Here's the paper showing no additional benefit after 5 years of Tamoxifen:
J Natl Cancer Inst 1996 Nov 6;88(21):1529-1542
Five versus more than five years of tamoxifen therapy for
breast cancer patients with negative lymph nodes and
estrogen receptor-positive tumors.
Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham DL, Wolmark N, Costantino J,
Redmond C, Fisher ER, Bowman DM, Deschenes L, Dimitrov NV, Margolese RG,
Robidoux A, Shibata H, Terz J, Paterson AH, Feldman MI, Farrar W, Evans J, Lickley
HL
University of Pittsburgh School of Medicine, PA 15261, USA.
BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a
randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of
adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen
receptor-positive tumors and no axillary lymph node involvement. The findings indicated that
tamoxifen therapy provided substantial benefit to patients with early stage disease. However,
questions arose about how long the observed benefit would persist, about the duration of therapy
necessary to maintain maximum benefit, and about the nature and severity of adverse effects from
prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10
years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy
were compared. METHODS: In the trial, patients were initially assigned to receive either tamoxifen
at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease
free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n =
322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the
same protocol eligibility requirements as the randomly assigned patients were registered to receive
tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were
also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n =
249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients
reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to
either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival,
and distant disease-free survival (relating to failure at distant sites) were estimated by use of the
Kaplan-Meier method; differences between the treatment groups were assessed by use of the
logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by
use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through
10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001;
relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P <
.0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative
risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive
tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years
of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of
contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of
tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free
survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01)
were found for those who discontinued tamoxifen treatment. Survival was 96% for those who
discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08).
A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5
years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not
increased with tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5
years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is
obtained from continuing tamoxifen therapy for more than 5 years.
Publication Types:
Clinical trial
Multicenter study
Randomized controlled trial
Comments:
Comment in: J Natl Cancer Inst 1996 Nov 6;88(21):1510-2
Comment in: J Natl Cancer Inst 1997 Nov 5;89(21):1631-2
PMID: 8901851, UI: 97057512 |
