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

70s Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
1084 General Poster Session (Board #25C), Sat, 8:00 AM-12:00 PM
Reduction of ovarian reserve in young early breast cancer patients: First
data of a prospective cohort trial. Presenting Author: Lea Sanders, OB/GYN,
University of Kiel, UKSH, Kiel, Germany
Background: Breast cancer is the most common malignancy in premenopausal
women. Sideeffects of chemotherapy are well known nevertheless
the precise effects on ovarian function are inadequately studied by now.
Premenopausal women undergoing chemotherapy are at risk for symptoms
of sexual hormone deficiency and impaired fertility. Searching for predictive
parameters of ovarian reserve after chemotherapy this prospective
cohort study has been set up. Methods: 36 young patients with primary
breast cancer have been included in this trial after written consent (April
2010 to November 2011) and after the study was approved by the local
review board. All women were premenopausal (� 46 years). They all
received anthracycline based “A” neo- or adjuvant chemotherapy (as FEC)
or combinations with taxanes “T” ( as TAC or FEC/Doc). Before and 6 and
12 months after initiation of chemotherapy age and chemotherapy related
changes in hormone (LH, FSH, E2 and Anti-Müllerian hormone) levels,
antral follicel count and amenorrhea as parameters of endocrine function
and fertility were assessed.The additional impact of parity, BMI and
nicotine use on ovarian reserve was also evaluated. Results: There is a
correlation of antral follicle count before and 1 year after chemotherapy and
a negative correlation of age and follicle count before and after chemotherapy
(n.s.). This analysis shows that patients receiving “T” compared to
those with “A” have a significant increase of LH (p�0.025) and FSH
(mean:24 vs.59 IU/l, p�0.021) between visit 1 and 3. The type of
chemotherapy has no influence on antral follicle count and AMH levels
within the first 3 visits. BMI is negatively correlated with AMH at all time
points (n.s.). BMI, nicotine abuse and age have no influence on the
duration of amenorrhea, whereas patients with �T� showed 12 months of
amenorrhea instead of 9 months in patients with �A� (n.s.). Conclusions: Our
study will contribute to a better understanding and prediction of ovarian
reserve of young early breast cancer patients undergoing chemotherapy.
The 12 months follow up data suggest to offer fertility preserving measures
before chemotherapy especially to patients planned for taxane containing
chemotherapy.
1086 General Poster Session (Board #26B), Sat, 8:00 AM-12:00 PM
Amrubicin as second- or third-line treatment for patients with HER2negative
metastatic breast cancer (MBC): A phase II trial of the Sarah
Cannon Research Institute (SCRI). Presenting Author: John H. Barton,
Tennessee Oncology, PLLC/Sarah Cannon Research Institute, Nashville,
TN
Background: Anthracyclines demonstrate significant activity in breast
cancer, but the potential for cardiotoxicity is dose-limiting. Amrubicin is a
novel anthracycline with broad-spectrum preclinical activity and low
potential for cardiotoxicity. We present phase II results from a phase I/II
trial of amrubicin as second/third- line therapy for HER2- negative MBC.
Methods: Women with measurable HER2-negative MBC with 1 or 2 prior
chemotherapy regimens for metastatic disease and normal LVEF were
eligible. Prior anthracycline- containing adjuvant therapy was allowed.
Amrubicin 110 mg/ m2 IV every 3 weeks was administered until disease
progression or intolerable toxicity. Tumor assessments were performed
every 6 weeks and LVEF assessments every 12 weeks. The primary
endpoint was progression free survival (PFS); a median PFS � 4.5 months
was considered a study result meriting further development of amrubicin.
Results: 48 evaluable patients (pts) were treated from 1/2010 to 9/2011.
Baseline characteristics included median age 57; 23% were triplenegative;
33% had 2 prior chemotherapy regimens for MBC; 38% had
anthracycline- containing adjuvant therapy. Median treatment duration
was 6 weeks (2 cycles), range 1- 12� cycles. 8 pts (17%) had objective
RECIST responses (1 CR, 7 PR); 5 of the 8 responders had received
anthracycline-containing adjuvant therapy. 24 additional pts (50%) had
stable disease at first reevaluation. The median PFS for all patients was 2.8
months (95% CI 1.6- 4.0 months); median PFS was similar for pts with 1
vs 2 previous regimens for MBC (95% CI 2.5 vs 4.0 months). 24% of pts
were progression-free at 6 months. Neutropenia was the most common
grade 3/4 toxicity (63%; 6% febrile neutropenia). No grade 3/4 nonhematologic
toxicity occurred in � 5% pts. No cardiotoxicity occurred. Only
1 pt discontinued amrubicin due to toxicity (grade 2 fatigue). Conclusions:
Amrubicin had good tolerability, no cardiotoxicity and was active as a
second/third-line treatment for HER2- negative MBC, including pts previously
treated with adjuvant anthracyclines. The median PFS was comparable
to other standard single agents in the MBC setting.
1085 General Poster Session (Board #26A), Sat, 8:00 AM-12:00 PM
Methallotionein expression and outcome in patients with metastatic breast
cancer (MBC). Presenting Author: Jorge Arturo Rios-Perez, University of
Pittsburgh Cancer Institute, Pittsburgh, PA
Background: Platinum-based agents are important components of therapy
of metastatic breast cancer (MBC) and triple negative breast cancer. Their
use can be limited by development of resistance. Metallothioneins (MT) are
low molecular weight proteins believed to bind bivalent metal ions such as
platinum and zinc. MT expression has been associated with decreased
survival in breast cancer patients. A proposed mechanism confers resistance
to platinum-based agents by their inactivation or limitation of their
activity by MT binding. Methods: MT expression in 99 women with MBC
(selected at random from our database of 800 women with MBC) was
determined from primary breast cancer tissue (n�80) or metastatic tissue
n�19). MT expression was determined by immunohistochemistry, and
graded as negative, weak, moderate or strong. Clinical data was obtained
through our database and supplemented by chart review. Overall survival
from breast cancer diagnosis (OS), progression free survival for first
metastastic regimen (PFS), and time from first metastasis to death or last
update (metastatic survival, MS), were calculated through December 2011
using the log rank test. Results: Consistent with prior studies, moderate to
strong MT expression was associated with decreased 5-year OS (p�.03).
There was no correlation between MT expression and PFS or MS in this
cohort. Surprisingly, MT expression at any degree was strongly associated
with better MS in patients with MBC that received carboplatin-based
regimens in the first line (n�25, p�.0005) or at any line (n�41,
p�.0437). Conclusions: Consistent with prior studies, MT expression was
associated with decreased survival in patients with MBC. Surprisingly, MT
expression was associated with longer MS in patients with MBC that
received carboplatin. These findings are inconsistent with the hypothesis
that MT expression causes chemoresistance to platinum based agents in
patients with metastatic breast cancer. Further studies are needed to
elucidate the mechanisms behind these findings.
1087 General Poster Session (Board #26C), Sat, 8:00 AM-12:00 PM
BCL2 protein in prediction of relapse in triple-negative breast cancer
(TNBC) treated with adjuvant anthracycline-based chemotherapy. Presenting
Author: Katerina Bouchalova, Laboratory of Experimental Medicine,
Institute of Molecular and Translational Medicine, Palacky University,
Olomouc, Czech Republic
Background: Preclinical data show an association of BCL2 expression and
resistance to anthracyclines. The absence of BCL2 expression in prechemotherapy
samples is associated with a higher probability of pathological
complete response to neoadjuvant doxorubicin-based chemotherapy. The
aim of our research is identification of markers predicting sensitivity to
adjuvant treatment in TNBC. Here we focus on BCL2 protein as a putative
predictor of sensitivity to adjuvant anthracycline-based chemotherapy. The
objective was to determine whether BCL2 expression predicts relapse in
TNBC patients treated with anthracycline-based regimens. Methods: The
study included 187 patients with TNBC, 178 of whom were treated with
adjuvant chemotherapy (164 had anthracyclines). BCL2 analysis was
performed using IHC, proportion score and intensity score were counted.
The data were analysed with software Statistica and R. Results: High BCL2
expression predicts poor relapse free survival (RFS) in patients treated with
adjuvant anthracycline-based regimens (logrank p�.035, hazard ratio, HR
2.37, 95%CI 1.04-5.41). High BCL2 predicts trend to poor overall survival
(OS) in patients treated with adjuvant anthracycline-based regimens
(logrank p�0.075, HR 2.31, 95%CI 0.90-5.97). In univariate analysis of
anthracycline treated patients, stage (RFS p�.0004, OS p�.0005), size
(RFS p�.003, OS p�.00009) and nodal status (RFS p�0.018, OS
p�.028) were associated with outcome, as well. In multivariate analysis of
athracycline treated patients, BCL2, size and nodal status had an independent
predictive significance for both RFS (p�.005, p�.056, p�.003)
(logrank test, p�0.0004) and OS (p�.014, p�.006, p�.012) (logrank
test p�0.0007). Conclusions: This study is the first to prove that high BCL2
expression predicts poor outcome in TNBC treated with adjuvant anthracycline-based
chemotherapy. BCL2 expression could facilitate decision
making on adjuvant treatment in TNBC patients and its assessment should
be included in standard diagnostics. In patients with high BCL2 expression
other types of adjuvant treatment should be considered. Grants: IGA
NS10286,IGA NS10357-3 and Biomedreg CZ.1.05/2.1.00/01.0030.
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