The Way Forward

When it comes to life-threatening diseases, people understandably want to maximize their chances for survival. So when considering the best practices to check for breast cancer, it makes intuitive sense that doctors and patients would prefer to screen early and often.

After all, approximately 224,000 women are diagnosed with the disease in the United States each year, and each year it kills nearly 41,000 women. Among American women who are 40 years old today, nearly 4 percent will develop breast cancer sometime before they reach 60, and the rates increase with age.

But different medical authorities offer different guidelines, which can lead to confusion for women facing an average risk for breast cancer. The issue can get even more complicated when considering the various imaging technologies used to screen for cancer and how to proceed with elderly patients or those already diagnosed with cancer in one breast.

Searching for Clarity Among Conflicting Breast Cancer Screening Guidelines

In January, the U.S. Preventive Services Task Force (USPSTF) released new recommendations on screening for breast cancer. These differed slightly from new recommendations by the American Cancer Society (ACS) and from recommendations by the American College of Obstetricians andGynecologists (ACOG) last updated in 2011.

But even while the three sets of guidelines offer slight disagreements about whether, for example, a 40-year-old woman should begin annual screening mammograms, experts stress the recommendations have more in common than not.

ACOG aimed to reach a consensus at a conference it hosted in Washington, D.C., later in January, attended by representatives from the ACS, the USPSTF, the National Comprehensive

Cancer Network, the American College of Radiology, and other groups, including patient advocate organizations.

“We saw this as a good next step,” said Dr. Mark DeFrancesco, President of ACOG. “There are different ways of interpreting evidence. We want to have stakeholders around the same table and try to find agreement.”

ACOG recommends annual mammograms for women of average breast cancer risk starting at age 40. The ACS suggests that 40-44-year-old women should have the choice to start annual mammograms but only recommends that 45-54-year-old women get mammograms annually, with women 55 and older switching to these screenings every other year and a choice to continue yearly. The USPSTF suggests that annual mammograms for women between the ages of 40 and 49 should be an individual choice. The group recommends biennial screening mammography for women aged 50 to 74.

One source of the conflicts stems from the groups possibly using different health outcomes to inform their recommendations. It’s also likely that the groups assign differing weights to the potential benefits of early detection and potential cures compared with the possible harms of looking too carefully or too often for cancer. For example, inherently imperfect physical examinations and imaging tests that rely on interpretation may show signs of cancer where none exists, potentially leading to unnecessary stress and expense caused by false positive tests.

After the conference, an ACOG spokeswoman said the groups will continue to address screening recommendations but did not announce any agreement.

USPSTF Vice Chair Dr. Kirsten Bibbins-Domingo said the group sent representatives to the ACOG meeting to present the evidence that informed their 2016 final recommendations, adding that the evidence is also posted on the USPSTF website (www.uspreventiveservicestaskforce.org) so patients and health care professionals can learn more about the science the group reviewed.

Dr. Bibbins-Domingo said that the USPSTF is an independent panel that cannot sign any consensus documents. But she said that most groups agree that mammography is a valuable tool to reduce deaths from breast cancer and that those benefits increase with age.

“Support of a personal, informed choice for women in their early 40s is a widely shared notion,” Bibbins-Domingo said. “We hope that the groups attending this meeting and others will focus on what the science shows about the balance of benefits and harms.”

Women’s Health Research at Yale Director Carolyn M. Mazure, Ph.D., shared that optimism.

“We still have much to learn about regional, racial and ethnic disparities in the prevalence of certain cancers, as well as individual risks based on family history,” Mazure said. “But we can all agree that individuals deserve the choice to know as much as possible as soon as possible when it comes to their risk for developing potentially life-threatening diseases. Our hope is that these respected authorities can reach an agreement on how to assess the available data and reach a shared conclusion to benefit everyone.”

Using MRI Before Breast Cancer Surgery in Elderly Patients to Detect Tumors in the Opposite Breast

When it comes to the more precise screening provided by magnetic resonance imaging (MRI), the ACS only recommends ordering such a scan for women who have a 20 percent or greater lifetime risk of developing breast cancer. Women in this category include those with a strong family history of breast or ovarian cancer or other risk factors such as a history of treatment for Hodgkin’s lymphoma with radiation to the chest, neck, and arms.

But even if a mammogram or an MRI reveals clear signs of what’s eventually confirmed as cancer, physicians are growing more wary of aggressively treating some of the early cancers for fear of overreacting to tumors that can be slow-growing or inert so as to present little or no threat to a patient’s life. This phenomenon, called overdiagnosis and overtreatment, is the subject of a study on MRIs performed on older women prior to surgery for breast cancer published by Yale researchers in a November issue of the Journal of Clinical Oncology. The study looked at the additional cancers detected by MRI in the opposite breast.

“Sometimes, these sensitive tests are able to detect cancers that would not have caused any harm to the patient,” said Dr. Cary Gross, senior author of the study, a Professor of Medicine, and Co-Director of the Robert Wood Johnson Foundation Clinical Scholars Program at Yale. “As a result, people are suffering. They get mastectomies. Chemotherapy. Very aggressive treatments when perhaps in some cases it’s not necessary.”

We should be cautious about being less aggressive about trying to find and treat all breast cancers.

Dr. Regina Hooley

But Dr. Regina Hooley, an Associate Professor of Radiology and Biomedical Imaging at the Yale Cancer Center, worries that the study could send the wrong message to health care providers
and patients.

“I understand the naysayers,” Hooley said. “But I think when it comes to using technology, instead of saying, ‘No, let’s not use this at all,’ let’s say, ‘How we can use this better?’”

A New Study

The study by Gross and his colleagues analyzed a database of 38,971 female Medicare patients with breast cancer, ages 67 to 94 when diagnosed, by dividing them into two groups: women who underwent an MRI prior to surgery to check for signs of cancer in the opposite (contralateral) breast and women who did not have an MRI.

Doctors diagnosed additional cancers in the opposite breast in 7.2 percent of women who had undergone an MRI compared with 4 percent of women who did not have an MRI. But after five years, the higher rate of initial cancer detection did not correspond with a decrease in advanced-stage life-threatening cancer in the opposite breast. The authors concluded that almost half of the cancers found after a preoperative MRI were likely overdiagnosed and may not have harmed the patient if left undiagnosed and never discovered by MRI.

“Patients and physicians need to balance the risks and benefits of the MRI,” said lead author Dr. Shiyi Wang, Assistant Professor of Chronic Disease Epidemiology at Yale School of Public Health and a faculty member in the Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center at the Yale Cancer Center. “They need to discuss that an MRI can potentially increase detection of an early stage cancer. But it may not improve health outcomes, because many of these additional cancers might not have caused any health problems.”

For elderly patients, who are more likely to die from some other cause before a slow-growing breast cancer can kill them, Wang found the evidence clearly points to one conclusion.

“Our analyses call into question whether older women are receiving any health benefit from routine preoperative MRI,” he said.

Hooley questioned how the authors defined older patients.

“I would argue that there are some women in their late 60s and early 70s who are in good health and have more very good years remaining,” Hooley said. “Depending on the type of cancer and their personal histories, preoperative

MRI may be beneficial to some selected groups of women over 65. I think to extrapolate the study’s conclusions to people of such a broad range of ages may not be fair to everyone.”

Hooley commended the authors, including COPPER Center data analyst Jessica Long and Yale faculty members
Drs. Brigid Killelea, Suzanne Evans, Kenneth Roberts, and Andrea Silber. But she felt their study confirmed established practices rather than blazed new ground.

“When I see a patient getting an MRI for the contralateral breast at 75-80 years old, I almost always try to cancel it,” Hooley said. “But there may be a reason based on an individual’s circumstance to go ahead, particularly if the woman is less than 75 years of age.”

Gross said that the team adjusted
for the patients’ ages when analyzing the data and found no age-related benefit of preoperative MRI on the incidences of advanced cancer in the contralateral breast.

Balancing Risks and Benefits

A review last year by the American Cancer Society found estimates of overdiagnosis of breast cancer vary from less than 5 percent to more than 50 percent. The review concludes that there is high quality evidence that overdiagnosis due to mammographic screening exists but that estimates of the magnitude of the problem remain clouded by low quality evidence.

Hooley said that even if up to 30 percent of cases screened by mammography can be deemed overdiagnosis, that does not negate findings that show mammography contributing to a 30 percent reduction in patient deaths.

“Unfortunately, no one knows which cancers are overdiagnosed,” Hooley said, noting that pathologists currently have some biomarkers which can predict which tumors may grow quickly and which may not, though their accuracy remains undetermined. “Hopefully someday soon we will figure it out. Until then, we should be cautious about being less aggressive about trying to find and treat all breast cancers.”

The new data published by Wang, Gross and their colleagues offers insight into the use of MRI for older women and overdiagnosis, a concept descriptive of large populations that can be helpful to craft a general rule of thumb for how to set screening guidelines.

But for clinicians examining an individual patient, the issue isn’t just one of overdiagnosis. It’s about finding abnormalities, making the correct diagnosis, and then managing and treating a diagnosed cancer appropriately.


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For questions, please contact Rick Harrison, Communications Officer, at 203-764-6610 or rick.harrison@yale.edu.

This article was submitted by Carissa R Violante on April 7, 2016.

BREAST CANCER IMAGING TECHNIQUES

  • Screening mammogram: An x-ray picture of the breast to detect tumors that may not be felt by hand in asymptomatic women.
  • Diagnostic mammogram: X-ray pictures of the breast to detect tumors if a lump or other possible signs of breast cancer are found.
  • Digital mammogram: X-ray images are stored as a computer file as opposed to film. Advantages include detection of subtle differences between normal and abnormal tissues, fewer follow-up procedures, and fewer repeat images, reducing the exposure to radiation.
  • 3-D mammogram: Also known as breast tomosynthesis, this is a type of digital mammography in which x-ray machines are used to take pictures of thin slices of the breast from different angles and computer software is used to reconstruct an image, allowing radiologists to better assess abnormalities.
  • Breast ultrasound: A diagnostic ultrasound uses sound waves to analyze tissue and is commonly used to investigate areas of concern discovered on a mammogram or for women with dense breast tissue that makes it difficult to find cancer on a mammogram alone.
  • MRI: Magnetic resonance imaging uses a magnetic field and radio waves, avoiding the ionizing radiation of a mammogram to create detailed images of organs and tissues.

Sources: The National Cancer Institute and the Mayo Clinic

Related People

Cary P Gross

Professor of Medicine (General Medicine) and of Epidemiology (Chronic Diseases)

Regina J Hooley

Associate Professor of Radiology and Biomedical Imaging

Carolyn M Mazure

Norma Weinberg Spungen and Joan Lebson Bildner Professor of Psychiatry and Professor of Psychology

Shiyi Wang

Assistant Professor of Epidemiology (Chronic Diseases)