In 2015, American Cancer Society (ACS) caused a stir in the oncology community—and among women in general—with the updated recommendation that women of average risk for breast cancer should commence annual mammography at age 45. Previously, ACS recommended that mammography begin at 40 years, which is the same age recommended within the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer Screening and Diagnosis. Moreover, the U.S. Preventive Services Task Force (USPSTF) recommended age 50.
Because breast cancer is the most prevalent cancer as well as the second leading cause of cancer death in U.S. women, the community wants answers.
To shed light on the screening conundrum, the National Comprehensive Cancer Network (NCCN) brought together experts from the three leading guidelines organizations to discuss the screening controversies during its 21st Annual Conference on April 2, 2016.
Facilitated by Mary Lou Smith, JD, MBA, Co-Founder, Research Advocacy Network, and 21-year member of the NCCN Guidelines Panel for Breast Cancer, the panel included Therese Bevers, MD, The University of Texas MD Anderson Cancer Center, representing NCCN; Kirsten Bibbins-Domingo, MD, PhD, MAS, University of California, San Francisco, representing USPSTF; and Kevin Oeffinger, MD, Memorial Sloan Kettering Cancer Center, representing ACS.
Following are citations for the three organizations' recommendations:
•ACS: Oeffinger KC, Fontham ET, Etzioni R, et al. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update from the American Cancer Society. JAMA 2015;314:1599-1614
•NCCN: NCCN Clinical Practice Guidelines for Breast Cancer Screening and Diagnosis (Version 1.2015) © 2015 National Comprehensive Cancer Network, Inc. Available at NCCN.org. Accessed [March 28, 2016].
•USPSTF: Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2016; 164:279-296.
The panel agreed that indeed there are benefits to breast cancer screening. However, there is debate over whether those benefits outweigh potential negative effects and as to where the value lies in cancer screening. And the conclusions vary by one's point of view.
In establishing treatment guidelines, experts consider not only reduction in breast cancer mortality, but in treatment-related morbidity, as well, said Dr. Bibbins-Domingo, who is the Lee Goldman, MD Endowed Chair in Medicine and Professor of Medicine and of Epidemiology and Biostatistics at UCSF School of Medicine.
According to Dr. Bibbins-Domingo, USPSTF has relied on randomized controlled trials and more than 200 observational studies to develop models for their evidence-based guidelines. She noted that observational studies are necessary to capture data on the newest screening techniques.
With old film screens from the 1970s and 80s, the randomized clinical trials for breast cancer screening showed about a 20% reduction in mortality, explained Dr. Oeffinger, Primary Care Physician and Director of the Cancer Survivorship Program at Memorial Sloan Kettering Cancer Center. Today's observational studies, in contrast, show that mammography is reducing mortality by closer to 30-35% in certain populations. The ACS recommendations are influenced by the burden of disease and the potential benefits and harms associated with screening, focusing on 5-year increments in age, he said.
The NCCN Guidelines Panel for Breast Cancer Screening and Diagnosis considers both the randomized clinical data and the data from modern screening used in the observational studies, noting that women who are screened are less likely to be diagnosed with an advanced stage cancer, said Dr. Bevers, Professor of Clinical Cancer Prevention, and Medical Director, Cancer Prevention Center and Prevention Outreach Programs, at The University of Texas MD Anderson Cancer Center.
She added that an often neglected, yet important measurement, is the life years gained. While, as a group women in their 40s show a lower number of deaths averted, they also have the highest number of years of life gained when cancer is found and treated.
With regard to earlier screening for breast cancer, there is controversy surrounding the belief that earlier breast cancer screening leads to overdiagnosis and greater incidence of false positives.
"How do you weigh false positives, overdiagnosis, and anxiety?" asked Ms. Smith.
"False positives mean two things," said Dr. Oeffinger. The first is a call back for imaging, which typically takes place the same day as mammography. Second, in a smaller percentage of women (6-7%), a core biopsy will be performed, he explained. "While there is anxiety related to having a false positive finding or a biopsy, this remains an understudied area in the U.S.," Dr. Oeffinger said.
Dr. Bevers explained the importance of differentiation between prevalent false positives (those found on the first mammogram) and incident false positives (those found on subsequent mammograms) in understanding the true incidence of false positives for women in their 40s and women in their 50s. More false positives are found on the initial screening mammogram; this occurs because there are no prior mammograms for comparison to reassure the radiologist that a finding is benign. She went on to explain that the higher incidence of false positive screenings in women in their 40s is due, in part, to the fact that screening typically commences in this decade.
"If we move the initiation of screening to 50, we will see an increase in prevalent false positives in women in their 50s and a jump in the overall false positive incidence for women in this decade," she said.
Overdiagnosis is a screen-detected cancer that would not have led to symptomatic breast cancer if undetected by screening, resulting in overtreatment. However, there remains much uncertainty about how common overdiagnosis is, the panel noted.
All things considered, "it comes down to understanding a woman's values and preferences and having a conversation with her physician about whether to start screening earlier," said Dr. Bibbins-Domingo.
Dr. Bevers agreed that there is some level of overdiagnosis that accompanies earlier screening, but that it's very difficult to quantify, and it doesn't speak to when to start screening or how often, but only whether to screen and when to stop screening.
"Overdiagnosis is a harm of screening that is incurred regardless of the age screening starts or the screening interval as the mammographic finding—be it a calcification or other finding—will not go away unless it is treated," she noted. "To address the issue of overdiagnosis, we need to know which lesions won't progress," she added.
The patient population that is most negatively affected by overdiagnosis, said Dr. Bevers, is the older women because of their likelihood for competing comorbidities.
Dr. Bevers argued that harms of screening should be weighed against the harms of not screening, rather than comparing the harms of screening to no harms. Women who do not get screened can incur significant harms, including breast cancers diagnosed at a later stage that require more intensive treatments and are more likely to recur, and they also are more likely to die of their breast cancer than women who get routine screening mammograms, she said. Often the discussion of the harms of screening does not mention the harms of not screening, making it falsely appear that there are no harms associated with not screening, added Dr. Bevers.
Ms. Smith asked the panel to consider the harms of biennial screening—every two years—opposed to annual screening, which is another area of the mammography controversy.
As mentioned earlier, higher rates of screening—at any interval—leads to higher incidence in false positives, said Dr. Bibbins-Domingo. The USPSTF has found that there is a small incremental benefit to screening annually but the harms of annual screening are higher.
Dr. Oeffinger explained that there is a significant difference in the benefits of annual versus biennial screening in premenopausal women compared to postmenopausal women because of tumor biology and the aggressiveness of the disease. But by the time women are postmenopausal—on average after age 55—biennial screening is effective.
He added that ACS believes it is very important for women to have the opportunity to continue annual screening after age 55 if that is in their best interest based on their personal preferences and values, he added. His fellow panelists agreed.
For NCCN, there were several factors considered in recommending annual screening, said Dr. Bevers. First, there are fewer cancer deaths in the annually screened population than those undergoing biennial screening; second, while there are fewer deaths from breast cancer averted for women in their 40s, their years of life gained are significantly greater, she said. The NCCN Panel strongly felt these benefits far outweighed the possibility of a recall and possible biopsy.
The fact that three groups have different recommendations based on the same data shows there is no consensus on what constitutes a harm and where the benefit/harm threshold lies, Dr. Bevers said.
To address this, a Breast Cancer Screening Consensus Conference was held in Washington, DC in January 2016, to start the process of formulating a consensus statement. The group is working toward a manuscript that will identify points on which all eight participating organizations can agree, as well as detailing where and why they disagree, Dr. Bevers said. These organizations are USPSTF, ACS, NCCN, American College of Radiology, American Academy of Family Physicians, American College of Physicians, American College of Surgeons and American College of Obstetricians and Gynecologists. Stakeholders from more than 22 other women's organizations and patient advocates also attended.
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