Last week's medical news centered on a New England Journal of Medicine (NEJM) article on breast cancer screening by mammography. The paper, authored by an international group of epidemiologists and biostatisticians, suggests that mammography has only a small influence on survival. The findings, along with an accompanying editorial, got front-page attention like this in the New York Times:
"...it indicates that improved treatments with hormonal therapy and other targeted drugs may have, in a way, washed out most of mammography's benefits by making it less important to find cancers when they are too small to feel."
But I'd say the opposite is true: It's precisely because there are effective treatments for early-stage disease that it's worth finding breast cancer early. Otherwise, what would be the point?
Mortality in the U.S. from breast cancer has declined by roughly a third since the implementation of wide-spread mammography screening around 1990. Despite so many advances in treating early-stage disease, the survival rate at five years for women with advanced tumors is only 25 percent. Metastatic breast cancer is quite costly to treat and remains incurable, even with treatments including new, expensive targeted therapies.
The new report:
The investigators looked at trends in breast cancer diagnosis and mortality in Norway over time after dividing the country into two sets of counties based on when a national screening program - which included mammography every other year for women between the ages of 50 and 69 - was implemented. The plan, which started in 1996 and required that each region establish a centralized, multidisciplinary breast cancer care team prior to participating, gradually expanded to include all of Norway by 2005. According to the study's authors, all Norwegian women between the ages of 50 and 69 years have been asked to participate in screening mammography since 2005; 77 percent have done so; Norway's nationwide cancer registry is nearly 100 percent complete. They evaluated a total of 40,075 women ("subjects") who received a diagnosis of BC between 1986 and 2005.
The main finding was that for women between the ages of 50 and 69, deaths from breast cancer fell from 25.3 to 18.1 (per 100,000 person-years) in counties where the mammography program was implemented around 1996. In counties where mammography was not covered until very recently, deaths from breast cancer also dropped: from 26.0 to 21.2 (per 100,000 person-years). Because breast cancer-associated deaths declined in all regions, regardless of whether mammography was offered, the authors concluded that screening doesn't account for most of the improvement.
By the authors' calculations, mammography accounts for roughly 10 percent of the enhanced survival since 1986. (This finding was not statistically significant.) They suggest that recent progress comes, for the most part, from better care and treatment of patients with this disease.
1. The average follow-up was only 2.2 years after diagnosis, with a maximum follow-up of 8.9 years. This is far too short an interval to measure the benefit of any sort of intervention in women who have breast cancer. When this disease recurs it's often after several years and, occasionally, decades after the initial diagnosis.
2. Among women under the age of 50 there was a slight increase in breast cancer deaths: A non-significant relative increase in mortality, of 4 percent, after the introduction of the screening program for older women. This worrisome finding is not adequately addressed by the authors. One might wonder: did fewer women in their forties go for mammograms after 1996, since they were only recommended and covered for older women? My question is whether reduced screening, now, among younger women is leading to an increase in breast cancer deaths.
3. Digital mammography was not evaluated in this study.
4. The authors detected the largest benefit of screening among women with Stage II breast cancer; there was a "marked" 29 percent reduction in mortality in that group relative to their historical counterparts, as compared to only a 7 percent reduction in mortality for women with Stage II tumors in areas where screening was not available. This observation suggests that mammography screening was life-saving for women with Stage II tumors. As an oncologist, I find this highly-plausible; the purpose of mammography is to identify tumors in early stage and spare women morbidity and mortality associated from advanced disease.
5. We should keep in mind the absolute number of lives saved in assessing mammography's value. Here, if the paper's conclusion is true -- that mammography reduces breast cancer deaths by just 10 percent, then in Norway -- with a total population of 4.8 million and 4,791 women who died in this study of breast cancer -- these results support that mammography spared approximately 480 lives over 20 years.
In the U.S., where some 45,000 women die each year of breast cancer, we'd save approximately 4500 lives per year if the added value of mammography is only 10 percent. If the benefit of screening mammography is higher -- say in the range of 45 percent, as was supported by a 2007 paper, also published in the NEJM -- then the value would exceed 20,000 women's lives per year. If the benefit is only 25 percent in terms of reduced mortality, that would result in over 11,000 lives saved, per year in the U.S.
My conclusions:
While the precise value of breast cancer screening by mammography remains uncertain, the recent paper confirms the marked progress in overall survival trends among women who have breast cancer. The question, really, is how much population-based screening helps women who are younger than 50, between the ages of 50 and 69, and older. Last week's publication was well-organized and carefully done, but it fell far too short in terms of follow-up to measure the potential impact of mammography on survival after breast cancer.
The Annals papers, which caused so much controversy last year, relied heavily on old data and did not at attempt to examine the efficacy of digital mammograms. What's needed, still, for public health policy in the U.S. is data regarding long-term outcomes after digital mammography performed in FDA-regulated, modern facilities by skilled, board-certified radiologists in the context of current pathology methods, decision tools and treatments.
As we espouse evidence-based medicine - which in principle should be cost-saving and spare patients from morbidity and mortality due to suboptimal care - we need think critically, more than ever before, about the limitations of medical knowledge and potential pitfalls in what's called "evidence."