Personalizing Breast Cancer Treatment:
A Collaboration from Lab Bench to Bedside

Minetta Liu, MD, wanted to understand why some of her breast cancer patients responded to chemotherapy and others did not. Current markers for chemotherapy responses, such as proteins associated with the proliferation of cancer cells, do not show a strong correlation with whether a treatment will be effective against an individual woman’s tumor.

“We needed to identify biomarkers that are more reliable and specific,” Dr. Liu said. “I wanted to be part of the effort to identify these factors, but I didn’t have the skills or knowledge to run a research laboratory on my own. This work requires the translation of research between the clinic and the lab, and I knew when I started that I needed to find a PhD who understood that.”

Enter Robert Clarke, PhD, DSc, a breast cancer researcher at Lombardi who heads a laboratory, and has the same passion for finding individualized treatments for breast cancer as Dr. Liu. “To be able to do research that has some meaning you can’t just sit and play with cell lines, you also have to work with the real thing – the patients,” he explained. “And you have to work with people who understand the real thing, like Minetta does.”

Together Drs. Clarke and Liu designed a truly translational study that attacks the same question from both the clinical and basic science perspectives: who will respond best to paclitaxel treatment? Paclitaxel, marketed as Taxol, is a powerful chemotherapy agent used to treat breast cancer.

In 2001 Dr. Liu began enrolling patients in a clinical research protocol in which patients received Taxol and other standard chemotherapy agents before their definitive breast surgery (a lumpectomy or mastectomy). Traditionally, breast cancer patients undergo surgery before beginning their chemotherapy, but studies have shown that the order of the treatments does not matter. So Dr. Liu enrolled patients who were willing to wait for the surgery. “What’s great about this study is that it was driven by the treatment,” she said. “If a tumor didn’t shrink while the patient was on the paclitaxel, I changed the treatment.”

With the help of surgeons like Shawna Willey, MD, Medical Director of the Ourisman Breast Health Center, Dr. Liu asked patients to undergo their chemotherapy before surgery so that she could biopsy the tumor four times throughout the four rounds of paclitaxel treatments. “The success of this project represents the collaborative effort of everyone involved, including the surgeons, radiologists, oncologists, pathologist, and researchers,” she said.

The order of treatment and the extra biopsies were the only differences from standard treatment for breast cancer. “The real stars of this study are the patients who participated in it. They are an amazing group of women who understood that the breast biopsies were being done strictly for research purposes and were still willing to participate,” Dr. Liu said. Earlier this year, she enrolled her 31st patient.

At the same time, Dr. Clarke had been developing cell lines and in vivo models of breast cancer which he also treated with paclitaxel. Tissue from the biopsies and the cell lines is now being analyzed by Dr. Clarke using microarrays, a technology that allows researchers to measure the status of 30,000 genes simultaneously. He and Dr. Liu expect to find similar patterns in the genes between tumors that responded well to the paclitaxel and different patterns in those tumors that did not respond at all.

Once these patterns are known, the biopsy from a new diagnosis of breast cancer can be analyzed by a microarray and compared to the known patterns for tumors that did and did not respond to Taxol. In other words, Dr. Clarke expects to find patterns in the biopsies taken before the chemotherapy that can predict who will respond to the paclitaxel treatments. This means that in the future, a doctor will know with a great deal of certainty whether paclitaxel is the right chemotherapy agent for their patient’s cancer.

By comparing and analyzing the patterns in these two datasets – from patients’ tumors and from cell lines in the lab – the two researchers will also begin to understand why one tumor responded to paclitaxel and another did not. Dr. Clarke will study specific classes of genes to determine which ones might be responsible for sensitivity to paclitaxel. The aim of this work is to create a better and more targeted treatment.

“We hope that because of this research people will first get the drugs to which they will best respond,” said Dr. Clarke. “And maybe we’ll begin to understand why that is, so we can do an even better job curing the disease.”