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

96s Cancer Prevention/Epidemiology
1543 General Poster Session (Board #1G), Sat, 1:15 PM-5:15 PM
Breast cancer in Irish families with Lynch syndrome. Presenting Author:
Emmet Jordan, Mater Misericordiae University Hospital, Dublin, Ireland
Background: Breast cancer is not among the recognised malignant manifestations
of Lynch Syndrome which include colorectal, endometrial, gastric,
ovarian and upper urinary tract tumours. In this study we report the
prevalence of breast cancer in Irish Lynch Syndrome families and determine
immunohistochemical (IHC) expression of mismatch repair proteins
(MMR) in available breast cancer tissue. Methods: Breast cancer prevalence
was determined among Lynch Syndrome kindreds from two institutions in
Ireland. One kindred was omitted due to a biallelic MMR and BRCA1
mutation.The clinicopathological data that was collected on breast cancer
cases included age of onset, morphology, and hormone receptor status, and
a genotype phenotype correlation was investigated. Immunohistochemical
staining was performed for MLH1, MSH2, MSH6, and PMS2 on all
available breast cancer tissue from affected individuals. Results: The
distribution of MMR mutations seen in sixteen pedigrees were as follows;
MLH1 (n�5), MSH2 (7), MSH6 (3), PMS2 (1). Sixty cases of colorectal
cancer and 14 cases of endometrial cancer were seen. Seven breast
cancers (5 invasive ductal and 2 invasive lobular cancers) and 1 case of
ductal carcinoma in situ were reported in 7 pedigrees. This compared with
4 cases of prostate cancer. Of the 7 LS kindreds containing breast cancer,
6 MSH2 mutations and 1 MSH6 mutations were identified. Median age of
breast cancer diagnosis was 49 years (range 38-57). Hormone receptor
status is available on 3 breast cancer cases at time of abstract submission;
all were ER positive and HER 2 negative. All cases had grade 2 or 3
tumours. 5 samples were available for IHC evaluation. 3 out of 5 cases
showed loss of MMR expression, all showed loss of MSH2 and MSH6
expression. One of the two cases with normal IHC expression in breast
tissue belonged to a kindred where 3 siblings with colorectal cancer and
documented deleterious mutations demonstrated no IHC loss. Conclusions:
Breast cancer occurred at an early age and was more common than prostate
cancer in Irish Lynch Syndrome pedigrees. All identified breast cancer were
in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer
screening may be warranted in certain Lynch Syndrome kindreds.
1545 General Poster Session (Board #2B), Sat, 1:15 PM-5:15 PM
BRCA carrier status as an independent prognostic factor associated with
earlier biochemical relapse in local prostate cancer. Presenting Author:
Elena Castro, The Institute of Cancer Research and The Royal Marsden
NHS Foundation Trust, London, United Kingdom
Background: Biochemical relapse after local treatment for prostate cancer
(PCa) indicates recurrent disease and is associated with shorter survival.
Germline BRCA mutations are associated with worse PCa outcomes. BRCA
carriers are currently treated with the same protocols used for non-carriers.
We analyzed biochemical-progression free survival (bPFS) after conventional
treatment for localized PCa in a cohort of BRCA patients (pts).
Methods: In this retrospective case-control study, each BRCA carrier (9
BRCA1 and 34 BRCA2) treated with radical prostatectomy (RP) or external
beam radiotherapy (RT) was matched with 3 non-carriers (NC) by age at
diagnosis (�5 yrs), TNM stage, Gleason score, presenting PSA, local
treatment , androgen-deprivation therapy (ADT) and year of treatment (�3
yrs). All NC were screened for BRCA1 and BRCA2 mutations. Biochemical
failure was reviewed according to ASTRO and NCCN criteria. The Kaplan-
Meier method and a multivariate Cox regression model adjusted by
matching factors were employed. Results: 172 pts were included. Median
follow-up was 76 months (ms). Median age at diagnosis was 58 yrs
(43-75). Tumour stages were I 11%, IIA 19%, IIB 28%, III 28%, IV 14%.
80 pts received RT (18 BRCA2, 5BRCA1, 57NC) and 85% also received
ADT (70% for �6 months). 92 pts underwent RP (16 BRCA2, 4 BRCA1
and 72 NC), and 9% of them received ADT (�6months). Overall, median
bPFS was 71ms. For those treated with RT, median bPFS was 65ms in NC
vs 39ms in BRCA carriers (p�0.023). bPFS was not affected by ADT
duration. Median bPFS after RP was 65ms in BRCA carriers. No difference
was observed in 3yrs-bPFS between BRCA carriers and NC (73% vs 76%).
The adjusted MVA confirmed the independent prognostic value of tumour
stage (p�0.004) and BRCA status (p�0.032) for bPFS. Among BRCA
carriers, the risk was greater when the analysis was limited to BRCA2 pts
(p�0.013, HR 2.1,.95%CI 1.2-3.7). Conclusions: Our results suggest that
BRCA carriers with PCa have worse local disease control than NC when
treated with RT, regardless of ADT duration. No differences in bPFS were
observed in pts treated with RP after �6 yrs median follow-up. These
results may have implications for tailoring clinical management for these
patients.
1544 General Poster Session (Board #2A), Sat, 1:15 PM-5:15 PM
Cost sharing and hereditary cancer risk: Predictors of willingness-to-pay for
genetic testing. Presenting Author: Jennifer Madeline Matro, Fox Chase
Cancer Center, Philadelphia, PA
Background: The increasing availability of genetic testing (GT) in cancer
(CA) care has been paralleled by increasing cost-sharing practices by
payors that are intended to reduce overuse of health care services. Patients
referred for hereditary CA risk assessment may be subject to financial
deterrents such as high out-of-pocket (OOP) costs. Little is known about
what factors may influence high-risk patients’ willingness-to-pay (WTP) for
GT. Methods: The Gastrointestinal (GI) Tumor Risk Assessment Registry
includes individuals referred for evaluation of genetic CA risk based on
personal and/or family hx. At enrollment, participants complete a survey
collecting detailed demographic, CA hx, and psychosocial items related to
CA risk. Baseline data on 406 participants were available; 21 who did not
respond to WTP items were excluded. WTP items included intention for: GT
only if paid by insurance; GT even if paid by self; and amount WTP (7 levels,
$25 to $2000). Multivariable models examined predictors of WTP (self vs
only if paid by insurance) (model 1, logistic), and predictors of amount WTP
(model 2, ordinal logistic, 5 levels). All statistical tests are two-sided
(��0.05). Results: Most participants were women (73%), white (92%) and
aged 45-64 (58%). 51% had � 4 yr college degree; 22% had household
income �$75,000; 42% had hx of GI CA; 56% had � 11st degree relative
(FDR) with colorectal CA (CRC). Overall, 82 (21.3%) were willing to have
GT only if paid by insurance, and 303 (78.7%) were WTP OOP. Of those
WTP, 271 (89%) stated an amount. Independent predictors of WTP (model
1) were: 1) expectation of positive result, 2) confidence to control CA risk,
3) fewer perceived barriers to CRC screening and 4) benefit of guiding
screening (all p�0.05). Subjects WTP a higher amount (model 2) were
male, more educated, and had greater CA worry, fewer FDR with CRC (all
p�0.05), and more positive attitudes toward GT (p�0.01). Conclusions:
Patients who are WTP some OOP costs for GT anticipate benefits to control
of CA risk afforded by GT. Women and less educated patients may face
greater barriers from high co-pays. Identifying patient-level factors associated
with WTP for genetic services is increasingly important as GT is
integrated into routine CA care.
1546 General Poster Session (Board #2C), Sat, 1:15 PM-5:15 PM
Comparison of BRCA1/2-positive and -negative women diagnosed with
metachronous breast and ovarian cancers. Presenting Author: Amanda C.
Brandt, University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: After a primary breast cancer (BC) or ovarian cancer (OC)
diagnosis, women have a risk to develop a second primary cancer,
significantly more so in women with a BRCA gene mutation. The objective
was to evaluate characteristics of BRCA positive and negative women
diagnosed with metachronous BC and OC. Methods: Women with metachronous
BC and OC were identified at the University of Texas MD Anderson
Cancer Center. BRCA test results, age at diagnosis of both BC and OC, first
degree relatives (FDR) with BC and/or OC, total relatives affected, and
histopathologic tumor features were obtained from a prospectively maintained
research database. Univariate and logistical regression analyses
were performed. Results: A total of 64 women with metachronous primary
cancers underwent BRCA genetic testing. Of the 45 BRCA positive women,
36 (80%) were diagnosed with BC (mean 40 years) prior to OC and 9 (20%)
were diagnosed with OC first (mean 47 years). Of the 19 BRCA negative
women, 10 (53%) were diagnosed with BC first (mean 63 years), and 9
(47%) diagnosed with OC first (mean 48 years). Women diagnosed with BC
first were more likely to be BRCA positive than women diagnosed with OC
first (p�0.03). Patients with a FDR with BC were more likely BRCA positive
than women without family history (p�0.0062). Patients with PR negative
BR (p�0.0199) or triple negative (TN) BC (p�0.0139) were more likely to
test BRCA positive. High grade ovarian carcinomas approached significance
(p�0.053) in BRCA positive when compared to BRCA negative
cohort. Ethnicity, total number of affected relatives with BC or OC, ER
status, Her2 status, and nuclear grade were not statistically significant
between the two groups. Conclusions: Women with OC preceding their BC
with lack of family history of BC and OC are significantly less likely to test
BRCA positive. BC is often the sentinel cancer in women with a BRCA
mutation compared to BRCA negative women with metachronous BC and
OC. This should be considered during the risk assessment to more
accurately estimate the chance of identifying a BRCA mutation in women
with metachronous BC and OC.
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