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

42s Breast Cancer—HER2/ER
643 General Poster Session (Board #14F), Sat, 8:00 AM-12:00 PM
Correlation of TOP2A expression in HER2-positive breast cancer with
pathologic response and clinical outcomes in patients undergoing neoadjuvant
treatment based on anthracycline. Presenting Author: Elizabeth S.
Santos, Hospital A.C. Camargo, São Paulo, Brazil
Background: Factors predictive of response to anthracyclines can help
selecting patients who really benefit from its use. TOP2A (a target of
anthracyclines) and HER2 genes are both amplified in 40% of breast
cancers. Data from literature are conflicting regarding the potential of
TOP2A as a predictor of response to anthracyclines. Methods: We retrospectively
analyzed data on the outcome of patients undergoing neoadjuvant
anthracycline-based chemotherapy and evaluated nuclear TOP2A protein
expression in breast cancer biopsies by immunohistochemistry (IHC) and
reviewed the pathological responses after completion of neoadjuvant
treatment. Results: From 2002 to 2011, data from 82 patients was
reviewed. Forty nine patients had the paraffin blocks corresponding to the
pre-treatment biopsy. All biopsies had some degree of TOP2A IHC
expression. Patients were considered positive for TOP2A if the level of
expression in IHC was higher than 10%. This was found in 77.6% of cases.
Forty percent of the patients achieved pathologic complete response in
pos-treatment surgical specimens. Correlation was observed between
TOP2A IHC expression and tumor pathological response (p0.02). It was
observed a difference in pathological complete response in favour of the
group positive for TOP2A (47.4% vs. 22.7%), although not significant
(p�0.09). No difference in PFS and OS was observed between patients
with complete response after median follow-up of 34 months. Conclusions:
The expression of TOP2A seems to be a promising marker to predict
pathological response to antracycline-based neoadjuvant chemotherapy in
HER2 breast cancer; however these findings would be better evaluated in
prospective trials.
645 General Poster Session (Board #14H), Sat, 8:00 AM-12:00 PM
Relationship between changes in left ventricular ejection and use of
angiotensin-converting enzyme inhibitors and/or betablockers during adjuvant
trastuzumab chemotherapy in early breast cancer: Data from the real
world. Presenting Author: Francesco Giotta, Medical Oncology Department,
National Cancer Institute of Bari, Bari, Italy
Background: Adjuvant trastuzumab chemotherapy (aTrastC) improves DFS
of pts with breast cancer and overexpression of HER-2. However, cardiovascular
complication (CV) such as heart failure (HF) or significant left
ventricular ejection fraction (LVEF) reduction may appear especially in
those pts at increased CV risk. Methods: 253 women treated with aTrastC
for EBC in 7 italian oncologic centers during the period 2008-2009
entered in a multicenter registry and were retrospectively studied in 4
subgroups according to the treatment with ACEi and/or BB. Occurrence of
symptoms of HF and/or decrease in 10 points % of LVEF were recorded
during the follow up. LVEF was measured at baseline and 3-6-9-12
months. Results: Symptoms of HF occurred in 2% of pts who did not take
either ACEi/ARB or BB. HF event-rate was similarly increased in pts
receiving one or both medications, partially justified by the increased CV
risk in these subgroups. Prevalence of decrease in LVEF � 10 points% was
similar in all study subgroups. Trends in LVEF were characteristics for each
study subgroup: at 3-month evaluation a significant decrease in LVEF was
detected in ACEi/ARB and ACEi/ARB � BB group. Multiple logistic
regression analysis showed that combined ACEi/ARB � BB therapy
depended on history of hypertension (OR 36.7, CI 4.3-315.5) and
reduction of LVEF from baseline to 3-month evaluation (OR 0.88, CI
0.78-0.97) (best prediction – 3.5 points %, AUC 0.78, IC 0.65-0.91).
Conversely, no association was found between changes in LVEF and
ACEi/ARB or BB therapy alone. LVEF recovery from 3 to 12-month
evaluation was inversely related to the changes in LVEF from baseline to
3-month evaluation and did not depend on any pharmacological treatment.
Conclusions: In clinical practice, a history of hypertension and changes in
LVEF during the first 3 months of aTrastC for early breast cancer influence
the use of ACEi/ARB and BB. This behaviour may explain the characteristic
trend in LVEF showed in the subgroups of patient receiving or receiving not
ACEi/ARB or BB. Subsequent recovery of LVEF does not seem to be related
to any medical treatment.
644 General Poster Session (Board #14G), Sat, 8:00 AM-12:00 PM
Time to brain metastasis (TTBM) from initial diagnosis of distant metastasis
in breast cancer: Prediction of TTBM according to breast cancer
subtypes and treatment effect. Presenting Author: Yeon Hee Park, Division
of Hematology-Oncology, Department of Medicine, Samsung Medical
Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Background: Brain metastasis (BM) from breast cancer (BC) is a growing
problem. About 10-15% patients with metastatic breast cancer (MBC)
developed BM, with a 1 year survival of 20%. Currently, one-third of MBC
patients with either HER2�ve tumors or triple negative BC (TNBC) tumors
develop brain metastases. We hypothesized that MBC patients may
predispose to BM differently during the disease courses according to BC
subtype and treatment. We analyzed TTBM from initial diagnosis of distant
metastasis how BC subtypes and treatment affect on TTBM. Methods: We
retrospectively investigated 189 consecutive patients who were diagnosed
with BM from BC between 2000 and 2009 at Samsung Medical Center. We
analyzed TTBM according to BC subtypes and treatment effect. Results:
The median age of 189 BM patients from BC was 48 (range 26-87) years.
The numbers of patients with hormone receptor (HR)�ve and HER2-ve,
HER2�ve irrespective of HR status, and TNBC were 43 (22.8%), 88
(46.6%), and 58 (30.7%), respectively. Median TTBM of all 189 patients
was 10.4 (95% CI, 7.7-13.1) months. We analyzed TTBC into four groups
considering BC subtypes and treatment; HR�ve/HER2-ve (n�43),
HER2�ve with trastuzumab (T) (n�59), HER2�ve without T (n�29), and
TNBC patients (n�58). The median TTBMs for each group were 17.7
months, 13.8 months, 4.3 months, and 2.9 months, respectively
(p�0.002). BM as an initial site of distant metastasis was much more
common in HER2�ve without T and TNBC patients than in the other
patients’ groups (40.2% vs 20.6%, p� 0.003). Conclusions: TTBMs were
much shorter in patients with HER2�ve without T and TNBCs than in other
BC patients. Different approaches for evaluation and therapeutic strategy
for BM at the time of distant metastasis may be considered for these
populations.
TPS646 General Poster Session (Board #15A), Sat, 8:00 AM-12:00 PM
An open-label randomized, multicenter, phase II study on neoadjuvant
treatment with trastuzumab plus docetaxel versus trastuzumab plus
docetaxel plus bevacizumab according to positron emission tomography
(PET) value modification in patients with early stage HER2-positive breast
cancer (AVATAXHER): Design description. Presenting Author: Alexandre
Cochet, Department of Nuclear Medicine, Centre Georges-Francois Leclerc,
Dijon, France
Background: For patients with early HER2� breast cancer at diagnosis,
addition of trastuzumab (T) to 6 cycles of preoperative docetaxel (D) can
reach a pathological complete response (pCR) in ~50% of cases, and a high
rate of conservative surgery. pCR can be predicted by changes of Fluorodeoxyglucose
(FDG) tumor uptake evaluated by Positon Emission Tomography
(PET) after one cycle of therapy. In order to increase this pCR rate, adding
an antiangiogenic compound could be considered. Pre-clinical and phase
I-II data support that the combination of bevacizumab (B) and T is
synergistic and safe when patients are chemotherapy naïve. The neoadjuvant
AVATAXHER trial (EUDRACT 2009-013410-26) investigates the
potential increase of pCR rate by combining B with T and D for patients with
HER2� breast cancer who are not predicted for pCR by FDG PET. Methods:
In this multicenter, open-label, phase II trial, 2 phases are planned after a
selection period: phase I: all patients receive two cycles of therapy
combining T (8 mg/kg at the first cycle, then 6 mg/kg) and D (100 mg/m2 ).
FDG PET is also performed within 7 days before cycle 1 (baseline) and less
than 3 days before cycle 2 in order to calculate changes of the tumor FDG
uptake between baseline and after cycle 1 (�SUV). Phase 2: if �SUV�70%,
patients will continue to receive T and D for (cycles 3 to 6: D 100 mg/m2 �
T 6 mg/kg); if �SUV�70%, patients are randomized 2:1 to arm A (cycles 3
to 6 D 100 mg/m2 � T 6 mg/kg � B 15 mg/kg) or arm B ( cycles 3 to 6: D
100 mg/m2 � T 6 mg/kg). The primary endpoint is pCR rate evaluated
post-surgery 4 to 6 weeks after the last treatment of cycle 6. Enrolment
began in May 2010 and 125 patients were to be recruited in 26 sites.
According to the hypothesis that 60% of patients will have a �SUV�70%,
it is presumed that 72 patients will be randomized. There are currently 107
patients included (as of 06 January 2012 ), 95 of them reached the phase
1; 52 of them (55%) showed a �SUV�70% and after randomization 34
were included in arm A and 18 in arm B.
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