Margin Status Predicts Local Recurrence After Lumpectomy

SAN ANTONIO--Final excisional margin status proved to be the strongestpredictor of local recurrence in a study of more than 300 breastcancer patients treated with breast-conserving surgery and radiation,Melanie C. Smitt, MD, said at the opening general session of theSan Antonio Breast Cancer Symposium.

Five- and 10-year freedom from local recurrence was 98% amongpatients who had negative final margins, compared with 90% and82%, respectively, for patients with non-negative excisional margins.

The combination of re-excision and negative final margin was associatedwith 100% local control versus 78% for patients who did not achievenegative final margins after re-excision.

Use of adjuvant chemotherapy was the only other significant predictorof local control, said Dr. Smitt, assistant professor of radiationoncology, Stanford University Medical Center.

The study involved 303 women with stage I or II invasive breastcancer. All patients were treated with lumpectomy and radiation.Adjuvant chemotherapy or tamoxifen (Nolvadex) was limited to patientswith positive lymph nodes and other high-risk features.

A surgical margin was defined as negative if a tumor-free zoneof greater than 2 mm was achieved. A close margin was less than2 mm. Positive margins were defined as focal or diffuse. Re-excisionwas performed as deemed appropriate.

Initially, only 17% of patients had a tumor-free margin. Morethan 40% had indeterminate margins after primary excision (seetable). Following re-excision, final margins were negative inhalf the patients and indeterminate in 35%.

Among all patients, 5-year freedom from recurrence was 94%, and87% at 10 years. Univariate analysis suggested that final marginstatus, nodal stage, histologic type, and use of adjuvant chemotherapyor tamoxifen were predictors of local recurrence. Multivariateanalysis, however, showed that final margin status and use ofadjuvant chemotherapy were the only significant predictors offreedom from local recurrence. The relative risk was 6.0 for apositive final margin, and 0.22 for use of chemotherapy.

The data suggested that a total radiation dose of at least 6,600cGy improved the chances of local control in patients who didnot achieve negative margins (96% versus 82% at 5 years). However,the difference was of borderline statistical significance, andDr. Smitt and colleagues noted a "continuing pattern of relapse,beyond 5 years, even in those patients who received higher radiationdoses."

"Attainment of a negative surgical margin, either initiallyor at the time of re-excision, was the most significant predictorof local control in this experience," Dr. Smitt concluded."Use of adjuvant chemotherapy and total tumor bed doses ofgreater than or equal to 6,600 cGy may reduce local recurrencerates in patients with non-negative margins."

In response to a question from the audience, Dr. Smitt said thatanalysis of data related to distant recurrence has not been completed.However, a preliminary review indicates that risk of distant recurrenceis related to young age and use of tamoxifen.

An unidentified physician questioned whether larger tumors weremore likely to be associated with non-negative margins. Dr. Smittsaid that tumor size did not emerge as a significant factor inthe multivariate analysis.

She acknowledged, however, that "obtaining a negative surgicalmargin may just be a marker for the amount of residual diseasein the breast, as opposed to the attainment of a negative excisionmargin in and of itself being the important difference."