The presence of extensive retraction clefts in invasive breast carcinomas correlates with lymphatic invasion and nodal metastasis and predicts poor outcome: a prospective validation study of 2742 consecutive cases.

We previously reported that the presence of extensive retraction clefts (RC) in breast cancers correlates with increasing tumor size and grade as well as lymphatic tumor spread and predicts poor outcome. This study is a prospective validation of our prior results. Consecutive cases of invasive breast carcinoma (n=2742) were reviewed to determine the diagnoses, including histologic type, grade, presence of lymphovascular invasion (LVI), and extent of RC. No differences were found in the extent of RC between corresponding core needle biopsy and surgical samples. Extent of RC showed a significant correlation with tumor size, grade, LVI, and nodal metastasis in both core needle biopsy and surgical specimens. These associations remained significant in subset analyses of small (≤1 cm), node-negative and node-positive tumors. Extensive RC predicted poor recurrence-free (P<0.0001) and overall (P<0.0001) survival and remained significant in subset analyses of node-negative (P=0.0015 and 0.0021, respectively) and node-positive (P=0.0039 and 0.0214, respectively) cases. Carcinomas without LVI but extensive RC were associated with better outcome than carcinomas with LVI but worse than those without LVI and low RC. This prospective study confirms that the presence of extensive RC in invasive breast carcinomas correlates with aggressive tumor features and lymphatic tumor spread. Extensive RC appears to be an independent factor predictive of poor outcome in node-negative and node-positive disease. Our results support the hypothesis that RCs are the morphologic reflection of biological changes in tumor cells playing a role in lymphatic tumor spread and likely represent an early stage of LVI with similar clinical implications.