WEDNESDAY, April 9 (HealthDay News) -- A new long-term analysis of breast cancer patient survival suggests it might be time to update the way pathologists test lymph node biopsies.

A team of New York City physicians found about one in four patients originally declared to be free of cancerous cells in their sentinel lymph nodes were actually not cancer-free, and that tiny cancer remnants called micrometastases reduced the women's survival over a 20-year period.

These findings address a long-standing question among breast cancer researchers: Are such micrometastases prognostically significant?

"This is the first study to show that there is a survival impact for the detection of micrometastases," said Dr. Stephen F. Sener, a professor of surgery at Northwestern University Feinberg School of Medicine in Chicago.

The results are published in the April 10 issue of the Journal of Clinical Oncology.

In the study, a team led by Dr. Hiram S. Cody III, a professor of clinical surgery at Memorial Sloan-Kettering Cancer Center in New York City, analyzed a population of 368 patients who were originally diagnosed with breast cancer in the 1970s. At the time, these patients were judged to be free of cancerous cells on the basis of a single tissue slice (standard procedure at that time). As a result of that diagnosis, these patients received no follow-up treatment for their disease.

Each of these patients was then monitored over the following 20 years or so. Cody and his team retrospectively reanalyzed the decades-old tissue samples using modern techniques. They then assessed how many of the slices did, in fact, contain cancerous cells, and whether those stray cancerous cells had affected the women's survival.

"What we found was that among these patients, 23 percent were converted to node-positive [cancer status], and among those who were converted, their survival was worse than among patients who remained node-negative," said Cody.

"The 23 percent number is very significant, because it argues that if pathologists just do one section, you may want to ask them to do more," he explained. "We think the information you get by doing more is significant."

According to Cody, 30 years ago the standard of care for breast cancer patients was complete dissection of the axillary lymph nodes (those found under the armpit) followed by cell-shape analysis using a single tissue slice from each node. Such a surgery would typically collect 15 to 20 nodes, on average. Today, however, a different, less traumatic approach called sentinel node biopsy is used.

In sentinel lymph node (SLN) biopsy, a patient's tumor is injected with a combination of dye and radioactive tracer molecules. The following day, only those lymph nodes to which the tracer molecules migrated (the SLNs) are biopsied and analyzed. So, instead of harvesting 15 to 20 nodes, on average only two are three are collected using the new technique.

That reduction in work per node has a real payoff, because pathologists can delve much deeper into each sample, Cody explained.

"Because you remove fewer nodes, you can study them more carefully, and we argue that the information you get by doing that is prognostically significant," he said.

Current guidelines from the College of American Pathologists recommend analyzing one tissue slice per biopsied lymph node, Cody noted. Yet for years, he said, physicians have known that the more carefully one looks, the more cancerous cells one can find. The problem has always been one of balancing the additional work and expense required against the likelihood of success -- some studies have suggested a pathologist would need to analyze as many as 1,600 additional sections to find a single additional node-positive case.

In the current study, Cody's team took four sections per node, analyzing two each for cell shape (morphology) and the presence of a molecular marker of cancer. Nine percent of patients were found to be node-positive using morphological criteria alone; the other 14 percent were detected using molecular markers. In both cases, survival was poorer than in patients who remained node-negative.

"What we are suggesting is that perhaps the staging system for lymph node metastases should be reevaluated in the next edition of the AJCC [American Joint Committee on Cancer] staging," he said.

Many sites already analyze more than one slice per node, he added. Sener's facility, for instance, uses 10.

According to Sener, the current findings underscore the need for additional systemic therapy, such as chemotherapy, in patients with SLN micrometastases. But he also noted that SLN micrometastases do not necessarily require surgical excision, as most patients with positive lymph nodes do not develop cancer under the arm.

Sener hypothesized that could be because each metastasizing cancer cell has a sort of molecular ZIP code, which governs where it can go. Under this hypothesis, the decreased survivability associated with micrometastases has less to do with the lymph nodes per se, than with what those positive nodes say about metastases elsewhere in the body.

"It may be that the presence of micrometastases in these lymph nodes may be a bystander phenomenon," Sener said, "a surrogate marker for the presence of the lung or liver ZIP code in these cells."

Cody noted one "significant caveat" to this study: Because breast cancer survival and treatment regimens have changed so dramatically over the past 30 years, this study says nothing about the prognostic implication of micrometastases discovered today. That will require prospective studies, several of which are ongoing.

Nevertheless, he said, "because we don't know the results of those studies yet, studies like our own may be the best available evidence at present, and our study suggests these micrometastases are prognostically significant."

More information

For more on breast cancer, visit the U.S. National Cancer Institute.

WEDNESDAY, April 9 (HealthDay News) -- Researchers at Stanford University have succeeded in transforming skin cells into what appear to be cancer stem cells, in a feat that could propel cancer research forward.

Cancer stem cells are thought to start the unhindered proliferation of cells which ultimately results in cancer.

"This has the potential for unlocking some of the secrets of cancer," said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, which supported the study.

"This means that now you have a good way to study cancer cells and the mechanisms involved versus getting a piece of the tumor," added Paul Sanberg, distinguished professor of neurosurgery and director of the University of South Florida Center for Aging and Brain Repair in Tampa. "Here, you have more control, more ability to look at genetic consequences and the effects of developing new therapies."

"This might allow you to identify cancers that are going to be more aggressive earlier on and allow you to tailor therapies," noted Dr. Fabrice Roegiers, co-director of the Keystone Program for Epigenetics and Progenitor Cells at Fox Chase Cancer Center in Philadelphia. "In the future, being able to identify which cancers are really being driven by the stem cell population will allow us to target those sooner."

The work, published in the April 10 issue of Cell Stem Cell, also noted that cancer stem cells are closer to embryonic stem cells (which can develop into all tissue types) than adult stem cells (which are more limited in what types of tissue they can become). This discovery could shed light on how tumors originate.

Thus far, however, researchers have been hindered in their efforts to understand this type of cell, because they are rare and difficult to grow in the lab. And, added Roegiers, there is still some controversy as to whether this type of cell actually exists in tumors.

For this study, researchers reviewed existing data on gene expression patterns in various stem cell populations and ultimately came up with two different groups: one that is closer to most adult stem cells and one that's closer to embryonic stem cells.

They were also able to detect the "signature" of the embryonic stem cells in certain tumor samples and to note that these tumors tended to be more aggressive.

The findings have implications for future therapies that might be derived from stem cells. The researchers found that one oncogene, "Myc," seems to be a key regulator in converting skin cells to stem cells. But when overexpressed, this gene can induce tumors. If stem cells are created with Myc, then put back into a patient for therapy, there is also the possibility that it will stimulate cancer growth.

"As they're clearly showing, Myc is capable of reprogramming cells into stem cells, but it does that in tumors as well," Roegiers said. "It will be really important to see what Myc is doing and whether it's possible to create these types of stem cells in the lab in a way that will not threaten people when you introduce these cells."

More information

Visit the American Cancer Society   for more on different types of cancer.

WEDNESDAY, April 9 (HealthDay News) -- High-intensity chemotherapy does not improve the survival rate of patients with small cell lung cancer (SCLC), a new Swiss study concludes.

Testing on 140 patients in a randomized trial showed no statistically significant differences in survival rate or tumor size between groups receiving either standard or high doses of chemo over a three-year period. The findings were published online April 8 in the Journal of the National Cancer Institute.

Researchers thought upping the amount of chemotherapy might help the patients live longer because laboratory data had suggested that higher doses kill SCLC cells resistant to standard doses.

"The approach explored in the present trial succeeded in raising the peak dose, total dose and dose intensity of (the chemotherapy drugs) by threefold but has clearly been ineffective and highly toxic," the authors wrote. "As a result, this strategy should be abandoned."

SCLC accounts for almost 13 percent of lung cancer cases in the United States. While many patients initially respond to chemotherapy, most suffer disease recurrence relatively quickly.

The study, lead by Dr. Serge Leyvraz of the University Hospital in Lausanne, Switzerland, compared high-dose and standard-dose chemotherapy using the drug agents: ifosfamide, carboplatin and etoposide (ICE).

The survival rates in the group were similar: 18 percent of the high-dose patients were alive after three years, 19 percent of standard-dose patients survived. Tumor shrinkage was also similar in the two groups: 78 percent among the high-dose recipients and 68 percent in the standard-dose arm.

More information

The National Cancer Institute has more about lung cancer.

TUESDAY, April 8 (HealthDay News) -- By combining a special type of chemotherapy (TACE) with another treatment called radiofrequency ablation (RFA), Chinese researchers boosted the survival of people with advanced liver cancer by an average of 13 to 15 months compared to either treatment alone.

"Our study demonstrates that combination therapy with TACE and RFA was an effective and safe treatment that may improve long-term survival for patients with hepatocellular carcinoma larger than three centimeters," said Dr. Bao-Quan Cheng, from the Qilu Hospital and Shandong University School of Medicine in Jinan, China.

Results of the study were published in the April 9 issue of the Journal of the American Medical Association.

Hepatocellular carcinoma is responsible for as many as 90 percent of all liver cancers, according to the U.S. National Institutes of Health. Cirrhosis of the liver, often caused by hepatitis B or C or alcoholism, is usually at the root of such cancers. Cirrhosis can make treatment for this type of cancer more difficult, because it damages the liver so much that the liver can't process medications effectively. Only 10 percent to 20 percent of these cancers can be successfully treated with surgery.

For those whose tumors can't be removed with surgery, liver transplantation, chemotherapy and radiofrequency ablation are all options. TACE (transarterial chemoembolization) is a special type of chemotherapy that delivers chemotherapy drugs directly to the blood vessels feeding the tumor. Radiofrequency ablation uses electrodes to produce heat and destroy cancerous tissue.

The most commonly used treatment in the United States for advanced liver cancer is transplantation, according to Dr. Milan Kinkhabwala, chief of abdominal transplantation at Montefiore Medical Center in New York City. "If the tumor can't be resected [surgically removed], liver transplantation is the definitive treatment," he said, adding that transplantation might not be as available in China as it is in the United States.

Although TACE and RFA used individually can extend survival, the Chinese researchers hoped that by combining the techniques, they could increase survival times even more.

In a randomized, controlled trial, the researchers used one of three treatment techniques on people with hepatocellular carcinoma larger than 3 centimeters. Ninety-six people were assigned to the TACE-RFA combination, 95 to TACE alone and 100 to RFA alone.

Average survival time was 37 months for the combination therapy group compared to 24 months for TACE alone and 22 months for RFA alone.

The rate of responses lasting for at least six months rose to 54 percent in the combination group, versus 35 percent for the TACE group and 36 percent for the RFA group, the researchers found.

Side effects were similar between the groups, though RFA had the lowest rate of certain side effects, such as a low white blood cell count.

Cheng cautioned that these results may not be as applicable in the Western world, such as the United States or Japan, because the underlying cause of liver cancer in China is hepatitis B, whereas in the Western world, it tends to be hepatitis C or alcohol abuse. He hopes that similar clinical trials will be performed in the United States, Europe or Japan to see if the results are the same.

"Many of us have become aware that the standard approach of attacking a tumor with one modality isn't as good. Multimodal therapy is the new buzzword in cancer treatment," said Kinkhabwala. "It's really a belt-and-suspenders approach. You're targeting the tumor in different ways. This paper is important, because it's the first to look at this combination in a controlled way, and the combo approach does work. This confirms what our expectations were."

Kinkhabwala said he'd also like to see how a combination of these therapies with the new targeted medication, sorafenib (Nexavar), could affect outcomes. "Combining sorafenib with either or these or using all three might give better survival," he said.

More information

To learn more about the liver cancer known as hepatocellular carcinoma, visit the U.S. National Library of Medicine.