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Women with a ductal carcinoma in situ (DCIS) diagnosis were over three times more likely to die from breast cancer versus those in the general population, a retrospective study found.

In over 140,000 women who underwent surgery after being diagnosed with DCIS, 1,540 died from invasive breast cancer compared with an expected 458 for cancer-free women (standardized mortality ratio [SMR] 3.36, 95% CI 3.20-3.53), reported Steven Narod, MD, and colleagues from the Women's College Research Institute in Toronto.

And this risk persisted beyond 15 years after diagnosis, according to the findings in .

"The SMR was lower among women who received lumpectomy plus radiation compared with women who received lumpectomy alone," the authors wrote. "The rate of breast cancer death was nearly 12-fold higher among women diagnosed with DCIS before age 40 years and 7-fold higher in Black women diagnosed with DCIS compared with the general population."

For patients treated with lumpectomy, SMRs were 3.42 without radiation therapy (95% CI 3.07-3.80) and 2.81 with radiation (95% CI 2.55-3.04). Among patients who did not receive radiation therapy, SMRs were 4.12 in those who underwent a single mastectomy (95% CI 3.59-4.67) and 4.14 with a double mastectomy (95% CI 2.83-5.59).

As the authors noted, SMRs varied widely according to age, ranging from a low of 2.65 for women ages 60-69 at the time of their DCIS diagnosis (95% CI 2.39-2.92) to a high of 11.95 for those under 40 years of age (95% CI 9.66-14.39).

SMRs varied widely in women according to race/ethnicity as well:

• East Asian (SMR 1.89, 95% CI 1.36-2.49)
• Southeast Asian (SMR 2.40, 95% CI 1.65-3.31)
• White (SMR 3.03, 95% CI 2.86-3.21)
• Black (SMR 7.56, 95% CI 6.76-8.42)

"This study is not designed to generate information on clinical managements of DCIS," Narod's group cautioned. "The lifetime risk of death following DCIS is approximately 3%, and this level of risk is too low to recommend chemotherapy."

However, they pointed out that some patients -- Black women and those under 40 -- had mortality rates that approached 10%. "[A]t this level, chemotherapy might be considered," the authors wrote. "Ideally, we would be able to identify the few women with DCIS with metastatic potential from the outset and offer them systemic therapy."

Stephanie Bernik, MD, of the Icahn School of Medicine at Mount Sinai in New York City, expressed caution over the findings that mastectomy patients had the highest recurrence risk, as this might have been driven by women with more extensive disease or close margins.

"They also could have been genetically positive, which would increase the likelihood of recurrence, even after undergoing a mastectomy," she told 名媛直播 by email, noting that the Surveillance, Epidemiology, and End Results (SEER) database -- used in the study to capture patients characteristics and outcomes -- has important limitations, including a lack of information on risk factors such as family history or BRCA status.

"These women were also younger and could have had longer follow-up and therefore were more likely to have a recurrence picked up in the database," said Bernik, who was not involved in the research.

"Bottom line is that we know women with DCIS are at a higher risk of invasive cancer in the future," she added. "These women need to continue monitoring for breast cancer. There has been a push recently to decrease treatment for DCIS, but this study might require taking a second look at less aggressive management."

Recent research from the Netherlands, however, found that while women diagnosed with DCIS there saw a greater risk of death from breast cancer, their overall mortality was actually lower than the general population.

The analysis from Narod's group included 144,524 women in the SEER registry with a diagnosis of DCIS from 1995 to 2014. Patients had a mean age of 57.4 years at the time of diagnosis and were followed for 20 years, until death, or through the end of 2016 (mean follow-up was 9.2 years). Most patients in the cohort were white (77.9%) and about 70% had grade II-IV tumors.

About half of the women received radiotherapy. Two-thirds underwent lumpectomy and 27% had a mastectomy, with the rest unknown.

During follow-up, 3.1% of patients had an ipsilateral invasive recurrence (20-year actuarial risk 13.9%), while 3.8% had a contralateral invasive recurrence (20-year actuarial risk 11.3%). Compared with deaths from breast cancer (1.1%), patients were more likely to have died from heart disease (2.7%), other cancers (2.7%), other diseases (2.5%), or from some unknown cause (1.8%).

Limitations cited by the authors included the fact that treatment was not randomized, as well as the observational design of the study. They also noted that SEER does not capture tamoxifen or other hormonal therapy use.

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