Discovery of gene’s link to survival could aid breast cancer treatment

July 16, 2015 | by Tami Dennis

genes and breast cancer Expression of the SERPINA1 gene appears linked to survival outcomes in women whose breast cancer tumors are both ER positive and HER2 positive, researchers have found.

Women diagnosed with breast cancer quickly learn their tumor’s type, meaning the characteristics that fuel its growth. That label guides the treatment of their disease, as well as their prognosis when it comes to treatment effectiveness.

Sometimes, however, doctors can’t accurately predict treatment effectiveness because their knowledge about tumor types has gaps. Each tumor genome is unique, and small variations in gene expression can affect how a particular tumor type responds to particular treatment regimens.

Women whose tumor types are both ER positive and HER2 positive, for instance, generally have more negative outcomes than women whose tumors are ER positive and HER2 negative. Estrogen receptor, or ER, positive tumors are fueled by the hormone estrogen. HER2 positive tumors make excessive amounts of a protein called HER2/neu and tend to be aggressive and fast-growing.

Researchers and physicians have known that women with tumors that are both ER positive and HER2 positive have poorer survival outcomes. What they haven’t known is how to predict how these women might fare.

The question is an important one because approximately 10 percent of breast cancer patients have such tumors. What researchers and physicians need are biomarkers – biochemical signs that can be reliably measured and analyzed for changes – that could help them predict outcomes for women with that particular tumor type.

They appear to have found one.

In a new study published in Oncotarget, City of Hope scientists say that high expression of the gene SERPINA1 appears linked to better survival in women whose tumors are both ER positive and HER2 positive.

“We have found that the expression of SERPINA1, an estrogen- and HER2-regulated gene, could be a predictive marker for the clinical outcome of ER positive/HER2 positive breast cancer,” said lead researcher Shiuan Chen, Ph.D., professor and chair of the Department of Cancer Biology. “Our study has found that patients with high levels of SERPINA1 have better clinical outcome than those with low levels of SERPINA1.”

The discovery that expression level of a specific gene is linked to survival outcomes gives researchers new direction, opening up an array of perhaps more treatment options and avenues of inquiry.

“Chemotherapy and HER2-directed therapy has been widely used as systemic treatment for patients with ER positive and HER2 positive disease,” Chen said. “But for patients with high levels of SERPINA1 expression, a less toxic or more cost-effective treatment may be also considered.”

The researchers based their conclusions on data from existing patient populations and now need to validate their findings, using data from larger groups of patients. The point is, they now have a new avenue to explore, one that could ultimately help 10 percent of breast cancer patients.

** The other authors of the study were Hie Jason Chan; Haiqing Li, Ph.D.; Zheng Liu, Ph.D., manager of the Biomedical Informatics Core facility; Yate-Ching Yuan, Ph.D., director of the Biomedical Informatics Core facility; and Joanne Mortimer, M.D., vice chair and professor of the Department of Molecular Oncology & Therapeutics Research.

Financial support: This study was partially supported by the National Institutes of Health (NIH) grant R01 CA44735, National Cancer Institute of the NIH (P30CA33572), and the California Breast Cancer Research Program (CBCRP) Dissertation Award 15GB-0027. Research reported in this publication included work performed in the Bioinformatics Core and Interactive Genomics Core supported by the National Cancer Institute of the NIH under award number P30CA33572.


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