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receptors and distinct patterns of
breast cancer relapse. Breast Cancer
Res Treat. 2003;78:105-118.
Survival After Adjuvant
Oophorectomy and Tamoxifen
in Operable Breast Cancer in
Premenopausal Women
Love RR, Van Dinh N, Quy TT, et al (Ohio
State Univ, Columbus, OH)
J Clin Oncol 26:253-257, 2008
Purpose.—Worldwide, approximately 750,000 new cases of breast
cancer are diagnosed annually in
premenopausal women with limited
economic resources. Longer-term
survival benefits from adjuvant therapies in such women with operable
breast cancer are unknown.
Patients and Methods.—From
1993 to 1999, we recruited 709
premenopausal women with operable
breast cancer to a multisite randomized
clinical trial of adjuvant oophorectomy
and tamoxifen for 5 years or observation and this combined hormonal
therapy on recurrence.
Results.—With a median followup of 7.0 years, disease-free and overall
survival
were
significantly
improved with the adjuvant treatment
(log-rank P ¼.0003 and .0002, respectively). Five year disease-free survival
(DFS) probabilities of 74% and 61%
(95% CI for difference, 7% to 21%)
and overall survival (OS) rates of
78% and 71% (95% CI for difference,
1% to 21%) were observed in the adjuvant and observation groups. Ten-year
DFS probabilities of 62% and 51%
(95% CI for difference, 4% to 22%)
and OS probabilities of 70% and 52%
(95% CI for difference, 6% to 34%)
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6. Korkola JE, DeVries S, Fridlyand J,
et al. Differentiation of lobular
versus ductal breast carcinomas
between adjuvant and observation
groups, respectively, were observed.
In the subset of estrogen receptor–positive patients, 5-year DFS probabilities
were 83% and 61%, and 10-year DFS
probabilities were 66% and 47%,
while 5-year OS probabilities were
88% and 74%, and 10-year OS probabilities were 82% and 49% in the
adjuvant and observation groups,
respectively.
Conclusion.—In premenopausal
women with operable breast cancer
not selected for estrogen receptor status
or with estrogen receptor–positive
tumors, 5- and 10-year DFS and OS
rates are significantly improved
following adjuvant oophorectomy and
tamoxifen.
Love and colleagues made 2
points in their conclusion. First, they
stated that ‘‘the survival of adjuvanttreated patients in this trial.supports use of [surgical oophorectomy
and tamoxifen] in many circumstances.’’ Probably. However, whereas
ovarian function suppression (OFS)
by oophorectomy has clear advantages in a resource-poor population,
its exact role in the treatment of
hormone receptor-positive breast
cancer in premenopausal women
remains unclear. Adjuvant tamoxifen
is now routinely recommended. The
benefit of OFS when added to 5 years
of tamoxifen is unproven. Previous
trials frequently utilized 2 years of
tamoxifen.1 The 1 randomized European Cooperative Oncology Group
trial addressing the issue in nodenegative breast cancer was under-
Breast Diseases: A Year BookÒ Quarterly
Vol 19 No 3 2008
by expression microarray
analysis. Cancer Res. 2003;63:
7167-7175.
powered and did not show a significant benefit.2 Chemotherapy followed
by tamoxifen is commonly recommended in high-risk patients, and the
advantage of adding OFS to this
combination is uncertain. OFS can
add significantly to toxicity and
should not be added without solid
evidence of benefit. The international
Suppression of Ovarian Function
Trial, which randomly assigns
premenopausal women with hormone
receptor–positive breast cancer to
tamoxifen versus OFS plus tamoxifen
versus OFS plus an aromatase
inhibitor, remains open to accrual
and has the potential to answer the
question definitively.
The second conclusion Love and
colleagues drew was that ‘‘the
increase in the hazard function for
recurrence between years 5 and 10
supports investigation of intervention
and treatment strategies directed to
this hazard.’’ Definitely. The risk of
recurrence for women with estrogen
receptor–positive breast cancer after
5 years of tamoxifen therapy remains
substantial. Few data have specifically
addressed the issue in premenopausal
women. In the study by Love and
colleagues, the hazard for recurrence
after year 5 appears to increase for
women who were treated (despite
permanent ovarian function ablation),
whereas women not treated appear to
have a continued decline in risk.
However, the confidence intervals on
these estimates are large. Over time,
an increasing proportion of the
untreated women would naturally
undergo menopause, which may have
influenced their risk of late relapse. A
recent abstract presenting preliminary
results of the Adjuvant Tamoxifen,
Longer against Shorter (ATLAS) trial
suggested that, contrary to previous
publication of smaller trials, the
recurrence rate was lower among
women allocated to continue tamoxifen.3 It would be interesting to see an
analysis of outcomes in the premenopausal women from the ATLAS trial.
G. F. Fleming, MD
P. Francis, MD
Quality of life and qualityadjusted survival (Q-TWiST) in
patients receiving doseintensive or standard dose
chemotherapy for high-risk
primary breast cancer
Bernhard J, Zahrieh D, Zhang JJ, et al
(IBCSG Coordinating Ctr, Bern,
Switzerland; IBCSG Statistical Ctr,
Dana-Farber Cancer Inst, Boston; Harvard
School of Public Health, Boston; et al)
Br J Cancer 98:25-33, 2008
Quality of life (QL) is an important consideration when comparing
adjuvant therapies for early breast
cancer, especially if they differ
substantially in toxicity. We evaluated
QL and Q-TWiST among patients
randomised to adjuvant dose-intensive
epirubicin and cyclophosphamide
administered with filgrastim and
progenitor cell support (DI-EC) or
standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the
duration of chemotherapy toxicity
(TOX), time without disease symptoms
and toxicity (TWiST), and time
following relapse (REL). Patients
scored QL indicators. Mean durations
References
1. Cuzick J, on behalf of the LHRHagonists in Early Breast Cancer
Group. Use of luteinising-hormonereleasing hormone agonsists as
adjuvant treatment in premenopausal
patients with hormone-receptorpositive breast cancer: a metaanalysis of individual patient data
from randomised adjuvant trials.
Lancet. 2007;369:1711-1723.
2. Robert NJ, Wang M, Cella D, et al.
Phase III comparison of tamoxifen
versus tamoxifen with ovarian
for the three transition times were
weighted with patient reported utilities
to obtain mean Q-TWiST. Patients
receiving DI-EC reported worse QL
during TOX, especially treatment
burden (month 3: P < 0.01), but a faster
recovery 3 months following chemotherapy than patients receiving
SD-CT, for example, less coping effort
(P < 0.01). Average Q-TWiST was 1.8
months longer for patients receiving
DI-EC (95% CI, 2.5 to 6.1).
Q-TWiST favoured DI-EC for most
values of utilities attached to TOX and
REL. Despite greater initial toxicity,
quality-adjusted survival was similar
or better with dose-intensive treatment
as compared to standard treatment.
Thus, QL considerations should not be
prohibitive if future intensive therapies
show superior efficacy.
On the basis of well-designed
randomized controlled trials,1-4 highdose chemotherapy (HDC) with stem
cell support has proven to be more
toxic and no more efficacious than
standard-dose chemotherapy for cases
of both high-risk and metastatic breast
cancer. This approach of hitting the
most serious cases of breast cancer
with the most aggressive or intense
ablation in premenopausal women
with axillary node-negative receptorpositive breast cancer < 3 cm
[abstract 16]. Proc Am Soc Clin
Oncol. 2003;22:5.
3. Peto R, Davies C, on behalf of the
ATLAS Collaboration. ATLAS
(Adjuvant Tamoxifen, Longer
Against Shorter): international
randomized trial of 10 versus 5 years
of adjuvant tamoxifen among 11,500
women-preliminary results [abstract
48]. Breast Cancer Res Treat. 2008;
109:585.
form of chemotherapy was initially
viewed as promising based on the
results of single-arm trials demonstrating results that appeared superior
to historical outcomes from standard
therapy.5 Accrual to randomized trials
was difficult due to patients’ and
physicians’ preferences, with the
majority of patients treated offprotocol or in single-arm studies.6
In this context, 2 recent publications, one by Bernhard and colleagues
in the British Journal of Cancer and
one by Crump and colleagues1 in the
Journal of Clinical Oncology present
results that are important both for the
clinical information they provide and
for their fulfillment of the obligation
between researcher and trial participants to analyze and publicize trial
results, even when the trial is negative.
The article by Crump and
colleagues presented the results of
a randomized multicenter trial conducted by the National Cancer Institute Clinical Trials Group, in which
386 patients with metastatic breast
cancer were treated with induction
chemotherapy, and those with
a significant response (224) wererandomized to HDC versus standarddose chemotherapy. Although this trial
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