Neoadjuvant chemotherapy (NAC) was reported to change the status of biomarker including estrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki67. However, the impact of these changes on clinical outcome still remains to be elucidated. The objective of this study is to evaluate the biomarker discordance of breast cancer patients treated with NAC and its prognostic impact.
From a prospective database of 243 patients receiving NAC from January 2005 to November 2016, 183 patients (75.3%) with non-pCR were analyzed. ER, PgR, HER2 and Ki67 status were assessed in core needle biopsy performed prior to NAC and surgical specimens. Ki67 status was classified as high (> 20%) and low (< 20%) level.
The median age was 56.0 (range: 29–79) years and the mean tumor size was 3.38 ± 2.19 cm. Clinical nodal status was positive in 59.0% of patients before NAC. ER, PgR and HER2 were positive in 71.6%, 58.5% and 29.4% of patients before NAC. Discordance in ER, PgR and HER2 status between before and after NAC were 9.3% (4.9% gain; 4.4% loss), 18.6% (6.6% gain; 12.0% loss) and 10.0% (2.8% gain; 7.2% loss), respectively. The rate of HER2 loss was significantly higher in patients treated with trastuzumab, when compared with patients without trastuzumab (31.7% vs. 0%, P = 0.028). Patients with a loss in ER status after NAC tended towards a worse disease-free survival (DFS) compared with patients who maintained the ER positivity (14.7 vs. 37.9 months, P = 0.196). Conversely, a loss in PgR status did not correlate with worse DFS (42.3 vs.42.5 months, P = 0.495). The median Ki67 status was significantly decreased after NAC (25.0% vs. 4.5%; P < 0.001). Among patients with high Ki67 status before NAC, clinical response rate was significantly higher in the group with decreased Ki67 status to low level after NAC, when compared with the group which maintained high Ki67 status (93.9% vs. 50.0%, P = 0.001). Patients with concordant-high Ki67 status had a significantly worse DFS compared with patients with concordant-low Ki67 status (8.7 vs. 22.5 months; P = 0.011).
These data suggested that biomarker status on residual disease after NAC might be helpful in selecting patients at different risk of relapse.
Teikyo University School of Medicine
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All authors have declared no conflicts of interest.