By Duke Medicine News and Communications

DURHAM, N.C. – Scientists at the Duke Comprehensive Cancer Center have shown they can use magnetic resonance imaging (MRI) to visualize and "score" a breast cancer tumor's ability to respond to cancer-killing drugs.

Using this novel technique, the researchers predicted with 90 percent accuracy which tumors would respond when treated with "neoadjuvant" chemotherapy and which tumors would not. Neoadjuvant means the drugs are given before surgery, rather than after, to shrink the tumor and improve the patient's outcome.

Women whose tumors are unlikely to respond to neoadjuvant chemotherapy could be spared the toxicity and discomfort of these drugs. Instead, they could be treated with hormones or other therapies that have a better chance of shrinking their drug-resistant tumors, said the Duke researchers.

Principal investigator Oana Craciunescu, Ph.D., will present the results of her team's findings at the 27th Annual San Antonio Breast Cancer Symposium, Dec. 8 - 11, 2004.

"Our goal is to shrink the tumor with chemotherapy prior to surgery, so that the surgeon has a greater ability to access and remove all of the tumor," said Craciunescu, a medical physicist at Duke. "But each tumor has its own unique form and structure, called morphology, and function called tumor physiology, which greatly impact how the tumor will respond to various drugs."

Knowing which factors can predict tumor response can reduce unnecessary treatments and individualize therapy for each woman, she said.

In the Duke pilot study of 20 women with locally advanced breast cancer, each woman was injected with a tracer, gadolinium-DTPA, which is preferentially absorbed in the tumor. Locally advanced breast cancer is a tumor larger than 5cm and that may have spread from the breast into the lymph nodes or other tissues next to the breast.

The researchers obtained MRI images of each woman's breast tissue. The rate at which the gadolinium washed in and out of the tumor was carefully measured, as it predicted how the chemotherapy would enter and leak out of the tumor. The MRI images were processed and several parameters relevant to tumor morphology and physiology were extracted.

"Each woman was given a score from 0 to 5 based on specific parameters of her tumor, and we then labeled them as likely to be responders to chemotherapy, non-responders or partial responders," said Craciunescu.

The three primary factors in predicting a tumor's response to chemotherapy were perfusion and permeability – the ability and speed of a substance to flow in and leak out of the tumor – and morphology/cellularity, or the number and placement of cancer cells in the tumor.

"You can see patterns where the tumor is more vascular and therefore more permeable," said Craciunescu. "Tumors with more efficient blood vessels can carry more of the tracer and hence more of the chemotherapy, too."

Tumors that were closely packed with cancer cells did not effectively retain the tracer, the study showed. "Tightly packed tumors are resistant to treatment," said Craciunescu. "If the tracer can't be retained by the tumor, the drug can't be either."

Tumors in which the blood vessels formed a ring pattern around the center were also resistant to chemotherapy because of collapsed blood vessels in the center, which will not carry the drug there, the study showed.

The best responders were homogenous tumors in which blood vessels were evenly distributed throughout the tumor. In these tumors, the gadolinium tended to wash into and out of the tumor slowly.

"We've demonstrated how important tumor morphology and physiology, such as perfusion, permeability and cellularity, can be as predictive tools in determining which tumors will respond to therapy," said Craciunescu. "Our ability to define an individual woman's response to treatment is greatly enhanced by technologies such as MRI and our increasing knowledge of tumor physiology."

The research was funded by a grant from the National Cancer Institute.