressive and more likely to recur even in the absence of invasion of the lymph nodes at diagnosis. "Approximately one-fourth of women without nodal involvement will experience a recurrence up to 12 years after surgery," Killary said. Of the 123 early-onset patients, 72 percent had no lymph node involvement at diagnosis.
While the researchers found that loss of DEAR1 expression correlated significantly with local recurrence, it did not correlate with overall survival in this young cohort.
However, lack of DEAR1 expression was associated with triple-negative breast cancer, which indicates poor prognosis because it lacks estrogen or progesterone receptors and does not express HER2, three targets for therapy. Lack of DEAR1 expression also was associated with a strong family history of breast cancer.
The team discovered the gene in a region of the human genome that has been implicated in other epithelial tumors, including colon and pancreatic cancers, and that the researchers suspected might harbor an important tumor suppressor gene. Finding that DEAR1 was mutated in breast cancer suggested that it could play a role in the initiation and progression of the disease.