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

590 General Poster Session (Board #8A), Sat, 8:00 AM-12:00 PM
Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in ER�
HER2- breast cancer. Presenting Author: Hiroshi Yagata, St. Luke’s
International Hospital, Tokyo, Japan
Background: Recently, docetaxel plus cyclophosphamide (TC) has been
established as a standard regimen for adjuvant chemotherapy in operable
breast cancer. However, the efficacy of TC as neoadjuvant chemotherapy
remains unclear, especially in hormone-responsive breast cancer. We
prospectively evaluated the response to TC neoadjuvant chemotherapy in
patients with ER� HER2- operable breast cancer. Methods: Eligible
patients had ER� and HER2- invasive breast cancer that measured more
than 2 cm in diameter or was node-positive clinically between March 2009
and February 2011. Four cycles of TC (75 and 600 mg/m2 ) were
administered intravenously every 3 weeks as neoadjuvant chemotherapy,
followed by breast and axillary surgery. We investigated the clinical
response on MRI and the pathological complete response (pCR) of primary
invasive breast tumors. Results: We enrolled 43 patients in 45 lesions.
Allred score of ER was 7 to 8 in 40 lesions, 6 in 3 lesions and 4 in 2 lesions.
PgR was 7 to 8 in 31 lesions, 5 to 6 in 6 lesions, 3 to 4 in 5 lesions, and 0 in
3 lesions. Nuclear grade was 1 in 31 lesions, 2 in 7 lesions, and 3 in 7
lesions. MIB-1 index was median 22% (range, 6 to 71%) in 40 measurable
lesions. Clinical response (CR and PR) was observed in 33 lesions (73%)
and SD in 12 lesions without any lesions of clinical PD. pCR was achieved
in only 1 lesions (ER 8, PgR 3, Nuclear grade 3, MIB-1 index 32.6%).
Conclusions: Neoadjuvant TC produced a good clinical response in ER�
HER2- operable breast cancer, while the pCR rate was very low, regardless
of the characteristics of cancer cells. Therefore, pCR is not an appropriate
prognostic factor in women with ER� HER2- operable breast cancer who
receive neoadjuvant TC. Whether clinical response is related to survival
should be addressed in future studies. The efficacy of neoadjuvant TC in
ER� HER2- operable breast cancer is very limited, and more effective
regimens are needed to achieve higher pCR rates.
592 General Poster Session (Board #8C), Sat, 8:00 AM-12:00 PM
ESR1 gene amplification and protein expression in 946 patients with
resected breast cancer: A Hellenic Cooperative Oncology Group (HeCOG)
translational research study. Presenting Author: George Pentheroudakis,
Hellenic Cooperative Oncology Group, Athens, Greece
Background: Discrepant data have been reported on the incidence of ESR1
gene amplification in breast cancer, its correlation to clinicopathologic
characteristics and its impact on prognosis. Methods: Formalin-fixed
paraffin-embedded (FFPE) tumor tissue samples from 946 patients participating
in two adjuvant chemotherapy phase III trials (HE10/97 and
HE10/00) were centrally assessed in tissue microarrays by immunohistochemistry
(IHC) for estrogen receptor (ER), progesterone receptor (PgR)
and human epidermal growth factor receptor 2 (HER2). FISH was also
performed for HER2, TOP2A and ESR1 using commercially available dual
(for ESR1) and triple (for HER2 and TOP2A) hybridization probes. Results:
The majority of patients had �T2 (69%), node-positive, ER-positive (�1%
stained cells, 73%) tumors managed with resection, chemotherapy and
hormonotherapy (76%). Only 38 tumors (4.0%) had ESR1 gene amplification
(ESR1/CEN6 ratio �2) and 514 (54.3%) ESR1 gene gain (1�ratio�2).
The number of ESR1 gene copies was 3-4 in 251 (26.5%) and
5-10 in 42 (4.4%) of cases. HER2 and TOP2A gene amplification was seen
in 234 (25.3%) and 101 (10.9%) of tumors, respectively. We studied the
immunohistochemical expression of ER protein by evaluating the percentage
of stained cells, the Allred score (0-2, 26.8%; 3-6, 62.5%; 7-8,
10.7% of tumors) and the semiquantitative H-Score (50-100, 13.8%;
101-200, 36.8%; 201-300, 15% of tumors). ESR1 gene amplification
was significantly associated with taxane therapy, age �50, postmenopausal
status, grade III-IV, absence of HER2 amplification and ER protein
expression (p�0.05). At a median follow-up of 92 months, univariate Cox
regression analysis showed that ER protein expression, but not ESR1 gene
status, was a predictor of favorable outcome. In multivariate analysis,
tumor size �5 cm, �4 involved nodes and negative/low ER protein
expression by Allred score were independent adverse prognostic factors.
Conclusions: Our data showed a rather low incidence of ESR1 gene
amplification and failed to confirm its prognostic/predictive utility. ESR1
mRNA expression data will be presented at the meeting.
Breast Cancer—HER2/ER
29s
591 General Poster Session (Board #8B), Sat, 8:00 AM-12:00 PM
A short-term neoadjuvant pilot study comparing exemestane and letrozole
in postmenopausal women with estrogen receptor-positive HER2-negative
breast cancer. Presenting Author: Daishu Miura, Toranomon Hospital,
Tokyo, Japan
Background: Current approaches of neoadjuvant endocrine therapy (NAET)
are focusing on biomarker analysis of the diagnostic specimens. One of the
important things in neoadjuvant treatment is to determine the in-vivo
responsiveness to the agent. Little is known regarding biomarker changes in
specific agents and the association with biomarker changes and treatment
duration. A pilot study was conducted to investigate the differences of
biomarker changes in short-term NAET (letrozole vs. exemestane) and also
the difference in treatment durations of each AI. Methods: Totally 120
samples from 60 postmenopausal women with ER positive HER2 negative
stage 1-3 breast cancers in NAET comparing letrozole (LET) and exemestane
(EXE) were analyzed with pre- and post-treatment mRNA expression of
ER�,ER�, PR, HER2, Ki67, PIK3CA, and MAPK using QuantiGene Assay.
Thirty-one patients took letrozole 2.5mg daily and 29 did exemestane
25mg daily until the surgery (median duration 22 days). Statistical tests
were two-sided. Results: Clinical characteristics were well balanced between
the two treatment arms. Median % changes of Ki67 were -58%, ER�
-44%, ER� �93%, and PR -69% in LET and Ki67 -59%, ER� -30%, ER�
�135%, PR -72% in EXE. There were no significant differences of these
marker changes between two agents. Dividing into 4 groups in treatment
duration, 10-14 days (q1), 15-21 days (q2), 22-28 days (q3), and over 29
days (q4), LET had 2 peaks in Ki67 decreases (-69% (q1), -28% (q2),
-78% (q3), -59% (q4)), whereas EXE had a peak in q2 (-62%, -77%,
-49%, -26%). Ki67 increasing cases including primary resistance and
tachyphylaxis were 5 (16%) in LET (3 in q2 and 2 in q4) and 3 (10%) in
EXE (one of each in q2-4). All 8 cases had increases of ER�, PIK3CA, and
MAPK. Conclusions: Although both LET and EXE for short duration had
significantly decreased Ki67 mRNA level irrespective of treatment duration,
no significant differences was found between two agents. Tumor
resistance with AIs may be associated with the other pathways.
593 General Poster Session (Board #8D), Sat, 8:00 AM-12:00 PM
Real-world aromatase inhibitor use and failure in women with metastatic
ER�/HER2- breast cancer. Presenting Author: Pamela Landsman-
Blumberg, Thomson Reuters, Washington, DC
Background: Aromatase Inhibitors (AIs) have replaced tamoxifen as firstline
therapy for postmenopausal women with metastatic, ER� breast
cancer (BC). However, little information is available on the real-world use of
AIs. The objectives of this retrospective claims study were to compare
demographic, clinical and treatment characteristics of postmenopausal
women with metastatic ER�/HER2- BC treated with AIs and experiencing
0, 1, 2 or � 3 AI failures (AIF). Methods: Women � 55 years old, newly
diagnosed with metastatic BC (index) were identified in the 2006-2010
Thomson Reuters MarketScan databases and followed until chemotherapy
or 03/31/2011. ER�/HER2- disease was defined as any endocrine therapy
(ET: tamoxifen, fulvestrant) or AI (anastrozole, letrozole, or exemestane)
use and no trastuzumab or lapatinib use in the 6-month pre-or variable
post-index periods. Those with any post-index AI use were retained for
study. AIF post-index was defined as a switch to an alternative AI, ET or
chemotherapy, or AI discontinuation with no further BC treatment. Patients
were stratified by number of post-index AIF: 0, 1, 2 or � 3. Results: Among
4,274 patients identified, 61% had � 1 AIF (1: 80%, 2: 15%, �3: 5%).
There was no difference in pre-index AI use across AIF cohorts: 0, 1, 2, and
�3 (54%, 52%, 48%, 56%; p�0.073). AIFs increased with Medicareeligibility
(51%, 56%, 60%, 61%) and bone metastases at index (48%,
53%, 62%, 63%). Among those with �1 AIF, median follow-up (FU)
increased with each failure but there was no notable pattern to reason for
FU end. Median FU of the 0 AIF cohort (408 days) fell between those of the
1 and 2 AIF cohorts, 335 and 517 days. Anastrozole was the most common
first line treatment for all cohorts except � 3 AIFs where letrozole was most
common. Pre-index and first line fulvestrant use both increased with the
number of post-index AIFs: 0.3%, 1.9%, 2.0%, 5.0% and 0.7%, 2.5%,
4.0%, 14.9% respectively. There was no association between number of
AIFs and chemotherapy use (36%, 29%, 38%). Conclusions: Over 60% of
women with ER�/HER2- metastatic BC treated with AIs failed at least 1
and 20% of those failed � 2. Surprisingly, increased rates of prior
fulvestrant treatment appear associated with increasing numbers of AIF.
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