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

1555 General Poster Session (Board #3E), Sat, 1:15 PM-5:15 PM
Variants of uncertain significance in BRCA testing: Impact on risk perception,
worry, prevention, and counseling. Presenting Author: Tracy Graham,
Sunnybrook Hospital, Toronto, ON, Canada
Background: Genetic testing for BRCA1 and BRCA2 is an instrumental tool
in clinical decision-making. Variants of uncertain significance (VUS) can
occur in up to 25% of individuals and pose clinical challenges. We
compared i) result recall ii) risk perception iii) worry and iv) risk modifying
behaviours in individuals with VUS, a pathogenic mutation (PM) or an
uninformative result (UR). Care provider attitudes to VUS were also
studied. Methods: A questionnaire was mailed to women testing positive for
a VUS, PM or UR. Items included demographics, time from disclosure,
result recall and cancer worry using the validated Trask score. Likelihood of
risk modifying behaviours or intensified screening was evaluated by 5 point
Likert scale. 9 regional genetic counselors and 11 referring physicians were
surveyed on VUS management. Responses were evaluated by chi square
and ANOVA. Results: All groups had similar age, marital status and
education. Failure to correctly identify a result as uninformative occurred in
32% of VUS; 90% had low economic status. 87% (VUS) and 44% (PMC)
had personal history of breast cancer. Perceived risk increased after
disclosure in 29% (VUS), 70%(PM) and 10% (UR) (p�0.001). Mean
Trask scores were 7.6 (VUS) and 9.8 (PMC) (p�0.006, t-test). In affected
patients, mastectomy was 22% (VUS) and 55% (PMC) (p�0.01), oophorectomy
39% (VUS) and 85% (PMCs) (p�0.001) with75% and 95%
intensified screening 75% in unaffected VUS and PM (p�0.16). 3% (VUS)
and 6% (PMC) agreed with chemoprophylaxis (p�NS). Genetic counselors
unanimously reported low comprehension in VUS vs PM. VUS was
disclosed only 75% of the time with poor comprehension, perceived anxiety
and negative family history as reasons. Referring physicians recommended
predictive testing for relatives of VUS carriers (100%). Conclusions: Nearly
1/3 of patients fail to recall their VUS as uninformative. Perceived risk was
increased after VUS disclosure but lower than PMC. Worry scores showed
impact on daily functioning. Uptake of prophylactic surgery was lower in
affected VUS vs PMC carriers with similar rates of intensified screening if
unaffected. Patients with low economic status or anxiety are at particular
risk of incomplete counseling.
1557 General Poster Session (Board #3G), Sat, 1:15 PM-5:15 PM
A comparison of simple single-item measures and the NCI Common
Toxicity Criteria version 3.0 measure of peripheral neuropathy. Presenting
Author: Suneetha Puttabasavaiah, Mayo Clinic, Rochester, MN
Background: Peripheral neuropathy (PN), a common and intrusive side
effect of chemotherapy in clinical trials, has been assessed via the
clinician-rated common terminology criteria for adverse events (CTCAE)
and/or patient-reported outcome (PRO) measures (Morton, ASCO, 2005).
We assessed the relative sensitivity of CTCAE and PRO measures for
evaluating interventions for preventing and ameliorating CIPN. Methods:
Data from285 patients in two prevention trials (N05C3, N04C7) and 432
patients from three intervention trials (N00C3, N01C3, N06CA) were
analyzed separately. CTCAE version 3.0 item for neuropathy was compared
to 2 NCCTG numerical analogue CIPN items, 6 EORTC CIPN20 individual
items, 2 McGill Pain Questionnaire items, and one Brief Pain Inventory
item. The sample size provided over 80% power to detect a true Spearman
rank correlation of 0.15 assessed the relationship between CTCAE and PRO
measures. Results: Results from both the prevention and treatment trials
were similar in terms of the relationship between the CTCAE and PRO
measures. No correlation coefficients between the CTCAE and any of the
PRO items at baseline were above 0.35, with the majority around 0.2.
Higher scores for the numbness items were observed than for the CTCAE in
47% of the patients at baseline and 39% during treatment in the treatment
trials. Many patients had severe numbness PRO scores but mild CTCAE
scores (12%) at baseline and (8%) during treatment in the treatment trials.
Results for the numbness and tingling PRO measures were redundant. The
correlations of the CTCAE with pain were weak, all below 0.35 at baseline
with differences as much as 29 points on average on a 0-100 transformed
scale. Conclusions: The CTCAE and PRO measures of PN measure different
constructs. The CTCAE includes both functional and ADL/motor aspects
which may or may not be related to the singular constructs of pain,
numbness, tingling, or adjectival characteristics of pain assessed by the
PRO measures. The two measures cannot be used in place of each other.
Cancer Prevention/Epidemiology
99s
1556 General Poster Session (Board #3F), Sat, 1:15 PM-5:15 PM
Differential effects of light at night and shift rotation pattern on the
circadian system in night workers. Presenting Author: Pedram Razavi,
Department of Medicine, University of Southern California, Los Angeles,
CA
Background: Light at night as in shift work suppresses nocturnal secretion
of melatonin, a pineal hormone with oncostatic properties. Several studies
have associated night shift work with higher risk of cancer, leading WHO in
2007 to classify rotating night shift work as “probably carcinogenic”. We
conducted one of the most comprehensive studies, to date, to evaluate the
effects of light and night shift work on melatonin measurements in the
field. Methods: Study participants were 130 active nurses (84 current
rotating night shift workers and 46 day shift workers) participating in
NHS2. Each nurse wore a head-mounted light- and accelerometer for a
3-day study period, during which each spontaneous urine was collected for
repeated urinary 6-sulfatoxymelatonin (melatonin) measurements. In addition,
nurses were asked to fill out paper questionnaires and diaries. We
used mixed models to evaluate the influence of light, activity and night shift
work on urinary melatonin level adjusting, for age, lifestyle, and occupational
history. We log-transformed main variables and report geometric
means (GM [standard deviation]). Results: Greater levels of light were
associated with lower melatonin (P � 0.0001), independent of activity
level. An increase in light intensity from 10 to 100 lux was associated with
a 12% decrease in geometric mean of melatonin level; however, this
inverse association was only significant at night (Ptrend � 0.01). At night,
each hour increase in exposure to � 20 lux light lowered melatonin level by
5.7% (Ptrend � 0.0001). A single night shift affected the circadian system
by lowering melatonin peak by 22% (day shift: GM � 17.57 [2.73]; night
shift: GM � 13.64 [2.54]) and induced a phase shift (PS) of 0.9 hours,
-changes that reset to normal by the next day. Two consecutive night shifts
had a similar effect as a single shift. However, the effect was worse after
three consecutive night shifts (GM � 10.11 [2.77]; PS � 2.2 hours).
Conclusions: We found significant inverse associations of intensity and
duration of exposure to light at night with urinary melatonin, independent
of activity level. Three consecutive night shifts affected the circadian
system more strongly than two consecutive, or a single night shift.
1558 General Poster Session (Board #3H), Sat, 1:15 PM-5:15 PM
Association of CYP19A1 gene variants with differences in disease progression
in breast cancer patients from different racial/ethnic backgrounds.
Presenting Author: Reina Villareal, University of New Mexico and New
Mexico VA Health Care System, Albuquerque, NM
Background: Polymorphisms in the aromatase (CYP19A1) gene result in
differences in the risk for breast cancer and response to treatment. We
hypothesize that allele frequencies in the CYP19A1 gene vary according to
race and may result in differences in progression of breast cancer among
women from different racial backgrounds. The objectives of this study are:
1) to determine the allele/genotype frequencies in the CYP19A1 gene
among women with breast cancer from different racial backgrounds, and,
2) to determine the association between disease progression and CYP19A1
gene variants. Methods: Clinical data and stored DNA from 327 patients
participating in the Expanded Breast Cancer Registry (EBCR) program at
the University of New Mexico were analyzed. These patients were followed-up
for a period of 1 to 6 years. Comprehensive genotyping for
CYP19A1 gene single nucleotide polymorphisms (SNPs) was performed
using microarray (Illumina). Results: Data from 164 non-Hispanic white
and 119 Hispanic women were analyzed. Four SNPs (rs1259269,
rs17703883, rs16964211, rs28757101) were associated with differences
in genotype/allele frequencies between the 2 racial groups. Furthermore,
3 SNPs (rs4646, rs17647478, and rs6493486) were associated
with differences in disease progression. The rare allele (G) for the
rs17647478 (G/T) is associated with poor progression compared those
without the allele (41.7% vs. 17.1%, p�0.04). Similarly the minor (A)
allele for the rs4646 (A/C) and the rs6493486 (A/G) is also associated with
a greater chance of worsening disease (23.2% vs. 12.4%, p�0.02 and
23.4% vs. 12.4%, p�0.02, respectively). A significant percentage of
women carrying the A allele for both rs4646 and rs6493486 and the T
allele for the rs17647478 have more advanced disease at the time of
presentation. None of the SNPs analyzed result in racial differences in
breast cancer progression. Conclusions: Polymorphisms in the CYP19A1
gene influence overall disease progression in breast cancer patients but
have no impact on the racial differences of disease behavior. Women
carrying the risk alleles present at a more advanced stage and are also at
greater risk of progression.
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