Breast cancer patients with even the tiniest spread of the disease to a lymph node have a much higher risk of it recurring years later and may need more treatment than just surgery, a new study by Dutch researchers suggests.

For years, doctors and patients have struggled with what to do about a microscopic tumor or stray cancer cells in a lymph node. Women with "micro tumors" usually are given estrogen-blocking drugs, chemotherapy or both; those with isolated cancer cells usually are not, because those were thought to be of low concern.

The new study challenges that view. It suggests that either type of metastasis, or spread, raises a woman's risk of having cancer show up in the breast or anywhere else in the next five years by about 50 percent.

"This took an area that was very gray and I think made it black and white," said Dr. Linda Vahdat, director of breast cancer research at Weill Cornell Medical College and an adviser for the breast cancer patient Web site of ASCO, the American Society of Clinical Oncology.

"I think it will influence treatment," she said of the study. "If we're considering treating the patient, we probably should."

Dr. Daniel Hayes, director of breast cancer treatment at the University of Michigan, agreed.

"It really does look like our biases are wrong," he said. "For the first time, it suggests that isolated tumor cells or micrometastases do have biological significance."

Vahdat and Hayes had no role in the study, which was done by researchers throughout the Netherlands. Results are in Thursday's New England Journal of Medicine.

The study is not ideal: It just observed a large number of women rather than assigning some to get treatment and comparing how they fared to others who were not treated. The study also was done at a time when treatment was less aggressive and in a country where doctors had been treating breast cancer more conservatively than in the United States.

In the U.S., many women with early stage breast cancer are given hormone blockers.

"The big issue is, should these patients also get chemotherapy?" Hayes said.

However, not all women benefit from chemotherapy even when their risk of a recurrence is high, said Dr. Eric Winer, breast cancer chief at the Dana-Farber Cancer Center in Boston.

"Patients are looking for more specific treatment" tailored to their individual tumor type — not necessarily more or less treatment, he said.

The Dutch study involved more than 2,700 women with low-risk, early stage cancer — small tumors that did not seem aggressive. All had surgery to remove their breast tumors. All of their armpit lymph nodes or a few key ones called "sentinel" nodes were removed and checked for signs of cancer. Doctors do this by examining tissue slices from the nodes and using special stains to make cancer cells show up.

Larger tumors in lymph nodes already trigger further treatment. A micro tumor is a cluster of cells less than 2 millimeters — smaller than one-tenth of an inch. Most, but not all, doctors would treat these, too. Isolated tumor cells are even tinier — "you can essentially count them" in a tissue sample, Winer said — and do not typically spur further treatment under current guidelines.

The Dutch researchers compared patients based on whether they received treatment beyond surgery and whether cancer of various amounts was found in a lymph node.

In most cases, breast cancer doesn't return after surgery. Among women in the study who were given no additional treatment, 86 percent of those with no cancer in lymph nodes were free of cancer five years later. Only 76 percent of those with micro tumors and 77 percent of those with isolated cancer cells were cancer-free.

That translates to a roughly 50 percent greater risk of recurrence if any sign of cancer was present in a node.

Also, women with micro tumors or stray cells who were given additional treatment had a 43 percent lower risk of a cancer recurrence than similar women not treated beyond surgery.

The differences should lead doctors to reconsider guidelines for how tumors are classified, which guides the amount of treatment a woman receives, the authors write. Now, a micro tumor is considered "node positive" cancer, warranting further treatment, while isolated cells are called "node negative."

A new version of the guidelines is due out soon, Hayes said.


On the Net:

New England Journal: www.nejm.org