In an Indian study reported in the British Medical Journal, Mittra et al found that breast cancer screening with clinical breast examination vs active surveillance resulted in younger age and significant downstaging of disease at diagnosis of breast cancer, a significant reduction in breast cancer mortality in women aged 50 years and older, and a numeric reduction among all women over 20 years of follow-up.

Study Details

The trial included 151,538 women aged 35 to 64 with no history of breast cancer. They were randomly assigned by cluster beginning in May 1998 to receive four screening rounds of clinical breast examination conducted by trained female primary health workers and cancer awareness information provided every 2 years followed by five rounds of active surveillance via home visits every 2 years (screening group, n = 75,360), or one round of cancer awareness information followed by eight rounds of active surveillance every 2 years (control group, n = 76,178). Cluster random assignment involved random assignment of 20 geographically distinct clusters in Mumbai, India, to 10 screening and 10 control clusters. The total trial duration was 20 years, with database lock in March 2019.

The primary outcome measures were downstaging of breast cancer at diagnosis and reduction in mortality from breast cancer.

Age and Stage at Breast Cancer Diagnosis

A total of 641 breast cancers were diagnosed in the screening group, including 199 (31%) during screening rounds 1 to 4 and 442 (69%) during the active surveillance rounds 5 to 9 after clinical breast examination screening. A total of 655 breast cancers were diagnosed after nine rounds of active surveillance in the control group.

At time of recruitment, 72.1% of women in the screening group and 71.2% of those in the control group were younger than age 50. Among women diagnosed with breast cancer, age at diagnosis was younger than 50 years vs 50 years or older in 25.2% vs 74.8% in the screening group and 22.4% vs 77.6% in the control group. The mean age at diagnosis of breast cancer was 55.18 years (standard deviation [SD] = 9.10 years, 95% confidence interval [CI] = 54.47–55.88 years) in the screening group vs 56.50 years (SD = 9.10 years, 95% CI = 55.80–57.20 years) in the control group (P = .01), representing a 16-month earlier diagnosis in the screening group.

Among women diagnosed with breast cancer, 220 (37%) in the screening group vs 271 (47%) in the control group had stage III or IV disease at diagnosis (P = .001). The proportions of women diagnosed with stage III or IV disease were 37% vs 47% among those younger than 50 at diagnosis (P = .005) and 35% vs 46% among those aged 50 or older (P = .05).

Mortality Outcomes

Among women diagnosed with breast cancer, mean adherence to treatment was 98.88% in the screening group and 97.63% in the control group.

In the overall study population, the rate of breast cancer mortality at 20 years was 20.82 deaths (95% confidence interval [CI] = 18.25–23.97) per 100,000 person-years in the screening group vs 24.62 (95% CI = 21.71–28.04) per 100,000 person years in the control group (rate ratio [RR] = 0.85, 95% CI = 0.71–1.01, P = .07). In post hoc analysis, rates per 100,000 person-years were 24.62 (95% CI = 20.62–29.76) vs 34.68 (95% CI = 27.54–44.37) among patients aged 50 or older (RR = 0.71, 95% CI = 0.54–0.94, P = .02) and 19.53 (95% CI = 17.24–22.29) vs 21.03 (95% CI = 18.97–23.44) among those younger than 50 (RR = 0.93, 95% CI = 0.79–1.09, P = .37).

Among all patients, the rate of all-cause mortality per 100,000 person-years at 20 years was 1,100.59 in the screening group vs 1,162.25 in the control group (RR = 0.95, 95% CI = 0.81–1.10,  P = .49). Rates were 2619.6 vs 2662.8 among women aged 50 or older (RR = 0.984, P = 0.71) and 583.09 vs 626.47 among those younger than 50 (RR = 0.931, P = 0.23).

The investigators concluded, “These results indicate that clinical breast examination conducted every 2 years by primary health workers significantly downstaged breast cancer at diagnosis and led to a nonsignificant 15% reduction in breast cancer mortality overall (but a significant reduction of nearly 30% in mortality in women aged ≥ 50 years). No significant reduction in mortality was seen in women younger than 50 years. Clinical breast examination should be considered for breast cancer screening in low- and middle-income countries.”

Indraneel Mittra, MD, PhD, of Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, is the corresponding author for the British Medical Journal article.

Disclosure: The study was funded by a grant from the U.S. National Institutes of Health, intramural funding from the Tata Memorial Centre, and others. For full disclosures of the study authors, visit bmj.com.