Apoptosis and proliferation related-proteins in breast carcinoma with neoadjuvant chemotherapy

Abstract

Listen

Translate article

838 Background: Apoptosis and proliferation deregulation plays a role in tumor pathogenesis and progression, and apparently in response to treatment. We studied whether the expression of proteins involved in these mechanisms can identify a subset of breast carcinoma (BC) patients who will respond to neoadjuvant chemotherapy (NACT). Methods: We selected 99 core needle biopsies (CNB) and the corresponding resection specimens from BC patients in NACT. Clinical response (CR) based on tumor size was classified as complete (100%), partial incomplete (>50%), minor (<50%) or progression. Tumor cellularity was assessed in CNB sections and specimens as the percentage invasive cells. Specimens were classified by a five-point grading system. Staining for Bcl2, Bad (pBad Ser136), cleaved Caspase-3, p53, Her2/neu and Ki67 was performed in CNB. All antibodies were scored based on the proportion except for pBad that was considered as negative (no/faint) or positive (moderate/strong). Results were correlated with CR, pathologic response (PR) and clinico-pathological factors. Results: Patients median age was 49 years (range 25–80). Median initial tumor size was 5.5 cm (range 1.5–12) and after treatment 3.2 cm (range 0–15) (p=0.02). 88% were of ductal type, 12% lobular and 63% grade 3. Overexpression of Bcl2 (>50%) or p53 (>20%) was observed in 51% and 41%, respectively; pBad was present in 44% tumors; activated caspase-3 (>50%) in 17% and Ki67 (>30%) in 27%. Complete CR was seen in 37% and PR and 17% (p=0.002). Tumor cellularity decreased from a median of 30% to 5% and 30% showed >90% reduction of the clinical size (p<0.000). Her2/neu was positive in tumors of older patients (p=0.02) with high Ki-67 (p=0.04) and predicted tumor reduction (p=0.03). Ki67 and p53 overexpression was seen in grade 3, with low Bcl2 (p30% (p=0.02) and as a trend with pBad (p=0.09). The grade of PR correlated with pathological size, cytological changes and lymph-node status (p<0.04), and as a trend with Bcl2 (p=0.07), Her2/neu (p=0.09) and Ki67 (p=0.11). Conclusions: In BC following NACT, Ki67 correlates with CR. The observed trend towards improved PR depending on the levels of Bcl-2, Her2/neu and Ki67 supports the idea that they may have predictive value. No significant financial relationships to disclose.