Rebecca L. Aft, MD, PhD, professor of surgery at the Washington University School of Medicine in St. Louis and a physician at Siteman Cancer Center, discusses the use of bisphosphonates for patients with breast cancer.

In a study, patients were randomized to receive a bisphosphonate at the time of neoadjuvant chemotherapy and were analyzed for the presence of disseminating tumor cells. Results demonstrated that patients who received a bisphosphonate had fewer disseminating tumor cells in their bone marrow. In a subgroup analysis, patients with triple-negative disease who received bisphosphonates had a decreased risk of developing metastatic disease.

The mechanism of action of bisphosphonates is hypothesized to affect the bone marrow's microenvironment. It is also hypothesized that cancer cells in the bone marrow or tumors can release activators into the bone marrow which cause increased bone turnover and activation of tumor-enhancing cells. By turning off osteoclasts, Aft says, it is possible to decrease bone turnover and decrease the release of growth factors, creating a more hostile environment for disseminating tumor cells in the bone marrow.

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Dr. Aft on Bisphosphonates for Breast Cancer

Rebecca L. Aft, MD, PhD, Professor of Surgery at the Washington University School of Medicine in St. Louis and a physician at Siteman Cancer Center, discusses the need to identify markers for patients with micrometastatic disease.

Aft says that there is a significant portion of patients who have completed conventional chemotherapy and are radiographically and clinically without evidence of disease and will harbor micrometastatic disease. Aft says she envisions a way of identifying these patients with specific markers.

To date, Aft says, researchers have screened over 250 genes associated with breast cancer for expression in normal bone marrow and found that approximately 44 have no expression in normal marrow. If these genes are expressed in bone marrow, it can be deduced that they are associated with breast cancer cells. Aft says that researchers are still working to analyze this panel of genes to determine if they are predictors of the development of metastatic disease.

It appears that seven genes have targeted therapies that predict metastatic disease development, but Aft says this is not confirmed yet.

Rebecca L. Aft, MD, PhD, from the Siteman Cancer Center, discusses the need to identify markers for patients with micrometastatic disease.

Dr. Aft on Identifying Markers for Micrometastatic Disease

Rebecca L. Aft, MD, PhD, Professor of Surgery at the Washington University School of Medicine in St. Louis and a physician at Siteman Cancer Center, discusses the identification of patients with breast cancer at high risk of recurrent disease development by detection of HER2-positive disseminated tumor cells in bone marrow of patients with HER2-negative tumors.

The study presented at the 2013 American Society of Clinical Oncology (ASCO) Meeting found that 20% of patients with HER2-negative tumors will have HER2-positive disseminating tumor cells. These patients, Aft notes, have a worse prognosis than patients with HER2-positive tumors and HER2-positive disseminating tumor cells who are treated with trastuzumab and other patients with HER2-negative tumor cells in their bone marrow.

The findings from this study are hypothesis-generating, Aft says, as it could be possible to treat patients with HER2-negative tumors with a high risk of recurrence due to HER2-positive disseminating tumor cells with targeted therapies.

View more from the 2013 ASCO Annual Meeting

Rebecca L. Aft, MD, PhD, discusses the identification of patients with breast cancer at high risk of recurrent disease development by detection of HER2-positive disseminated tumor cells in bone marrow of patients with HER2-negative tumors.

Rebecca L. Aft, MD, PhD

Articles

Dr. Aft on Bisphosphonates for Breast Cancer

Dr. Aft on Identifying Markers for Micrometastatic Disease

Dr. Aft on Disseminating Tumor Cells and Prognosis