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

50s Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
1004 Oral Abstract Session, Tue, 9:45 AM-12:45 PM
RTOG 9804: A prospective randomized trial for “good risk” ductal
carcinoma in situ (DCIS), comparing radiation (RT) to observation (OBS)
Presenting Author: Beryl McCormick, Memorial Sloan-Kettering Cancer
Center, New York, NY
Background: Whole breast RT following conservation surgery (BCS) for low
risk DCIS has remained controversial despite several large trials comparing
RT to OBS, all showing significant benefit in local control with RT. RTOG
9804 compares RT to OBS for mammographically detected disease, of low
or intermediate nuclear grade, �2.5 cm size, and surgical margins � 3
mm. Tamoxifen (TAM) use for 5 years was allowed but not required.
Methods: The primary endpoint was ipsilateral breast local failure (LF). LF
and contralateral breast failures (CBF) were estimated by the cumulative
incidence method and treatment arms compared by log-rank test. Diseasefree
(DFS) and overall survival (OS) were estimated by the Kaplan-Meier
method and treatment arms compared by log-rank test. Patients were
stratified by age, margin width, grade, TAM use, and primary size. With
1790 patients, 80% power and using a 2-sided log rank test at 0.05, the
study was designed to detect a reduction in 5-year local recurrence from
6% to 3.5% with RT. Results: Accrual goals for the planned 1790 patients
were not met; the study was closed early. From December 1999 to July
2006, 636 women were randomized to receive 50 Gy in 5 weeks vs. OBS.
43 women were ineligible on review and 8 withdrew consent. Median
follow-up (F/U) time was 6.46 years. Mean age was 59; TAM was used in
62% of women. There were 2 LF in the RT arm vs. 15 in the OBS arm: at 5
years 0.4% RT vs. 3.2% OBS (p�0.0023, HR [95%CI] � 0.14 [0.03,
0.61]). With limited events, LF is not correlated with size, grade, margin
status, or age. The rate of CBF at 5 years was 3.0% for the RT arm vs. 1.9%
for the OBS arm (p�0.42, HR [95%CI] � 1.46 [0.59, 3.62]) and does not
appear to be influenced by TAM use (3.6 versus 2.7% TAM). The DFS and
OS results were excellent. Rate of grade 1-2 toxicity was 76% in the RT arm
vs. 30% in the OBS arm, and the rate of � 3 grade toxicities was 4% on
both arms. Conclusions: In this “good risk” subset of DCIS, the LF rate was
decreased significantly with the addition of RT. Longer follow-up is
planned.
1006 Oral Abstract Session, Tue, 9:45 AM-12:45 PM
Targeting the androgen receptor (AR) in women with AR� ER-/PR- metastatic
breast cancer (MBC). Presenting Author: Ayca Gucalp, Memorial Sloan-Kettering
Cancer Center, New York, NY
Background: Patients (pts) with ER-/PR- MBC do not benefit from endocrine
treatment (tx). Doane et al (Oncogene 2006;25:3994) described a subset of
ER-/PR- BC with a gene expression profile similar to ER� BC but characterized
by AR expression and AR-dependent growth in vitro. Hence, we conducted a
multicenter phase II trial (NCT00468715) of the AR antagonist, bicalutamide
(B) for pts with AR� ER-/PR- MBC. Methods: Pts with ER-/PR- (IHC �10%) MBC
were consented to AR testing, confirmed centrally at MSKCC. If AR� (DAKO IHC
�10%), pts were eligible for tx if ECOG performance status (PS) �2 and normal
organ function. No limit on prior tx except prior trastuzumab required if HER2�.
Eligible AR� pts who consented to tx received B 150mg orally daily in 28-day
cycles (C). Toxicity assessed q4wks, response q12wks. Primary endpoint �
clinical benefit rate (CBR): CR � PR � stable disease (ds) �6mo (SD). B would
be considered worthy of further study if �4/28 pts have clinical benefit. Results:
As of 12/21/11,436 pts consented for AR testing. 24 were ineligible, 12 await
testing. 47/400 tested were AR� (12%). 26 received tx with B (6 ineligible for
tx, 15 are eligible for tx with B at progression (POD) if clinically appropriate and
study slots remains). Two AR� pts treated with B were ER� and removed from
study. Three have received tx �12wks. Treated pt characteristics (n�24):
median (med) age 64 (41-83), PS 0 (0-1), HER2� 1, visceral metastases 17.
Prior chemotherapy: neo/adjuvant 16; med # regimens for MBC 1 (0-8). Med C#
3 (2-49�). Best response: (21 evaluable pts): CBR 19% (95% CI 5-42%),
SD�6mo 4, CR/PR 0, SD�6mo 3, POD 14. Conclusions: ~12% of ER-/PR- MBC
pts are AR�. For these pts, AR-inhibition with B is feasible, well tolerated, and
has activity based on pre-specified criteria. This study has closed to accrual for
AR testing as of 1/2012. These results of the primary endpoint are not expected
to change by accrual of the 2 remaining pts. Supported by TBCRC/Breast Cancer
Alliance/AstraZeneca.
Tx-related toxicity (n�26).
Grade (n)
Toxicity
1 2 3
AST/ALT/ bilirubin 5 2 3
Nausea 2 0 1
Bone pain 6 2 0
Anorexia 3 1 0
Constipation 2 1 0
Vaginal dryness 1 1 0
Anemia 0 1 0
Headache 0 1 0
Hot flashes 6 0 0
Fatigue 5 0 0
Edema 5 0 0
Diarrhea 3 0 0
Anxiety 2 0 0
Rash 2 0 0
Dyspnea
No grade 4/5 events
2 0 0
1005 Oral Abstract Session, Tue, 9:45 AM-12:45 PM
Correlation between the DCIS score and traditional clinicopathologic
features in the prospectively designed E5194 clinical validation study.
Presenting Author: Sunil S. Badve, Indiana University School of Medicine,
Indianapolis, IN
Background: We previously reported that in the E5194 clinical trial patients
with ductal carcinoma in situ (DCIS) treated with wide local excision (WLE)
without radiation (RT), the DCIS Score was significantly associated with 10
year risk of an ipsilateral breast event (IBE - recurrence of in situ or invasive
carcinoma), whether evaluated as a continuous or categorical variable
(P�0.02 for both). Here we evaluate correlation between DCIS Score and
clinicopathologic (CP) features and if DCIS Score provides independent
recurrence risk information. Methods: The study population included 327
women with DCIS prospectively selected for treatment with WLE without
RT, including low-intermediate grade tumors �2.5 cm or high-grade �1
cm. CP variables included age, menopausal status, tamoxifen treatment
(used in 29%) and expert centrally determined tumor size, grade, comedo
necrosis, tumor type, and margin status. The association between DCIS
Score and CP variables was examined by spearman rank correlation, and
proportional hazards regression models were used to determine variables
significantly associated with IBE. Results: Lesion size (p�0.009) and
menopausal status (p�0.03) were significantly associated with IBE, while
grade (p�0.69) and comedo necrosis (p�0.47) were not. DCIS Score was
significantly associated with IBE after adjustment for CP features and
tamoxifen use (p�0.02). DCIS Score was moderately correlated with grade
(rs�0.46; 95% CI 0.37,0.54), percentage comedo necrosis (rs�0.49; CI
0.41,0.57), and lesion size (rs�0.18; CI 0.08,0.29) but not other
features. Exploratory analyses in all CP subgroups, including the multicomponent
Van Nuys Prognostic Index, showed a wide range of DCIS Scores in
each subgroup. Concordance of the grades among readers was low: local vs
parent central, 68%; local vs central nuclear grade, 45%; parent central vs
central nuclear grade, 37%. Conclusions: DCIS Score is moderately
correlated with grade, comedo necrosis, and tumor size. DCIS Score
provides recurrence risk information independent of these features and
identifies subjects with DCIS who are at high risk for local invasive and
in-situ local recurrence after WLE alone.
1007 Oral Abstract Session, Tue, 9:45 AM-12:45 PM
Use of microRNA (miR) expression profiling to identify distinct subclasses
of triple-negative breast cancers (TNBC). Presenting Author: Charles L.
Shapiro, Division of Medical Oncology and the Breast Program, Columbus,
OH
Background: TNBC is divided into basal and non-basal subclasses. To
further subclassify TNBC we performed microRNA (miR) expression profiles
and linked them to patient overall survival. Methods: During 1996-
2005, 365 consecutive TNBC (phenotypically estrogen, progesterone and
HER2 negative by immunohistochemistry [IHC]) were identified from the
NCCN Breast Cancer Data Base/Tumor Registry at OSU Medical Center.
One hundred fifty-eight (43%) formalin-fixed paraffin embedded (FFPE)
breast cancer and 40 normal breast tissue blocks were available and tissue
cores were obtained for RNA. RNA was isolated using the Ambion recoverall
total nucleic acid isolation kit and the expression of ~700 miRs was
assessed for each sample using the nanoString nCounter method. A
consensus-clustering algorithm (ConsensusClusterPlus, Bioconductor www-
.bioconductor.org) was used to identify subclasses of TNBC and Kaplan-
Meier overall survival curves were compared using the log-rank test.
Censoring occurred at the date of death from causes other than breast
cancer or at time of the last known follow-up, whichever occurred first. The
median follow-up was 67 mo. (range 4-171 mo.). Results: The median age
was 52 yrs. (range 20-84 yrs.); 81% white and 9% African-American;
stages I, II, and III were 31%, 54% and 15%, respectively; and most
patients received adjuvant anthracycline-based regimens with (25%) or
without taxanes (75%). The algorithm identified 5 distinct subclasses; 1
clustering with normal breast miR expression whereas the other 4 each had
a unique pattern of deregulated miRs. The median overall survivals were
significantly different across the 5 cancer subclasses (log-rank p�0.028)
(Table). Conclusions: miR expression profiling identifies and discriminates
5 TNBC subclasses, which do not coincide with those identified as basal
and non-basal by IHC. Molecular analyses are ongoing to associate the
miR-based subclasses with specific clinical features or the expression of
specific pathways.
Group N
Median overall
survival (mo.) Log-rank p
1 12 46 0.028
2 10 50
3 51 66
4 48 67
5 37 82
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