New study seeks answers in advanced breast cancer
by Richard Saltus
Kerry Silvestre (left) reads a patient consent form related to a new clinical trial, while her physician, Dr. Nancy Lin, is ready to answer questions.
In the United States alone, the estimated number of women living with metastatic breast cancer – about 200,000 – is greater than the entire population of Providence, R.I. Their disease has spread from the breast to other parts of the body, usually the bones or liver, and their long-term prognosis is limited – though some will be alive quite a few years from now.
A diagnosis of metastatic disease causes a heavy burden on a woman and those around her. Yet there's been surprisingly little research on the experience from the patient's point of view. A new Dana-Farber study led by Nancy Lin, MD, may change that, as well as shed light on the biology of metastatic breast cancer itself.
In the study, patients with recently diagnosed metastatic breast cancer are being asked to undergo additional blood sampling and tissue biopsies. The extra procedures may not affect their own care, but the women's generosity could have future payoffs in improving breast cancer treatment for others.
These women will also be asked to describe how the disease and its treatment affect their quality of life – information that could improve care and support for patients like them.
In return, physician-scientists have designed the project to be helpful for the women volunteers as well, says Dr. Lin, an oncologist in the Women's Cancers Program who is the study's principal investigator.
"We want to give back to the women in the trial," she explains. "So as part of the study, we are planning to publish newsletters every six months on new developments in breast cancer, listing ongoing treatment studies and trials of supportive interventions, such as exercise or expressive writing, being offered at Dana-Farber or in the community. This aspect of our study will help fill gaps in communication which we, as busy clinicians, don't always do as well as we should."
The extra blood and tissue specimens are crucial to the main objective of the new project, called a "cohort" study because it will follow a group of women with metastatic breast cancer over a number of years. These samples can be compared to biopsies from women whose cancers did not spread to other parts of the body to help scientists understand why some cancers recur and become life-threatening, while others never return following initial surgery. Researchers want to know more about the genetic differences in tumor cells that remain contained and those that escape to migrate through the body.
"There are two competing ideas," says Dr. Lin. "One is that some primary cancers have the capacity to spread from the get-go, and others don't. The other hypothesis is you start with a cancer that slowly picks up genetic changes that allow it to spread to the lymph nodes and then to other organs."
Analysis of biopsies taken over time could reveal how the cancer cells change genetically from the initial tumors to the metastases, Dr. Lin says. The volunteers in the study underwent biopsies when their primary cancer was diagnosed, and DNA from those tissues can often be retrieved. The genetic patterns, or "signatures," of those early tumors will be compared with signatures in the advanced cancers for clues to whether the cancer was always capable of metastasizing, or did so only through successive genetic changes.
Scrutinizing gene signatures in the tissue samples may help Dr. Lin and her co-workers shed light on another enigma: What accounts for the variable effectiveness of the potent targeted drug Herceptin when used to treat metastatic breast cancers that have an overactive cell growth signal, HER2?
"Herceptin plus chemotherapy works incredibly well at first in 60 to 70 percent of patients with advanced HER2-positive breast cancer – but then it almost always stops working," she says. "We don't understand that, so we think we need to take biopsy tissue from different time points and test it for gene changes that might explain the discrepancies."
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