Like father, like son? That is not necessarily the case when it comes to breast cancer.

George Somlo (Photo by p.cunningham)

A study by City of Hope’s George Somlo, M.D., and scientists at City of Hope and the Palo Alto Research Center (PARC) found that 20 to 60 percent of metastasized breast cancer cells circulating through the body are significantly different from the tumors that originally unleashed them. That may mean that, in some patients, therapies suitable against a primary tumor could be inappropriate to treat cancer that has spread.

The findings add to increasing evidence supporting clinical trials of strategies that incorporate the characteristics of metastasized breast cancer cells into treatment decisions.

Published in Breast Cancer Research and Treatment, the study focused on what are called circulating tumor cells — cells that have broken off from a primary tumor and entered the bloodstream — in women with either metastatic breast cancer, inflammatory breast cancer or locally advanced breast cancer. The study was released online on April 16.

Women with inflammatory or locally advanced breast cancer (a tumor that is large or has spread to surrounding tissue or lymph nodes) are highly likely to see their cancer return after treatment, and women with metastatic cancer often face a poor prognosis.

“It is critical that we find more effective, individualized treatments for these cancers,” said Somlo, professor in the Department of Medical Oncology & Therapeutics Research, director of breast oncology and co-director of the Breast Cancer Program. “We believe that studying circulating tumor cells will help us discover how to customize treatment based on variations between circulating tumor cells and the primary tumor and metastatic sites.”

As Somlo explained, when a patient has breast cancer, doctors usually recommend therapies that target certain characteristics of the primary tumor. Patients whose tumors have an abundance of estrogen receptor (ER), progesterone receptor or human epidermal growth factor receptor 2 (HER2), for example, receive anticancer treatments that target these receptors. Patients who test negative for the receptors have fewer treatment options and a poorer prognosis.

Studies by the group and others have shown that receptor-negative tumors, however, may actually spawn circulating cells that are receptor-positive.

Somlo and his colleagues are using a tool developed at PARC called Fiber Array Scanning Technology to search for circulating tumor cells in patients’ blood. The technology was developed by Richard Bruce, Ph.D., director of the Scripps-PARC Institute for Advanced Biomedical Sciences and the study’s senior author.

The team studied 36 City of Hope patients with metastatic, inflammatory or locally advanced breast cancer, looking for circulating tumor cells. In 26 of these patients, they also determined whether patients’ primary tumors expressed high levels of ER or HER2.

Their findings:

• Among women with metastatic breast cancer, three of 13 (23 percent) had a HER2-negative primary tumor and HER2-positive circulating tumor cells.
• Two in five women with metastatic breast cancer (40 percent) had an ER-negative primary tumor and ER-positive circulating tumor cells.
• Among women with locally advanced or inflammatory breast cancer, one of five (20 percent) had a HER2-negative primary tumor and HER2-positive circulating tumor cells.
• Three of five women with locally advanced or inflammatory breast cancer (60 percent) had an ER-negative primary tumor and ER-positive circulating tumor cells.

“We hypothesize that circulating tumor cells can act like stem cells, which would help them evolve and metastasize,” Somlo said.

Other City of Hope contributors to the study included Paul Frankel, Ph.D., Sean Lau, M.D., and Lixin Yang, Ph.D. The work is supported by the National Institutes of Health.