title: Activated Caspase 3 Expression in Remnant Disease After Neoadjuvant Chemotherapy May Predict Outcomes of Breast Cancer Patients.
abstract: A number of studies have indicated that patients obtaining a pathological complete response (pCR) from neoadjuvant chemotherapy (NAC) have a good prognosis; however, prognostic factors for non-pCR patients are not yet well-established. By examining remnant cancer in non-pCR patients, the expression of cleaved Caspase 3 (Casp3), an activated apoptotic marker, was immunohistochemically investigated to determine whether this protein has the potential to serve as a novel marker for predicting patient outcomes.
  
  
  
  We investigated 218 patients with invasive breast cancer who received NAC and underwent surgery during the 2006 through 2008 period at our institution. Following surgery, standard adjuvant endocrine therapy was administered if a tumor was hormone receptor-positive. Casp3 was evaluated in remnant cancer based on the number of positive cells in five high-power fields.
  
  
  
  pCR was obtained in 49 patients, and 50 of the 169 non-pCR patients developed recurrences during the median 82-month observation period. We found large tumor size, lymph node involvement, lymph vessel invasion, estrogen receptor-negative, progesterone receptor-negative, high Ki67 and high Casp3 expression to be factors related to tumor recurrence. A logistic regression model revealed that lymph node involvement, as well as high Ki67 and Casp3, to be factors independently predicting recurrence, while lymph vessel invasion and high Ki67 expression were found to be related to breast cancer mortality.
  
  
  
  Patients with remnant cancer showing high Casp3 expression had poor outcomes. Our results showed that Casp3 is a potential prognostic marker for non-pCR patients.
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Himuro
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan. yoshiyahorimoto@hotmail.com.|Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan. yoshiyahorimoto@hotmail.com.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Horimoto
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arakawa
authors.affiliation: Clinical Research Support Center, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Joe
authors.initials: J
authors.lastname: Matsuoka
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Tokuda
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tanabe
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C505407:CASP3 protein, human; D053148:Caspase 3