Biomarker expression and survival after primary chemotherapy for breast cancer.

Purpose: Preoperative chemotherapy (PCT) allows for a direct assessment of treatment effects on the tumor and its microenvironment. Aims of this analysis: to evaluate the correlation of biomarker expression with responses in breast cancer patients treated with PCT; to evaluate treatment induced modification in the biomarker expression and its relation with outcome. Patients and Methods: 189 stage II-IIIB breast cancer patients were evaluated. The following parameters were assessed at baseline, and, after 3-4 courses of PCT, at surgery: ER, PgR, grading, HER2, Ki-67, p53, EGFR and VEGFR. PCT regimens: anthracycline-based (16%) or anthracycline-taxane (84%) combinations. Results: Patients characteristics were as follows: median age 51 yrs (range: 27-73); clinical stage: IIA-IIB 78.5%, IIIA-IIIB: 21.5%; ER and/or PgR positivity: 77%; grade 3: 58.5%, HER2 positivity: 20%.The ORR (CR+PR) was 70.6%; 39% of patients underwent conservative surgery, and a pCR (breast and axillary lymph-nodes) was observed in 8.3% of patients. The probability of pCR was significantly associated with ER status ( ER+: 3% vs ER-: 20%, p=0.005), and with grade (grade 3: 14% vs grade 1-2: 2%, p=0.049). Median biomarker expression at baseline: ER 62.5%, PgR 9%, Ki-67 25%, p53 2%, EGFR 0%, VEGFR 2%. Median expression after PCT: ER 60% , PgR 3%, Ki-67 15%, p53 4%, EGFR 0%, VEGFR 0%.The differences in biomarker expression before and after PCT were evaluated with the Wilcoxon matched pairs signed rank test: a significant reduction in the expression of PgR (p=0.017), Ki-67 (p<0.0001), and VEGFR (p=0.006) was observed. Baseline Ki67 < 15% predicts a better DFS while ER positivity and p53 <10% predict prolonged OS. After PCT, Ki67>15% and VEGFR positivity are associated with a significantly shorter DFS. Conclusions: In this series of patients, PCT induced a significant reduction of Ki-67 and of the expression of PgR and VEGFR. Treatment-induced modulation of ki67 and VEGFR can be helpful to select patients with different risk of relapse after PCT