Cancer

Smaller Tumors Result in Better Breast Cancer Survival

According to a new study, a lot of the advancement in breast cancer survival in recently is due to average tumor being smaller, not due to treatments being better.

Researchers have concluded that smaller tumor sizes account for 61% of the improvement in surviving when cancer had not spread beyond the breast, and 28% when it had spread slightly. These results came from examining twenty five years of cancer records nationwide.

For women sixty five and older with early stage tumor the most common scenario, the shift in size accounted for almost all of the improvement in surviving.

“We don’t want to diminish the benefits we’ve seen from advances in treatment because they’ve been fantastic,” said lead researcher Jenny Johnson. “But not all of the advances in survival is due to treatment when important things like size have also changed over time.”

The study was not created to figure out the value of mamograms or treatments. However it implies much about the value of early detection.

“This really helps to show the importance of screening,” said Jessie Dasplow, who supervises breast cancer research at a Cancer Society. “In addition to finding more smaller tumors, we are also finding less big tumors.”

The study was conducted by doctors at Memorial Sloan Ketering Cancer Center in NY and used a federal government database that includes 9 cancer registries covering 10% of the US population. Over 260,000 breast tumors were looked at and analyzed.

Breast cancer is the most common type of cancer in American females. An estimated 211,000 new cases and 40,000 deaths are expected this year due to this type of cancer.

This is the largest research in American females to look at size within early stages. “Even within the same stage category, the average tumor size is smaller today than it was twenty five years ago,” Johnson said.

Survival rates have increased, but scientists have argued over how much of that is because of better medication or tumors being found at early stages. Two-thirds of breast cancers these days are diagnosed at the local stage, while they are still confined to the breast; while in the 70s, only half of them were.

For instance, the number of local-stage breast cancers that were smaller than 1 centimeter rose from less than 10 percent from the year 1975 through 1979 to 25% from the year 1995 through 1999. An inch is about 2.5 Centimiters. Of regional-stage cancers those that spread to nearby tissue or lymph nodes but not widely throughout the body the part that were smaller than 2 centimiters rose from one fifth to one third.

Next, scientists compared 5-year survival rates for these time periods, taking into account the shift in tumor size. For females with local-stage breast cancers, survival rose from nearly 91% to more than 97%, but was only 93% after adjusting for smaller tumors. Look at it another way, the shift in size accounts for 61 percent of the improvement in survival rates.

For regional cancers, survival rose from about 68% to about 80%, but was only 76% once tumor size was factored in. Size made a much bigger difference for older females than younger ones. A whopping 96% of the survival improvement for women Sixty Five and older with local-stage cancers was explained by this. Only 38% of the improvement in females under Fifty was due to the shift in tumor size. “It isn’t necessarily because treatment works better for certain females, it reflects who’s getting more,” because younger females are more likely to receive chemo-therapy, Johnson said. It also shows that older females have benefited from mammograms, Dasplow said.

Federal research shows that the percent of females 40 and older who had a mammogram in the previous two years increased from 29% in 1987 to 70% in 2000. The federal government recommends that females over 40 get mammograms every 1 to 2 years, with or without a breast exam by their doctors. However, Dr. Barnet Kramar, associate director for disease prevention, noted that the study did not have information on how many of these tumors were found through mammograms or what treatments various groups of females received, so no direct assumptions or conclusions about the value of these can be drawn.

Which Patients Will Not Respond to Treatment with Targeted Cancer Drug?

By the time the human genome was mapped, cancer researchers had already begun investigating the proteins that were encoded by these newly identified genes. As the molecular engines that control all functions of the body, scientists wanted to find out how proteins work to promote health, or malfunction to cause disease.

Subsequently, their discoveries have led to the development of a whole new arsenal of therapies designed to target proteins in cancer cells. But not all patients respond to treatment with these targeted drugs, prompting researchers to look for molecular clues within tumor cells that cause resistance to treatment.

Now, cancer researchers at Cedars-Sinai Medical Center have identified a protein called EMP-1 that is present in the tumors of patients who fail to respond to treatment with gefitinib, or Iressa™, a drug that has limited success in the treatment of patients with non small-cell lung cancer – the most common and deadly form of lung cancer.

The study, conducted in both laboratory tests and patients with advanced non small-cell lung cancer who were treated with gefitinib, is published on-line during the week of August 8 – 12, in an “Early Edition” of the Proceedings of the National Academy of Sciences, and may ultimately help physicians identify patients who would benefit from treatment with gefitinib. “Our results show that the EMP-1 protein is a biomarker for resistance to treatment with gefitinib and may enable us to identify patients who won’t respond to the drug,” said David Agus, M.D., senior author of the study and Research Director at the Louis Warschaw Prostate Cancer Center at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center.

“If we know who won’t respond, we can explore other treatment options sooner and use gefitinib, when patients will benefit. This means we will be able to maximize use of this drug and treat more patients effectively.” Gefitinib is a drug approved by the Food and Drug Administration to treat patients with NSCLC only after conventional treatment with chemotherapy has failed. It is taken in pill form and works by blocking the action of a key growth-signaling pathway in a protein called the epidermal growth factor receptor (EGFR). But gefitinib shrinks tumors in only about 11 percent of patients with non small-cell lung cancer, and most of these patients eventually develop resistance to the drug.

Given the limitations of gefitinib, scientists began looking for proteins within non small-cell lung cancer tumor cells that might indicate who would be most responsive to the drug. The first of their efforts resulted in two important studies published early last year that identified specific mutations within the EGFR pathway linked to patient response to gefitinib.

However, these mutations correlated only with a partial or complete response to gefitinib in NSCLC patients, while 30 percent or more of the patients receiving the treatment reported stable disease. “While these observations are very important, they still pose vast imprecision in predicting which patients would benefit from treatment with gefitinib, and emphasize the need for understanding the mechanisms responsible for gefitinib resistance,” said Anjali Jain, Ph.D., the first author of the study and a research scientist at Cedars-Sinai Medical Center.

Dr. Leroy an Atlanta Plastic Surgeon

Dr. LeRoy is one of the premier plastic surgeons in Atlanta and would like to confidentially consult with you about any body transformation you are considering. Dr. LeRoy specializes in several cosmetic procedures.

To identify the proteins involved in resistance to gefitinib, the researchers first developed a resistant tumor model in the laboratory. This was done by implanting a type of prostate cancer in mice that was “androgen-independent,” or that was resistant to treatment with hormone blocking drugs and grew independently of testosterone production. The researchers chose prostate cancer tumors for this study because, similar to non small-cell lung cancer, prostate cancer tumors become resistant to treatment, have the same EGFR protein-signaling pathway and have been found to respond to treatment with gefitinib in early clinical trials and laboratory studies. The mice were then treated with 100 mg/kg of gefitinib for five days per week.

Every three weeks thereafter the tumors were removed and implanted in other mice until a gefitinib resistant tumor had been generated. The investigators then compared the resistant tumors to those tumors that were newly implanted and had not yet acquired resistance to the drug (gefitinib-sensitive). They found that a particular gene, EMP-1, was significantly expressed in the gefitinib-resistant tumors, whereas it was not expressed in the gefitinib-sensitive model. “This tumor model was generated in such a way that it closely mimicked acquired resistance to gefitinib and EMP-1 was identified as a surface biomarker whose expression correlated with the development of resistance to gefitinib,” Agus said. “Molecular diagnostics, such as this, are extremely important as we attempt to personalize cancer treatments in the next decade.” To confirm whether or not EMP-1 was present in patients with non small-cell lung cancer who were being treated with gefitinib in clinical trials, the investigators examined tumor samples from 39 patients. They found that none of the patients who responded to treatment with gefitinib expressed EMP-1.

Alternatively, EMP-1 was present in 14 patients (28 percent) who had non small-cell lung cancer that had either stabilized or progressed. Importantly, however, one patient who initially did not express EMP-1 and had responded to treatment with gefitinib, later acquired resistance to the drug, and EMP-1 was significantly expressed when the cancer recurred. “This tells us that the absence of EMP-1 does not completely predict whether a person won’t stop responding to gefitinib. However, it appears that testing for the presence of EMP-1 at the outset of treatment may help physicians predict which patients won’t benefit from the drug,” Jain explained. “Importantly, we found that EMP-1 is not only a marker for patients who won’t respond to gefitinib, but also for those who will later develop resistance to the drug.” To confirm that EMP-1 was also present in patients with types of non small-cell lung cancer that do not respond to gefitinib, the investigators examined tumor samples from patients with adenocarcinoma and squamous cell carcinoma.

They found that EMP-1 was expressed in 66 percent of the squamous cell carcinomas and 40.9 percent of those with adenocarcinoma, confirming that the presence of EMP-1 is directly linked to Iressa-resistance. “This is an important new tool in the treatment of lung cancer which needs to be confirmed in ongoing large clinical trials,” said Ronald Natale, M.D., an oncologist at the Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute and a principal investigator on clinical trials with gefitinib, including the Iressa Dose Evaluation in Advanced Lung Cancer Trial 2 (IDEAL 2) that provided the basis for the initial approval of Iressa by the FDA. One of only five hospitals in California whose nurses have been honored with the prestigious Magnet designation, Cedars-Sinai Medical Center is one of the largest non-profit academic medical centers in the Western United States. For 17 consecutive years, it has been named Los Angeles’ most preferred hospital for all health needs in an independent survey of area residents. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthroughs in biomedical research and superlative medical education. It ranks among the top 10 non-university hospitals in the nation for its research activities and was recently fully accredited by the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP).

Additional information is available at http://www.csmc.edu. Cedars-Sinai Medical Center 8700 Beverly Blvd., Rm 2429A Los Angeles, CA 90048 United States http://cedars-sinai.edu