Long-term outcome of DCIS patients: p53 as a biomarker of ipsilateral recurrence.

Abstract

39 Background: Ductal carcinoma in situ (DCIS) is a heterogeneous and potentially curable disease with a long natural history. DCIS represents 21% of breast cancers diagnosed in 2010. The risk of dying after a diagnosis of DCIS is low, emphasizing the importance of treatment-related morbidity, yet the risk of recurrence remains substantial. Optimum individualized therapy remains elusive. We previously identified p53 overexpression as a biomarker for ipsilateral tumor recurrence (IBTR). The purpose of the current study was to investigate its prognostic validity in an expanded patient cohort with long-term follow-up. Methods: We studied 186 consecutive pure DCIS patients from our Breast Cancer Registry and identified 142 cases with sufficient histopathologic material to perform evaluable immunostaining for p53. Median follow-up was 11 years. Statistical analysis was performed with SAS software. Results: Median patient age was 66 (range 35-91) years and 47/153 (31%) presented with palpable disease. Median tumor size was 10 (range 2-165) mm. Predominant histologic subtype included 34 (24%) comedo, 43 (30%) solid, 50 (35%) cribiform and 15 (11%) micropapillary/papillary cases. Necrosis was present in 74/142 (52%) of tumors. Overexpression of p53 was identified in 33/142 (23%) and was associated with necrosis, but not with any other patient, tumor or treatment variables. Fifteen patients (11%) were diagnosed with an IBTR at a median of 56 (range 11-154) months after their initial diagnosis; 3 recurrences were DCIS, while 12 were invasive cancer. p53 overexpression, present in 10/15 (68%) of cases with recurrence versus 23/127 (18%) of non-recurrent tumors, p < 0.001, and no adjuvant tamoxifen, p = 0.003, were associated with IBTR. No other patient, tumor or treatment factors studied were predictive of IBTR. The type of IBTR did not correlate with the p53 status of the index tumor. Conclusions: These data suggest that p53 may be a biomarker for elevated risk of IBTR after a diagnosis of DCIS and support the value of adjuvant tamoxifen for DCIS patients. Further investigation to validate these findings and to identify clinically useful individualized risk stratification for DCIS patients is warranted.