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

540 General Poster Session (Board #1E), Sat, 8:00 AM-12:00 PM
BOLERO-2: Everolimus with exemestane versus exemestane alone in Asian
patients with HER2-negative, hormone receptor-positive breast cancer.
Presenting Author: Shinzaburo Noguchi, Osaka University, Department of
Breast and Endocrine Surgery, Osaka, Japan
Background: Estrogen-receptor–positive (ER�) breast tumors can become
refractory to aromatase inhibitor (AI) therapy. The mTOR pathway plays a
critical role in hormone-resistant advanced breast cancer (ABC). Accordingly,
the addition of everolimus (EVE) to exemestane (EXE) was evaluated
in an international, phase III study (BOLERO-2) in patients with ER� aBC
refractory to letrozole or anastrozole. This report presents updated analyses
from the population of Asian patients enrolled in this study. Methods:
Eligible patients were randomized (2:1) to EXE (25 mg/day) with EVE (10
mg/day) or with matching placebo. The primary endpoint was progressionfree
survival (PFS). Secondary endpoints included overall survival, response
rate, quality of life, and safety. Results: EVE � EXE significantly
improved PFS versus EXE alone (HR � 0.44; 95% CI, 0.36-0.53; P �
.0001) in the overall study population at median follow-up of 12.5 months.
Of 143 patients of Asian origin (n � 106; 74% Japanese) enrolled in this
study, 98 received EVE � EXE and 45 received EXE � placebo. At the time
of database lock, 55 Asian patients (56%) in the combination arm had
experienced disease progression compared with 34 patients (76%) in the
EVE � placebo arm. Combination therapy reduced the risk of disease
progression versus EXE alone by 44% among Asian patients (HR � 0.56;
95% CI, 0.37-0.87; P � .05). Commonly reported adverse events in the
combination arm were consistent with previous clinical studies of mTOR
inhibitors and included stomatitis (80%), rash (49%), dysgeusia (31%).
Adverse events that occurred more frequently in the Asian subset versus
Caucasians included stomatitis (80% vs 54%) and rash (49% vs 37%),
whereas dyspnea (8% vs 24%) and asthenia (1% vs 17%) occurred less
frequently in the Asian subset versus Caucasians. Conclusions: The addition
of EVE to EXE significantly prolonged PFS in Asian patients versus EXE
alone. Adverse events were higher in the combination arm but generally
manageable. Combining EVE with an AI is a safe and effective treatment
option for Asian women with non-steroidal AI resistant/refractory ER� ABC.
542 General Poster Session (Board #1G), Sat, 8:00 AM-12:00 PM
Impact of the EndoPredict-clin score on risk stratification in ER-positive,
HER2-negative breast cancer after considering clinical guidelines. Presenting
Author: Martin Filipits, Institute of Cancer Research, Comprehensive
Cancer Center, Medical University of Vienna, Vienna, Austria
Background: Many ER-positive, HER2-negative breast cancer patients are
treated by adjuvant chemotherapy according to current clinical guidelines.
We retrospectively assessed whether the combined gene expression/
clinicopathological EndoPredict-clin (EPclin) score improved the accuracy
of risk classification in addition to considering clinical guidelines. Methods:
Three clinical breast cancer guidelines (National Comprehensive Cancer
Center Network (NCCN), German S3 and St. Gallen 2011), and the EPclin
score - assessed by quantitative RT-PCR in formalin-fixed paraffinembedded
tissue - were used to assign risk groups in 1,702 ER-positive,
HER2-negative breast cancer patients from two randomized phase III trials
(Austrian Breast and Colorectal Cancer Study Group 6 and 8) treated with
endocrine therapy only. Results: Although all analyzed clinical guidelines
identified a low-risk group with improved metastasis-free survival, the
overwhelming majority of all patients (81-94%) were classified as intermediate
/ high risk. In contrast to that, the EPclin classified only 37% of all
patients as high risk and that stratification resulted in the best separation
between low and high risk groups (p � 0.001, HR � 5.11 (3.48-7.51).
Consequently, the majority of all patients deemed intermediate / high risk
by the clinical guidelines was re-classified as low risk by the EPclin score.
Kaplan Meier analyses demonstrated that the re-classified subgroups (47
to 57% of all patients) had an excellent 10-year metastasis-free survival of
95% comparable to the clinical assigned low-risk groups although encompassing
a higher proportion of the trial patients. Conclusions: The EPclin
score predicted distant recurrence more accurately than all three clinical
guidelines and is especially useful to reclassify patients considered as
intermediate / high risk by the guidelines. The data suggests that the EPclin
score provides clinically useful prognostic information beyond common
clinical guidelines and can be used to accurately identify the clinically
relevant group of patients who are adequately and sufficiently treated with
adjuvant endocrine therapy alone.
Breast Cancer—HER2/ER
17s
541 General Poster Session (Board #1F), Sat, 8:00 AM-12:00 PM
Response pattern in 844 patients with infiltrating lobular carcinoma (ILC)
of the breast after neoadjuvant chemotherapy. Presenting Author: Cristina
Pirvulescu, Helios Klinikum Berlin-Buch, Berlin, Germany
Background: Patients (pts) with infiltrating lobular carcinoma (ILC) have a
different response to neoadjuvant chemotherapy compared to patients with
non-lobular carcinoma (NLC). The aim of our analysis was to characterize
correlates of the outcome impact of neoadjuvant chemotherapy in ILC and
to compare those with NLC. Methods: Between 1998 and 2006; 6377
breast cancer patients were enrolled to 7 randomized neoadjuvant chemotherapy
trials in Germany. For 6205 (98.3%) pts the histological type was
available. 844 (13.6%) were classified as ILC, 5361 (86.4%) were
classified as NLC. Endpoints of the analyses were: pathological complete
response (pCR) defined as no invasive and no in-situ residuals in the breast
and the lymph nodes, type of surgery, disease-free (DFS), local recurrence
(LRFS) and overall survival (OS). Results: ILC was associated with older age,
larger tumor size, negative nodes, lower grading, and hormone receptor
(HR) positivity (all p�0.0001). The majority of pts with ILC were HR
positive (717 pts, 86.9%) and had G1-G2 tumors (603 pts, 78.6%).
Patients with ILC had a significant lower pCR rate than pts with NLC (pCR
6.04% vs. 16.4%, p�0.001). In the ILC group, pts with HR positive,
triple-negative and HER2-positive tumors had a pCR rate of 5%, 18.3%
and 9.2%, respectively. One of 35 pts with G1 and HR positive ILC had a
pCR. Breast conservation therapy (BCT) in pts with pCR was 72.5% in the
ILC group and 85.5% in the NLC group (p�0.0001). Predictors for pCR in
the multivariate analysis were for ILC: patient age, grading and HR status.
ILC pts had a significantly longer LRFS compared to NLC pts (with or
without pCR after neoadjuvant chemotherapy, mean 112 months 95%CI
[109.7-115.7] vs. 106 months 95%CI [104.4-107.4], p�0.002).
Conclusions: In patients with ILC age, grading and HR status were
predictive for pCR. Pts with ILC have a more favourable outcome after
neoadjuvant chemotherapy despite a significantly lower pCR rate compared
to pts with NLC.
543 General Poster Session (Board #2A), Sat, 8:00 AM-12:00 PM
Interpathologists discrepancies in Ki67 assessment in the PACS01 trial:
An independent prognosis factor. Presenting Author: Frederique Madeleine
Penault-Llorca, Centre Jean Perrin, Clermont-Ferrand, France
Background: Several reports suggest an inter-observer variability in Ki67
assessment. Nevertheless, there is no large study that evaluates the rate of
discrepancies, together with their impact. Methods: Ki67 expression was
assessed on 663 samples from patients with ER-positive breast cancers
included in the PACS01 trial (Roche, J Clin Oncol, 2006). Ki67 staining
was done using MiB1 antibody (Dako, Copenhagen, Denmark, Dilution
1:250). Prognostic and predictive values have been reported previously
(Penault-Llorca, J Clin Oncol, 2009). A second central review was done by
a senior breast pathologist from a French Cancer center. A discrepancy was
defined as either a false positive or false negative result. Cut-off for
positivity was defined at 15% according to data from Cheang et al (JNCI,
2009). Results: The rate of discrepancy was correlated with the percentage
of stained tumor cells. A 10% discrepancy rate between the 2 pathologists
was observed when the first pathologist reported �10% tumor cells
stained. Same low rate of discrepancy (10%) was observed if more than
30% cancer cells were stained according to the first assessment. At the
opposite, discrepancy rates were 47%, 45%, 22%, 34% when the first
pathologist reported 10-15%, 15-20%, 20-25% and 25-30% tumor cells
stained. Overall, 36% of the patients presented a grade II tumor together
with Ki67 �10% or �30%. We then evaluated the impact of discrepancy
in terms of prognosis. Patients presenting a concordant result between the
two pathologists showed a better outcome as compared to patients
presenting a discrepancy, independently to the percentage of tumor
stained (p�0.05, patients with concordant Ki67 ranged between 10-30%
versus those with one reader �10% and the other one �10%-�30%).
Conclusions: Discrepancy rates between pathologists are acceptable when
Ki67 is either �10% or �30%. A Ki67 ranged between 10 and 30% could
define a grey zone in which Ki67 should be reported with caution or be
double checked by another pathologist. Survival analysis suggested that
inter-observer discrepancies could act a prognostic factor. Such finding
could reflect underlying intra-tumor heterogeneity.
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