Indraneel Mittra, MD, PhD
In an Indian study reported in the British Medical Journal, Indraneel Mittra, MD, PhD, of Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, and colleagues at Tata Memorial Centre 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 and a significant reduction in breast cancer mortality in women aged ≥ 50 years and a numeric reduction among all women over 20 years of follow-up.1
Study Details
In the trial, 151, 538 women aged 35 to 64 years with no history of breast cancer 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 randomization involved randomization of 20 geographically distinct clusters in Mumbai 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
Mean adherence to screening after four rounds was 67.1%; overall, 94.8% of the screening group underwent at least one screening. Average adherence to rounds 5 to 9 of active surveillance after clinical breast examination screening was 77.6%. In the control group, adherence to the single round of cancer awareness was 90.9%, and average adherence to the subsequent eight rounds of active surveillance was 78.1%.
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 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 the 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 < 50 years vs ≥ 50 years 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 55.2 years (standard deviation [SD] = 9.1 years, 95% confidence interval [CI] = 54.5–55.9 years) in the screening group vs 56.5 years (SD = 9.1 years, 95% CI = 55.8–57.2 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 aged < 50 years at diagnosis (P = .005) and 35% vs 46% among those aged ≥ 50 years (P = .05).
Mortality Outcomes
Among women diagnosed with breast cancer, mean adherence to treatment was 98.9% in the screening group and 97.6% in the control group.
In the overall study population, the rate of breast cancer mortality at 20 years was 20.8 deaths (95% confidence interval [CI] = 18.3–24.0) per 100,000 person-years in the screening group vs 24.6 (95% CI = 21.7–28.0)/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 24.6 (95% CI = 20.6–29.8) vs 34.68 (95% CI = 27.5–44.4) among patients aged ≥ 50 years (RR = 0.71, 95% CI = 0.54–0.94, P = .02) and 19.5 (95% CI = 17.2–22.3) vs 21.0 (95% CI = 19.0–23.4) among those aged < 50 years (RR = 0.93, 95% CI = 0.79–1.09, P = .37).
KEY POINTS
- Screening with clinical breast examination was associated with significant downstaging at diagnosis of breast cancer.
- Screening with clinical breast examination was associated with a numeric reduction in breast cancer mortality among all women and a significant reduction among women aged ≥ 50 years.
Among all patients, the rate of all-cause mortality per 100,000 person-years at 20 years was 1,100.6 in the screening group vs 1,162.3 in the control group (RR = 0.95, 95% CI = 0.8–1.1, P = .5). Rates were 2,619.6 vs 2,662.8 among women aged ≥ 50 years (RR = 0.984, P = 0.71) and 583.1 vs 626.5 among those aged < 50 years (RR = 0.9, P = 0.2).
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). 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.”
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. Dr. Mittra reported no conflicts of interest.
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