Surgery for Phyllodes Breast Tumors Varies Widely

Wide surgical margins did not reduce local recurrence of phyllodes breast tumors, and re-excision of negative margins for benign tumors offered no apparent benefits, according to a review of 550 cases.

The overall recurrence rate was 3.3%, consisting of 15 local recurrences and three distant recurrences. Although wider negative surgical margins (≥2 mm vs <2 mm) were associated with a numerical reduction in the odds ratio for recurrence, the difference did not achieve statistical significance (OR 0.39, 95% CI 0.07-2.10, P=0.27).

Recurrence risk was similar between patients who underwent second operations, regardless of initial margin status, and those with positive margins who did not have second operations, Laura H. Rosenberger, MD, of Duke University Medical Center in Durham, North Carolina, and co-authors reported in the Journal of Clinical Oncology.

"This series highlights the critical need for prospective, cooperative-group collaboration to provide substantial evidence necessary to revise the national guidelines for margin management," the authors concluded. "While we endorse current margin recommendations for borderline and malignant PTs (phyllodes tumors), guideline revision for benign PT should be considered, which comprise 70% of all PT and are responsible for the majority (60%) of second operations.

"Based on the totality of available data, we do not recommend re-excision of a negative margin for benign PT, regardless of negative margin width, as progressively wider surgical margins do not reduce local or distant recurrences. While we suspect a positive margin will similarly not impact LR (local recurrence) for benign PT, we recommend awaiting forthcoming prospective data to support this hypothesis."

Phyllodes tumors account for fewer than 1% of all breast lesions. The World Health Organization classifies PTs as benign, borderline, and malignant on the basis of multiple stratified histopathologic parameters. The National Comprehensive Cancer Network recommends wide local excision (margins ≥1 cm) for all PT grades, omission of axillary staging, and cautious consideration of adjuvant therapy, Rosenberger and coauthors noted.

Multiple large clinical series have shown that local recurrence is associated with positive surgical margins. However, adequate margin width remains controversial, as some series have suggested that a tumor-free margin is sufficient to prevent local recurrence. Other studies showed that only a positive margin predicted an increased risk of local recurrence and no effect of increasingly wider margins, the authors continued.

A growing body of literature suggests that avoidance of positive margins might not be necessary, they continued. Some series showed that positive margins lose significance in a multivariate analysis. A recent meta-analysis showed an association between positive margins and local recurrence only for malignant PTs.

To contribute data representing contemporary clinical practice, Rosenberger and colleagues collected data on PT management from 2007 to 2017 at 11 centers. Data points included surgical margin status, width of closest negative margin, subsequent operations and margin outcomes, and patient's last known status.

The 550 patients included in the analysis had pathology-confirmed benign PTs in 379 cases, borderline lesions in 108 cases, and malignant lesions in 58 cases. Median tumor size was 3 cm, and a majority of the patients had a palpable mass at diagnosis. Initial management was excisional biopsy with no attention to margins in 54.9% of cases, lumpectomy with wide local excision in 38.2% of cases, and mastectomy in 6.2%. Twelve (2.2%) patients had lymph node evaluations.

The authors found that 37.6% of the patients had second operations, including 51 patients who had initial negative margins. Of the 209 patients who had second operations, 87.1% had re-excision lumpectomy, and 11% completed a mastectomy.

Initial procedures resulted in negative margin status in 56.5% of patients and positive margins in 42%. A third of patients with positive margins did not undergo re-excision. At completion of surgical management, more than 10% of patients had a positive margin as final margin status.

During median follow-up of 36.7 months, 18 patients had recurrences (3.3%), which were local in 15 cases. The 208 women who underwent re-excision (including 51 with initially negative margins) had a recurrence rate of 2.9%. The authors found that 74 patients with initially positive margins did not undergo a second operation, and they had a recurrence rate of 2.7%.

Neither a wider negative margin (P=0.27) nor final margin status (positive vs negative, OR 0.96, P=0.96) predicted recurrence.

The study reflects the current variation in surgical practice related to phyllodes tumors, Carla Fisher, MD, of Indiana University Health in Indianapolis, told MedPage Today by email.

"While the NCCN guidelines currently recommend negative margins of greater than 1 cm, many surgeons are not practicing this – and this paper helps explain why," said Fisher, a clinical expert for the American Society of Breast Surgeons. "In this retrospective multi-institutional analysis, local recurrence rates were low at 2.7%, and there was no association with margin status. In fact, the only findings that were associated with increased risk of local recurrence were specific pathologic findings of the tumor.

"The authors appropriately note other studies with close but varying results regarding appropriate margin status. They also emphasize the need for prospective, pooled data to allow for more modern recommendations for treatment of phyllodes tumors."

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