Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer

Br J Cancer. 2013 Apr 30;108(8):1587-92. doi: 10.1038/bjc.2013.151. Epub 2013 Apr 11.

Abstract

Background: The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response (pathCR) and assess Ki-67 expression as an early predictor of response.

Patients and methods: This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer (clinical stage ≥ T2, N0-1), from three sequential cohorts (cohort A of 40, cohort B of 40 and cohort C of 40 patients, respectively) based on different duration of the neoadjuvant letrozole. Biological markers such as ER, progesterone receptor, HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery.

Results: A total of 89 patients (75.4%) achieved an objective response with 44 (37.3%) clinical CRs and 45 (38.1%) partial responses. The clinical CRs were significantly observed in cohort C (23 out of 40 patients, 57.5%) and B (16 out of 38 patients, 42.1%) compared with cohort A (5 out of 40 patients, 12.5%) (P-value for trend <0.001). Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts. The pathCR rate was significantly more frequent in cohort C (7 out of 40 patients, 17.5%) than in cohort A (1 out of 40 patients, 2.5%) and B (2 out of 40 patients, 5.0%) (P-value for trend <0.04).

Conclusion: One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Aromatase Inhibitors / administration & dosage
  • Aromatase Inhibitors / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Drug Administration Schedule
  • Female
  • Humans
  • Ki-67 Antigen / biosynthesis
  • Ki-67 Antigen / metabolism
  • Letrozole
  • Neoadjuvant Therapy
  • Nitriles / administration & dosage*
  • Nitriles / adverse effects
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Triazoles / administration & dosage*
  • Triazoles / adverse effects

Substances

  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Ki-67 Antigen
  • Nitriles
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Triazoles
  • Letrozole