Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen.
OBJECTIVE
The National Cancer Institute of Canada Clinical Trials Group MA.17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET.


METHODS
This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding.


RESULTS
There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [HR], 0.37; 95% CI, 0.23 to 0.61; P < .0001) and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P = .004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2% v 3.1%, P = .02).


CONCLUSIONS
Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen.
Goss
Paul E
PE
Massachusetts General Hospital Cancer Center, 55 Fruit St, Lawrence House, LRH-302, Boston, MA 02114, USA. pgoss@partners.org
Ingle
James N
JN
Pater
Joseph L
JL
Martino
Silvana
S
Robert
Nicholas J
NJ
Muss
Hyman B
HB
Piccart
Martine J
MJ
Castiglione
Monica
M
Shepherd
Lois E
LE
Pritchard
Kathleen I
KI
Livingston
Robert B
RB
Davidson
Nancy E
NE
Norton
Larry
L
Perez
Edith A
EA
Abrams
Jeffrey S
JS
Cameron
David A
DA
Palmer
Michael J
MJ
Tu
Dongsheng
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos; D017698:Postmenopause; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
D000970:Antineoplastic Agents; D009570:Nitriles; D010919:Placebos; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole