Gene Test Hope For Personalised Breast Cancer Treatment

Cancer Research UK scientists have developed a system to identify faulty or missing genes that could prevent specific chemotherapy regimes from working. This opens the doors for targeted breast cancer treatment, according to research published in the Lancet Oncology.

An international team of scientists led by Cancer Research UK’s London Research Institute* together with the Technical University of Denmark developed a bespoke method to scan 829 genes involved in response to a breast cancer drug, in breast cancer tumour cells. They selected those which if missing or faulty would prevent a chemotherapy drug called paclitaxel, from working effectively in patients with breast cancer.

Taxanes** block the growth of cancer cells by stopping cell division. The group includes paclitaxel (Taxol) and docetaxel (Taxotere) which is given to patients with breast cancer before surgery.

The team used a technique called RNA interference*** to delete each of the 829 genes, one at time in cancer cells, to explore how well paclitaxel worked in tumour cells if one particular gene was not working normally.

They narrowed the search down to find six genes which if faulty prevent paclitaxel from working effectively in breast cancer cells in the laboratory. They then showed in patients that these same six genes in breast cancer cells could be used to predict which of them will derive the most benefit from paclitaxel before they are exposed to treatment. Read more

Mammographic Density And Risk Of Breast Cancer

Women who have a breast density of 75 percent or higher on a mammogram have a risk of breast cancer that is four to five times greater than that of women with little or no density, making mammographic breast density one of the strongest biomarkers of breast cancer risk.

At the American Association for Cancer Research 101st Annual Meeting 2010, held in Washington, D.C., April 17-21, researchers will present the latest data on mammographic density and breast cancer risk.

“These abstracts strengthen the observation that high breast density is associated with increased risk for breast cancer, and they strengthen the hypothesis that under some conditions, reducing breast density may be associated with reduced risk for breast cancer,” said Carol J. Fabian, M.D., professor of medicine in the division of clinical oncology and director of the Breast Cancer Prevention Center at the University of Kansas Medical Center.

Mammographic density refers to the amount of white or radiodense area compared to the amount of grey or radiolucent area on a mammogram. The radiodense area is reflective of the amount of ductal and lobular epithelium, connective tissue and fluid in the breast. The radiolucent area is reflective of the amount of fat in the breast.

While increased breast density is a known risk factor for breast cancer, having a lower breast density doesn’t necessarily mean a low risk of developing breast cancer, according to Fabian. Other risk factors are at play, and mammographic density is one tool to help determine a women’s risk.

“The cancer research community is always looking for new methods to better define short-term risk to supplement the known risk factors for breast cancer like family history, genes associated with hereditary breast cancer, reproductive variables and age,” said Fabian. “Modifiable risk biomarkers like mammographic density are increasingly being used in small early phase prevention trials to help us decide which interesting strategies should be carried further into very large Phase III studies with cancer incidence as an endpoint.”

The AACR has highlighted the following abstracts on new research in mammographic density, which will be presented at the Annual Meeting:

4828. Longitudinal breast density and risk of breast cancer

Women who have a decrease in breast density over a six-year period may have a decreased risk of developing breast cancer compared with women whose breast density remained stable.

“A decrease in breast density appears to be associated with a lower breast cancer risk, and importantly, this result takes into account baseline breast density, as well as changes in BMI that occurred between mammographic assessments,” said lead researcher Celine M. Vachon, Ph.D., associate professor of epidemiology in the College of Medicine at the Mayo Clinic, Rochester, Minn.

Vachon and colleagues evaluated whether changes in breast density over time are associated with breast cancer risk using data collected as part of the Mayo Mammography Health Study, which included 19,924 women who had a mammogram at the Mayo Clinic between 2003 and 2006. Participants had never had breast cancer and were more than 35 years old at time of the mammogram. Read more

Common Genetic Variation Impacts Breast Cancer Diagnosis In Older Women

Researchers from The Cancer Institute of New Jersey (CINJ) are converging on Washington, D.C., this week for the 101st Annual Meeting of the American Association for Cancer Research (AACR) to share their findings on how a common genetic variation can impact diagnosis of breast cancer in postmenopausal women. They are joining other top investigators from around the globe for the event, which is highlighting interdisciplinary approaches to cancer research. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.

At focus is the tumor-suppressor gene known as TSC1 and the role it plays in tumor growth in breast cancer. Mutation in either TSC1 or a companion gene known as TSC2, a relatively rare occurrence, is known to cause non-cancerous growths in multiple vital organs – a genetic condition known as tuberous sclerosis. Less clear is a possible association between more common variations in these genes known as polymorphisms, and the formation of breast cancer. These variations are the subject of the CINJ research.

Investigators, led by Kim M. Hirshfield, MD, PhD, medical oncologist at CINJ and assistant professor of medicine at UMDNJ-Robert Wood Johnson Medical School, selected TSC1 because it plays a role in the cell growth pathway regulated by a protein known as mTOR. The mTOR pathway is being used for targeted treatment of several types of cancers including breast cancer. The Hirshfield laboratory previously reported on polymorphisms in p53 tumor suppressor pathway genes that associate age with diagnosis of breast cancer and on how these associations depend on the genetic and environmental characteristics of breast cancer. Read more

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