Mammography Screening Guidelines Muddy the Waters

PHILADELPHIA, April 3 -- A new skirmish has broken out over whether a medically mandated routine annual mammogram for low-risk women younger than 50 is a good idea, rekindling a quiescent issue that once embroiled breast-cancer screening.

The American College of Physicians issued new breast cancer screening guidelines suggesting that a routine annual mammogram for low-risk women in their 40s may cause more harm than good, and that the decision on whether to have one should be relegated to a doctor-patient discussion rather than to unvarnished advice.

The ACP recommendations, published in the April 3 issue of the Annals of Internal Medicine, run contrary to guidelines issued by the National Comprehensive Cancer Network, American Cancer Society, United States Preventive Services Task Force, and American College of Obstetricians and Gynecologists.

The NCCN, American Cancer Society, U.S. Preventive Services Task Force, and ACOG guidelines all recommend that women at a normal risk who are age 40 or older get annual or biennial mammograms and physical exams to screen for breast cancer.

Until 2002, there was still a raging debate about whether the risks of false positives and other factors outweighed the relatively small benefits of mammography screening for women younger than 50. Then the data grew overwhelming for benefit, and the U.S. Preventive Services Task Force was one of the last to fall in line.

In the ACP guidelines, authors Amir Qaseem, M.D., Ph.D., and colleagues acknowledged that mammography can reduce breast cancer mortality in women ages 40 to 49.

"However, the reduction in this age group is smaller than that in women 50 years of age or older, is subject to greater uncertainty about the exact reduction in risk, and comes with the risk for potential harms (such as false-positive and false-negative results, exposure to radiation, discomfort, and anxiety)," they wrote.

The cancer society disagreed. "The average woman who is 40 to 49 and facing questions about mammography needs to consider how were these recommendations were made and what were they based on," said Debbie Saslow, Ph.D., director of breast and gynecologic cancers at the ACS, in an interview.

"If she looks at guidelines from the American Cancer Society and several other national organizations, then she would see just how much data there are to support annual screening and the real opportunity and likelihood for saving lives for women who are going to be diagnosed with breast cancer at a young age."

Radiologist Daniel B. Kopans, M.D., of Harvard, director of breast imaging at Massachusetts General Hospital, was vitriolic. "This was an incredibly irresponsible decision by the American College of Physicians," he said. "They clearly don't understand the screening trials of mammography and they don't understand the data. They just totally misinterpreted things."

Yet according to authors of a systematic review used in part to support the new ACP recommendations, the benefits of annual mammograms in the women under 50 may in some cases be outweighed by the risks.

"Because the incidence of breast cancer and the effectiveness of mammography are lower among women in their 40s than among women 50 years of age or older, mammography screening results in less absolute benefit and greater absolute risk for women 40 to 49 years of age than for women 50 years of age or older," wrote review authors Katrina Armstrong M.D., of the University of Pennsylvania, and colleagues.

The ACP guideline recommendations are:

• 1: In women 40 to 49 years of age, clinicians should periodically perform individualized assessment of risk for breast cancer to help guide decisions about screening mammography.
• 2: Clinicians should inform women 40 to 49 years of age about the potential benefits and harms of screening mammography.
• 3: For women 40 to 49 years of age, clinicians should base screening mammography decisions on benefits and harms of screening, as well as on a woman's preferences and breast cancer risk profile.
• 4: We recommend further research on the net benefits and harms of breast cancer screening modalities for women 40 to 49 years of age."

According to the guidelines, women in their 40s who have specific risk factors have a higher risk for breast cancer than an average 50-old woman, These risk factors include:

• Two first-degree relatives with breast cancer
• Two previous breast biopsies
• One first-degree relative with breast cancer and one previous breast biopsy
• A previous diagnosis of breast cancer, ductal carcinoma in situ, or atypical hyperplasia
• Previous chest irradiation
• BRCA1 or BRCA2 susceptibility mutations

Other risk factors that may warrant earlier routine screening include younger age at menarche and older age at first childbirth.

In their systematic review, Dr. Armstrong and colleagues looked at 117 studies of screening mammography, and found that in meta-analyses of randomized, controlled trials, mammography reduced breast cancer mortality in women in their 40s by 7% to 23%.

They also found that screening mammography was associated with an increased risk for mastectomy, but a decreased risk for adjuvant chemotherapy and hormonal therapy.

In addition, false-positive rates were high, ranging from 20% to 56% after 10 mammograms. On the other hand, "false-positive results have little effect on psychological health or subsequent mammography adherence," they wrote.

They concluded that "although few women 50 years of age or older have risks from mammography that outweigh the benefits, the evidence suggests that more women 40 to 49 years of age have such risks."

But Dr. Kopans emphasized that the age ranges used in the clinical trials cited were for the purposes of data classification, and should not be used as the basis for screening recommendations.

"They have reinforced this thinking that something happens at age 50 and at menopause, when there is absolutely no data that show that anything happens at age 50 or at any other age," he said. "It's just the way that analysts have grouped the data. It's like asking, when do hairs turn gray? If you say let's analyze every 45 and younger and everyone 45 and over, it would look like everybody turned gray at 45/ It's exactly the same with breast cancer screening."

He noted that the ACP recommendations about basing decisions on individual risk profiles are not evidence based, because the trials used to support the recommendations were not stratified by risk. "We have no idea whether if you just save women who are high risk you'll save anyone's life," Dr. Kopans said.

The cancer society's Dr. Saslow said that "the ACP guidelines were not based on evidence -- they were actually based on some reports that had proven not to be legitimate or well accepted and had been widely critiqued. They looked at a couple of articles and interpreted them the way they wanted to."

In an accompanying editorial, Joann G. Elmore, M.D., M.P.H., and John H. Choe, M.D., M.P.H.. of the University of Washington in Seattle, suggested that "no simple recommendation applies to all women in their 40s. We must learn to become comfortable with using the art of medicine to translate the existing science. We must listen carefully to our patients and communicate honestly the benefits and limitations of our imperfect tests."