The reactions to the updated breast cancer screening guideline from the American Cancer Society (ACS) have been many, varied, and not consistently favorable but not surprising to Kevin C. Oeffinger, MD, who chaired the ACS panel that issued the guideline. Breast cancer screening “is an area that people have strong opinions on,” Dr. Oeffinger, Director of the Cancer Survivorship Center at Memorial Sloan Kettering Cancer Center, New York, said in an interview with The ASCO Post. “So, no, we were not surprised at all.”
The updated guideline, published in The Journal of the American Medical Association,1 recommends that for women at average risk of breast cancer, screening mammography should start at age 45 and be done annually until age 54. The previous ACS guideline (as well as current guidelines from the National Comprehensive Cancer Network and other organizations) recommended that women start having screening mammography at age 40. The updated ACS guideline recommends that women aged 40 to 44 “should have the opportunity to begin annual screening,” and women 55 or older “should transition to biennial screening or have the opportunity to continue screening annually.”
Very Deliberate Wording
Asked if the wording that women from 40 to 44 and over 55 “should have the opportunity” for annual screening was used out of concern that those women who wanted annual screening not be denied it, Dr. Oeffinger replied, “You bet. We strongly, strongly, strongly support full, first dollar insurance coverage, affordable copayment, and adequate access to care for women 40 to 44 who choose to have a screening mammogram, just as we strongly support women aged 55 and older who choose to continue to have an annual mammogram,” he said.
“The word ‘opportunity’ is used very deliberately,” Dr. Oeffinger continued. “The American Cancer Society continues to be one of the most vocal supporters of access to mammography for women. That has not changed. That will not change.”
It is a misunderstanding of the guideline to say that the ACS “moved” the age of annual screening mammography from 40 to 45, Dr. Oeffinger noted. “In fact, we didn’t move from 40 to 45; we recommended that women talk with their health-care provider and have the opportunity to start at 40. And if they haven’t started at 40, 41, 42, 43, or 44, then at 45, definitely, they need to start.”
The updated guideline also calls for screening to continue as long as a woman has overall good health and a life expectancy of 10 or more years. In addition, “the ACS does not recommend clinical breast examination for breast cancer screening for average-risk women of any age.” (For details about the updated ACS guideline, see the related Journal Spotlight.)
Differing Screening Recommendations
The updated guideline differs not only from the previous ACS recommendations, but from current recommendations issued by other organizations. “We have had different recommendations for a long time, from country to country and within the United States. Prior to the release of this guideline, the U.S. Preventive Services Task Force [USPSTF] recommended starting at age 50. Both the American College of Physicians and the American Academy of Family Physicians largely adopted that guideline. The American Cancer Society had specified age 40 and annual screening, and the American College of Obstetricians and Gynecologists as well as the American College of Radiology had largely adopted that,” Dr. Oeffinger said.
“In some ways, the messages from ACS and the USPSTF, two major guidelines, are now more consistent,” noted an editorial accompanying the article.2 Asked if he saw a movement toward agreement on breast cancer screening, Dr. Oeffinger replied, “I would love to see agreement; I think everybody would. But people have very strong opinions and biases that are tied in with the way that they view evidence.”
A Rigorous Process
The update was a rigorous process, following a “roadmap” outlined by the Institute of Medicine, Dr. Oeffinger explained. The Guideline Development Group selected the Duke University Evidence Synthesis Group to conduct an independent systematic evidence review of breast cancer screening literature. “In addition, the ACS commissioned the Breast Cancer Surveillance Consortium to update previously published analyses related to the screening interval and outcomes,” according to the guideline update.
“Sometimes people hearken back to the days of the old consensus guidelines, when people got behind closed doors and the loudest voice spoke,” Dr. Oeffinger said. “But in this situation, we had a critical review of the evidence by an independent group, and then the panel assessed that review and assigned a strength of recommendation based upon the strength of evidence.” The first recommendation—that women at average risk should have regular screening mammography starting at age 45—was a “strong recommendation,” whereas all the others were considered “qualified” recommendations.
Accounting for Modern Technology
The evidence “included studies both from the original randomized clinical trials and from modern observational studies using contemporary technology,” Dr. Oeffinger noted. “Contemporary technology takes into account not only advances in screening technology, but also in breast cancer treatment. It is very hard to disentangle which accounted for the benefit,” Dr. Oeffinger said.
“The randomized clinical trials were done with our early technology and mammography, which was often a single-view, film-based technology,” Dr. Oeffinger explained. “More recently, we have seen the transition to digital, and we looked at the evidence across digital mammography, in work from the Breast Cancer Surveillance Consortium and the large European observational studies that have incorporated both digital and film-based technologies.”
The panel did not yet have enough evidence to make a recommendation on tomosynthesis. “Although we are all quite excited by the potential of this newer technology, it has to be studied and we have to really understand what added value we get in terms of performance metrics,” Dr. Oeffinger stated. “Does it really decrease false-positive findings, and more importantly, does it decrease false-negatives? False-negatives constitute an important area that we don’t understand quite as well. That leads to our interval cancers.”
Mammography ‘Trashing’
“Advances in the treatment of breast cancer have led some to suggest that mammography is passé, that it outlived its usefulness,” Dr. Oeffinger noted. He referred to articles “published in high-impact journals that question whether mammography is really necessary anymore, now that we have these great treatments even when we diagnose somebody a little later in the process.”
“Mammography has been trashed in recent years,” Dr. Oeffinger and another member of the ACS Guideline Development Group, Ruth Etzioni, PhD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, wrote in an “Opposing View” article in USA Today.3
“We obviously push back against that,” Dr. Oeffinger told The ASCO Post. “There is no question in the minds of the panel that mammography remains a very effective tool. It remains our most effective tool in diagnosing and preventing the premature death of a woman with breast cancer. But it is a tool that needs to be used wisely and prudently.”
“If we want to save screening, we have to acknowledge its potential downside,” Drs. Oeffinger and Etzioni wrote.
Screening Interval
The recommendation to start screening mammography at age 45 was based on a combination of factors, including burden of disease, frequency of cancers, performance metrics of mammography, and outcomes of women diagnosed with cancer, Dr. Oeffinger noted.
“We decided early on that there is no reason to lock in on 10-year intervals. Much happens during a 10-year interval. Can we discern differences by 5 years? We even looked at 1 year, but 5 years was more realistic,” he said.
“What we found is that women between the ages of 45 and 49 are actually quite similar to those who are aged 50 to 54 with respect to how common breast cancer is and the performance of mammography, in terms of the false-positive rate, sensitivity, specificity, and outcomes. We couldn’t distinguish those two groups with any confidence. There is really no rationale for waiting until age 50 to start screening. We thought 45 was the time point at which all women should have started,” he said.
“I am extremely respectful of the benefit for women being diagnosed at a young age, but if you follow 10,000 40-year-old women in the United States for 1 year, 9 of those women will be diagnosed with breast cancer. If instead you follow 10,000 39-year-olds for a year, 8 of them are going to be diagnosed with breast cancer. And yet, did you hear clamoring for 39-year-olds to be screened?”
The reason not, he said, is “because we recognize that 8 or 9 out of 10,000 is actually a fairly small number” and represents a lot of screening. “If we take the logic of saving every life that we can, we would extend that continuum down into the 30s. But I don’t think anybody is ready to do that because we recognize that, at some point, you are simply doing too much testing.”
Earlier Screening Should Be Annual
For women who do choose to start mammography at age 40, it should “most definitely” be done annually, Dr. Oeffinger said. He cited a study using data from the Breast Cancer Surveillance Consortium, which found that premenopausal women diagnosed with breast cancer following biennial screening mammography were more likely to have tumors with less favorable prognostic characteristics than women screened annually. Women considered to have less favorable prognostic characteristics had one or more of the following findings: tumors stage IIB or higher, tumors larger than 15 mm, or positive lymph nodes.
For postmenopausal women who did not use hormone therapy, the proportion of tumors with less favorable prognostic characteristics was the same following biennial or annual screening mammography. The results for women using postmenopausal hormone therapy were less clear.
“We were convinced by that analysis, which was published in JAMA Oncology,4 that annual screening was beneficial for younger women,” Dr. Oeffinger stated.
Mammography Improves With Age
“As a woman ages, the ability of the mammogram to detect smaller tumors becomes better and better,” Dr. Oeffinger added, because generally the breast tissue becomes less dense. “In addition, the tumors tend to be slower-growing. That doesn’t mean that they don’t cause death. We still see a significant proportion of breast cancer deaths, even related to women aged 75 to 79 who are screened,” he pointed out.
“You maintain the vast majority of the benefit of screening mammography by going to every other year as you move through your 50s into your 60s—but not all of the benefit. If you screened every year, you would maintain the most benefit. But the tradeoff is the potential for false-positive findings. That is why we said that the person who should best understand that tradeoff is the woman herself; we wanted to avoid being paternalistic and saying, ‘This is what you should do.’ We think that women should really talk with their health-care providers and share their values and preferences.”
Is Menopausal Status More Important?
Findings from the study about breast tumor prognostic characteristics suggest that “menopausal status may be more important than age when considering breast cancer screening intervals, which is biologically plausible,” according to the authors.4
“We discussed that point for hours and hours,” Dr. Oeffinger commented. “At the end of the day, we were moving from a very simple, everybody-can-remember, one-size-fits-all guideline, to something that is a bit more complex and nuanced, and we did not want to add another layer. The majority of women have gone through menopause by age 55. We were being on the conservative side and trying to capture the majority of people after menopause when they make that [screening] transition. We felt that would make it easier for people to remember than menopausal status, which can sometimes be a little bit hard to distinguish for women with longer perimenopausal time periods.”
Competing Causes of Mortality
Although the benefit of screening in older women needs to be balanced by competing causes of mortality, “recent studies suggest that many women who have serious or terminal health conditions are still receiving mammograms,” the ACS Guideline Development Group noted.
“We definitely need to consider the overall health of a woman,” Dr. Oeffinger advised. “Some groups have recommended a specific stopping age, and that’s because our clinical trials went up to a specific stopping age—74—and there aren’t much data beyond that. But you don’t have to look around too far to see some very healthy 80-year-old women who have a high likelihood of living another 10, 15, or 20 years. Basically, you will receive benefit from screening if you have a reasonable likelihood of another 10 years of health.” Risk calculators can be used to identify women who may or may not live another 10 years.
Women at Average vs High Risk
The recently updated ACS guideline is only intended for women at average risk of breast cancer. They were defined as “women without a personal history of breast cancer, a confirmed or suspected genetic mutation known to increase the risk of breast cancer (eg, BRCA), or a history of previous radiotherapy to the breast at a young age.” Dr. Oeffinger emphasized that this means actual radiation treatment, not just radiation exposure. Women who were treated with radiation for a childhood or young adult cancer prior to age 30 have a breast cancer risk “comparable to what we see in BRCA1 gene mutation carriers,” he noted.
“The data are more complex for women at high risk of breast cancer because you have to consider not only gene mutations or prior radiation therapy, but you also have to think through some of the more intermediate-risk factors such as breast density,” Dr. Oeffinger stated. These issues will be considered at a summit meeting in 2016. The evidence review has been completed, and “we will supplement that with discussions at the summit meeting. Then we will release a more fully updated guideline that will include women who are at high risk,” he reported.
In the meantime, “I encourage people to refer back to the 2007 American Cancer Society guideline that laid the groundwork for screening in high-risk populations,” Dr. Oeffinger said.
Clinical Breast Examinations
A recommendation against clinical breast examination for breast cancer screening among average-risk women of any age has not received nearly as much media coverage as the mammography guidelines. The ACS Guideline Development Group found that clinical breast examination was not shown to be effective. In fact, there was some evidence that “adding clinical breast examination to mammography screening increased the false-positive rate,” the guideline panel noted.
“Wasn’t that a little bit of a surprise?” Dr. Oeffinger said. “We have traditions that we have carried on for many years, sometimes without supporting evidence, and it is time to reevaluate them. We have time-limited visits with patients because of the way the health-care system is set up. And when we look closely at the evidence, there simply is no evidence—for a woman who is at average risk and asymptomatic—that a clinical breast examination adds anything above and beyond what a mammogram does. If you are in a resource-poor area, like some areas of Africa, or you don’t have access to mammography, that’s a different situation. But in the United States, where we should have access to mammography, that shouldn’t be an issue,” he said.
“Moreover, we do see evidence that there is an increased risk of false-positives [when clinical breast exam is added to mammography]. You have no benefit and you do have harm, so we said it’s time to rethink this,” Dr. Oeffinger added.
“I am a physician who believes highly in the healing effect of touching an individual, but I want to also be respectful of the time my patients are with me,” Dr. Oeffinger commented. That time would be better spent, he said, ascertaining risks, counseling patients, and answering patients’ questions.
“I anticipate that many physicians will continue to incorporate clinical breast examination,” Dr. Oeffinger said. “I do not fault them for doing that. That is part of their decision on the patient-physician relationship. But we are trying to encourage a general trend in using your time wisely.” He noted that this dovetails nicely with the Choosing Wisely campaign, an initiative promoted by the American Board of Internal Medicine and backed by ASCO to encourage conversations between physicians and patients about medical tests and procedures for which widespread use is not supported by evidence. ■
Disclosure: Dr. Oeffinger is Chair of the American Cancer Society’s breast cancer guideline panel.
References
1. Oeffinger KC, Fontham ETH, Etzioni R, et al: Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. JAMA 314:1599-1614, 2015.
2. Keating NL, Pace LE: New guidelines for breast cancer screening in US women. JAMA 314:1569-1571, 2015.
3. Etzioni R, Oeffinger K: New mammogram guideline balances risks: Opposing view. USA Today. October 25, 2015.
4. Miglioretti DL, Zhu W, Kerlikoswke K, et al: Breast tumor prognostic characteristics and biennial vs annual mammography, age, and menopausal status. JAMA Oncol. October 20, 2015 (early release online).
