Annual Meeting Proceedings Part 1 - American Society of Clinical ...

86s Cancer Prevention/Epidemiology
1500 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
A phase III prevention trial of low-dose tamoxifen in HRT users: The HOT
trial. Presenting Author: Bernardo Bonanni, European Institute of Oncology,
Milan, Italy
Background: Primary prevention trials have shown that tamoxifen (T) lowers
ER� breast cancer (BC) incidence, but adverse events are a barrier to its
broad use. The Italian Tamoxifen Prevention Trial showed a positive
risk/benefit ratio in the subgroup of hormone replacement therapy (HRT)
users in the T arm, with fewer BC and no cardiovascular disease (CVD)
excess. In a dose-ranging study, T 5 mg/day showed a favorable biomarker
modulation in HRT users. We conducted a multicentre, phase III, BC
prevention trial in current or de novo HRT users, randomized to either T 5
mg/day or placebo (P) for 5 yrs, with 5yrs follow-up. Methods: The study was
powered to detect a 40% decrease of BC on T from an annual rate of
4/1000 on P with 20% dropout and 5y recruitment. All analyses were
performed on ITT basis. The cumulative incidence of events was determined
using Kaplan-Meier methods. The two treatment groups were
compared by using the log-rank test. Hazard ratios (HRs) and 95%
confidence intervals were obtained using Cox proportional regression
model. All P values were two-sided. Results: Due to the WHI-HRT trial
results, recruitment was lower than anticipated, with a total of 1884
subjects being randomized (946 P and 938 T arm, respectively). 79% were
�50 years old at study entry. 66% were normal weight, 21% were
hysterectomized; 80% were already on HRT at baseline, 53% were on
trasdermal route and 28% had 5y-Gail risk�1.5%. At 7.7y mean follow-up,
43 BC were diagnosed, 24 (annual rate 4.1/1000) on P and 19 (3.3/1000)
on T (HR 0.80, 95%CI 0.44-1.46). The efficacy of T was greater in
luminal-A type (HR�0.32, 95% CI, 012-086). CVD events were rare
(including 1 DVT on T), with no statistical difference between arms. A HR of
4.74 (95% CI, 1.96-11.5) was observed for benign endometrial polyps,
but no increase of uterine cancers (3 on P vs 1 on T). Menopausal
symptoms were more frequent on T, whereas headache was less frequent on
T. Conclusions: The combination of low-dose T and HRT is safe and provides
a promising way to retain the benefits while reducing the risks of either
agent. While the insufficient power of our study prevents firmer conclusions,
it supports further studies of low-dose T in the prevention setting.
1502 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
BMI, long-term changes in BMI, and risk of cancer mortality in a large
cohort study. Presenting Author: Niloofar Taghizadeh, Department of
Epidemiology, University Medical Center Groningen, Groningen, Netherlands
Background: There are indications of an association between Body Mass
Index (BMI) and risk of different cancer types. There is dispute whether this
association differs between males and females. Methods: We studied the
association of BMI at the first survey with risk of mortality from the most
common types of cancer (lung, colorectal, breast and prostate cancer) in a
large general population-based cohort study (Vlagtwedde-Vlaardingen,
1965-1990) with follow-up on mortality status until 2009. Additionally,
we assessed this association based on tertiles of the annual change in BMI
(defined as the difference between BMI at last survey and first survey
divided by the time between last and first survey). We used 3 categories of
BMI (� 25 kg/m2 , 25-30 kg/m2 , and � 30 kg/m2 ) and changes in BMI
(� 0.02 kg/m2 /yr, 0.02-0.2 kg/m2 /yr, and � 0.2 kg/m2 /yr) in the analyses.
The multivariate Cox regression model was adjusted for age, smoking,
gender. Analyses were additionally stratified by gender and smoking.
Results: Among all 8645 subjects, 1194 died due to cancer (lung cancer:
275; colorectal cancer: 134; breast cancer: 117; prostate cancer: 83).
Mortality from all types of cancer was significantly increased in subjects
with BMI � 30 kg/m2 (HR (95 % CI)) � 1.22 (1.00-1.48)), especially in
females (1.38 (1.06-1.81)) and in never smokers (1.39 (1.02-1.90)).
Prostate cancer mortality was significantly increased in males with BMI
25-30 kg/m2 (2.04 (1.90-3.83)) and � 30 kg/m2 (2.61 (1.02-6.67)). This
association between prostate cancer mortality and BMI was higher in
smokers. Lung cancer mortality risk was decreased in subjects with BMI
25-30 kg/m2 (0.71 (0.54-0.93)) and � 30 kg/m2 (0.82 (0.50-1.32)),
especially in males, in smokers, and in smoking males. There were no
significant associations between BMI and colorectal or breast cancer
mortality nor between change in BMI and mortality from all analyzed types
of cancer. Conclusions: We show that an increase in BMI is associated with
an increased risk of mortality from all types of cancer in females and with
an increased mortality risk from prostate cancer in males but with a
decreased lung cancer mortality risk, especially in males. More research is
needed into the biological mechanisms that link BMI to cancer.
1501 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Estrogen plus progestin (E�P) and breast cancer incidence and mortality.
Presenting Author: Rowan T. Chlebowski, Los Angeles Biomedical Research
Institute at Harbor-UCLA Medical Center, Torrance, CA
Background: In the WHI clinical trial, E�P increased both breast cancer
incidence and breast cancer mortality (JAMA 2010;304:1684). In contrast,
breast cancers associated with E�P use in most observational studies
have a more favorable prognosis. To address differences, a cohort of WHI
Observational Study participants with characteristics similar to the WHI
clinical trial was identified to examine E�P association with invasive breast
cancer incidence and outcome. Methods: 41,449 postmenopausal women
with no prior hysterectomy and mammogram negative for breast cancer � 2
years before who either were not hormone users (25,328) or were using
E�P (16,121) were identified. Breast cancers were verified by centralized
medical record review. Adjusted Cox proportional hazard regression was
used to calculate hazard ratios (HRs) with 95% confidence intervals (CI).
Additional analyses adjusted for breast cancer screening, censoring participants
for incidence analyses who had a � 2 year interval without a
mammogram. Results: After a mean (SD) follow-up 11.3 (3.1) years, 2,236
breast cancers were diagnosed. Breast cancer incidence was higher in E�P
users (0.60% vs 0.42%, annualized rate, respectively: HR 1.55, 95% CI
1.41-1.70, P�0.001). Screening adjusted analyses had stronger breast
cancer association (0.63% vs 0.39%, HR 1.72, 95% CI 1.54-1.93;
P�0.001). Survival following breast cancer, measured from diagnosis
date, was similar in E�P users and non-users (HR 0.95, 95% CI
0.74-1.23). Breast cancer mortality, analyzed from cohort entry date, are
shown in the table. Conclusions: E�P use is associated with increased
breast cancer incidence. As breast cancer prognosis following diagnosis on
E�P is similar to that of nonusers, the higher incidence with E�P leads to
increased breast cancer mortality.
Deaths from breast cancer HR (95% CI) P values
Screening adjusted*
No 1.32 (0.90-1.93) 0.15
Yes 1.54 (1.00-2.39) 0.052
Deaths after breast cancer diagnosis
Screening adjusted *
No 1.65 (1.29-2.12) �0.001
Yes 2.21 (1.66-2.94) �0.001
* Censored for breast cancer diagnosis when time w/o mammogram � 2 yrs.
1503 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Long-term therapy with thiazolidinediones and the risk of bladder cancer: A
cohort study. Presenting Author: Ronac Mamtani, Perelman School of
Medicine at the University of Pennsylvania, Philadelphia, PA
Background: The US Food and Drug Administration and other regulatory
agencies recently warned prescribers that use of pioglitazone, a thiazolidinedione
(TZD), may increase the risk of bladder cancer. France and Germany
removed the drug from their markets, although the rest of Europe did not.
However, no information was available about the risk from alternative TZDs.
We aimed to compare bladder cancer risk over time with use of TZDs
relative to sulfonylureas (SUs), and between pioglitazone and rosiglitazone.
Methods: We conducted a cohort study of patients with type 2 diabetes who
initiated treatment with a TZD or SU using The Health Improvement
Network (2000-2010), a UK general practitioner medical record database.
Incident cancers within the database were identified. We computed hazard
ratios (HRs) of bladder cancer for TZDs in comparison to the reference
group of SU users. Results: There were 60 incident diagnoses of bladder
cancer in the TZD cohort (n�18,459) and 137 in the SU cohort
(n�41,396). There was no significant difference in bladder cancer risk
between the cohorts (HR 0·93, [95% CI 0·68-1·29]), but most use was
short-term use. In contrast, the risk of bladder cancer increased with
increasing time since initiation of TZD versus SU therapy (HRs 1·15, 1·40,
and 1·72 for 3-4, 4-5, and � 5 years, respectively; P-trend�0·033).
Bladder cancer risk also increased with increasing time since initiation of
pioglitazone (P-trend�0·001) and rosiglitazone (P-trend�0·006). Direct
comparison of pioglitazone to rosiglitazone did not demonstrate significant
differences in cancer risk with increasing time since initiation (Ptrend�0·12)
or duration of therapy (P-trend�0·75). Conclusions: Longterm
TZD therapy is associated with an increased risk of bladder cancer,
which appears to be a class effect.
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