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

557 General Poster Session (Board #3H), Sat, 8:00 AM-12:00 PM
Predicting the Oncotype DX score: An inexpensive guesstimation. Presenting
Author: Catherine Pesce, Memorial Sloan-Kettering Cancer Center,
New York, NY
Background: Oncotype DX Recurrence Score [RS] is used to predict the
benefits of chemotherapy added to adjuvant hormone therapy in ER
positive early stage breast cancer. It is also prognostic. However, its
expense may be a concern in some health care systems and communities.
In addition, it is labor intensive, requiring shipment of tissue samples to a
single laboratory with an average 10-14 day turnaround time (in the US). A
reliable and inexpensive estimator of the Oncotype DX risk score using
readily available pathologic variables from tumor specimens could be
useful. Methods: We reviewed our prospective database of patients with
Oncotype DX results obtained over 2.5 years (1155 specimens with
Oncotype DX scores, September 2008 – March 2011) and identified 766
invasive ductal carcinomas with known ER status, PR status, histologic
grade, and nuclear grade. Through linear regression analysis, we predicted
recurrence score for each tumor using these four parameters. After
categorizing according to the same risk classification as in Oncotype DX
(low risk: RS�18, intermediate risk: RS 18-30, or high risk: RS�30) we
compared our predicted recurrence score to actual Oncotype DX recurrence
score. Results: Overall 69.7% of specimens were assigned the same risk
category as with the Oncotype DX level. In the predicted low risk group,
1.7% of patients were actually high risk. None of the predicted high risk
patients had a low score. Conclusions: We found a strong correlation
between scores estimated using our model and actual reported Recurrence
Scores. If validated, our model could provide a clinically useful estimation
of risk at lower cost.
Predicted risk level Actual risk level
Low risk Intermediate risk High risk Total
Low risk 358
97
8 463
(77.3%) (21.0%) (1.7%) (59.7%)
Intermediate risk 95
168
34 297
(32.0%) (56.6%) (11.5%) (38.3%)
High risk 0
1
15 16
(0%) (6.2%) (93.8%) (2.1%)
Total 453
266
57 776
(58.4%) (34.3%) (7.4%)
559 General Poster Session (Board #4B), Sat, 8:00 AM-12:00 PM
Everolimus for postmenopausal women with advanced breast cancer:
Updated results of the BOLERO-2 phase III trial. Presenting Author:
Martine Piccart, Institut Jules Bordet, Université Libre de Bruxelles,
Brussels, Belgium
Background: Current treatment options for postmenopausal patients with
estrogen-receptor–positive (ER� ) breast cancer (BC) who relapse or progress
on a nonsteroidal aromatase inhibitor (NSAI) are limited. The BO-
LERO-2 trial supports the activity of everolimus (EVE; an oral mammalian
target of rapamycin [mTOR] inhibitor) added to the steroidal aromatase
inhibitor exemestane (EXE) to prolong progression-free survival (PFS) in
this patient population. Long-term PFS and survival data are awaited.
Methods: BOLERO-2 is a phase III double-blind, randomized, international
trial comparing EVE (10 mg once daily) plus EXE (25 mg once daily) versus
placebo (PBO) plus EXE in postmenopausal women with advanced ER� BC
progressing or recurring after NSAIs (letrozole or anastrozole). Patients
were randomized (2:1) to EVE � EXE or PBO � EXE. The primary endpoint
was PFS by local investigator assessment. Main secondary endpoints
included centrally assessed PFS, overall survival (OS), safety, bone
turnover, and overall response rate (ORR). Results: Baseline disease
characteristics including tumor burden and prior cancer therapy were well
balanced between treatment arms (N � 724). Median PFS was doubled
and response rates were consistently improved with EVE � EXE (n � 485)
vs PBO � EXE (n � 239) in interim analyses. Median PFS by local
assessment was ~3 mo with PBO � EXE vs 6.9 mo (hazard ratio [HR] �
0.43; P � .0001) and 7.4 mo (HR � 0.44; P � .0001) with EVE � EXE at
7.5 mo and 12.5 mo follow-up, respectively. Fewer deaths were reported
with EVE � EXE (17.2%) vs PBO � EXE (22.7%) at 12.5 mo follow-up.
Safety profiles were consistent with previous reports for mTOR inhibitors.
PFS data including 528 events (protocol-specified final analysis), and
updated OS and safety data will be presented. Conclusions: Adding EVE to
EXE markedly prolonged PFS in patients with NSAI-refractory advanced
ER� BC. There were fewer deaths among patients receiving EVE, and
further follow-up will evaluate the effect of EVE on OS.
Breast Cancer—HER2/ER
21s
558 General Poster Session (Board #4A), Sat, 8:00 AM-12:00 PM
Aromatase inhibitors and cardiac outcomes in women undergoing cardiac
angiography after early breast cancer. Presenting Author: Bostjan Seruga,
Institute of Oncology Ljubljana, Ljubljana, Slovenia
Background: Data show that in post-menopausal women with early breast
cancer, longer use of aromatase inhibitor (AI) is associated with increased
odds of ischemic heart disease. Here we explore the association between
adjuvant AI use and cardiac disease in women undergoing cardiac
angiography after a diagnosis of early breast cancer. Methods: We linked a
database of 7,681 women who underwent cardiac angiography at the
University Clinical Center of Ljubljana between December 2004 and
November 2010 with the Cancer Registry for Slovenia. Women with early
breast cancer that subsequently underwent cardiac angiography were
identified. Information on cardiovascular risk factors was retrieved from the
patients’ charts and from discharge letters after cardiac angiography. The
endpoint of interest was a diagnosis of ischemic heart disease or left
ventricular dysfunction (IHD-LVD) without evidence of valvular heart
disease at the time of angiography. Conditional, logistic regression was
used to test for associations between variables. Results: Among 117 eligible
women 75% (n�88) were postmenopausal and 62% (n�73) had hormonal
receptor positive (HR�) disease. Of these 42% (n�31) were treated with
AI. Overall, 48% (n�56) of women were found to have IHD-LVD. In
patients with HR� breast cancer, use of AIs was significantly associated
with IHD-LVD as compared to tamoxifen alone (HR 2.50, 95% CI
1.01-6.29, p�0.046). For each year of AI therapy, there was a trend for
higher odds of IHD-LVD (OR: 1.25, 95% CI 0.95-1.67, p�0.116). This
effect appeared independent of age, body mass index, baseline hypertension,
hypercholesterolemia, diabetes and heart disease or prior anthracyclines
exposure. Among all patients, use of anthracyclines and left-sided
irradiation was associated with non-significant increases in IHD-LVD (HR
2.37, 95% CI 0.89-6.09, p�0.45 and HR 1.28, 95% CI 0.69-2.40,
p�0.44 respectively). Conclusions: Compared to tamoxifen, AIs are associated
with a time dependent increase in IHD-LVD. This risk appears
independent of other risk factors for heart disease. Anthracycline exposure
and left breast or chest wall radiation showed non-significant associations
with IHD-LVD in this small cohort.
560 General Poster Session (Board #4C), Sat, 8:00 AM-12:00 PM
The impact of the Oncotype Dx breast cancer assay in clinical practice:
Systematic review and meta-analysis. Presenting Author: Josh John Carlson,
University of Washington, Seattle, WA
Background: Many studies have evaluated the Oncotype Dx Breast Cancer
Assay (ODX) and its impact on adjuvant chemotherapy (ACT) treatment
decisions. However, it can be difficult for clinicians and other stakeholders
to interpret the collective findings of these studies, as they were conducted
in diverse settings and have limited sample sizes. To address this issue, we
conducted a systematic review and meta-analysis to synthesize ODX results
and provide insights about the utility of ODX in actual clinical practice.
Methods: We performed a systematic review of ODX studies using PubMed,
Embase, ASCO, and SABCS. Studies were included if patients had ER �,
node -, early stage breast cancer, reported use of ODX to inform actual ACT
decisions, and reported outcomes of interest, including: 1) distribution of
ODX recurrence scores (RS); 2) impact of ODX on ACT recommendations;
3) impact of ODX on ACT use; and 4) proportion of patients following the
treatment suggested by the ODX RS. Results: A total of 28 studies met
inclusion criteria. The distribution of RS categories was 48.8% low, 39.0%
intermediate, and 12.2% high (21 studies, 4,156 patients). ODX changed
the clinical-pathological ACT recommendation in 33.4% of patients (8
studies, 1,437 patients). In patients receiving ODX, receipt of ACT was:
28.2% overall, 5.8% low, 37.4% intermediate, and 83.4% high. High RS
patients were significantly more likely to follow the treatment suggested by
ODX vs. low RS patients RR: 1.07 (1.01–1.14). Conclusions: The pooled
results for the impact of ODX on ACT recommendations are consistent with
most individual studies to date. However, the proportion of intermediate RS
results is nearly 2-fold higher than reported in the ODX development
studies by Paik et al., which may have implications for the clinical utility
and cost impacts of testing. Also, high RS vs. low RS patients were more
likely to follow the ODX results, suggesting a tendency toward aggressive
treatment despite a low ODX RS. Finally, there was a lack of studies on the
impact of ODX on ACT use vs. standard approaches, suggesting additional
studies are warranted.
Count Mean % classified (95% CI)
High RS 509 12.2% (10.5-14.0)
Int RS 1,487 39.0% (36.3-41.7)
Low RS 2,026 48.8% (45.2-52.3)
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