title: Tumour-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to neoadjuvant chemotherapy of aggressive breast cancer.
abstract: BACKGROUND
  Tumour-infiltrating lymphocytes (TILs) can be used to monitor the immune response, and are important in predicting treatment responses and outcomes for various types of cancer. Recently, specific TIL subsets have been reported to be clinically useful in predicting treatment responses. The CD8+/FOXP3+ TIL ratio (CFR) may be a more sensitive indicator for monitoring immune function. This study investigated the clinical significance and value of CFR as a biomarker to predict treatment responses to neoadjuvant chemotherapy for breast cancer.
  
  
  METHODS
  Patients with resectable early-stage breast cancer treated with neoadjuvant chemotherapy at Osaka City University Hospital, Japan, between 2007 and 2013 were included. Oestrogen receptor, progesterone receptor, human epidermal growth factor receptor (HER) 2, Ki-67, CD8 and FOXP3 status were assessed by immunohistochemistry, and correlated with pathological complete response (pCR).
  
  
  RESULTS
  A total of 177 patients were included, of whom 90 had a high CFR and 87 a low CFR. Triple-negative breast cancer (TNBC) was more common in the high-CFR group than in the low-CFR group (46 versus 23 per cent; P = 0·002), as was HER2-enriched breast cancer (HER2BC) (27 versus 14 per cent; P = 0·033). Among these patients, the pCR rate was significantly higher in the high-CFR group than in the low-CFR group (TNBC: P = 0·022; HER2BC: P < 0·001). In multivariable analysis high-CFR status was an independent predictor of a favourable prognosis: hazard ratio 0·24 (95 per cent c.i. 0·05 to 0·72; P = 0·015) for TNBC and 0·10 (0·10 to 0·90; P = 0·041) for HER2BC.
  
  
  CONCLUSIONS
  The CFR may be a useful biomarker to predict treatment response to neoadjuvant therapy in aggressive breast cancer subtypes, such as TNBC and HER2BC.
authors.affiliation: Departments of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Asano
authors.affiliation: Departments of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kashiwagi
authors.affiliation: Departments of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Goto
authors.affiliation: Departments of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kurata
authors.affiliation: Departments of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Noda
authors.affiliation: Departments of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takashima
authors.affiliation: Departments of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Onoda
authors.affiliation: Departments of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Departments of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohsawa
authors.affiliation: Departments of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008408:Mastectomy; D015412:Mastectomy, Segmental; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C418974:FOXP3 protein, human; C508053:ERBB2 protein, human