title: Outcomes of special histotypes of breast cancer after adjuvant endocrine therapy with letrozole or tamoxifen in the monotherapy cohort of the BIG 1-98 trial.
abstract: BACKGROUND
  We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial.
  
  
  METHODS
  The intention-to-treat BIG 1-98 monotherapy cohort (5 years of therapy with tamoxifen or letrozole) included 4922 women, of whom 4091 had central pathology review. Histotype groups were defined as: mucinous (N = 100), tubular/cribriform (N = 83), ductal (N = 3257), and other (N = 651). Of 183 women with either mucinous or tubular/cribriform tumors, 96 were randomly assigned to letrozole and 87 to tamoxifen. Outcomes assessed were disease-free survival (DFS), overall survival (OS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI). Median follow-up in the analytic cohort was 8.1 years.
  
  
  RESULTS
  Women with tubular/cribriform breast cancer had the best outcomes for all end points compared with the other three histotypes, and had less breast cancer recurrence (97.5% 5-year BCFI) than those with mucinous (93.5%), ductal (88.9%), or other (89.9%) histotypes. Patients with mucinous or tubular/cribriform carcinoma had better DRFI (5-year rates 97.8% and 98.8%, respectively) than those with ductal (90.9%) or other (92.1%) carcinomas. Within the subgroup of women with special histotypes, we observed a nonsignificant increase in the hazard of breast cancer recurrence with letrozole [hazard (letrozole versus tamoxifen): 3.31, 95% confidence interval 0.94-11.7; P = 0.06].
  
  
  CONCLUSIONS
  Women with mucinous or tubular/cribriform breast cancer have better outcomes than those with other histotypes, although the observation is based on a limited number of events. In postmenopausal women with these histotypes, the magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with mucinous or tubular/cribriform disease.
  
  
  BACKGROUND
  NCT00004205.
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan, Italy elisabetta.munzone@ieo.it.
authors.forename: E
authors.initials: E
authors.lastname: Munzone
authors.affiliation: Department of Biostatistics and Computational Biology, International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute, Boston, USA.
authors.forename: A
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.affiliation: Institute of Cancer Sciences, Glasgow University, Glasgow.
authors.forename: B A
authors.initials: BA
authors.lastname: Gusterson
authors.affiliation: Southern General Hospital, Glasgow, UK.
authors.forename: E
authors.initials: E
authors.lastname: Mallon
authors.affiliation: Department of Pathology and Laboratory Medicine, IBCSG Central Pathology Laboratory, European Institute of Oncology, and University of Milan, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.affiliation: Breast Center, Kantonsspital, St Gallen Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Thürlimann
authors.affiliation: Danish Breast Cancer Cooperative Group (DBCG), Rigshospitalet, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Ejlertsen
authors.affiliation: Department of Pathology, Institut Bergonié, Bordeaux.
authors.forename: G
authors.initials: G
authors.lastname: MacGrogan
authors.affiliation: Department of Pathology, Val d'Aurelle Cancer Institute, Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Bibeau
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: Lelkaitis
authors.affiliation: International Breast Cancer Study Group (IBCSG) Statistical Center.
authors.forename: K N
authors.initials: KN
authors.lastname: Price
authors.affiliation: Department of Biostatistics and Computational Biology, International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute, Boston, USA Harvard T.H. Chan School of Public Health, Harvard Medical School, Frontier Science and Technology Research Foundation, Boston, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.affiliation: International Breast Cancer Study Group, Bern, Switzerland University of Sydney, Sydney, Australia.
authors.forename: A S
authors.initials: AS
authors.lastname: Coates
authors.affiliation: Program of Breast Health, European Institute of Oncology, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Colleoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000188:drug therapy; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy; D009570:Nitriles / Q000008:administration & dosage*; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole
keywords: breast cancer; cribriform; letrozole; mucinous; tamoxifen; tubular