More aggressive surgery, endocrine treatment of ER-positive breast cancer reduced the risk over time

Women who are diagnosed with ductal carcinoma in situ (DCIS) on screening mammography are more than twice as likely to develop invasive breast cancer and die from it than women who do not have DCIS, even those with low and intermediate grade DCIS, a population-based, observational cohort study has shown.

Among 35,024 women who were diagnosed with DCIS through the NHS Breast Screening Programme (NHSBSP) between 1988 and 2014, the rate of invasive breast cancer was 8.82 (95% CI, 8.45-9.21) per 1000 women per year and did not vary significantly with age at diagnosis, Gurdeep Mannu, MD, clinical research fellow in cancer surgery, University of Oxford, United Kingdom, and colleagues reported in the BMJ.

This rate was more than double the expected rate of breast cancer incidence in the general population, researchers add, at an observed to expected ratio of 2.52 (95% CI, 2.41 to 2.63P<0.001).

The rate of death from breast cancer was 1.26 (95% CI, 1.13-1.41) per 1000 women per year which was 70% higher than that expected from national breast cancer mortality rates at an observed to expected ratio of 1.70 (95% CI, 1.52-1.90; P<0.001), researchers added.

Again, the death rate did not vary significantly with age of DCIS diagnosis.

For both invasive breast cancer and death from it, the increased risks continued for at least 20 years.

“In the UK… most women are recalled for yearly surveillance mammograms for five years, after which further follow-up is three yearly via the national screening program up to age 70 years,” Mannu and colleagues observed.

“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,” they added.

Study Endpoint

By study endpoint, 13,606 women had been followed for up to 5 years; 10,998 for 5 to 9 years; 6,861 for 10 to 14 years; 2,620 for 15 to 19 years, and 939 for at least 20 years.

“Since the introduction of the NHSBSP, all women diagnosed as having DCIS detected by screening in England have been registered prospectively by organizations that are now unified into the National Cancer Registration and Analysis Service,” researchers pointed out.

By the end of 2014, 2076 women in the study had developed invasive breast cancer.

The observed to expected ratio was 1.06 (95% CI, 0.81-1.37) from 0.5 to 0.9 years after diagnosis but this ratio increased to 2.13 (95% CI, 1.86-2.44) between 1.0-1.9 years after the diagnosis and to 2.67 (95% CI, 2.35-3.02) between 2.0-2.9 years after the diagnosis.

Beyond three years, the observed to expected ratio was 2.69 (95% CI, 2.56-2.83) with no further increase over time, investigators noted.

“During the first five years after diagnosis of DCIS, the cumulative risk of death from breast cancer was similar to that expected but after that, the cumulative observed risk increased more rapidly than expected,” the authors noted.

After 5 years, the breast cancer death rate increased with values of 1.98 (95% CI, 1.65-2.37) in years 5 to 9; 2.99 (95% CI, 2.41-3.70) in years 10 to 14, and 2.77 (95% CI, 2.01-3.80) 15 years and more after the diagnosis of DCIS.

More Aggressive Treatment

The authors also found that women who were treated more aggressively had lower rates of developing ipsilateral invasive breast cancer over time.

For example, the rate of ipsilateral invasive breast cancer among women who underwent breast conserving surgery, but no radiotherapy was 43% higher at an adjusted rate ratio of 1.43 (95% CI, 1.05-1.96) compared to women who had breast-conserving surgery accompanied by radiation.

For women who underwent mastectomy, the rate of ipsilateral breast cancer was 35% lower at an adjusted rate ratio of 0.65 (95% CI, 0.45-0.92; P<0.001) again compared to women who had breast-conserving surgery accompanied by radiation.

Furthermore, the cumulative rate of invasive breast cancer increased more steeply for women who had undergone breast conserving surgery—with or without radiotherapy—than for those who had undergone a mastectomy.

“The rate of ipsilateral invasive breast cancer was [also] strongly associated with final margin status,” the authors continued.

For example, the adjusted rate ratio for women with involved margins was 3.73 (95% CI, 2.04-6.83) compared to women whose final margin distance was at least 5 mm.

Moreover, the rate of ipsilateral invasive breast cancer among women with estrogen receptor-positive disease treated with endocrine therapy was 38% lower at an adjusted rate ratio of 0.62 (95% CI, 0.49-0.80).

Fifteen years after the diagnosis, the cumulative rate of ipsilateral invasive breast cancer was 4.7% (95% CI, 3.2-6.2%) in women with estrogen receptor-positive breast cancer treated with endocrine therapy compared with 7.3% (95% CI, 6.1-8.5%) in women who were not treated with hormonal therapy.

Findings also showed the 15-year cumulative rate of ipsilateral invasive breast cancer among women with low and intermediate grade DCIS was higher than that of women with high grade tumors.

This might reflect the fact that low and intermediate tumors are subject to a continuing risk of progression or may simply be the result of women being undertreated, as most of these women received breast conserving surgery alone.

“We have shown that women diagnosed as having DCIS detected by screening in England have experienced substantially increased risk of both invasive breast cancer and death from breast cancer compared with women in the general population, despite having lower overall mortality,” the authors underscored.

“[This] increase affected women of all ages and applied to women with unilateral DCIS who were treated surgically, as well as to the few women with bilateral DCIS, or for whom no surgery was reported,” they stated, adding, nevertheless, that death rates from breast cancer among women with a more recent diagnosis of DCIS are declining, likely a reflection of improved treatment of invasive disease.

  1. A diagnosis of DCIS on screening mammography more than doubled the risk of invasive breast cancer and death over a long-term follow-up even among those with low and intermediate grade DCIS.

  2. Mastectomy and more aggressive surgery as well as endocrine treatment of estrogen receptor-positive breast cancer reduced the risk of invasive breast cancer over time.

Pam Harrison, Contributing Writer, BreakingMED™

Funding was provided by Cancer Research UK, the National Institute for Health Research Oxford Biomedical Research Centre, and the UK Medical Research Council.

None of the authors had any conflicts of interest to declare.

Cat ID: 22

Topic ID: 78,22,730,22,691,192