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Larger margin width reduces local recurrence for early-stage breast cancer
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SAN ANTONIO — Excision margins wider than “no tumor on ink” further decreased risk for local recurrence compared with narrower, uninvolved margins among patients undergoing breast-conserving treatment for early-stage breast cancer, according to data from a meta-analysis presented at the San Antonio Breast Cancer Symposium.
“We have been addressing the issue of what is the appropriate margin for breast-conserving therapy for the past 30 to 40 years,” Frank A. Vicini, MD, of Michigan Institute for Radiation Oncology, said during his presentation. “Previous research published in 2014 concluded that negative margins were unlikely to have substantial local control benefit over ‘no tumor on ink’ and led to the Society of Surgical Oncology-American Society for Radiation Oncology guidelines a few years ago. The question that remains now is whether this recommendation is still correct.”
The researchers conducted a systemic review of studies published between 1995 and 2016 that had a minimum follow-up of 50 months, explicit pathologic definition of margin status and local recurrence reported in relation to margin status.
The final study cohort included 55,302 patients (median age, 55 years; 74% T1 tumors; 72% node-negative disease) from 38 studies.
Researchers defined positive margins as invasive cancer or ductal carcinoma in situ at the surgical margin; negative margins as no tumor within specified distance from the margin; and close margins as no tumor on ink, but tumor in the less-than-specified distance from the margin.
The analysis used the following three models:
- Model 1: All patients with at or equal margin width were compared with all patients with wider margins (similar to a previous analysis of negative vs. close/positive margins);
- Model 2: Assessed impact of margin width “range” rather than a set margin width of 0 mm to 2 mm, 2 mm to 5 mm, or greater than 5 mm; and
- Model 3: Margin distance divided by three cut points of –1 mm, 2 mm and 5 mm. This model allowed division into close and negative margins within studies (similar to previous analysis of negative vs. close/positive margins).
Median follow-up was 7.2 years.
The crude rate of local recurrence was 10.3% for patients with positive margins vs. 3.8% for those with negative margins (P < .001).
When the researchers considered follow-up time on univariate analysis for model 1, they found that endocrine therapy appeared significant across all margins (0-mm margin, P = .001; 1-mm margin, P = .002; 2-mm margin, P < .001; and 5mm margin, P < .001), whereas only patient-age remained significant for the first two margins (0-mm margin, P = .048; 1-mm margin, P = .04).
Researchers calculated ORs for local recurrence for negative vs. close/positive margins of 0.46 (95% CI, 0.4-0.53) for margins larger than 0 mm, 0.43 (95% CI, 0.36-0.51) for margins larger than 1 mm, 0.49 (95% CI, 0.42-0.55) for margins larger than 2 mm, and 0.53 (95% CI, 0.43-0.66) for margins larger than 5 mm.
Thus, these results are consistent with previous analyses that showed negative margins lowered rates of local recurrence. But, because the ORs all appeared similar, researchers could not identify the optimal margin.
In the analysis of margin ranges from model 2, a wider margin further reduced local recurrence. Local recurrence decreased by 7.2% for patients with margins greater than 0 mm and less than 2 mm (OR = 0.56; 95% CI, 0.49-0.63), 3.6% for margins between 2 mm to 5 mm (OR = 0.44; 95% CI, 0.35-0.56), and 3.2% for margins wider than 5 mm (OR = 0.32; 95% CI, 0.26-0.41; P < .001 for each).
Modeling as negative, close or positive margins in model 3 showed the lowest rates at 2 mm (negative, 3.6%; close, 5.5%; positive, 9.5%) and 5 mm (negative, 2.9%; close, 4.1%; positive, 12.8%).
ORs for local recurrence by margin status showed improvement with 2 mm vs. 1 mm (OR = 0.5; 95% CI, 0.42-0.59) and 5 mm vs. 1 mm (OR = 0.4; 95% CI, 0.33-0.48).
Study limitations included the variability of multivariable analysis and the studies did not account for the morbidity or cost associated with re-excisions.
“The finding that positive margins are associated with higher rates of local recurrence was expected and consistent with previous analyses,” study researcher Chirag Shah, MD, of Cleveland Clinic, told HemOnc Today. “We expected to see a relationship between negative, close and positive margins. However, we were surprised that margin width was found to be a potential factor associated with recurrence.
“The results confirmed the SSO-ASTRO guideline in some ways, but suggested that further study may be required to determine if the local recurrence benefit with negative margins is enhanced with a larger margin width,” Shah added. “I would like to see a large prospective database or registry put together so that this topic can be evaluated more thoroughly.” – by Jennifer Southall
References:
Houssami N, et al. Cancer Biol Med. 2014;doi:10.7497/j.issn.2095-3941.2014.02.001.
Moran MS, et al. Ann Surg Oncol. 2014;doi:10.1245/s10434-014-3481-4.
Shah C, et al. Abstract GS5-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: Shah, Vicini and the other authors report no relevant financial disclosures.