Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial.
OBJECTIVE
To determine the relationship between quantitative estrogen-receptor (ER) and progesterone-receptor (PgR) expression and human epidermal growth factor 2 (HER-2) status with time to recurrence (TTR) in postmenopausal women with hormone receptor-positive primary breast cancer treated with anastrozole or tamoxifen as adjuvant therapy.


METHODS
Formalin-fixed, paraffin-embedded tumor blocks were retrospectively collected from patients in the monotherapy arms of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial and centrally tested for ER, PgR and HER-2. ER and PgR were scored using continuous scales and HER-2 was scored as 0 to 3+ with 2+ cases being analyzed by fluorescence in situ hybridization.


RESULTS
Blocks were collected from 2,006 of 5,880 eligible patients. Tissue was assessable and ER and/or PgR positivity confirmed centrally in 1,782 cases. In these, TTR was longer for anastrozole than for tamoxifen by a similar extent to that in the overall trial. None of the three biomarkers identified a set of patients with differential benefit from anastrozole over tamoxifen. Patients with low ER, low PgR, and high HER-2 expression had a poorer prognosis with either drug. Only 2.6% of patients in the highest quartile of PgR experienced recurrence after 5 years, compared with 13.2% in the lowest quartile.


CONCLUSIONS
Quantitative expression of ER and PgR and HER-2 status did not identify patients with differential relative benefit from anastrozole over tamoxifen: TTR was longer for anastrozole than for tamoxifen in all molecular subgroups. Low ER or PgR or high HER-2 expression are associated with a high risk of recurrence with either anastrozole or tamoxifen.
Dowsett
Mitch
M
Academic Department of Biochemistry, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, United Kingdom. mitch.dowsett@icr.ac.uk
Allred
Craig
C
Knox
Jill
J
Quinn
Emma
E
Salter
Janine
J
Wale
Chris
C
Cuzick
Jack
J
Houghton
Joan
J
Williams
Norman
N
Mallon
Elizabeth
E
Bishop
Hugh
H
Ellis
Ian
I
Larsimont
Denis
D
Sasano
Hironobu
H
Carder
Pauline
P
Cussac
Antonio Llombart
AL
Knox
Fiona
F
Speirs
Valerie
V
Forbes
John
J
Buzdar
Aman
A
D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology* / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage; D017698:Postmenopause; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
D000077384:Anastrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D014230:Triazoles