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

1088 General Poster Session (Board #27A), Sat, 8:00 AM-12:00 PM
Quantitative measures of FDG PET after neoadjuvant chemotherapy to
predict breast cancer patient survival. Presenting Author: Erin-Siobhain R.
Currin, University of Washington, Department of Medicine, Seattle, WA
Background: In patients with locally advanced breast cancer (LABC),
qualitative FDG positivity following neo-adjuvant chemotherapy (NC) has
been shown to be inversely associated with survival (Emmering, Annals
Oncol, 2008). We investigated quantitative measures of post-therapy FDG
uptake, namely standardized uptake value (SUV) and glycolytic flux (Ki), as
predictors of breast cancer survival. Methods: Forty-seven patients with
LABC underwent dynamic FDG PET scans close to or at the end of NC and
prior to surgical resection. Post-therapy FDG uptake at the primary tumor
site was measured by mean SUV from 45-60 minutes after FDG injection,
maximum SUV (SUVmax) from 50-55 minutes, and FDG glycolytic flux
(Ki). Pathologic response (PR) was assessed for at the time of surgical
resection. Cox proportional hazards models were used to estimate associations
between log-transformed measures of post-therapy FDG uptake, PR
and outcome. Results: Median SUVmax was 1.9 (0.9 – 9.2) and median Ki
was 2.2 (0.02 – 47.7) mL/min/g. Median follow-up for relapse was 5.7
years with 11 events and 6.3 years for survival with 10 deaths. PR was not
significant for DFS (p � .39) or OS (p� .48). Post-therapy FDG uptake
measures showed a statistically significant ability to predict survival.
SUVmax predicted DFS (p�0.02) and OS (p�0.01). Ki was associated
with DFS (p �0.01) and OS (p �0.01). PET measured hazard ratios were
not attenuated in multivariate analysis controlling for known prognostic
markers such as primary tumor PR and nodal status. However, multivariate
survival models appeared highly influenced by one patient with the shortest
survival time (1.3 years) and highest SUVmax and Ki. Without this patient,
Ki remained a borderline independent predictor of DFS (p� .08) and OS
(p� .07), but SUVmax was no longer significant for DFS (p� .32) or OS
(p�0.26). Conclusions: Our analysis suggests that quantitative measures of
post-therapy FDG PET provide information beyond PR for predicting which
LABC patients are at highest risk for relapse and death. This information
may be useful in directing post-surgery treatment. Supported by NIH grants
CA42045, CA138293, and CA148131.
1090 General Poster Session (Board #27C), Sat, 8:00 AM-12:00 PM
Circulating tumor cells in metastatic breast cancer: Are they a strong and
independent predictor of poor progression-free and overall survival? Presenting
Author: Markus Wallwiener, Department of Obstetrics and Gynaecology,
University of Heidelberg, Heidelberg, Germany
Background: Circulating tumor cells (CTCs) are detected in 30–60% of
patients with metastatic breast cancer (MBC). The aim of this prospective
multi-center study was to evaluate the impact of CTCs on progression free
survival (PFS) and overall survival (OS) in a large cohort of 486 patients
with progressive metastatic disease. Methods: CTC levels were determined
for 486 patients at nine German University Breast Cancer Centers between
12/2007 and 06/2011. Samples of 7.5 ml blood were taken before
initiation of a new line of therapy and CTCs were enumerated using the
CellSearch System (Veridex LLC, Raritan, NJ, USA). CTC status (� 5 CTCs
vs. � 5 CTCs per 7.5 ml blood) was assessed as a prognostic factor for PFS
and OS using univariate (log-rank test) and multivariate (Cox regression
model) statistical methods. Results: CTCs were detected in 205/486 (42%)
patients. The median CTC count was 2 (range 0–6380) per 7.5 ml blood.
The presence of � 5 CTCs/7.5 ml blood did not correlate with any of the
established clinicopathological factors except estrogen receptor status (p
� 0.038). PFS and OS were both significantly shorter in patients with � 5
CTCs/7.5 ml than in those with � 5 CTCs/7.5 ml blood. PFS was 5.0 [95%
CI 4.1–5.8] months vs.7.6 [95% CI 5.9–9.3] months, p � 0.001; and OS
was 15.0 [95% CI 13.5–16.5] months vs. 18.3 [95% CI 17.4–19.2]
months, p � 0.001. In the multivariate analysis considering all clinicopathological
factors and the CTC status, independent predictors of reduced OS
and PFS were site of metastasis (visceral vs. bone), number of metastatic
sites (multiple sites vs. one site), and CTC status. Conclusions: The
presence of � 5 CTCs/7.5 ml blood is a strong and independent predictor of
poor PFS and OS in patients with MBC.
Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
71s
1089 General Poster Session (Board #27B), Sat, 8:00 AM-12:00 PM
Evaluation of overall survival (OS), progression-free survival (PFS), or time
to progression (TTP) in systematic review of randomized clinical trials
(RCT) in patients with metastatic breast cancer (MBC). Presenting Author:
Terence Mukonje, Medical College of Wisconsin, Milwaukee, WI
Background: Limited data exists to establish if the introduction of newer
agents has been associated with a trend towards an improved OS over time
in women with MBC. Methods: Trough a computer-based systematic search
of PubMed we identified RCT that treated patients with MBC published
between 1980 and 2011. Trials that compared systemic chemotherapy for
MBC, and reported a median OS were included. We excluded trials that use
concomitant hormonal treatment, investigated only immunotherapy, or if
they enrolled only responders to an initial regimen. The data abstracted
included: year of publication, number of patients, regimens used, number
of patient treated as 1st line vs. refractory patients, median PFS, TTP and
OS. Linear regression analysis was used to establish trends. Results: An
initial searched revealed 5485 publications, 134 RCT that enrolled
38,090 patients fulfilled our entry criteria and were included. First line
therapy was studied in 99 trials and 35 evaluated mostly refractory
patients. The use of adjuvant therapy has increased substantially, trials
reported in the 1980’s had a mean of 0.07% of patients having had
adjuvant chemotherapy compare to a mean of 48% in the last decade.
Overall survival has significantly improved; the slope of the fitted line for
first line clinical trials was 0.39 (p�0.001), which indicates a 0.39-month
increase in median survival time per year. In trials of subsequent lines of
therapy this slope was 0.19 (p�0.001). PFS or TTP was reported in 98
trials, interestingly in contrast to OS, this has not significantly changed, the
slope for the fitted line has remained almost flat in both first line (0.002,
p�0.97) and refractory trials (0.01, P�0.81). Conclusions: Our study is
the first of its kind conducted in trials of patients with MBC. It shows that
progress has been made in the last 3 decades OS in women affected with
MBC, however the lack of change in PFS or TTP appears to indicate that the
increase in OS is driven by a combination of newer agents, more
subsequent lines of therapy being offered to patients and improved
palliative care.
1091 General Poster Session (Board #28A), Sat, 8:00 AM-12:00 PM
Validation of NAD(P)H quinone oxidoreductase (NQO1) expression as a
predictive factor for adjuvant chemotherapy benefit in patients with early
breast cancer. Presenting Author: Monica Arnedos, Institut Gustave Roussy,
Villejuif, France
Background: NAD(P)H:quinone oxidoreductase-1 (NQO1) has important
antioxidant functions by stabilizing p53 from proteasomal degradation.
NQO1 knockdown is associated with higher susceptibility to oxidative
stress. Polymorphisms suppressing NQO1 are predictors of poor survival in
patients with breast cancer (BC) treated with anthracyclines. BC cell lines
with impaired NQO1 function showed resistance to epirubicin chemotherapy
(CT) independently of p53 status suggesting NQO1 as predictive
factor for anthracycline benefit. In this study we hypothesized that lack of
NQO1 could predict resistance to anthracycline-containing CT in patients
with early breast cancer (EBC). Methods: Patients were identified from two
French multicentric trials that randomized patients with EBC to adjuvant
anthracycline-based CT vs no CT between 1988 and 1995. NQO1 was
determined in TMAs by automated quantitative assessment of immunofluorescence
(On-Q-ity Inc, Waltham). Cut-off for positivity was the median
value of NQO1 expression. Univariate and multivariate Cox regression
models were performed. Treatment effect was assessed on long term overall
survival (OS). Results: NQO1 expression was assessed in 600 patients.
75% were postmenopausal, had more often grade II (62%), LN-negative
(58%) and ER-positive (67%) BC. Higher NQO1 expression was observed
in postmenopausal (P�0.02) patients. No relation with other clinicopathological
factors (grade, LN or ER) was observed. Effect of adjuvant CT on
death rates was dependant on NQO1 level. Hazard ratio (HR) for treatment
efficacy at the four quartiles of NQO1 were 1.07 (95%CI: 0.69-1.7), 0.87
(0.64-1.19), 0.66 (0.45-0.97), 0.46 (0.22-0.95) (interaction test: 0.1).
Interaction test was statistically significant (0.02) when NQO1 expression
was considered as binary variable with median value taken as cut-off.
NQO1 remained predictive among ER� patients only. HR for OS was 0.61
(0.36-1.02) and 1.25 (0.79-1.99) in patients with high and low NQO1
respectively. Conclusions: This study adds to the existing data suggesting
NQO1 expression as an independent predictor of efficacy for adjuvant
anthracycline-containing CT.
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