Wider negative margins do not improve local control in early breast cancer

Issue: January 25, 2016

SAN ANTONIO — Although a final positive margin increased risk for ipsilateral breast tumor recurrence, wider negative margins did not improve local control compared with narrow margins, according to study results presented at the San Antonio Breast Cancer Symposium.

However, researchers also noted the detection of residual disease during re-excision increased risk for ipsilateral breast tumor recurrence (IBTR).

“In Denmark, the majority of patients with invasive early breast cancer will receive breast conserving surgery,” Anne Bodilsen, MD, a PhD student at Aarhus University Hospital in Denmark, said during her presentation. “Despite this, some of the central aspects of the surgical treatment are being discussed.”

Bodilsen and colleagues sought to evaluate the association between margin width and IBTR and to identify factors associated with residual disease after repeat surgery.

The analysis included data from 11,900 women aged 18 to 75 years who underwent breast conserving surgery for unilateral invasive cancer in Denmark between 2000 and 2009. Women also received whole-breast irradiation and were offered systemic adjuvant treatment in accordance with Danish Breast Cancer Cooperative Group guidelines.

Median follow-up was 4.9 years.

Overall, the rate of IBTR was 2.4% at 5 years and 5.9% at 9 years.

Based on an HR of 1 for margins of 5 mm or larger, researchers observed no decrease in risk for IBTR with margins between 0 mm and 1 mm (1.54; 95% CI, 0.81-2.93) and margins 2 mm to 4 mm (0.94; 95% CI, 0.56-1.62).

However, women with a final positive margin had an increased risk for IBTR (HR = 2.51; 95% CI, 1.02-6.23). An increased risk for IBTR also appeared linked to younger age (HR = 3.1; 95% CI, 1.89-5.1), having more than four positive lymph nodes (HR = 1.8; 95% CI, 1.24-2.62) and re-excision (HR = 1.53; 95% CI, 1.16-2.02).

A lower risk for IBTR occurred among women who received chemotherapy (HR = 0.45; 95% CI, 0.33-0.61), who received boost therapy (HR = 0.43; 95% CI, 0.31-0.6) or who had ER-positive disease (with adjuvant endocrine therapy, HR = 0.35; 95% CI, 0.25-0.49; without endocrine therapy; HR = 0.43; 95% CI, 0.31-0.6).

Re-excision occurred in 1,342 women (11%) within 2 months of breast conserving surgery, and 6% of patients proceeded to mastectomy. Bodilsen and colleagues found the use of repeat surgery with re-excision or mastectomy decreased over time, from 27% in 2000 to 16% in 2009.

Researchers detected residual disease in 20% of resected tissue, the majority of which was ductal carcinoma in situ (DCIS; 63%) followed by invasive carcinoma (23%) or a combination of the two (14%). Residual disease appeared more common among women with DCIS outside the invasive tumor (OR = 2.69; 95% CI, 1.99-3.63), a positive initial margin (OR = 2.26; 95% CI, 1.7-2.99) or who were aged younger than 50 years (OR = 1.53; 95% CI, 1-2.31).

Patients who had residual disease after re-excision had an increased risk for IBTR regardless of whether the residual disease was DCIS (HR = 2.58; 95% CI, 1.5-4.45) or invasive disease (HR = 2.97; 95% CI, 1.57-5.62). However, there was no significant difference in OS among women who underwent only breast conserving surgery vs. those who underwent repeat surgery with or without residual disease.

Bodilsen noted that the Danish guidelines on margin width changed during the study period. Also, the small number of patients in the narrow margin subgroups may be a limitation to these analyses.

“After breast conservation, if you have a final positive margin it increased your risk for local recurrence, whereas we saw no difference between the negative margins,” Bodilsen said. “The increased risk associated with re-excision was just for the patients who had residual tumor left, and that was not reflected in the OS of these patients.” – by Alexandra Todak

Reference: Bodilsen A, et al. Abstract S2-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 8-12, 2015; San Antonio.

Disclosure: The researchers report no relevant financial disclosures.