Pathology grade predicts risk of local relapse after breast-conserving therapy

NEW YORK (Reuters Health) - High-grade pathology, but not margin status, is associated with an increased risk of local relapse after breast-conserving therapy for stage I and II invasive breast cancer, according to a report published online ahead of print in the Journal of Clinical Oncology.

"In contrast with the opinion of several clinicians, margin involvement with limited microscopic tumor spread is not a relevant predictive factor for a local breast recurrence," Dr. Harry Bartelink from The Netherlands Cancer Institute, Amsterdam, told Reuters Health by email. "Other factors like age and high grade invasive tumors are much more relevant prognostic factors."

Dr. Bartelink and colleagues in the EORTC Boost Versus No Boost Trial investigated the long-term impact of pathological characteristics on local relapse in 1616 women whose stage I or II invasive breast cancer had been treated with breast-conserving therapy and whole breast irradiation, with or without an extra boost dose of 16 Gy (with negative margins) or 10 to 26 Gy (with positive margins).

On multivariate analysis, the presence of high-grade invasive ductal carcinoma and age younger than 50 years were associated with a significantly increased risk of local relapse, the authors report, whereas the additional boost dose to the tumor bed significantly reduced the local relapse rate.

In patients with high grade invasive ductal carcinoma, the boost reduced the cumulative 10-year local relapse rate from 18.9% to 8.6%. In addition, in women younger than 50, the extra irradiation reduced the 10-year cumulative local relapse rate from 19.4% to 11.4%.

Margin involvement and differentiation in grade of ductal carcinoma in situ did not have a significant impact on the local relapse rate.

"(In) the last 10 years, too much focus was given to margin involvement by surgeons and pathologists," Dr. Bartelink said. "The consequence of this finding is that (fewer) re-excisions or even mastectomies are required when focal involvement of the margins is found by the pathologists."

"We are at present involved in the development of a nomogram (based upon the classical criteria coming from tumor size, pathological features and planned systemic treatment) to predict the chance of a local breast recurrence in an individual patient," Dr. Bartelink added.

In a linked editorial, Drs. Shannon MacDonald and Alphonse G. Taghian at Harvard Medical School, Boston, suggest that the lack of association between positive margins and relapse could be explained by the small number of patients with a positive margin or the way the patients were grouped.

"Although this subgroup analysis did not find margins to be a prognostic factor for local recurrence, numerous studies have found it to be one of the strongest prognostic factors," the editorialists write. "Surgical re-excision for positive margins should continue to be routinely performed."

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