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Adjuvant radiotherapy confers modest survival benefit for ductal carcinoma in situ

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August 10, 2018

Adjuvant radiotherapy after lumpectomy offered a modest, yet significant, survival benefit among patients with ductal carcinoma in situ compared with lumpectomy or mastectomy alone, according to study findings.

“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect,

which appears to be attributable to systemic activity rather than local control,” Vasily Giannakeas, MPH, epidemiologist at Women’s College Research Institute in Toronto, Canada, and colleagues wrote. “How exactly radiotherapy affects survival is an important question that should be explored in future studies.”

Radiotherapy is commonly used for the treatment of ductal carcinoma in situ (DCIS) to reduce risk for local invasive recurrence after breast-conserving surgery. However, the association between radiotherapy with survival among patients with DCIS remained unknown, and it remains a need to identify subgroups of women with DCIS who will benefit the most from radiotherapy.

Researchers used the SEER database to evaluate data from 140,366 women (mean age, 58.8 years; 78.2% white) diagnosed with primary DCIS.

Investigators matched patients 1:1 based on year of diagnosis (same year), age at diagnosis (within 2 years), tumor grade, ER status and propensity score to conduct analyses for three separate comparisons: lumpectomy with radiation vs. lumpectomy alone; lumpectomy alone vs. mastectomy; and lumpectomy with radiation vs. mastectomy.

Crude and adjusted 15-year breast cancer-specific mortality served as the primary outcomes.

Among the patients, 25% underwent lumpectomy alone, 46.5% underwent lumpectomy and radiotherapy, and 28.5% underwent mastectomy.

Patients who underwent mastectomy tended to be younger than patients treated with lumpectomy (mean age, 56.5 years vs. 59.8 years). Also, likelihood of undergoing mastectomy increased with tumor size and grade of disease.

Researchers reported an actuarial 15-year breast cancer mortality rate of 2.33% for patients treated with lumpectomy alone, 1.74% for patients treated with lumpectomy and radiation, and 2.26% for patients treated with mastectomy.

Among 29,465 propensity-matched pairs, patients who underwent lumpectomy and radiotherapy had an adjusted HR for mortality of 0.77 (95% CI, 0.67-0.88) compared with patients who underwent lumpectomy alone.

Among, 20,832 propensity-matched pairs, patients who underwent mastectomy alone had an adjusted HR for mortality of 0.91 (95% CI, 0.78-1.05) compared with lumpectomy alone.

Among 29,865 propensity-matched pairs, patients who underwent lumpectomy and radiotherapy had an adjusted HR for mortality of 0.75 (95% CI, 0.65-0.87) compared with mastectomy.

Researchers measured the protective effect of radiotherapy on mortality for different subgroups of patients who underwent lumpectomy.

The protective effect of radiotherapy on mortality appeared greater for those aged younger than 50 years (HR = 0.59; 95% CI, 0.43-0.8) than those aged 50 years and older (HR = 0.86; 95% CI, 0.73-1.01).

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Researchers reported HRs of 0.67 (95% CI, 0.51-0.87) for ER-positive cancer, 0.5 (95% CI, 0.32-0.78) for ER-negative cancer, and 0.93 (95% CI, 0.77-1.13) for patients with an unknown ER status.

For black women, the protective effect of radiotherapy on mortality had an HR of 0.69 (95% CI, 0.50-0.96), compared with 0.83 (95% CI, 0.71-0.98) among white women.

Patients with low- or intermediate-grade tumors had an HR for protective effect of radiotherapy on mortality of 1 (95% CI, 0.79-1.27), and those with high-grade tumors had an HR of 0.59 (95% CI, 0.47-0.75).

Researchers cited missing data on tamoxifen use, a lack of randomized treatments, and a possible association between the decision to undergo radiotherapy and other favorable prognostic factors as study limitations.

“These results support our conclusion that the survival benefits of radiotherapy seen in both patients with DCIS and patients with invasive breast cancer cannot be explained by improving local control,” researchers wrote. “We must seek an alternative explanation, namely that radiation to the breast acts as a systemic therapy to eradicate subclinical latent metastases.”

These findings are “reassuring,” given the current trend of overdiagnosis and potential overtreatment of DCIS, Mira Goldberg, MD, and Timothy J. Whelan, BM, BCh, both from McMaster University in Ontario, Canada, wrote in a related editorial.

“The risk of breast cancer mortality in patients with DCIS was very low, and the potential absolute benefit of radiotherapy was quite small,” Goldberg and Whelan wrote. “Such data continue to support a strategy in patients with DCIS of omitting radiotherapy after lumpectomy in low-risk patients, especially when one considers the negative effects of treatment: the cost and inconvenience of 5 to 6 weeks of daily treatments, acute adverse effects such as breast pain and fatigue, and potential long-term toxic effects of cardiac disease and second cancers.” – by Melinda Stevens

Disclosures: Giannakeas reports support from the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award. All other authors report no relevant financial disclosures.