Study Evaluates Breast Cancer Mortality in Women With DCIS
In a study reported in JAMA Oncology, Narod et al found that the risk of breast cancer mortality was elevated in some patients with ductal carcinoma in situ compared with the general population, with the risk being higher in younger vs older women and black vs white women. Approximately half of breast cancer deaths occurred without development of in-breast invasive recurrence. Breast cancer mortality was not reduced with prevention of ipsilateral invasive recurrence with the addition of radiotherapy to lumpectomy or with unilateral mastectomy vs lumpectomy.
Study Details
The study involved Surveillance, Epidemiology, and End Results (SEER) registries database data on 108,196 women diagnosed with ductal carcinoma in situ from 1988 to 2011. Patients had a mean age at diagnosis of 53.8 years (range = 15–69 years), and the mean duration of follow-up was 7.5 years (range = 0–23.9 years).
Among all patients, estrogen receptor status was positive in 43%, negative in 8%, and unknown in 49%; tumor grade was low in 10%, intermediate in 30%, high in 34%, and unknown in 26%. A total of 45% received radiotherapy, 69% had lumpectomy, 21% had unilateral mastectomy, 6.6% had bilateral mastectomy, and 2.4% had no surgery. A total of 7.1% had a second primary breast cancer.
Mortality and Risk Factors
At 20 years, overall breast cancer–specific mortality was 3.3% (95% confidence interval [CI] = 3.0%–3.6%), with the risk being 1.8 times higher vs the general population (standardized mortality ratio = 1.8, 95% CI = 1.7–1.9); the standardized mortality ratio decreased with increasing age, from 17.0 among women aged < 35 years (1.2% of study population) to 1.4 among those aged > 65 years. The 10-year breast cancer mortality rate was 1.1%.
On multivariate analysis, 20-year risk was significantly higher for women diagnosed at age < 35 years vs older women (7.8% vs 3.2%; hazard ratio [HR] = 2.58, P < .001) and for black vs white women (7.0% vs 3.0%; HR = 2.55, P < .001). Other factors that predicted breast cancer mortality included tumor size (HRs of 1.28, P = .02, 1.58, P < .001, and 1.8, P < .001, for 1.0–1.9, 2.0–4.9, and ≥ 5.0 cm vs < 1.0 cm), grade (HR = 1.73, P < .001, for poorly vs well differentiated), estrogen receptor status (HR = 0.61, P < .001, for positive vs negative), and comedonecrosis (HR = 1.20, P = .02, vs solid type intraductal).
Invasive Recurrence and Mortality
Among 42,250 women who received lumpectomy and radiotherapy, 547 (1.3%) developed ipsilateral invasive recurrence, and 163 (0.4%) died of breast cancer. Among 19,762 women who received lumpectomy without radiotherapy, 595 (3.0%) developed ipsilateral invasive recurrence, and 102 (0.5%) died of breast cancer. Among 25,527 who received unilateral or bilateral mastectomy, 200 (0.8%) had ipsilateral invasive recurrence, and 154 (0.6%) died of breast cancer.
Among all patients, estimated 20-year risks were 5.9% for ipsilateral invasive recurrence and 6.2% for contralateral invasive recurrence, with estimated risks of 9.5% among patients with breast-conserving surgery without radiotherapy and 4.5% among those with breast-conserving surgery with radiotherapy. Risk of death from breast cancer increased after ipsilateral invasive recurrence (HR = 18.1, P < .001) and contralateral invasive recurrence (HR = 13.8, P < .001) but not after ductal carcinoma in situ ipsilateral or contralateral recurrence.
No Invasive Recurrence in Half of Deaths
A total of 956 women died of breast cancer; of them, 517 (54%) did not develop in-breast invasive recurrence, and 395 (41%) developed ipsilateral (n = 210) or contralateral (n = 165) invasive recurrence. No in-breast invasive recurrence before death was observed in 94 (58%) of 163 who received lumpectomy and radiotherapy, 51 (50%) of 102 who received lumpectomy without radiotherapy, and 112 (73%) of 154 who received unilateral or bilateral mastectomy.
No Survival Benefit With Reduced Risk of Ipsilateral Recurrence
Among patients who received lumpectomy, the 10-year risk of ipsilateral invasive recurrence was significantly reduced among those receiving vs not receiving radiotherapy (2.5% vs 4.9%; adjusted HR = 0.47, P < .001), but no reduction in the risk of death from breast cancer was observed (0.8% vs 0.9%; adjusted HR = 0.81, P = .10). The 10-year risk of ipsilateral invasive recurrence was significantly lower among women receiving unilateral mastectomy vs lumpectomy (1.3% vs 3.3%; adjusted HR = 0.81, P < .001).
On unadjusted analysis, breast cancer mortality at 10 years was significantly higher in those receiving unilateral mastectomy (1.3% vs 0.8%; unadjusted HR = 1.45, P < .001), but the increased risk was no longer significant after adjustment for age at diagnosis, year of diagnosis, income, estrogen receptor status, tumor size, tumor grade, and ethnicity (HR = 1.20, P = .11).
The investigators concluded: “Important risk factors for death from breast cancer following a ductal carcinoma in situ diagnosis include age at diagnosis and black ethnicity. The risk of death increases after a diagnosis of an ipsilateral second primary invasive breast cancer, but prevention of these recurrences by radiotherapy does not diminish breast cancer mortality at 10 years.”
And, they noted: “Some cases of ductal carcinoma in situ have an inherent potential for distant metastatic spread. It is therefore appropriate to consider these as de facto breast cancers and not as pre-invasive markers predictive of a subsequent invasive cancer. The outcome of breast cancer mortality for ductal carcinoma in situ patients is of importance in itself and potential treatments that affect mortality are deserving of study.”
Steven A. Narod, MD, FRCPC, of Women’s College Research Institute, Women’s College Hospital, and University of Toronto, is the corresponding author of the JAMA Oncology article.
Javaid Iqbal, MD, has received a Canada Graduate Scholarship (Master’s) from the Canadian Institute of Health Research. Dr. Narod holds a Canada Research Chair in Breast Cancer. No other disclosures were reported.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
