Utah technique could one day predict aggressive breast cancer
Researchers at Huntsman Cancer Institute announced Monday they can successfully grow fragments of breast cancer cells into tumors in mice a step in a long path toward better diagnosis and treatment of women with aggressive forms of the disease.
The goal is to find a molecular biomarker that will indicate whether a breast tumor is likely to spread, which could then determine how doctors treat the cancer, said Alana Welm, assistant professor of oncological sciences at the University of Utah and an investigator at Huntsman. She said another goal is to grow patients' tumors in mice to test new drug therapies.
"The long-term goal is to generate models of personalized medicine for particular breast tumors," said Welm, who co-wrote the study with 14 other Utah researchers, including Huntsman's Breast Disease Oriented Team.
The team includes surgeons, oncologists, pathologists and laboratory scientists like Welm. The article was published online in Nature Medicine, a peer-reviewed biomedical research journal.
To get to personalized medicine, the team needed to see if they could implant the tumors in mice. Welm said traditionally tumors are grown in laboratories, but they don't retain the same characteristics as the original tumors. The Utah team initially tried growing the cells in a lab and then implanting them in mice, fearing that placing the tumor cells in mouse mammary glands would be a waste.
But it wasn't. The team used 49 tumor cells from 42 Utah women. They were obtained following the women's surgery and were fragments that would have been discarded. Placed inside of the cleared mammary fat pads of female immunodeficient mice (so they wouldn't reject the human cells), tumors from 18 of the samples grew. A dozen of the tumor lines were maintained through serially transplanting them.
Welm said the tumors retained their essential human characteristics, from what a pathologist would see under a microscope to their DNA sequence.
The tumors also spread to the same places that the cancer spread in the women. A team in France has also implanted breast cancer tumors in mice, but they placed them under the skin and the tumors didn't metastasize the same way as they did in the patients.
The Utah team followed the outcomes of the women's cancer and found that the tumors that grew in the mice were from women who had the most aggressive disease.
The tumors that didn't grow in the mice weren't aggressive in the women.
"If the tumor grows in the mouse that's a poor prognostic factor for that particular patient," Welm said. A possible explanation: "It's a lot to ask of a tumor to grow in a completely new environment. By asking the tumor to grow in a mouse mammary gland, we're selecting for the most aggressive tumors."
She said the main hurdle for using the technique to predict a woman's prognosis is that it can take a couple of months before the tumors grow in the mice. Doctors will have already determined how to treat the cancer by then.
So the team will sequence the genome of all 49 tumors to find the differences between the aggressive tumors and the ones that didn't grow in the mice. The hope is to develop a surrogate marker for growth that could be determined within a week.
The team will also be treating the mice with the same treatment regimen the patients received, to validate whether chemotherapy and radiation works on the mice the same way it did in the women. That's the first step to eventually treating the tumors in the mice with new drug therapies that could be used later in humans.
"Right now it's just a research tool," Welm said. "It's kind of exciting to think about it in terms of the clinical implications some time in the future."
Jeffrey Pollard, deputy director of the Albert Einstein Cancer Center in New York, reviewed the study for The Salt Lake Tribune and said many people have tried to grow the tumors in mice with varying degrees of success. What's interesting about the Utah study is that some of the tumors metastasized and the tumors kept their essential human characteristics, he said.
Still, he said it would take "years and years" before the technology which still needs to be proven, he noted could turn into therapies.
But the need is great, said Pollard, who won a medal from the American Cancer Society for his basic science research on halting tumor progression. The lack of progress in improving survival rates for women with metastatic breast cancer "tells you we need to have new drugs or new therapies and we need systems to test that out."
The Utah study was funded by the U.S. Department of Defense Breast Cancer Research Program, the American Association for Cancer Research, the Breast Cancer Research Foundation and Huntsman Cancer Foundation.
A deadly spread
The vast majority of deaths from breast cancer happen when it spreads to other parts of the body.
About 160,000 U.S. women are estimated to be living with metastatic breast cancer, with about 49,000 diagnosed in a year.
30 percent of women in developed countries with early-stage breast cancer will eventually develop metastatic breast cancer.
Only 27 percent of patients whose cancer has spread to other organs survive five years, compared to 98 percent whose cancer has not spread beyond the breast.
Source: Metastatic Breast Cancer Network