Perspective Matters
By Beth W. Orenstein
Radiology Today
Vol. 20 No. 8 P. 16

New ACP guidelines reignite the debate about optimal breast cancer screening protocols.

Every year, more than 40,000 women die from breast cancer in the United States, according to the American Society of Clinical Oncology. Experts agree that, when detected early, breast cancer is more treatable and women are more likely to survive long term. Screening mammography is widely considered the best way to detect early breast cancers. But that’s where agreement ends—and controversy arises.

Recommendations on when most women should start screening mammography and how often they should have mammograms—yearly or every other year—have changed over the years. In 2003, the American Cancer Society (ACS) recommended women begin annual mammograms at age 40 and continue annually as long as they are at average risk for breast cancer, in reasonably good health, and candidates for treatment. The recommendation stood and was supported by others, including the ACR and the Society for Breast Imaging, for a number of years. 

Contrasting Views
In November 2009, the US Preventive Services Task Force (USPSTF) recommended that all women start routine biennial mammography screenings at the age of 50. The USPSTF also said that women may choose to start routine mammography screenings between ages 40 and 49, after talking with their doctors about their personal values and preferences. In 2015, the ACS updated its recommendation to say women should begin screening at 45 and undergo annual screening until 55. The group also recommended that women 55 and older could continue annual screening with mammography or transition to every other year, if they wish. Both groups’ recommendations stirred controversy when they were issued.

Now, the American College of Physicians (ACP) has raised the question of when and how often an average-risk woman should have mammograms, once again sending concern rippling through the communities of radiologists and oncologists who specialize in breast cancer. In April, the ACP published a guidance statement in the Annals of Internal Medicine stating that its goal is to help clinicians care for women at average risk for breast cancer in making decisions regarding breast cancer screening. The ACP reviewed selected guidelines and evidence from around the world to develop a set of guidance statements of its own.

The ACP guidance statements recommend that, starting at age 40, women of average risk for breast cancer talk with their doctors regarding breast cancer screening and mammography to determine what’s best for them. The statement also says: “Discussion should include the potential benefits and harms and a woman's preferences. The potential harms outweigh the benefits in most women aged 40 to 49 years.” Based on the evidence, the ACP guidance statement notes that, for average-risk women aged 50 to 74, screening for breast cancer would best be every other year. After age 75, an average-risk woman can discontinue screening, as she would be more likely to die of other causes, the ACP says.

Ana Maria Lopez, MD, MPH, MCAP, a medical oncologist and the immediate past president of the ACP, affirms that “early detection is important,” but notes that, in reviewing the literature, the ACP did not see a significant benefit in screening average-risk women starting at age 40 or in screening those over 50 annually rather than biennially. “When you look at observational studies, there was not a difference in mortality for women age 50 or older being screened annually or biennially,” she says. “There are not as much data for women over 70, and we need more trials that include older women. ACP’s recommendations about who should be screened and when are grounded in the data.”

The ACP and the USPSTF say they recommend fewer screenings because of an increase in false-positives that lead to unnecessary biopsies and overtreatment of some breast cancers. Alex H. Krist, MD, MPH, a member of the USPSTF, says that out of every 1,000 women who are screened starting at age 40, an additional 200 or so will be called back for additional views because of a potentially suspicious finding on their mammograms. Of those women, about 50 will go on to get biopsies that turn out to be negative, he says. “It’s more than just anxiety,” he says. “It’s the further testing, and it can lead to a woman and her doctor being worried or concerned that there’s something wrong for some time.”

Krist says screening can also result in some cancers being overdiagnosed, ie, if left alone, they would never affect the woman’s health. “You can’t tell whether it’s an overdiagnosed cancer or not, but we often treat it, once we know it’s there,” he says. 

The ACR vehemently disagrees. “We believe that the guidelines that don’t have women starting until age 50, and then only every other year, could result in up to 10,000 unnecessary and additional breast cancer deaths in the United States each year,” says Dana H. Smetherman, MD, FACR, chair of the ACR’s Breast Imaging Commission.

Smetherman believes most women would prefer to be screened and, if necessary, called back—or even undergo biopsies—only to be reassured that everything is all right, rather than have a cancer missed in its early stages because it wasn’t caught on mammography. Smetherman agrees with the USPSTF and ACP that every medical procedure requires weighing risks and benefits but disagrees with them that the harms of screening mammography outweigh the benefits. Indeed, she says, the opposite is true.

Risk vs Benefit
The ACP says its guidance statement only applies to women at average risk of breast cancer. For screening purposes, a woman is considered to be at average risk if she doesn't have a personal history of breast cancer, a strong family history of breast cancer, a genetic mutation known to increase the risk of breast cancer (eg, a BRCA gene), and has not had chest radiation therapy before the age of 30. “While our guidelines are for women at average risk, we are saying that it depends on the woman and her individual preferences,” Krist says. “As a physician, I have found that when discussing this with women, there are some who say, ‘I am worried about breast cancer, and I want to start screening earlier.’ And there are plenty of others who say, ‘It sounds like there are a lot of false-positives, and I don’t want to start earlier.’ Women deserve the right to make that decision for themselves.”

The USPSTF, having scrutinized the data, associated a negligible mortality benefit with screening women earlier. “If you start screening at 40, out of 1,000 women, you save eight from dying of breast cancer. If you start screening at 50, out of 1,000 women, you save seven,” Krist says. “This benefit needs to be balanced against the harms of false-positives and overtreatment.” 

Smetherman believes the ACP and the USPSTF are looking at the issue the wrong way. She agrees that false-positives can be “anxiety provoking” but says that most women aren’t traumatized by being called back for additional screenings if a potential abnormality is identified.

“There’s anxiety with getting that phone call that says you need to come back for some additional images,” Smetherman says. “And as a breast imager, I would never want to minimize that. But that anxiety is usually short lived and resolves quickly. Most of the time, when women find out from additional images that everything is all right, they are relieved and go out and have a good rest of their day.”

Even if a woman is told she must have a biopsy, Smetherman says, “I don’t think that kind of anxiety should outweigh the potential life-saving of having had a mammogram.” Research on the anxiety associated with callbacks is limited, Smetherman says, “but what there is shows anxiety to be of short duration and usually doesn’t have any lasting effect.”

While researchers are learning more and more about breast cancer, they’re not at the point where they are able to identify those that will be fatal and those that may be survivable without treatment, Smetherman says. As with all cancers, “there is a range; some are relatively indolent and some are more aggressive. In breast cancer, it’s a very important question.” No provider wants to give a woman a treatment she does not need, Smetherman says. “But because, at this time, no one can tell a patient how aggressive their cancer will be, we have to treat them all as if they would have consequences,” she says.

Smetherman also takes issue with the ACP’s claim that biennial mammography screening results in no significant difference to breast cancer mortality. “This is incorrect,” she says. “There have been no randomized controlled trials to test this claim.” To the contrary, the National Cancer Institute/Cancer Intervention and Surveillance Modeling Network models that the USPSTF and the ACS used show a major decline in deaths among women screened annually vs every other year, Smetherman says. Using the Swedish Cancer Registry, a study published in Cancer in February 2019 showed that women screened regularly for breast cancer have a 47% lower risk of dying from the disease within 20 years of diagnosis than those not regularly screened. Other large studies—eg, Otto and colleagues in Cancer Epidemiology Biomarkers and Prevention in 2011 and Coldman and colleagues in the Journal of the National Cancer Institute in 2014—show that undergoing regular mammography cuts the risk of dying from breast cancer nearly in half.

Not Worth the Wait
Stamatia Destounis, MD, FACR, FSBI, FAIUM, of Elizabeth Wende Breast Care in Rochester, New York, also says that following the ACP and USPSTF screening guidelines would greatly reduce the mortality benefit. Destounis, who is a member of Radiology Today’s Editorial Advisory Board, says screening every other year could lower the chance of survival should a cancer develop.

“The data show that if you start with annual screening at age 40, you will reduce breast cancer–specific mortality by 40%,” she says. “If you wait until 50 and then screen every other year, you will reduce mortality overall by 23%. So, if you follow the ACP and USPSTF guidelines, you’re reducing the mortality benefit by approximately 50%.”

If an aggressive cancer goes undiagnosed because of a longer interval between screenings or starting screening at an older age, it delays treatment. Like most cancers, breast cancer is most treatable in its early stages, Destounis says. When a cancer is found in its early stages, a woman has more treatment options available as well, she says.

“If you have a tumor that is one-third of an inch, why would you wait for the tumor to be over an inch to address it? Tumor cells can travel through the lymphatic channels and end up in the bloodstream via the lymph nodes, and that can affect the staging of that tumor and the type of treatment required,” Destounis says. “Most women, when told they have breast cancer, don’t want to follow the tumor to see if it grows. They want to take care of it.” It’s true that some breast cancers are slower-growing tumors, “but you don’t know that until you biopsy them,” she adds. “There is no characteristic on a mammogram or an ultrasound that you can hang your hat on and say, ‘This is slow growing, and you can probably afford to wait on it.’ We don’t know that. So, we biopsy them.”

The ACP and USPSTF recommendations are for women who are at average risk, Destounis says. Approximately 70% of breast cancers are found in women who have no family history of the disease. “We need to screen average-risk women because we know the biggest risk factors for breast cancer are being female and aging.” Also, she adds, starting at 40 gives your radiologist a baseline. “Then, if you come back every year, we can look for subtle changes that may develop year to year. It makes it more difficult to identify subtle cancers if you don’t have a prior mammogram for comparison.”

Emily Conant, MD, a professor and the chief of the division of breast imaging in the department of radiology at the Hospital of the University of Pennsylvania in Philadelphia, says the recommendations to begin at 50 are based mostly on older data from randomized controlled trials that used older equipment, often longer screening intervals, and different detection thresholds. Those methods “lead to underestimations of the benefit of routine screening,” she says.

Also, Conant says, while it is true that the incidence of breast cancer increases with age, it is also known that women who develop breast cancer at a younger age, ie, premenopausal women, tend to have more rapidly growing cancers. “By screening women later in life and less frequently, as recommended by the ACP guidelines, the number of breast cancers diagnosed at later stages will increase. A later stage at diagnosis means more extensive surgeries, more aggressive treatment, including chemotherapy, and less chance for cure,” she says.

A Better Outlook
Some are concerned that insurance companies will use the latest salvo in this debate to reduce coverage for screening mammography, further reducing the number of women who are screened. In 2015, according to the Centers for Disease Control and Prevention, slightly more than 65% of women older than age 40 had a screening mammogram within the last two years. That means about 35% did not.

The various guidelines from different medical societies must be confusing for women and their physicians, Destounis says. And the ACP’s revisitation of the issue—not based on new research—does a disservice to women, she says. Destounis isn’t worried that insurance companies will reconsider and stop paying for screenings, however. “I’m more concerned that the different recommendations from the different medical societies will confuse women and they won’t know what’s the best for them,” she says. “That’s detrimental to our patients’ health.”

Joseph P. Russo, MD, a breast imaging radiology specialist at St. Luke’s University Health Network in Bethlehem, Pennsylvania, says he’s surprised that groups continue to debate what the best mammography cancer screening routines are. “The detail of when to get mammograms is less important than determining the best way to implement newer technologies,” he says. “The fact of the matter is that mortality has gone down 35% since the advent of screening mammography. It’s such a great modern medicine success story that it boggles my mind why it’s still being tinkered with. It works and, in combination with new technology, continues to get significantly better. We should never dissuade women from taking advantage of these incredible breast imaging tools that are now available to them.”

Conant agrees that newer tools should have changed the debate: “Recent tomosynthesis screening studies, including our multisite study published in JAMA Oncology in February, have shown that with this new modality, the outcomes for 40- to 49-year-olds in terms of improved cancer detection and decreased false-positives becomes very similar to what has been accepted for women aged 50 to 59 years who were screened with conventional 2D mammography. If we accept the 2D outcomes for women aged 50 to 59 years as beneficial, and we can obtain similar outcomes with 3D in women aged 40 to 49 years, why not screen these younger women and give them this proven benefit—reduction in breast cancer mortality?”

 — Beth W. Orenstein of Northampton, Pennsylvania, is a freelance medical writer and regular contributor to Radiology Today.