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

64s Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
1060 General Poster Session (Board #22C), Sat, 8:00 AM-12:00 PM
Phase II study of a novel neoadjuvant chemotherapy (NAC) for breast
cancer (BC). Presenting Author: Miguel E. Albino, Veterans Affairs Hospital,
San Juan, PR
Background: The goal of this NAC study was to improve the pathologic
response of pts with localized BC. Methods: 51 pts with localized BC �1cm
were treated with this novel regimen consisting first of docetaxel 75 mg/m 2 ,
epirubicin 80 mg/m2 , and cyclophosphamide 500 mg/m2 (TEC) and PEG
Filgrastim for 4 cycles. Pretreament PET scan was done and repeated after
course 1. Following the 4th course, ER�/HER2- patients received 4
additional TEC cycles if they achieved CR by MRI, or were switched to a non
cross-resistant regimen (vinorelbine, bevacizumab, capecitabine) if they
had � CR. HER2� pts were given docetaxel � trastuzumab for 4 additional
cycles, or were switched to a different regimen if � PR. MD Anderson
residual cancer burden (MDARCB) score was used to measure pathologic
response and correlation with several prognostic factors was studied.
Results: Median age � 53; 27 were postmenopausal; 42 had invasive
ductal carcinoma, 5 invasive lobular; 12 triple negative, 11 HER2�, and
28 ER� or PR�/HER2-. MDARCB was significantly better in HER-2� and
triple negative tumors (table). ER� or PR�/Her2- pts had the least
favorable MDARCB with none achieving 0 and only 21% attaining
MDARCB�1. 59% of pts with � 5% SUV drop attained MDARCB score 0-1
vs 13% with � 5% drop. %Ki-67 correlated well with MDARCB (table).
Ki-67 correlated well with receptor status: 85% of Triple Neg or Her2� pts
had Ki-67 �17 vs only 29% of ER� or PR�/Her2-. Conclusions: a) This
novel NAC regimen leads to markedly favorable MDARCB scores in triple
negative and Her-2� cases. b) Several factors may be useful in predicting
response to chemotherapy, including receptor status, Ki-67, and PET scan
response after 1st chemotherapy course. c) Ki-67 proliferative rate is
closely correlated with receptor status. d) Early PET could be used to
predict MDARCB. The challenge now is to improve response in ER� or
PR�/Her2- pts.
Factor
MDARCB
0
MDARCB
1
MDARCB
2
MDARCB
3 p N
Triple neg or HER2� 18 (82%) 1 (5%) 2 (9%) 1 (5%) 22
ER� or PR�/HER2- 0 6 (21%) 17 (61%) 5 (18%) 0.00001 28
50*
Ki-67 >17 13 (54%) 2 (8%) 8 (33%) 1 (4%) 24
Ki-67 < 17 2 (9%) 5 (22%) 11 (48%) 5 (22%) .04 23
% drop SUV > 5% 18 (44%) 6 (15%) 14 (34%) 3 (7%) 41
% drop SUV < 5% 0 1 (13%) 4 (50%) 3 (38%) .04 8
*One progressed in liver while on treatment and did not undergo surgery.
1062 General Poster Session (Board #22E), Sat, 8:00 AM-12:00 PM
Current patterns of chemotherapy and supportive care for early-stage breast
cancer (ESBC). Presenting Author: Gary H. Lyman, Duke University,
Durham, NC
Background: ESBC is commonly treated with myelosuppressive chemotherapy,
and high relative dose intensity (RDI) correlates with improved
overall survival. A retrospective analysis of patients with ESBC treated from
1997–2000 showed that 56% received an RDI � 85% (Lyman et al. JCO.
2003;21:4524-4531). To determine current practice, we evaluated ESBC
treatment patterns at 24 US community- and hospital-based oncology
practices. Methods: Data were abstracted from medical records of 532
patients with ESBC treated from January 2007–December 2009. Inclusion
criteria included surgically resected ESBC (stage I-IIIA); � 18 years old;
and completion of at least 1 standard chemotherapy cycle on an every 2 or
3 week schedule. The primary endpoint was RDI over planned cycles. Other
endpoints were incidence of dose delays � 7 days, dose reductions � 15%
from standard, grade 3/4 neutropenia (SN), febrile neutropenia (FN),
FN-related hospitalization, granulocyte-colony stimulating factor (G-CSF)
use, and antimicrobial therapy. Descriptive statistics were generated for all
endpoints. Results: In this study, mean (range) age was 55 (29–85) years.
Relative to previously published results, chemotherapy regimens have
shifted from mainly doxorubicin � cyclophosphamide (AC) (previously
35%) to docetaxel � cyclophosphamide (TC; n � 221; 42%) and AC
followed by paclitaxel (AC-T; n � 163; 31%). Mean RDI is now higher
(93% for both TC and the most common AC-T schedule [dose dense AC-T;
n � 84] vs 79% previously); the incidence of dose delays (16% vs 25%
previously) and dose reductions (21% vs 37% previously) have decreased;
and primary prophylactic use of G-CSF has increased (76% vs 3%
previously). In this study, 40% of patients had SN, 3% had FN, 2% had an
FN-related hospitalization, and 30% received antimicrobial therapy. These
measures were not available in the previously published results. Conclusions:
The observed changes between the two studies are noteworthy though
inferential comparisons are limited by changes in treatments and other
factors. RDI has improved over time, but 16% of patients in this study
received an RDI � 85%. Further evaluation is needed to identify factors
associated with lower RDI and determine outcomes for these patients.
1061 General Poster Session (Board #22D), Sat, 8:00 AM-12:00 PM
The first two lines of chemotherapy for anthracycline-naïve metastatic
breast cancer: A comparative study of efficacy between anthracyclines and
nonanthracyclines. Presenting Author: Wei-Wu Chen, National Taiwan
University Hospital, Taipei, Taiwan
Background: For anthracycline-naïve metastatic breast cancer (AN-MBC)
patients, past evidence indicated that anthracyclines are beneficial in the
first-two lines of palliative chemotherapy but with considerable toxicities.
However, with the provision of newer chemotherapies, comparative studies
addressing the efficacy between anthracyclines and non-anthracyclines in
the first-two lines of palliative chemotherapy for AN-MBC were lacking.
Methods: We collectedclinicopathological characteristics of AN-MBC patients
who had received palliative chemotherapy in National Taiwan
University Hospital between 2001 and 2006. Patients were classified as
anthracycline or non-anthracycline group according to the first-two lines of
chemotherapy. Kaplan-Meier method and log-rank test were used for the
estimation and comparison of both overall survival (OS) and time to
treatment failure of the first-two lines (TTF2).Cox proportional hazard
model was used for OS and TTF2. Best composite response rate (BCRR)
were compared with logistic regression test. Results: A total of 109 (43.1%)
patients in the anthracycline group and 144 (56.9%) patients in nonanthracycline
group were analyzed. Between these two groups, the distributions
of clinicopathological variables were generally similar and their
median OS (33.3 vs 34.2 months, p � 0.179), TTF2 (13.3 vs 12.7
months, p � 0.104), and BCRR (59.5 vs 61.1%, p � 0.81) were not
significantly different. Subgroup analysis showed that patients in the
anthracycline group had a trend toward better OS in the estrogen receptor
(ER) negative/ human epidermal growth factor receptor type II (HER2)
positive subtype (median OS 58.0 vs 31.2 months, p � 0.081). In
multivariate analysis, patients in the anthracycline group had a trend
toward better OS (HR 0.72, 95% CI 0.52 - 1.00, p � 0.052). However, the
exclusion of ER-/Her2� subtype attenuated the impact of early anthracycline
treatment on OS (HR 0.82, 95% CI 0.56 - 1.18, p � 0.28).
Conclusions: Our study demonstrated that anthracyclines may not be
mandatory in the first-two lines of palliative chemotherapy for AN-MBC but
may be more beneficial to ER-/Her2� subtype patients.
1063 General Poster Session (Board #22F), Sat, 8:00 AM-12:00 PM
Chemotherapy of methioninase-synchronized S/G2 phase-blocked cancer
cells identified by cell cycle-specific fluorescent reporters. Presenting
Author: Shuya Yano, AntiCancer Inc., San Diego, CA
Background: Cancer cells of all types have a generally elevated requirement
for methionine compared to normal cells. This phenomenon is termed
methionine-dependence and may be due to excessive methylation reactions
in cancer cells, since methionine is the global source of cellular
methyl groups (Biochim. Biophys. Acta, Reviews on Cancer 738, 49-87,
1984). Deprivation of methionine selectively arrests cancer cells during
late S-phase (Proc. Natl. Acad. Sci. USA 77, 7306-7310, 1980), where
they are highly sensitive to chemotherapy drugs which damage DNA (J.
Natl. Cancer Inst. 76, 629-639, 1986). Methods: Cancer cells, transformed
to express different color fluorescent reporters during specific
phases of the cell cycle (Cell 132, 487-498, 2008), were used to monitor
the onset of the S/G2-phase block due to methionine deprivation effected
by recombinant methioninase (rMETase). The S/G2-phase blocked cancer
cells fluoresced yellow or green in contrast to cancer cells in G1 which
fluoresced red. Cancer cells, including MKN45 stromal cancer and MCF-7
breast cancer, synchronously blocked in S/G2-phase by rMETase, were
identified by their yellow-green fluorescence and allowed to accumulate to
the maximum extent. At the point of maximum yellow/green cells in the
culture, the cells were administered chemotherapy drugs which interact
with DNA or block DNA synthesis such as doxorubicin, cisplatin or
5-fluorouracil. We termed this procedure color-coded chemotherapy (CCC).
Results: CCC was highly effective against the cancer cells (90% cell kill). In
contrast, treatment of cancer cells with drugs only, and without rMETaseeffected
S/G2-phase synchrony, led to the majority of the cancer cell
population being blocked in G1 phase (red fluorescent) where they were
resistant to the drugs (40% cell kill). Conclusions: CCC, which identifies, by
fluorescent color, when cancer cells are blocked in S/G2-phase by a unique
cell-cycle-blocking agent, rMETase, demonstrates the potential of cellsynchronization-based
chemotherapy.
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