title: Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: predictive value of centrally reviewed expression of estrogen and progesterone receptors--International Breast Cancer Study Group.
abstract: OBJECTIVE
  To centrally assess estrogen receptor (ER) and progesterone receptor (PgR) levels by immunohistochemistry and investigate their predictive value for benefit of chemo-endocrine compared with endocrine adjuvant therapy alone in two randomized clinical trials for node-negative breast cancer.
  
  
  METHODS
  International Breast Cancer Study Group Trial VIII compared cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for 6 cycles followed by endocrine therapy with goserelin with either modality alone in pre- and perimenopausal patients. Trial IX compared three cycles of CMF followed by tamoxifen for 5 years versus tamoxifen alone in postmenopausal patients. Central Pathology Office reviewed 883 (83%) of 1,063 patients on Trial VIII and 1,365 (82%) of 1,669 on Trial IX and determined ER and PgR by immunohistochemistry. Disease-free survival (DFS) was compared across the spectrum of expression of each receptor using the Subpopulation Treatment Effect Pattern Plot methodology.
  
  
  RESULTS
  Both receptors displayed a bimodal distribution, with substantial proportions showing no staining (receptor absent) and most of the remainder showing a high percentage of stained cells. Chemo-endocrine therapy yielded DFS superior to endocrine therapy alone for patients with receptor-absent tumors, and in some cases also for those with low levels of receptor expression. Among patients with ER-expressing tumors, additional prediction of benefit was suggested in absent or low PgR in Trial VIII but not in Trial IX.
  
  
  CONCLUSIONS
  Low levels of ER and PgR are predictive of the benefit of adding chemotherapy to endocrine therapy. Low PgR may add further prediction among pre- and perimenopausal but not postmenopausal patients whose tumors express ER.
authors: Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy. giuseppe.viale@ieo.it
authors: Giuseppe
authors: G
authors: Viale
authors: Meredith M
authors: MM
authors: Regan
authors: Eugenio
authors: E
authors: Maiorano
authors: Mauro G
authors: MG
authors: Mastropasqua
authors: Rastko
authors: R
authors: Golouh
authors: Tiziana
authors: T
authors: Perin
authors: Robert W
authors: RW
authors: Brown
authors: Anikó
authors: A
authors: Kovács
authors: Komala
authors: K
authors: Pillay
authors: Christian
authors: C
authors: Ohlschlegel
authors: Stephen
authors: S
authors: Braye
authors: Piergiovanni
authors: P
authors: Grigolato
authors: Tiziana
authors: T
authors: Rusca
authors: Richard D
authors: RD
authors: Gelber
authors: Monica
authors: M
authors: Castiglione-Gertsch
authors: Karen N
authors: KN
authors: Price
authors: Aron
authors: A
authors: Goldhirsch
authors: Barry A
authors: BA
authors: Gusterson
authors: Alan S
authors: AS
authors: Coates
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008593:Menopause; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000188:drug therapy; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D017273:Goserelin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate