A randomised study of the effects of letrozole and anastrozole on oestrogen receptor positive breast cancers in postmenopausal women.
BACKGROUND
Changes in proliferation as measured by Ki67 occur within 14 days of starting treatment with an aromatase inhibitor and these changes have been shown to be predictors of long term outcome. This study aimed to compare changes in proliferation following 14 days of treatment with anastrozole and letrozole.


METHODS
Two hundred and six women with 209 estrogen receptor (ER) positive operable breast cancers (three bilateral) were randomly allocated to receive either 14 days treatment with 2.5 mg of letrozole or 1 mg of anastrozole prior to surgery. Changes in expression of estrogen (ER) and progesterone receptors (PgR) as assessed by ALLRED scores and proliferation as assessed by Ki67 were analysed. The HER2 status of each tumour was also assessed using a combination of the Hercept test and FISH.


RESULTS
Both letrozole and anastrozole reduced ER expression (ALLRED score) by a mean of 0.32 (0.20-0.44), P<0.001 and PgR fell by a mean of 2.54 (2.20-2.89) P<0.0001. Letrozole reduced proliferation from a geometric mean of 6.37% to 0.81%, P<0.0001 and anastrozole reduced proliferation from 5.81% to 0.77%, P<0.0001. There was no differences between drugs in the fall in ER, PgR or proliferation. Both letrozole and anastrozole produced significant falls in proliferation in both HER2 positive and HER2 negative cancers, all P<0.001.


CONCLUSIONS
14 days of both letrozole and anastrozole reduces proliferation, ER and PgR expression. No significant difference between these two drugs was identified.
Murray
J
J
Edinburgh Breast Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
Young
O E
OE
Renshaw
L
L
White
S
S
Williams
L
L
Evans
D B
DB
Thomas
J St J
JS
Dowsett
M
M
Dixon
J M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D011980:Receptors, Progesterone / Q000096:biosynthesis; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D009570:Nitriles; D011980:Receptors, Progesterone; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole