Screening every 2 years may reduce breast cancer incidence, mortality

Clinical breast examination conducted every 2 years by trained health workers has led to a substantial downstaging of breast cancer at diagnosis and a significant reduction in mortality in women aged ≥50 years, but not in those younger than 50, reveals a 20-year study.

“Clinical breast examination should be considered for breast cancer screening in low- and middle-income countries,” the researchers said.

This randomized controlled trial was conducted in 20 geographically distinct clusters located in Mumbai, India, which were randomly allocated to 10 screening and 10 control clusters. Women aged 35–64 with no history of breast cancer were randomized to either the screening arm (n=75,360) or the control arm (n=76,178). The recruitment began in May 1998 and locked in March 2019 for analysis.

Participants in the screening cluster received four screening rounds of clinical breast examination and cancer awareness every 2 years, followed by five rounds of active surveillance every 2 years, while those in the control cluster received one round of cancer awareness, followed by eight rounds of active surveillance every 2 years.

Women in the screening arm, relative to those in the control arm, had detected breast cancer at an earlier age (mean, 55.18 vs 56.50 years; p=0.01) and had a lower proportion of patients with stage III or IV disease (37 percent [n=220] vs 47 percent [n=271]; p=0.001). [BMJ 2021;372:n256]

The screening group also showed a nonsignificant 15-percent reduction in breast cancer mortality relative to controls (age 35–64 years; deaths per 100,000 person-years: 20.82, 95 percent confidence interval [CI], 18.25–23.97 vs 24.62, 95 percent CI, 21.71–28.04; rate ratio [RR], 0.85, 95 percent CI, 0.71–1.01; p=0.07).

In a posthoc subset analysis, a nearly 30-percent relative reduction in breast cancer mortality was seen in women aged ≥50 years (deaths per 100,000 person-years: 24.62, 95 percent CI, 20.62–29.76 vs 34.68, 95 percent CI, 27.54–44.37; RR, 0.71, 95 percent CI, 0.54–0.94; p=0.02), but there was no significant mortality reduction in those <50 years of age (deaths per 100,000 person-years: 19.53, 95 percent CI, 17.24–22.29 vs 21.03, 95 percent CI, 18.97–23.44; RR, 0.93, 95 percent CI, 0.79–1.09; p=0.37).

Furthermore, the screening arm showed a 5-percent reduction in all-cause mortality compare to the control arm, but this did not reach statistical significance (RR, 0.95, 95 percent CI, 0.81–1.10; p=0.49).

A previous meta-analysis of seven breast cancer screening trials revealed an excess breast cancer mortality up to the fifth year of screening in women aged <50 years and in the first year in older women. [Online J Curr Clin Trials 1993;Doc No 32]

“This excess was, however, not apparent in a combined analysis of Swedish trials. The possible finding of early excess cancer mortality needs exploring,” the researchers said. [Lancet 2002;359:909-919]

Of note, the theory of biological predeterminism (pre-existing micrometastases before diagnosis and surgery) does not explain this excess mortality; however, this could point towards an impact of events at the time of diagnosis and surgery on mortality, they added. [Curr Opin Obstet Gynecol 2003;15:1-8]

The current study “validates clinical breast examination as an alternative modality of breast screening. It demonstrates that … screening is effective in reducing breast cancer mortality in Indian women aged 50 and older without any overdiagnosis,” the researchers said.

“Our study suggests that implementation of population screening by clinical breast examination in low- and middle-income countries is feasible, provided that adequate training of screening providers, careful monitoring, and quality of performance are assured,” they added.