Substantial or Modest? UK Breast Screening Cuts Deaths 21%

Nick Mulcahy

February 01, 2017

There was a "substantial," statistically significant reduction in breast cancer mortality between 1991 and 2005 associated with the national breast screening program in the United Kingdom, say the authors of a new retrospective, observational study.

The UK National Health Service Breast Screening Programme (NHSBSP) is one of the largest in the world and has invited women aged 50 to 64 years to be screened every 3 years.

The implementation period of the program was gradual and staggered, with the first round of screening invitations starting in 1988 and not finishing until 1995. This allowed the study authors to compare invited women to an uninvited control group.

Invitation to be screened, when compared with not being invited, was associated with a reduction in breast cancer mortality in 1991 to 2005 of 21% (rate ratio [RR], 0.79; 95% confidence interval [CI], 0.73 - 0.84; P < .001) after adjustment for three major variables (age, socioeconomic status, and lead-time).

"This is important in public health terms," conclude the authors, led by Louise Johns, PhD, from the Institute of Cancer Research in London. They point out that their study is the first to use individual-level data for both screening and outcomes in the NHSBSP, which are labor intensive to gather but are more accurate than population-level data.

This is important in public health terms. Johns et al.

The new study was published in the January 17th edition of the British Journal of Cancer.

Nancy Keating, MD, MPH, a professor of healthcare policy and medicine at Harvard Medical School and a physician at Brigham and Women's Hospital in Boston, Massachusetts, who was asked for comment, praised the study as well done overall.

She also said that the relative risk reduction in breast cancer mortality seen in the new observational study was "similar" to the results of more authoritative randomized, controlled trials of breast screening, "which is nice to see."

However, Dr Keating called attention to the absolute numbers in the study, which reveal a "relatively modest" effect.

In the final study population of 988,090 women, there were 146,539 deaths during the study period, of which only 8002 (5.5%) were breast cancer related.

Also, during the study period, 41,120 cases of breast cancer were diagnosed. Thus, "the vast majority of women diagnosed with breast cancer did not die of breast cancer," she noted in an email to Medscape Medical News.

Dr Keating acknowledged that the likelihood of death from breast cancer decreased by 21%, but she observed that the absolute risk decreased from 7.4 per 1000 women followed for 10 years (7.4 per 10,000 person-years) to 6.2 per 1000 women followed for 10 years (comparing the uninvited to invited groups).

About 1 fewer woman died per 1000 women followed for 10 years…a relatively modest benefit. Dr Nancy Keating

"About 1 fewer woman died per 1000 women followed for 10 years, which is important if you are that woman, but a relatively modest benefit," she summarized.

Medscape Medical News asked Dr Johns, who has retired since completing this study, whether British participants would be surprised to learn the number of women and length of time needed to screen to save 1 additional death from breast cancer. "Yes, I suspect they may be surprised," she said.

I suspect they may be surprised. Dr Louise Johns

The study authors point out that their new results are in keeping with recent other findings, including two evaluations of large-scale organized breast screening in Norway and Finland, which reported reductions in death from breast cancer of 25% to 28% associated with invitation to screening (BMJ. 2014;348:g3701; Br J Cancer. 2015;112:918-924).

Dr Keating is the coauthor of a 2015 study that reviewed 50 years of data from breast cancer screening studies around the world. The analysis indicated that screening was associated with a 19% overall reduction of breast cancer mortality, which is similar to the current study's finding.

The new British study "supports evidence that mammography has benefits," Dr Keating commented. "These data and many other data suggest that the mortality benefit is particularly true for women in their 50s and 60s," she added.

But Dr Keating also emphasized that, in the clinic, a fuller picture of breast cancer screening needs to be drawn. "Women need to understand that these benefits are relatively modest and that there are some downsides to breast cancer screening," she said, referring to false-positives and overdiagnosis.

Overdiagnosis Not Found

In the new study, Dr Johns and colleagues also analyzed outcomes among women who actually attended screening (after being invited for the first time) vs those who did not attend. In this comparison, risk reduction was more dramatic.

Breast cancer deaths among first invitation attenders were 46% lower than among nonattenders (RR, 0.54; 95% CI, 0.51 - 0.57; P < .001). However, when the investigators adjusted for age, socioeconomic status, and self-selection bias, breast cancer deaths were only 32% lower (RR, 0.68; 95% CI, 0.63 - 0.73; P < .001).

However, Dr Johns explained why the results among women who were invited/not invited to screening are given greater emphasis than the results among those who attended/did not attend.

"Those who chose to come along will be different from those who don't — they will tend to be more interested in their health and comply with health advice/treatments, etc," Dr Johns said in an email. "These factors mean that as a group they would be less likely to die from breast cancer whether or not they were offered screening….This is self-selection bias or a 'healthy attendee' effect — which operates in a lot of health care situations."

In their results, the study authors also highlighted that there was "little evidence" of overdiagnosis associated with invitation to the first screening.

Overdiagnosis exists, they acknowledge. "As a consequence of breast screening, some early-stage tumors are diagnosed which would never progress to become clinically apparent during a woman's lifetime. This represents overdiagnosis," they write.

However, in the current study, only 0.3% of the breast cancers detected were overdiagnosis associated with the first invitation, they report.

This is less, the authors say, than previous overdiagnosis estimates of roughly 10% to 15% in the NHSBSP and other screening programs. However, those earlier estimates were based on screening histories, including multiple attendances per woman (Breast Cancer Res. 2013;15:R41; J Med Screen. 2016;23:192-202).

"The potential for overdiagnosis increases with the number of screens you have," acknowledged Dr Johns.

This work was funded by the Policy Research Programme of the Department of Health for England. The authors and Dr Keating have disclosed no relevant financial relationships.

Br J Cancer. 2017;116:246-252. Full text

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