Breast cancer breakthrough

By Dr. Ananya Mandal, MDSep 30 2010

New research on gene expression provides a breakthrough in breast cancer treatment. Women who have triple-negative breast cancer are a small proportion of breast cancer cases, but it is difficult to treat and might have a more aggressive clinical course than other forms of the disease. Triple negative refers to breast cancers that test negative for estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2(HER2), all of which fuel most breast cancer growth. This usually means that the woman is negative for hormonal markers that are targeted by newer therapies.

The research team suggests insulin-like growth-factor 1 receptor (IGF-1R) is overexpressed and amplified in a subset of triple-negative breast cancer patients. This IGF-IR could be a potential therapeutic target, explained study coauthor Agnieszka K. Witkiewicz, associate professor of pathology at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania.

IGF-1R was overexpressed in 25% of cases, and a significant association was observed between IGF-1R protein expression and IGF1R gene amplification. In patients 55 years and younger, a high IGF-1R score was associated with prolonged survival found the team. Dr. Witkiewicz explained that even though triple-negative breast cancer accounts for only 15% to 20% of patients with the disease, it leads to half of all breast cancer deaths. “This is one of the subsets that is most challenging to treat… It is more common in young women, more common in African American women, and is characterized by an aggressive course,” Dr. Witkiewicz said. Therefore, there is a significant need for a better understanding of the pathogenesis of triple-negative breast cancer and a need to identify new molecular targets for treatment, she added.

Authors write that IGF-1R has been known to play a major role in cancer cell proliferation, survival, and resistance to treatment in a number of human malignancies, including breast cancer. It is also a target of several investigational drugs, both in clinical and preclinical development.

For this study the team evaluated IGF-1R expression in 99 women with triple-negative breast cancer. The authors observed that IGF-1R expression was high in 29 of 99 (29%) cases and correlated with negative lymph nodes. Gene amplification was seen is 8 of 35 cases (23%). Low IGF-1R expression was associated with lymph node metastases and conversely, high IGF-1R expression was associated with a tumor size that was borderline significantly smaller.

However Dr. Witkiewicz pointed out, “In patients older than 65 years, there was no difference in survival between patients with low and high IGF-1R expression…But in patients younger than 65, those with high IGF-1R expression had longer survival than those with low expression.” The longest survival was seen in younger patients with high IGF-1R expression, and the poorest survival was seen in older patients (>55 years) with low IGF-1R expression. She added, “For now, we know that it is there and we know it is a marker of better prognosis…The next step is to learn if triple-negative breast cancer patients benefit from targeting IGF-1R.”

Program chair Gordon B. Mills from the Department of Systems Biology at the University of Texas M.D. Anderson Cancer Center, in Houston said, “…we have developed a pathway to the development of molecular diagnostics and biomarkers…Importantly, we have a much better concept of the limitations, challenges, and hurdles that need to be overcome for the implementation of molecular diagnostics.”

This latest research was presented at the 4th American Association for Cancer Research International Conference on Molecular Diagnostics in Cancer Therapeutic Development, in Denver, Colorado.

In a separate finding, Australian researchers were able to identify specific targets for future breast cancer treatments. They used the latest protein screening technology to profile basal breast cancer. Dr Falko Hochgräfe and Professor Roger Daly of Sydney's Garvan Institute of Medical Research studied protein behavior in basal breast cancer through a process known as phosphorylation.