Higher long-term breast cancer risks with non-screen-detected ductal carcinoma in situ

Key takeaways:

• A significant number of women with non-screen-detected ductal carcinoma in situ had invasive cancer or breast cancer mortality.
• Mastectomy vs. breast-conserving surgery led to lower invasive breast cancer rates.

Women with ductal carcinoma in situ not detected by routine screening had higher long-term invasive breast cancer and mortality risks than with women in the general population and those with screen-detected cancer, according to researchers.

The U.K. National Health Service breast screening program has been attributed to an increase in ductal carcinoma in situ incidence. However, many women are diagnosed outside of the screening program either because they are outside of the age range or do not responding to screening invitations, the researchers noted.

“Many diagnoses of ductal carcinoma in situ occur as a result of screening, which has led to concerns that ductal carcinoma in situ may be overtreated in some women, something that is being investigated in various ongoing randomized trials evaluating nonoperative management of ductal carcinoma in situ,” Gurdeep S. Mannu, DPhil, clinical research fellow in the department of population health and the department of surgical sciences at the University of Oxford, U.K., and colleagues wrote. “However, alongside these concerns, it is also the case that the rates of invasive breast cancer and breast cancer death in women with screen-detected ductal carcinoma in situ are more than double those of women in the general population and remain raised for at least 20 years after diagnosis.”

Mannu and colleagues conducted a population-based cohort study using data from the National Disease Registration Service. The researchers identified 27,543 women in England who were diagnosed with ductal carcinoma in situ from 1990 to 2018. Researchers assessed long-term risks for invasive breast cancer and breast cancer mortality following non-screen-detected ductal carcinoma in situ. Risks for women with ductal carcinoma in situ identified through the National Health Service (NHS) breast screening program were compared with women in the general population and women with screen-diagnosed ductal carcinoma in situ.

The primary outcomes were incidence of invasive breast cancer and breast cancer mortality.

Overall, 3,651 women with non-screen-detected ductal carcinoma in situ developed invasive breast cancer by December 2018, which was more than four times higher than expected based on national cancer incidence rates, according to the researchers. The ratio of observed to expected rates for developing invasive breast cancer consistently increased throughout follow-up among women aged 45 to 70 years. The 25-year cumulative risks for invasive breast cancer by age at ductal carcinoma in situ diagnosis were 27.3% for those younger than 45 years, 25.2% for those aged 45 to 49 years, 21.7% for those aged 50 to 59 years and 20.8% for those aged 60 to 70 years.

A total of 908 women with non-screen-detected ductal carcinoma in situ died from breast cancer, which was almost four times higher than expected based on breast cancer death rates in the general population, according to the researchers. The ratio of observed to expected rate of breast cancer mortality consistently increased throughout follow-up. The 25-year cumulative risks for breast cancer mortality by age at ductal carcinoma in situ diagnosis were 7.6% for those younger than 45 years, 5.8% for those aged 45 to 49 years, 5.9% for those aged 50 to 59 years and 6.2% for those aged 60 to 70 years.

Among women aged 50 to 64 years who were eligible for NHS breast cancer screening, researchers observed an increased risk for invasive breast cancer rates (1.26; 95% CI, 1.17-1.35) and an increased risk for breast cancer mortality (1.37; 95% CI, 1.17-1.6) for women with non-screen-detected ductal carcinoma in situ compared with screen detected cancer.

Of the 22,753 women with unilateral ductal carcinoma in situ undergoing surgery, those who had mastectomy had a lower 25-year cumulative rate of ipsilateral invasive breast cancer (8.2%) compared with breast-conserving surgery with radiotherapy (19.8%) or breast-conserving surgery without radiotherapy (20.6%). However, the reductions did not translate to lower 25-year cumulative breast cancer mortality rate for those with mastectomy (6.5%) vs. breast-conserving surgery with (8.6%) or without radiotherapy (7.8%).

“These findings should inform considerations regarding the frequency and duration of surveillance following a diagnosis of ductal carcinoma in situ, particularly for women diagnosed at younger ages,” the researchers wrote. “Our results also suggest that, although not affecting breast cancer mortality, women who receive a mastectomy have lower long-term risks of invasive disease than those who receive breast conserving surgery, even when accompanied by radiotherapy — but this difference has yet to be confirmed in a randomized trial.”