title: Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer.
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.
  
  
  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).
  
  
  CONCLUSIONS
  One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure.
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, Laboratorio di Oncologia Molecolare Senologica, A.O. Istituti Ospitalieri di Cremona, Viale Concordia 1, Cremona 26100, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Allevi
authors.forename: C
authors.initials: C
authors.lastname: Strina
authors.forename: D
authors.initials: D
authors.lastname: Andreis
authors.forename: V
authors.initials: V
authors.lastname: Zanoni
authors.forename: L
authors.initials: L
authors.lastname: Bazzola
authors.forename: S
authors.initials: S
authors.lastname: Bonardi
authors.forename: C
authors.initials: C
authors.lastname: Foroni
authors.forename: M
authors.initials: M
authors.lastname: Milani
authors.forename: M R
authors.initials: MR
authors.lastname: Cappelletti
authors.forename: F
authors.initials: F
authors.lastname: Gussago
authors.forename: S
authors.initials: S
authors.lastname: Aguggini
authors.forename: R
authors.initials: R
authors.lastname: Giardini
authors.forename: M
authors.initials: M
authors.lastname: Martinotti
authors.forename: S B
authors.initials: SB
authors.lastname: Fox
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
authors.forename: A
authors.initials: A
authors.lastname: Bottini
authors.forename: A
authors.initials: A
authors.lastname: Berruti
authors.forename: D
authors.initials: D
authors.lastname: Generali
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000378:metabolism; D000077289:Letrozole; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D019394:Ki-67 Antigen; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D000077289:Letrozole