title: Clinicopathological features of early failure of neoadjuvant chemotherapy in locally advanced breast cancer.
abstract: OBJECTIVE
  Neoadjuvant chemotherapy (NAC) has been used widely in patients with locally advanced breast cancer (LABC). NAC has the added advantage of increasing breast conservation rates with similar disease-free and overall survival compared with adjuvant chemotherapy. A subset of patients receiving NAC experience early failure during the course of therapy or within a short period after breast surgery. There are no established predictors of early therapy failure in LABC patients who received NAC. This study was performed to identify patient groups that may not benefit from NAC.
  
  
  METHODS
  This study was a retrospective single-centre study. Patients with LABC (cT2-4N0-3) were recruited into this analysis from January 2005 to December 2011 at the Samsung Medical Center. The cohort included 397 patients. The clinicopathological characteristics and disease courses of the patients whose disease progressed within 1 year of receiving neoadjuvant chemotherapy were analysed.
  
  
  RESULTS
  Thirty-eight of the 397 patients (9.6 %) exhibited progression within 1 year after receiving neoadjuvant chemotherapy. Seven of the 37 patients (18.9 %) with a known disease subtype, as assessed by IHC, were hormone receptor (HR)+ and HER2-. The number of HER2+ irrespective of HR status and triple-negative breast cancer (TNBC) patients was 13 (35.1 %) and 17 (45.9 %), respectively. Pathological complete remission was found in two patients (5.3 %, 2/38). The median overall survival period was 20.4 months (95 % CI 17.3-23.5) in patients with early failure and 69.1 months (95 % CI 52.7-85.4) in the late failure group (p < 0.001), with a median follow-up period of 35.7 months. The central nervous system (CNS) was the most common site of first distant metastasis (31.6 %, 12/38), and CNS failure was more common in patients with early failure compared with those with late failure (32.4 vs. 3.1 %, p = 0.000). HER2 positivity or TNBC and the presence of lymphovascular invasion were independent predictors of early failure.
  
  
  CONCLUSIONS
  A fraction of patients with LABC may not benefit from neoadjuvant chemotherapy. The results of our study suggest that early failure marks a high-risk group of patients who require innovative therapeutic approaches.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Moon Ki
authors.initials: MK
authors.lastname: Choi
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Park
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kil
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000556:secondary; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D017211:Treatment Failure; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human