Breast (Oct 2021)

Clinicopathological response to neoadjuvant therapies and pathological complete response as a biomarker of survival in human epidermal growth factor receptor-2 enriched breast cancer – A retrospective cohort study

  • Matthew G. Davey,
  • Eoin Kerin,
  • C. O'Flaherty,
  • Elizabeth Maher,
  • Vinitha Richard,
  • Peter McAnena,
  • Ray P. McLaughlin,
  • Karl J. Sweeney,
  • Michael K. Barry,
  • Carmel M. Malone,
  • William Wyns,
  • Osama Soliman,
  • Nicola Miller,
  • Maccon M. Keane,
  • Aoife J. Lowery,
  • Michael J. Kerin

Journal volume & issue
Vol. 59
pp. 67 – 75

Abstract

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Background: Human epidermal growth factor receptor-2 (HER2) is overexpressed in 20–25% of breast cancers. Complete eradication of disease following neoadjuvant therapies and chemotherapy has been referred to as pathological complete response (pCR). Aims: To determine clinicopathological predictors of pCR to neoadjuvant therapies and to evaluate pCR as a surrogate to enhanced survival. Methods: Consecutive female patients with HER2 positive (HER+) breast cancer managed surgically in a single institution between 2005 and 2015 were included. Descriptive statistics and binary logistic regression were used to determine predictors of pCR. Appraisal of pCR as a predictor of survival was performed using Kaplan-Meier curves and Cox regression analysis. Results: 451 patients were included with a mean age of 56.6 ± 13.4 years (range 23–95). Disease-free (DFS) and overall survival (OS) was 82.3% (371/451) and 82.6% (376/451) respectively with a median follow-up of 108.0 months (range 3–184.0). 118 were treated in the neoadjuvant setting (26.2%): tumour size <50 mm (Odds Ratio (OR): 12.156, P = 0.023) and progesterone receptor negativity (OR: 2.762, P = 0.008) independently predicted breast pCR, while ductal carcinoma (OR: 3.203, P = 0.030) and grade 3 disease (OR: 2.788, P = 0.018) predicted axillary pCR. Both breast and axillary pCR predicted enhanced DFS (Hazard Ratio (HR): 0.470 & HR: 0.449) and OS (HR: 0.383 & HR: 0.307). Axillary pCR independently predicted improved OS (HR: 0.326). Conclusion: pCR is sensitive biomarker and surrogate to survival outcomes in HER2+ breast cancer. Patients likely to achieve pCR may be predicted from traditional clinicopathological characteristics and molecular parameters.

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