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

582 General Poster Session (Board #7A), Sat, 8:00 AM-12:00 PM
Relationship between body mass index (BMI) at diagnosis of ER� node negative
breast cancer (BC) and Oncotype DX recurrence score. Presenting Author:
Caroline A. Lohrisch, British Columbia Cancer Agency, Vancouver, BC, Canada
Background: Inferior stage-adjusted survival for BC among obese (O) women has
been reported. This may reflect differences in treatment planned for O women, in
treatment received (due to toxicity), or in tumor biology arising in different
cellular environments, such as high serum insulin levels, which are associated
with a higher risk of recurrence. Methods: We examined whether overweight (BMI
25-30) or obese (BMI �30) women had a higher Oncotype Dx Recurrence Score
(RS) after ER�, node negative (NN) or N0i� BC than normal weight women.
Included were all participants at the BC Cancer Agency in a RS clinical utility
study in consecutive ER� NN, N0i� BC (n�156) at the BC Cancer Agency and
in the TAILORx trial (n�56). Sixteen were excluded (n�5 withdrew consent; 1
triple negative; 3 test failed; 2 her2�; 1 neoadjuvant treatment, n�4 height and
weight missing). Results: A similar proportion of O patients had low, intermediate,
and high RS tumors. Cancers with a high RS were more likely to be grade 3
(55% of grade 3 tumours had high RS, 33% intermediate RS, 12% low RS) and
fewer were strongly ER positive (69% of high RS versus 97% of intermediate and
low RS). Conclusions: While this data does not support differences in tumor risk
arising in O versus non obese environments in ER�, NN BC, examination of a
larger data set may be more informative.
All
RS low
(35, n (%)
8 (4)
2 (2)
4 (6)
2 (6)
584 General Poster Session (Board #7C), Sat, 8:00 AM-12:00 PM
Immunocytochemistry staining for ER and PR in circulating tumor cells as
compared to primary tumor or metastatic biopsy. Presenting Author:
Farideh Z. Bischoff, Biocept Inc., San Diego, CA
Background: Hormone receptor (estrogen receptor [ER] and progesterone
receptor [PR]) status in all breast cancer patients is recommended for
selection of treatment options. However, the analytical sensitivity of
immunohistochemistry (IHC) in detecting low levels of ER/PR is often poor
and is likely due to methodological variation. Because biopsy is not often
feasible in all patients with recurrent and/or metastatic breast disease,
circulating tumor cells (CTCs) offer an attractive alternative source of tumor
tissue for determining ER/PR status and can be monitored more readily to
enable a more effective course of treatment. Methods: Twenty mL of
peripheral blood was collected prospectively from 15 patients diagnosed
with late stage metastatic/recurrent breast cancer. CTCs were isolated
using the microfluidic OncoCEE platform. A cocktail of antibodies was
utilized for CTC capture and detection with an expanded anti-cytokeratin
(CK) cocktail mixture and anti-CD45. ER/PR protein expression was
assessed by immunocytochemistry (ICC) on the cells captured within the
microchannels and compared to IHC performed on the primary tumor or
metastatic biopsy. Results: CK�/CD45-/DAPI� cells were located and
assessed for ER/PR ICC. Among the 15 cases, a high concordance (13/15;
87%) in ER/PR status between IHC and ICC results was observed. Two
cases were found to be discordant where one was positive by IHC and
negative on the CTCs, and the other was negative by IHC and positive on the
CTCs. However, both cases that were discordant had low numbers of
detected CTCs. Conclusions: There is significant heterogeneity between
ER/PR protein expression in CTCs and primary tumor/metastatic biopsy,
and this status may change over time due to therapy. ER/PR ICC on CTCs
from peripheral blood using the OncoCEE platform is shown to be feasible
with high concordance (87%) in ER/PR status between primary tumor/
metastatic biopsy (by IHC) and CTCs (by ICC). The significance of
heterogeneity at the ER/PR protein level in CTCs ascertaining to the
prognosis and predictive response to anti-estrogen therapy needs further
evaluation in larger prospective clinical trials.
Breast Cancer—HER2/ER
27s
583 General Poster Session (Board #7B), Sat, 8:00 AM-12:00 PM
The role of Ki-67 in molecular breast cancer classification. Presenting
Author: George Stathopoulos, Errikos Dunant Hospital and Oncology Clinic,
Athens, Greece
Background: The Ki-67 antigen was identified the involvement in early steps
of polymerase I-dependent ribosomal RNA synthesis. Although it seems
that the protein has an important function in cell division, its exact role is
still obscure and there is little published work on its overall function. The
aim of the present study is to evaluate the contribution of Ki-67 level in
respect of tumor recurrence in molecular classified groups of breast cancer
patients. Methods: Breast cancer tumor samples were examined for
histological confirmation and for estrogen and progesterone receptors,
c-erb-B2 expression, proliferation with Grade and Ki-67. Ki-67 was divided
in percentage levels, up to 20 and higher than 20%. Immunohistochemistry
and Fluorescence in situ hybridization is described for the results of ER,
PR, c-erb-B2, Ki-67 biomarkers. Formaldehyde – fixed breast samples were
paraffin wax embedded and processed for paraffin sections. The primary
antibodies used were: The monoclinal antibody ID5 (M7047, Dakocytomation,
Carpinteria, CA) for the detection of ER, the monoclonal anti-PR
antibody 636 was used. For the detection of Ki-67 we used monoclonal
mouse anti-human Ki-67 MIB-1. The patients molecular classification was
Luminal A, Luminal B, Her-2 subtype and basal cell (triple negative).
Results: 847 breast cancer patients were recruited. 291 were group as
Luminal A, 228 as Luminal B, 221 Her-2 subtype and 107 triple negative.
Follow-up was from 3 years to 15 years since diagnosis. It was found that in
Luminal A patients, none had Ki-67 higher than 20% and the recurrence
was in 10.65%. In Luminal B, the Ki-67 was higher than 20% in 61% of
the patients and recurrence 23.68%. In Her-2 subtype �20% Ki-67 was
78.94%, recurrence 17.19%. In triple negative � 20% Ki-67 was in
68.75% and recurrence in 29.90% of the patients. Conclusions: The data
presented here indicate that Ki-67 level may be considered as one of
valuable biomarkers in breast cancer patients process and recurrence.
585 General Poster Session (Board #7D), Sat, 8:00 AM-12:00 PM
Correlation, comparison, and combined analysis of Ki-67 and histological
grade for early luminal breast cancer. Presenting Author: Yoichi Naito,
National Cancer Center Hospital East, Chiba, Japan
Background: Both Ki-67 and histological grade are established prognostic
factors in patients with early breast cancer. Recent international expert
consensus employs Ki-67 to classify luminal breast cancer, and histological
grade is described as an alternative. We investigated the prognostic
value of Ki-67, histological grade, and their combination. Methods: Patients
with early breast cancer treated with surgery between January 2000 and
December 2008 were retrospectively reviewed. Inclusion criteria were as
follows: estrogen receptor positive, HER2 negative, available for Ki-67 and
histological grade. Clinicopathological data were retrieved from medical
records. Ki-67 labeling index was investigated using MIB-1 antibody and
subdivided into three categories: low 0-9%; intermediate 10-19%; high
�20%. Histological grade was scored between 1 and 3. Disease-free
survival (DFS) was defined as time from surgery to the first documented
disease recurrence or death. Ki-67 categories and histological grade were
analyzed respectively and then concomitantly for prognostic impact on
DFS. Results: A total of 606 patients were included. Median age was 58 and
28.1% were over 65 years. 65.4% were postmenopausal women. Progesterone
receptor was positive in 84.0% of patients. 29.6% received neoadjuvant
or adjuvant chemotherapy. Number of lymph node metastasis was 0 in
70.0%, 1-3 in 21.3%, and �4 in 8.7% of patients. Ki-67 categories and
histological grade showed weak but significantly correlation (Spearman’s
rho � 0.385, p�0.001). High Ki-67 and histological grade 3 were
correlated with worse prognosis to the same extent (HR 2.518, p � 0.002
and HR 2.541, p � 0.048, respectively). For combined analysis, patients
represented concomitant with high Ki-67 and histological grade 3 showed
worse prognosis compared with those with Ki-67 low and histological grade
1 (HR 3.137, p � 0.021). Conclusions: Ki-67 and histological grade were
significantly but weakly correlated. Combined use of these two factors
could better predict recurrence of early luminal breast cancer.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.