Surveillance Mammography Extends Overall Survival in Older Breast Cancer Survivors

Tuma, Rabiya S. PhD

doi: 10.1097/01.COT.0000298593.38664.a3
Article

Older breast cancer survivors benefit from annual mammograms, according to data from a large retrospective study, and experts agree that these new data should guide clinical practice at both the level of health care systems and for individual patients.

Clinical practice guidelines already recommend annual mammograms for breast cancer survivors of all ages. The goal of these surveillance mammograms, as they are called, is to discover local recurrent disease or second primary cancers at an early stage while they are still treatable. Yet no randomized trials have been done to demonstrate that surveillance mammography has an impact on survival. Rather, experts have extrapolated from mammography screening data, reasoning that if screening works in the general population, then surveillance mammography must be beneficial in this high-risk group of women.

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The original screening trials, however, included few women over 65. Thus extrapolating from those trials into older breast cancer survivors requires two assumptions: that surveillance mammography is effective and that such preventive care is valuable in older women.

To find out if those assumptions are likely to be correct, Rebecca A. Silliman, MD, PhD, Chief of the Geriatrics Section at Boston Medical Center, and colleagues took advantage of the Cancer Research Network, a group of 12 health maintenance organizations spread across the United States. As the study reported in the July 20th issue of the Journal of Clinical Oncology, the research team (first author was Timothy L. Nash, DSc, of the Department of Epidemiology at Boston University School of Public Health) enrolled 1,846 women who were over age 65 when diagnosed with Stages I or II breast cancer at one of six integrated health care systems.

Using medical records and the National Death Index, the researchers estimated the survival benefit gained from each annual mammogram in the survivors.

During the five-year follow-up period, 175 women died of breast cancer. Each annual surveillance mammogram was associated with a 31% reduction in the risk of breast cancer-related death.

“We have to be careful about hanging our hats too much on the actual size of the effect,” Dr. Silliman said in a telephone interview. Women who get surveillance mammography probably get other care as well, so the magnitude [of the effect] is probably due to many things, and surveillance is one aspect of the care.

“We always need to be reasonably cautious of observational studies. On the other hand, this is the best evidence there is going to be, because clinical trials won't be done on surveillance mammography in younger women or older women.”

Unfortunately the team also found that many of the women did not have regular surveillance mammograms, despite receiving care in a health maintenance organization. Forty percent of the women had no surveillance mammograms, 32% had only one, and 41% had four or more during the five-year follow-up period.

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Immediate Clinical Applicability

Edward H. Wagner, MD, MPH, Professor of Medicine at the Group Health Cooperative Center for Health Studies in Seattle and Primary Investigator for the Cancer Research Network, said that the study has immediate clinical applicability.

“Here is a study that was done in our own institutions that demonstrates a difference in survival with the receipt of certain generally recommended practices. I don't see how we can not act on them, frankly.”

Although he was not involved in Dr. Silliman's study, he has already talked with her about how the Cancer Research Network group as a whole will react upon hearing the data.

One key question, he expects, is whether surveillance mammography rates have improved since the study period, which ended on December 31, 2004. With that question in mind, he is planning to team up with her to quickly review Group Health's recent data.

“If we find that the practices haven't changed since the period of observation of the study—which we have reason to believe they haven't changed—then I think it is very important,” he said in a telephone interview.

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The Importance of Health Services Research

The study not only answers an important specific question about caring for older cancer survivors, but also points to the value of health services research, says the author of an accompanying editorial, Jeanne Mandelblatt, MD, MPH, Director of Cancer and Aging Research at the Lombardi Cancer Center at Georgetown University School of Medicine.

“We haven't known about the [survival benefit] before, because older women were not included in large numbers in the original screening trials of mammography, and no one has ever tested the effectiveness of screening after breast cancer in older women. Observational research is a very important tool when you have a well defined population, as [Dr. Silliman] did, that can fill in the gaps from clinical trials.”

And given the tight research budgets, such health services research becomes a cost-effective means of answering questions.

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Dendritic Cell Vaccine Induces Strong Immune Response Against DCIS

A novel dendritic cell vaccine against HER2/neu induced strong immune responses in women with ductal carcinoma in situ (DCIS) and led to an apparent reduction in tumor size prior to surgery, according to a small trial reported at the American Association for Cancer Research's Fifth Annual International Conference on Frontiers in Cancer Prevention Research.

While the dendritic cell vaccine is not likely to be translated into a common clinical approach, the data from the study elucidating what cytokines and immune cells are required to gain an effective immune response could guide the development of more clinically applicable vaccines in the future, said Brian Czerniecki, MD, PhD, Surgical Director of the Rena Rowan Breast Center at the University of Pennsylvania, who led the trial.

Dendritic cells were isolated from each of the 17 women in the trial and activated and exposed to peptides from the HER2 protein. The immune cells were then reintroduced into the patients via four weekly vaccinations.

“By and large we have seen very high rates of immune activation in the patients,” Dr. Czerniecki said. According to preliminary data from the ongoing trial, 11 of 13 patients had CD4+ T-cells that recognized one or more of the HER2/neu peptides, and eight of 10 patients had CD8+ T-cells that recognized one or more of the peptides.

The residual DCIS lesions of seven out of 11 patients had significantly less HER2/neu expression after vaccine therapy. By comparison, there was no such decrease in expression detected in biopsy and surgical samples from several women who were treated in the clinic but either opted not to participate in the trial or were treated before the trial started.

There also was an apparent decrease in the size of disease upon surgery in seven out of 11 patients, even though the patients received the vaccine for only four weeks in the neoadjuvant setting. For example, the apparent DCIS area detected on a mammogram in one patient was 4.5 cm prior to vaccination, but at surgery the lesion was 11 mm in size.

Several patients who were initially identified as mastectomy-only candidates were able to opt for lumpectomies after vaccine therapy, although the trial was not designed to affect the women's treatment.

According to pathology reports, there were a large number of immune cells infiltrating the breast tissue after vaccination, even though the vaccine was injected in healthy nodes in the patient's groin.

Compared with vaccines targeting infections agents that cause cancers, such as HPV, it is much more difficult to use a vaccine to decrease or treat cancer once it exists, said Martin Cheever, MD, Director of Solid Tumor Research at Fred Hutchinson Cancer Research Center, who spoke during the same session.

However, “Dr. Czerniecki has very good data showing that it might be possible” to create this latter type of vaccine, Dr. Cheever added.

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Countering Age Bias in Care

Both the study's senior author, Rebecca A. Silliman, MD, PhD, Chief of Geriatrics at Boston Medical Center, and the author of an accompanying editorial (“To Screen or Not to Screen Older Women for Breast Cancer: A New Twist on an Old Question or Will We Ever Invest in Getting the Answers”), Jeanne Mandelblatt, MD, MPH, Director of Cancer and Aging Research at Lombardi Cancer Center, emphasized the importance of including older adults in clinical trials.

These are the individuals at highest risk of cancer, yet relatively few are enrolled. In fact, when asked if they would be willing to participate in trials, many older adults say they would. But they are not typically asked to do so by their physicians.

“There is a practice bias in offering it,” Dr. Mandelblatt said. “Practicing clinicians can offer enrollment to older patients; they should not assume they do not want to be enrolled.”

There appears to also be treatment bias, with both underuse and overuse of preventive care, such as surveillance mammography. “I think clinicians need to have a little more education on how to estimate life expectancy on individual patients,” she said. Many older women are extremely healthy and have a long life expectancy and will benefit from a whole range of preventative services, whereas other older women, even at a younger age, may be in worse health and not live as long and may not benefit.

“This kind of triaging people to the appropriate treatment based on life expectancy as well as women's individual preferences needs more attention.”

That said, many physicians do not know how to appropriately assess their individual patients and so thus treat all older patients in a similar manner. Dr. Mandelblatt suggests, though, that there are good “back of the envelope” calculations for life expectancy.

For example, there are tables that calculate life expectancy based on an individual's age and self-reported general health. Someone who says she has excellent health and good ability to do things has a much improved life expectancy over someone who says her health is only fair or poor.

Although this is a relatively simple approach, it is surprisingly accurate and can be used to identify patients who are likely to benefit from surveillance mammography and other preventive care, Dr. Mandelblatt said.

© 2007 Lippincott Williams & Wilkins, Inc.
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