Compared with a no-screening strategy, the average number of mammography sessions through a woman’s lifetime would increase from seven 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 1,000 women (T50)–13.2 per 1,000 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-year (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 1,000 women who underwent the least frequent triennial mammography screening schedule (T50) to 567.3 per 1,000 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,” Dr. 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.
Dr. Kerlikowske and Dr. 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 50-59 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.”
Dr. Shih told this news organization 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. Dr. Shih also said that Dr. Kerlikowske and Dr. 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 Dr. Shih notes, women with 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,” Dr. 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. Dr. 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. Dr. Kerlikowske is an unpaid consultant for GRAIL for the STRIVE study. Dr. Bibbins-Domingo has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.