Breast cancer: Clues to better treatment may be in the blood

September 25, 2011 | by City of Hope Staff

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

George Somlo, M.D., and other scientists at City of Hope, along with colleagues at the Palo Alto Research Center (PARC), recently uncovered something interesting. They found that 20 to 60 percent of breast cancer cells that circulate through the body are very different from the tumors that originally unleashed them.

That may mean that, in some patients, therapies that work against the original tumor could be less effective, or even useless, against cancer that has spread, or metastasized.

The findings add to a growing body of evidence that clinical trials may need a new edge. Patients could benefit if doctors incorporate the characteristics of metastasized breast cancer cells into treatment decisions.

Somlo’s study focused on what are called circulating tumor cells — cells that have broken off from a primary tumor and entered the bloodstream. He and his colleagues looked at women with either metastatic breast cancer, inflammatory breast cancer or locally advanced breast cancer.

In inflammatory breast cancer, tumor cells cause redness and swelling. Locally advanced breast cancer describes a tumor that is large or has spread to nearby surrounding tissue or lymph nodes. Women with these diagnoses are highly likely to see their cancer return after treatment. And women with metastatic cancer often face a poor outcome.

“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, doctors usually recommend breast cancer therapies that target certain characteristics of the original, or primary, tumor. Patients whose tumors have an abundance of certain proteins — estrogen receptor (ER), progesterone receptor or human epidermal growth factor receptor 2 (HER2), for example — receive anticancer treatments that target these proteins. Patients who test negative for these receptors have fewer treatment options and usually poorer outcomes.

Studies by the group and others have shown that primary tumors, however, may actually spawn circulating cells that do have one or more of these receptors.

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.breast cancer cells

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 checked whether their primary tumors expressed high levels of estrogen receptor or HER2.

Their findings:

  • Among women with metastatic breast cancer, three of 13 (23 percent) had a primary tumor that lacked HER2 but circulating tumor cells that did have it.
  • Two in five women with metastatic breast cancer (40 percent) had a primary tumor lacking ER but circulating tumor cells with it.
  • 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 ER-negative primary tumors and ER-positive circulating tumor cells.
  • The results could help physicians better tailor treatments to patients. They also brought to light another interesting characteristic of circulating tumor cells. 
“We hypothesize that circulating tumor cells can act like stem cells, which would help them evolve and metastasize,” Somlo said.

That knowledge could help researchers better understand how cancer spreads. It also may point them to drugs that may knock out circulating tumor cells — improving patients’ chances for positive outcomes.

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