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New Approach to Breast Screening Based on Breast Density at 40

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A new approach to breast screening proposes that all women should have a baseline  evaluation of breast density by mammography at the age of 40.

The result would then be used to stratify further screening, with annual screening starting at age 40 for average-risk women who have dense breasts, and screening every 2 years starting at age 50 for women without dense breasts.

Such an approach would be cost-effective and offers a more targeted risk-based strategy for the early detection of breast cancer when compared with current practices, say the authors, led by Tina Shih, PhD, University of Texas MD Anderson Cancer Center, Houston.

Their modeling study was published online today in the Annals of Internal Medicine.

However, experts writing in an accompanying editorial are not persuaded. Karla Kerlikowske, MD, and Kirsten Bibbins-Domingo, MD, PhD, both from the University of California, San Francisco, point out that not all women with dense breasts are at increased risk for breast cancer. They caution against relying on breast density alone when determining screening strategies, and say age and other risk factors also need to be considered.

New Approach Proposed

Current recommendations from the United States Preventive Services Task Force (USPSTF) suggest that women in their 40s can choose to undergo screening mammography based on their own personal preference, Shih explained to Medscape Medical News.

However, these recommendations do not take into consideration the additional risk that breast density confers on breast cancer risk — and the only way women can know their breast density is to have a mammogram. “If you follow [current] guidelines, you would not know about your breast density until the age of 45 or 50,” she commented.

“But what if you knew about breast density earlier on and then acted on it — would that make a difference?” This was the question her team set out to explore.

For their study, the authors defined women with dense breasts as those with the Breast Imaging Reporting and Data System (BI-RADS) category C (heterogeneously dense breasts) and category D (extremely dense breasts).

The team used a computer model to compare seven different breast screening strategies:

  • No screening

  • Triennial mammography from age 50 to 75 years (T50)

  • Biennial mammography from age 50 to 75 years (B50)

  • Stratified annual mammography from age 50 to 75 for women with dense breasts at age 50, and triennial screening from age of 50 to 75 for women without dense breasts at the age of 50 (SA50T50)

  • Stratified annual mammography from age 50 to 75 for women with dense breasts at age 50, and biennial screening from age 50 to 75 for those without dense breast at age 50 (SA50B50)

  • Stratified annual mammography from age of 40 to 75 for women with dense breasts at age 49, and triennial screening from age 50 to 75 for those without dense breasts at age 40 (SA40T50)

  • Stratified annual mammography from age 40 to 75 for women with dense breasts at age 40, and biennial mammography for women from age 50 to 75 without dense breasts at age 40 (SA40B50)

Compared with a no screening strategy, the average number of mammography sessions through a woman’s lifetime would increase from 7 mammograms per lifetime for the least frequent screening (T50) to 22 mammograms per lifetime for the most intensive screening schedule, the team reports.  

Compared with no screening, screening would reduce breast cancer deaths by 8.6 per 1000 women (T50) to 13.2 per 1000 women (SA40B50).

A cost-effectiveness analysis showed that the proposed new approach (SA40B50) yielded an incremental cost-effectiveness ratio of $36,200 per quality-adjusted life-years (QALY) compared with the currently recommended biennial screening strategy. This is well within the willingness-to-pay threshold of $100,000 per QALY that is generally accepted by society, the authors point out.

On the other hand, false-positive results and overdiagnosis would increase, the authors note.

The average number of false positives would increase from 141.2 per 1000 women who underwent the least frequent triennial mammography screening schedule (T50) to 567.3 per 1000 women with the new approach (SA40B50).  

Rates of overdiagnosis would also increase from a low of 12.5% to a high of 18.6%, they add.

“With this study, we are not saying that everybody should start screening at the age of 40, we’re just saying, do a baseline mammography at 40, know your breast density status and then we can try to modify the screening schedule based on individual risk,” Shih emphasized.

“Compared with other screening strategies examined in our study, this strategy is associated with the greatest reduction in breast cancer mortality and is cost-effective, [although it] involves the most screening mammograms in a woman’s lifetime and higher rates of false-positive results and overdiagnosis,” the authors conclude.  

Fundamental Problem With This Approach 

The fundamental problem with this approach of stratifying risk on measurement of breast density — and on the basis of a single reading — is that not every woman with dense breasts is at increased risk for breast cancer, the editorialists comment.

Kerlikowske and Bibbins-Domingo point out that, in fact, only about one quarter of women with dense breasts are at high risk for a missed invasive cancer within 1 year of a negative mammogram and these women can be identified by using the Breast Cancer Surveillance Consortium risk model.

“This observation means that most women with dense breasts can undergo biennial screening and need not consider annual screening or supplemental imaging,” the editorialists write.

“Thus, we caution against using breast density alone to determine if a woman is at elevated risk for breast cancer,” they emphasize.

An alternative option is to focus on overall risk to select screening strategies, they suggest. For example, most guidelines recommend screening from age 50 to 74 — so identifying women in their 40s who have the same risk of a woman aged 50 to 59 is one way to determine who may benefit from earlier initiation of screening, the editorialists observe.

“Thus, women who have a first-degree relative with breast cancer or a history of breast biopsy could be offered screening in their 40s and, if mammography shows dense breasts, they could continue biennial screening through their 40s,” the editorialists observe. “Such women with nondense breasts could resume biennial screening at age 50 years.”  

Shih told Medscape Medical News that she did not disagree with the editorialists’ suggestion that physicians could focus on overall breast cancer risk to select an appropriate screening strategy for individual patients.

“What we are suggesting is, ‘Let’s just do a baseline assessment at the age of 40 so women know their breast density instead of waiting until they are older,’ ” she said.

“But what the editorialists are suggesting is a strategy that could be even more cost-effective,” she acknowledged. Shih also said that Kerlikowske and Bibbins-Domingo’s estimate that only one quarter of women with dense breasts are actually at high risk for breast cancer likely reflects their limitation of breast density to only those women with BI-RADs category “D” — extremely dense breasts.

Yet as Shih notes, women with both category C and category D breast densities are both at higher risk for breast cancer, so ignoring women with lesser degrees of breast density still doesn’t address the fact that they have a higher-than-average risk for breast cancer.

“It’s getting harder to make universal screening strategies work as we are learning more and more about breast cancer, so people are starting to talk about screening strategies based on a patient’s risk classification,” Shih noted.

“It’ll be harder to implement these kinds of strategies but it seems like the right way to go,” she added.

The study was funded by the National Cancer Institute. Shih reports grants from the National Cancer Institute during the conduct of the study and personal fees from Pfizer and AstraZeneca outside the submitted work. Kerlikowske is an unpaid consultant for GRAIL for the STRIVE study. Bibbins-Domingo has disclosed no relevant financial relationships.

Ann Internal Med. Published online February 8, 2021. Abstract, Editorial

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