Long-Term Risk of Invasive Breast Cancer Increases Following a Diagnosis of DCIS

Ductal carcinoma in situ (DCIS) is a noninvasive, or localized, form of breast cancer that is contained in a woman’s milk ducts. Overall, this subtype of breast cancer represents close to 20% of cases of the disease detected through screening methods, and this is partially due to the greater numbers of women who get screened for breast cancer.

Unfortunately, in the 2 decades following their diagnosis for DCIS that was a result of their being screened, women in a study out of England demonstrated a risk of invasive breast cancer and mortality from breast cancer that was more than 2 times greater compared with the general population, reported the authors of a recent study in The BMJ.

Because DCIS isn't always a life-threatening cancer and it typically has a good prognosis, noted the press release announcing the study results, the authors of this study decided to investigate the true extent of this extra risk. Using data from the National Health Service Breast Screening Programme on 35,024 women in England who received their diagnosis of DCIS because of their participation at any time between 1998 and March 2014, they studied the risk as it pertained to the following:

• Incidence of invasive breast cancer
• Mortality from breast cancer
• Mortality from breast cancer after unilateral DCIS and surgery
• Invasive disease after unilateral DCIS and surgery, no endocrine treatment
• Invasive disease after unilateral DCIS and surgery, endocrine treatment

Overall, the follow-up periods in this study serve as one of its greatest strengths. By the data analysis cutoff of December 2014, there had been follow-ups of less than 5 years on 13,606 women; 5 to 9 years on 10,998; 10 to 14 years on 6861; 15 to 19 years on 2620; and 20 years on 939.

The results demonstrated that 2076 eventually developed invasive disease, which equated to 8.82 (95% CI, 8.45-9.21) cases per 1000 women per year. This is a risk that is 3.5 times greater compared with the national rate of 2.52 (95% CI, 2.41-2.63) cases per 1000 women per year. Importantly, this risk began to show a marked divergence in just the second year after the DCIS diagnosis.

This group also had close to a 15% mortality rate, in that 310 of the women died as a result of their cancer, or 1.26 (95% CI, 1.13-1.41) cases per 1000 women per year, which marks a 70% higher risk of death compared with breast cancer mortality among the general population. The observed:expected ratio (OER) was 1.70 (95% CI, 1.52-1.90).

Similar mortality rates were observed between patients with DCIS in the 5 years after their diagnosis and nationally, with an OER of 0.87 (95% CI, 0.69-1.10), but that did not last. Between follow-up years 5 and 9, 10 and 14, and 15 or more, the OER ticked up to 1.98 (95% CI, 1.65-2.37), 2.99 (95% CI, 2.41-3.70), and 2.77 (95% CI, 2.01-3.80), respectively.

In addition, the risk of invasive disease was negatively correlated with treatment intensity. Of the 83% (29,044) of the women in the study who had unilateral DCIS and underwent surgery as treatment, more intensive methods (eg, mastectomy, radiotherapy with breast-conserving surgery, endocrine therapy in cases of estrogen receptor—positive disease) typically led to lower rates of invasive breast cancer down the line.

“Our finding of higher breast cancer mortality in invasive disease occurring after larger DCIS tumour size has not previously been reported, and confirmation is needed in other studies before we can conclude that the association is causal,” the authors concluded. “We have, however, provided evidence of the long-term nature of the risk of invasive disease after a diagnosis of DCIS, even for women with low- or intermediate-grade disease.”

To study the increased long-term risk of invasive disease that seems to accompany a diagnosis of DCIS, as well as to evaluate treatment outcomes, they recommend randomized trials with extensive follow-up.

Reference

Mannu GS, Wang Z, Broggio J, et al. Invasive breast cancer and breast cancer mortality after ductal carcinoma in situ in women attending for breast screening in England, 1988-2014: population based observational cohort study. BMJ. Published online May 27, 2020. doi: 10.1136/bmj.m1570