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

98s Cancer Prevention/Epidemiology
1551 General Poster Session (Board #3A), Sat, 1:15 PM-5:15 PM
NAD(P)H: Quinone oxidoreductase 1 (NQO1) C609T polymorphism and
lung cancer risk: A meta-analysis. Presenting Author: Yuqing Lou, Department
of Pulmonary, Shanghai Chest Hospital, Jiaotong University, Shanghai,
PR China, Shanghai, China
Background: No clear consensus has been reached on the NAD(P)H:
quinone oxidoreductase 1 (NQO1) gene C609T polymorphism and lung
cancer risk. We performed a meta-analysis to summarize the possible
association. Methods: We conducted a computer retrieval of PUBMED and
EMBASE databases prior to January 2012. References of retrieved articles
were also screened. According to the inclusion criteria, 24 articles (31
studies) were finally included. The fixed-effects model and the randomeffects
model were applied for dichotomous outcomes to combine the
results of the individual studies. Results: There was no statistical association
between C609T polymorphism and lung cancer risk in overall, East
Asians, African-Americans or Hispanics. In Caucasians, significant association
was found in allele comparison model (T vs. C) (P�0.04, OR�1.09,
95%CI [1.00–1.19], Pheterogeneity�0.24, fixed-effects model). In Hawaiians,
significant association could be found in dominant genetic model
((TT�CT) vs. CC) (P�0.04, OR�0.52, 95%CI [0.28–0.96], fixed-effects
model). In the subgroup of squamous cell carcinoma, a borderline
significance could be found in the dominant genetic model ((TT�CT) vs.
CC) (P�0.05, OR�1.20, 95%CI [1.00–1.43], Pheterogeneity�0.65, fixed-effects model). Significant association could also be found in
allele comparison (T vs. C) (P�0.03, OR�1.21, 95%CI [1.01–1.44],
Pheterogeneity�0.68, fixed-effects model). In the subgroup of small cell lung
cancer risk, significant association were found in allele comparison (T vs. C)
(P�0.03, OR�1.68, 95%CI [1.05–2.68], Pheterogeneity�0.10, randomeffects
model) and in the homozygote comparison (TT vs. CC) (P�0.02,
OR�2.79, 95%CI[1.14–6.85], Pheterogeneity�0.72, fixed-effects model).
No association was observed in adenocarcinoma subgroup. Conclusions:
NQO1 C609T polymorphism might associate with lung cancer risk in
Caucasians and Hawaiians. NQO1 C609T polymorphism might also associate
with squamous cell carcinoma and small cell lung cancer risk.
1553 General Poster Session (Board #3C), Sat, 1:15 PM-5:15 PM
Why do breast cancer programs fail to refer patients to genetic counseling
upon obtaining family history? Presenting Author: Julia R. Trosman, Center
for Business Models in Healthcare, Chicago, IL
Background: Women with personal or family history suggestive of susceptibility
to hereditary breast or ovarian cancer should be referred to genetic
counseling (US Preventive Services Task Force, Ann Intern Med. 2005).
Our goal is to examine whether this guideline is followed by breast cancer
programs providing screening and treatment in a large urban area; and if
not followed, why. Funded by Susan G. Komen for the Cure. Methods: Using
the framework approach of qualitative research, we conducted interviews
with 130 providers of breast cancer screening and treatment at 26
institutions in Chicago (18 community, 4 academic and 4 public hospitals).
We interviewed radiologists, mammography technologists, nurses,
surgeons, oncologists, internists, and patient navigators. Interviews were
transcribed and coded; theme analysis was conducted; simple frequencies
and Fisher’s exact test were calculated. Results: While all 26 programs
collect patient personal and family history, only one program has both a
protocol for referral to genetic counseling and a genetic counseling service.
All six interviewees from that program (6/130, 5%) report referring
appropriate patients to genetic counseling, compared to none from other
programs (p�0.0001). 90% of interviewees (118/130) did not perceive
any role in raising patient awareness or referring them to genetic counseling.
Among the 124 interviewees not referring to genetic counseling, 51
(41%) have genetic counseling available, but only 12% (6/51) of them view
referring or making patients aware of genetic services as their responsibility;
while none of the interviewees without genetic counseling services view
this their responsibility (p�0.0001). None of the interviewees noted
reimbursement of genetic counseling as a barrier to referral. Conclusions:
The lack of accountability by care providers is a barrier to referring patients
with personal or family history of breast or ovarian cancer to genetic
counseling, even when the service is available. A comprehensive approach
addressing access to genetic counseling, adoption of referral protocols and
clear assignment of referral responsibilities is needed to ensure that women
appropriately receive genetic assessment.
1552 General Poster Session (Board #3B), Sat, 1:15 PM-5:15 PM
Ethnic difference of driver mutation frequencies and correlations between
driver mutations and histologic subtypes in lung adenocarcinoma. Presenting
Author: Yuki Yamane, Division of Thoracic Oncology, National Cancer
Center Hospital East, Kashiwa, Chiba, Japan
Background: The frequencies of known driver mutation in lung adenocarcinoma
from patients in the United States have been reported by the NCI’s
Lung Cancer Mutation Consortium (LCMC), indicating driver mutations
were detected in 54% (280/516) of tumors. In this report, mutations
found: EGFR 17%, KRAS 22%, HER2 0.6%, PIK3CA 1.2%, BRAF 2%,
MET amplification 0.6%, MAP2K1 0.4%, NRAS 0.4%, AKT 0%, ALK
rearrangements 7%. However little is known about ethnic difference of
driver mutation frequencies and correlations between driver mutations and
histological subtypes in lung adenocarcinoma. Methods: Known driver
mutations in tumors from 97 Japanese patients with lung adenocarcinoma
who underwent surgical resection between 1999 and 2003 in National
Cancer Center Hospital East were analyzed by next-generation sequencing
and confirmed by Sanger sequencing. Correlations between driver mutations
and histological subtypes were also assessed. Results: Driver mutations
were detected in 72% of tumors. Mutations found: EGFR 57%,
KRAS9%, HER2 2%, PIK3CA 2%, BRAF 1%, MET amplification 1%,
MAP2K1 0%, NRAS 0%, AKT 0%. Due to the limitation of rearrangement
detection by exon-sequencing, ALK rearrangements were not analyzed.
Compared with the report by LCMC, the frequency of EGFR mutations was
high and that of KRAS mutations was low in the present study. All
mutations were mutually exclusive. The number of predominant histological
subtypes of tumors harbored EGFR mutations were papillary 28, acinar
3, solid 5, lepidic 19. That with KRAS mutations showed papillary 2, acinar
2, solid 2, lepidic 3, and HER2 mutations showed papillary 1 and acinar 1.
Two tumors harbored PIK3CA mutations showed both histological acinar
pattern. Each of BRAF mutation and MET amplification showed lepidic and
papillary pattern, respectively. Conclusions: It was suggested that there
should be ethnic difference of driver mutation frequencies in lung adenocarcinoma
between Asian and non-Asian patients, although the details of
ethnic distribution included in LCMC study has not been opened. In
addition, each driver mutations did not correspond to specific histological
subtypes of lung adenocarcinoma.
1554 General Poster Session (Board #3D), Sat, 1:15 PM-5:15 PM
Breast cancer prognosis in BRCA1/2 mutation carriers: A case control
study. Presenting Author: Grazia Arpino, Medical Oncology, Endocrinology
and Oncology Department, University Federico II of Napoli, Napoli, Italy
Background: We evaluated the clinical impact of germ-line BRCA1/2
mutations and variants of unknown clinical significance (VUS) for BRCA1/2
in patients (pts) with early breast cancer (BC). Methods: Twenty-eight
BRCA-positive (BRCA�) BC pts with germ-line BRCA1 /2 mutations and
16 VUS BC pts were selected from our database and matched (1:3) with
154 nonhereditary BC controls (sporadic controls, SC, defined by no
associated personal history of breast cancer and no family history of breast
and ovarian cancer or an uninformative BRCA mutation test) for stage,
histologic subtype, age, and year of diagnosis. Clinical characteristics,
recurrence (rec) pattern, disease free survival (DFS) and overall survival
(OS) were analyzed. Results: Compared with VUS and SC, BRCA� pts were
less likely to express estrogen receptor (64% vs. 89% vs. 54% respectively
p�.005) and progesterone receptor (64% vs. 86% vs. 59% respectively
p�.005) but more likely to be triple negative (0 vs. 3.4% vs 47.4%
respectively p�.005). Compared with VUS and SC, BRCA� pts were more
likely treated by radical mastectomy (37.5% vs. 26.4% vs. 59.3% %
respectively p�.005). Pattern of rec was also different. Compared with
VUS and SC, BRAC� pts developed more second tumors (11% vs. 6.3% vs.
1.9% respectively p�.0001) but less local or distant rec (31% vs. 2.6 vs.
0% for local rec and 12% vs. 16% vs. 11% for distant rec respectively
p�.0001). Controlateral BC was more frequent in VUS compared to the
BRAC� and SC pts (12% vs. 7% vs. 1% respectively, p�.0001). At a
median follow up of 88 months, at univariate analysis, BRAC� but not VUS
pts had worse OS compared to SC (p�.006). No difference in DFS was
observed for VUS or BRAC� when compared to SC pts. After adjustment for
age, stage, grade, nodal status, hormone receptors, adjuvant therapy and
year of diagnosis, BRCA� pts continued to have and increased risk of death
compared to SC (HR 5.9, 95% CI 1.9-18.1, p�.002). Most of the deaths
observed in BRAC� pts were not cancer related. Conclusions: Despite
decrease incidence of local or distant recs, BRAC� pts seems to be more
likely to die compared to SC. Development of second cancers and unknown
effects of BRCA1/2 mutations on nonneoplastic diseases that cause death
may account for this findings.
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