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

60s Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
1044 General Poster Session (Board #20C), Sat, 8:00 AM-12:00 PM
Association of body mass index and outcome in advanced breast cancer.
Presenting Author: Claudia Andreetta, Department of Oncology, University
Hospital of Udine, Udine, Italy
Background: Obesity represents a well-known risk factor for the development
of breast cancer and an adverse prognostic factor in early disease.
Overweight is associated with reduced efficacy of aromatase inhibitors in
adjuvant setting. Few data have been reported about the potential relationship
of overweight and outcome in advanced breast cancer (ABC). Methods:
We retrospectively evaluated body mass index (BMI) in a consecutive series
of 400 ABC patients treated at our institution. BMI was calculated at
baseline of diagnosis of ABC. We evaluated association of BMI and other
prognostic and predictive markers with Progression Free Survival (PFS) and
Overall Survival (OS). We evaluated PFS at first and subsequent lines of
chemotherapy (CT) and endocrine therapy (ET). Overweight patients were
defined as having BMI � 25. Results: Overweight patients were 52%.
Median age of the population was 58 years. Median OS was 33.7 months.
Overall, 76% of patients presented with ER� and 17.7% with HER2�
ABC.Overweight was associated with increased age at diagnosis, menopausal
status and luminal B or triple negative immunophenotype. At
multivariate analysis, BMI � 25 was associated with better PFS at first-line
ET (HR� 0.68, 95% CI 0.46-0.99). BMI was not associated with OS.
Conclusions: BMI at baseline does not seem to be an adverse prognostic
factor for ABC patients. Overweight may be associated with better PFS in
endocrine responsive ABC treated with ET, especially in first-line setting.
The role of BMI in ABC deserves to be further investigated.
1046 General Poster Session (Board #20E), Sat, 8:00 AM-12:00 PM
Patterns in circulating microRNA in black (B) versus white (W) patients
with triple-negative (TN) breast cancer (BC). Presenting Author: Iuliana
Shapira, Hofstra North Shore-LIJ School of Medicine, Lake Success, NY
Background: Breast cancer is by far more common in W than in B women.
Black women have more aggressive disease that occurs almost a decade
earlier, it is usually triple negative and has a lower survival. Objectives to
determine 1) if plasma miRNA expression differs between B and W women,
and 2) if variation in miRs may explain the observed survival difference in
TNBC in W compared to B women. Methods: We determined miRNA profiles
in plasma collected before removal of breast tumors in three groups of W
and B women: 1) normal controls (N), 2) TN and 2) ER/PR positive BC.
Expression miRNA profiling of 754 miRNAs on the ABI Open Array
detected 101miRNAs in plasma. We compared miRNA expression in
cancer patients and race-matched controls. A moderated t-statistic through
the R/Bioconductor ’limma’ was used to compare the mean response
between subject factors of interest. Results with a p�0.05 were considered
statistically significant. Characteristics: 32 patients were included in this
analysis (mean age 50 years; range 31-68), 10 had stage III TNBC (5 B & 5
W); 10 had stage III ER/PR�BC (5 B, 5 W); and 12 were controls (6 B, 6 W)
Results: W TNBC patients overexpressed (15 fold higher than normal) 20
miRs in plasma (let-7d, let7g, miR-103, -10a, 15a, -9, -99b, -181a, -18a,
-502, -187, -365 and others), these miRs were not found in any of the B
patients. Six microRNAs (such as miR-34a, -127 and others) were 15 fold
higher than normal controls in B cancer patients, these miRs were not
detected in W patients with TNBC. Four miRs in B and 8 miRs in W were not
previously reported in association with breast cancer suggesting that they
may be connected to the host response. Conclusions: The striking difference
in the patterns of plasma miRNA expression between B and W
patients may provide the key to the large difference in outcome between
these groups when receiving similar treatments, the worse prognosis group
may carry the miRs that promote metastasis. The seed-soil hypothesis may
explain the better prognosis in W patients. W women may carry those
miRNAs that support an “exaggerated” response to systemic treatment,
while the B may have the miRs that favour metastasis.
1045 General Poster Session (Board #20D), Sat, 8:00 AM-12:00 PM
Neoadjuvant weekly nab-paclitaxel (wA), carboplatin (Cb) plus bevacizumab (B)
with or without dose-dense doxorubicin-cyclophosphamide (ddAC) plus B in
ER�/HER2-negative (HR�) and triple-negative (TN) breast cancer (BrCa): A
BrUOG study. Presenting Author: Natalie Faye Sinclair, Department of
Medicine, Warren Alpert Medical School of Brown University, Providence,
RI
Background: High risk BrCa patients (pts) often receive weekly paclitaxel
(wP) as well as ddAC. Switching to wA(Abraxane) or adding B or Cb may
enhance its efficacy, especially in TN pts. Methods: Pts with clinical stage
IIA-IIIC BrCa received wA 100 mg/m2 , Cb AUC 6 � B 15 mg/kg q3wks x 12
wks only (cohort 1/Yale) or followed by ddAC � B x 4 (cohort 2/Brown).
Endpoints: pathologic complete response (pCR) - absence of invasive BrCa
in breast � axillary nodes, residual cancer burden (RCB), clinical CR/
partial response (cCR/cPR), and toxicity. Correlative studies are being
performed on biopsies obtained at baseline and after run-in doses of wA or
B only. Post-op pts resume B for 34 wks; other systemic therapy, including
ddAC in cohort 1, is at MD discretion. Results: 55 of 60 pts (median age 47,
range 25-68; 31 HR�/29 TN) are evaluable for response (see table below).
Median # doses wA 11,Cb 4, ddAC 4. Dose reductions: wA 25% for
neutropenia (ANC), Cb 15% for thrombocytopenia (tcp). B 7% held for
hypertension. Grade 3-4 toxicities (�5%): ANC 85%, tcp 35%, anemia
25%. Serious adverse events during wA: 3 nausea/dehydration (N/D), 3
infection w/o neutropenic fever (FN), 2 GI bleed; during ddAC: 6 (21%) FN
despite G-CSF, 3 N/D. Conclusions: The combination of wA, q3wk Cb � B
was well tolerated, with cCR�cPR 84%. However, overall pCR was only
11% (27% in TN) after 12 wks of this regimen (cohort 1). Subsequent
preop ddAC raised overall pCR to 54%, and 81% in TN, demonstrating that
longer treatment duration or inclusion of anthracycline-based therapy
improves responses. Results for cohort 2 compare favorably with those from
I-SPY, GeparQuinto and NSABP B-40; the addition of Cb and/or B in TN is
being evaluated in CALGB 40603.
N
cCR/cPR
after wA
cCR/cPR
after ddAC pCR
Total 55 13/33 (84%) 19 (35%) 29 (53%) 26
HR � 28 5/17 (79%) 3 (11%) 7 (25%) 21
TN 27 8/16 (89%) 16 (59%) 22 (82%) 5
Cohort 1 27 4/18 (81%) 3 (11%) 10 (37%) 17
HR� 16 2/10 (75%) 0 4 (25%) 12
TN 11 2/8 (91%) 3 (27%) 6 (55%) 5
Cohort 2 28 9/15 (86%) 13/11(92%)* 15 (54%) 18 (64%) 10
HR � 12 3/7 (83%) 3/7 (91%) 2 (17%) 2 (17%) 10
TN 16 6/8 (88%) 10/4 (93%) 13 (81%) 16 (100%) 0
*2 pts not restaged after ddAC excluded.
1047 General Poster Session (Board #20F), Sat, 8:00 AM-12:00 PM
Molecular comparison of human triple-negative inflammatory breast cancer
(TN-IBC) and human triple-negative noninflammatory breast cancer (TNnon-IBC).
Presenting Author: Hiroko Masuda, Morgan Welch Inflammatory
Breast Cancer Program and Clinic, University of Texas M. D. Anderson
Cancer Center, Houston, TX
Background: IBC has a poor prognosis because of its high rate of recurrence.
There is an urgent need to define the biology of IBC to develop molecularbased
targeted therapies for this disease. TNBC has a similar poor
prognosis. Recently, Lehmann et al. (JCI, 2011) identified 7 subtypes of
TNBC: basal-like (BL) 1 and 2, immunomodulatory (IM), mesenchymal
(M), mesenchymal stem-like (MSL), luminal androgen receptor (LAR), and
“unknown.” In light of these findings, we hypothesized that the distribution
of TNBC subtypes differs between TN-IBC and TN-non-IBC. Methods: We
qualitatively reproduced the Lehmann et al. experiments using Affymetrix
CEL files from the same datasets to ensure the reproducibility of their
findings. We quantified all arrays using frozen robust multiarray analysis
with a linear model adjustment to account for batches. Then validated the
results in a TNBC cohort from the World IBC Consortium for which IBC
status was known (41 cases of TN-IBC; 53 cases of TN-non-IBC). We used
the Fisher exact test to determine associations between TNBC subtypes
and IBC status. We used Kaplan-Meier curves and log-rank tests to
compare clinical outcomes between TNBC subtypes. Results: We found the
7 subtypes for both TN-IBC and TN-non-IBC. While the correspondence
between our findings and those of Lehmann et al. was not perfect, there was
a very significant correlation (P�2.2x10-16 ). We found no association
between TNBC subtype and IBC status (P�.5023). As expected, we found
that patients with IBC had significantly worse recurrence-free survival
(RFS) than a comparison cohort of patients with advanced non-IBC that
included not only patients with TNBC but also patients with ER-positive
and HER2-amplified tumors (P�.0054). However, TNBC subtype did not
predict RFS. IBC status was not a significant predictor of RFS or overall
survival in the TNBC cohort. Conclusions: Both TN-IBC and TN-non-IBC are
heterogeneous. TNBC subtypes are unrelated to IBC status. TN-IBC and
TN-non-IBC have the same subtypes and clinical outcome.
% IBC Non-IBC
Relative M 9.7 13.2
IM 7.3 22.6
BL1 21.9 15.0
BL2 7.3 3.7
LAR 14.6 11.3
Unk 19.5 18.8
MSL 19.5 15.0
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