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

1048 General Poster Session (Board #20G), Sat, 8:00 AM-12:00 PM
Racial differences in outcomes of triple-negative breast cancer. Presenting
Author: Jose Pacheco, Washington University, St. Louis, MO
Background: The incidence and mortality of breast cancer can differ
significantly among racial and ethnic groups. African American (AA) women
have a lower incidence of breast cancer, but higher mortality compared to
other racial groups. Triple negative breast cancer (TNBC: negative for the
expression of estrogen receptor, progesterone receptor and HER2), which is
an aggressive type of breast cancer, occurs more frequently in AA women.
The few studies addressing whether racial differences exist in the outcomes
of patients with TNBC have yielded inconsistent results. Methods: The
Washington University Medical Oncology Database captures the clinical
information for all new patients (pts) seen at the Breast Oncology Clinic.
Most of these pts reside in the St. Louis metropolitan area. Using this
database, we performed a retrospective analysis to examine the association
of race with the clinical presentation and outcome of TNBC in this
geographically defined patient population. Results: Between May 2006 and
March 2011, 506 pts with TNBC were entered in the database. Analysis
was done on 499 patients for whom follow up data is available. The median
follow up (F/U) time was 24.5 months and the median age at diagnosis was
53 (24 to 98) years. Thirty percent of pts were AA. Only 5% presented with
stage IV at diagnosis and the majority of tumors (86%) were high grade.
Neoadjuvant chemotherapy was administered in 151 pts, 22% of whom
achieved a pathologic complete response (pCR). There was no significant
difference between races in the age of diagnosis, F/U time, tumor stage,
grade, frequency of receiving neo/adjuvant chemotherapy and pCR rate to
neoadjuvant chemotherapy. There was no difference in disease free survival
(DFS) and overall survival (OS) between AA and other racial groups by
either univariate or multivariate analysis that took into account tumor
stage, grade, patient age and menopausal status. The HR for OS was 1.154
(CI 0.772 – 1.725, p value 0.4860) and for DFS it was 0.947 (CI 0.650 –
1.380, p value 0.7764) in AA compared to other races. In the 92 pts who
recurred, there was no racial difference in time from recurrence to death.
Conclusions: Race does not significantly affect the clinical presentation or
outcome of TNBC in the St. Louis metropolitan area.
1050 General Poster Session (Board #21A), Sat, 8:00 AM-12:00 PM
Evaluation of a multiparametric system able to predict nonsentinel lymph
node status in breast cancer patients with a micrometastatic sentinel node
assessed by the one step nucleic acidamplification (OSNA) assay. Presenting
Author: Simonetta Buglioni, Regina Elena National Cancer Institute,
Rome, Italy
Background: Axillary lymph node dissection (ALND) may not be necessary in
women with breast cancer (BC) who have micrometastasis in a sentinel
lymph node (SLN), owing to the low risk of non-SLN (NSLN) involvement.
In our Institute we validated and adopted the molecular diagnostic tool
OSNA based on the quantitative measurement of Cytokeratin 19 (CK19)
mRNA.The aims of our work in a subgroup of women with micrometastatic
SLN, were: 1) to correlate the copy numbers of CK19 mRNA with the risk of
additional positive NSLNs; 2) to assess the relationships between the
molecular subtype classification and the probability of a positive ALND; 3)
to verify whether a combination of the new above mentioned parameters is
able to identify a subgroup of patients with a micrometastatic SLN and a
negligible risk of positive NSLNs in whom ALND may be avoided. Methods:
The SLN lysates from 709 patients were analyzed by OSNA assay. We
considered only patients with a micrometastatic SLN (copy numbers
between 250 and 5000/�L) and the probability of having a positive ALND
was calculated by the logistic regression model. This series of BC patients
were divided into four main subtypes taking in account the BC classification
as defined by a combination of estrogen, progesteron receptors and
HER2 status. Results: OSNA positivity for micrometastasis was reported in
91/709 cases (12,8%).The number of patients with positive ALND was 20
(22%). The statistical analyses showed that the metastatic involvement of
NSLNs is associated with SLNs with a high copy numbers (�2000) of
CK19 mRNA together with HER2 subtype. Otherwise none of the luminal A
patients with a positive SLN but presenting a copy number �1000, had a
positive NSLNs. Conclusions: We showed that biologically-driven analyses
may be able to build new models with higher performance in terms of breast
cancer axillary status prediction after positive SLN biopsy for micrometastasis.
The copy numbers of CK19 mRNA and the molecular subtypes are
more advantageous than traditional parameters because they are not
pathologist-dependent and therefore they are more reliable and reproducible.
Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
1049 General Poster Session (Board #20H), Sat, 8:00 AM-12:00 PM
A prognostic model for predicting breast cancer (BC)-related survival in
operable triple-negative (TN) patients (pts). Presenting Author: Elisabetta
Munzone, European Institute of Oncology, Medical Oncology, Milan, Italy
Background: TNBC represent a heterogeneous disease in terms of biology,
prognosis, and treatment response. We propose a prognostic model to
identify homogeneous subgroups of patients and tailor risk-adapted adjuvant
therapies indications. Methods: We analyzed 1,049 pts operated in our
institute from 1997 to 2007 for early TNBC. Pts who received neoadjuvant
chemotherapy (CT), with T4 tumors or previous history of cancer were
excluded. Death from BC was the primary endpoint of the study. We
calculated an individual predicted risk using a multivariable Cox regression
model, with age, tumor size, number of positive lymph nodes and Ki-67
analyzed as continuous covariates, and tumor grade and perivascular
invasion as categorical covariates. Results: Median age was 52 years, 562
(53.4%) and 670 (65.1%) pts had a pT1 and pN0 TNBC, respectively.
Median Ki-67 was 48%. Adjuvant CT regimens were distributed as follows:
classical CMF 388 (37.0%), anthracycline containing regimens 455
(43.4%), taxanes 12 (1.1%), other regimens 66 (6.3%) and no CT 128
(12.2%). After a median follow-up of 6 years, 131 deaths from BC were
observed (5-year cumulative incidence 11.9%). At multivariable analysis,
age, tumor size, number of positive lymph nodes, Ki-67, tumor grade and
perivascular invasion were associated with the risk of death and were
included in the prognostic model. Its predictive accuracy was good (C-index
0.73). We subsequently identified three homogeneous prognostic subgroups
- low, medium and high-risk - according to the tertiles values of the
predicted risk. The outcomes are shown in the table. Conclusions: We could
identify homogeneous prognostic subgroups of TNBC pts according to
clinical-pathological features. This prognostic model suggests that the use
of CT in TN low-risk pts might be questionable. We are currently externally
validating this model on a different series of pts.
Risk subgroup Treatment No. (%)
Deaths
from BC
61s
5-year
survival % P value
Low-risk CT 262 (75.1) 15 95.5 0.72
No CT 87 (24.9) 4 96.2
Medium-risk CT 326 (93.1) 31 91.0 0.29
No CT 24 (6.9) 4 81.6
High-risk CT 334 (95.4) 70 78.8 0.03
No CT 16 (4.6) 7 53.9
1051 General Poster Session (Board #21B), Sat, 8:00 AM-12:00 PM
Impact of biomarkers in predictivity of the efficacy and toxicity of a
combination of panitumumab plus FEC 100 followed by docetaxel in a
phase II neoadjuvant trial for triple-negative breast cancer (TNBC) patients.
Presenting Author: Jean-Marc Nabholtz, Centre Jean Perrin, Clermont-
Ferrand, France
Background: We evaluated the combination of a standard chemotherapy
with panitumumab as neoadjuvant therapy of operable TNBC. Complete
pathologic response (pCR) was the primary endpoint, with toxicity and
biologic ancillary studies as secondary endpoints. Methods: Sixty patients
with stage II-IIIA disease were prospectively included in this multicentre
pilot study. Systemic therapy (ST) consisted of 4 cycles of FEC 100
(500/100/500 mg/m2 ) q.3 weeks followed by 4 cycles of T (100 mg/m2 )
q.3 weeks, in combination with panitumumab (9 mg/kg) for 8 cycles q.3
weeks. All patients underwent surgery at completion of ST. Paraffinembedded
samples and frozen samples have been systematically realised
before and after neaodjuvant treatment in order to evalutate the biological
profile of the tumor. Patients characteristics are : median age 50 ; median
tumor size : 40 mm ; invasive ductal carcinoma : 96% ; Scarff-Bloom-
Richardson Grade III : 70%, grade II : 30%, ki-67-positive : 100%,
EGFR-positive : 78%, cytokeratine5-6-positive : 48% and p53-positive :
59%. Pathological response showed a pCR according to Sataloff’s classification
of 52.38% and according to Chevallier’s classification of 46.52%.
Skin toxicity was the main side-effect : Cutaneous toxicity grade IV : 5%,
grade III : 30%, grade II : 20%. Neutropenia grade IV : 27% ; febrile
neutropenia : 5%. Infection : 0%. Hand-foot syndrome grade III : 3.3%.
Ungueal toxicity grade III : 1.6%, grade II : 20%. Results: We have tested
the predictive value of ki-67, EGFR, cytokeratine 5-6 and p53. Only ki-67
is predictive of a pCR according to Chevallier’s classification (p�0.026),
with a cut-off of 40% of positive cells (ROC curve): 62% of pCR if ki-67�
40% versus 23% if not (relative risk : 2.7). Low EGFR, high p53, and high
cytokeratine 5-6 tended to be associated with poor reponse. No correlations
were found between cutaneous toxicities and these biomarkers. The
cutaneous toxicities were not predictive. Conclusions: HighKi-67 is predictive
of more pCR. High EGFR, low p53 and low cytokeratine 5-6 tended to
be associated with better response, but the data are not significant.
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