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Advances in Breast Cancer Detection and Management

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Advances in Breast Cancer Detection and Management January 7, 2009 Rowan T Chlebowski MD, PhD Professor of Medicine David Geffen School of Medicine at UCLA – PowerPoint PPT presentation

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Title: Advances in Breast Cancer Detection and Management


1
Advances in Breast Cancer Detection and
Management
January 7, 2009
  • Rowan T Chlebowski MD, PhD
  • Professor of Medicine
  • David Geffen School of Medicine at UCLA
  • Los Angeles Biomedical Research Institute
    at Harbor-UCLA Medical
    Center

2
DISCLOSURE
  • Dr. Chlebowski receives research support from
    Amgen and is a consultant for Amgen, Astrazeneca,
    Novartis, Eli Lily and Wyeth.

3
LEARNING OBJECTIVES
  • To become familiar with the Womens Health
    Initiative results and impact on breast cancer
    incidents
  • To become familiar with current issues regarding
    breast cancer detection
  • To become familiar with recent results from the
    San Antonio Breast Cancer Symposium

4
WHI Hormone Program Design
CEE (Conjugated equine estrogens) 0.625 mg/d
YES
N 10,739
Placebo
Prior Hysterectomy
CEE 0.625 mg/d medroxyprogesterone acetate
(MPA) 2.5 mg/d
NO
N 16,608
Placebo
Initially CEE only (N331), CEEMPA, or Placebo
WHI Writing JAMA 2002 288 321 Chlebowski JAMA
2003 289 3253
5
Available online _at_ http//jama.ama-assn.org/
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7
Clinical Trial Sensitivity Analysis CEEMPA vs.
Placebo Breast Cancer Risk During Intervention
and Postintervention
HR1.62 (1.10, 2.39)
HR1.26 (0.73, 2.20)
P Trend-Diff 0.005
Linear time varying Hazard Ratio during Clinical
Trial

Linear time varying Hazard Ratio during
Postintervention

HR (95 CI) based on
events accumulated in each 6 month window
8
WHI Clinical Trial Ppts With Mammograms by Year
and Randomization Group
Ppt with Mammograms ()
Intervention End
Chlebowski RT, Kuller L, Prentice R, et al.
SABCS 2008, Abstract 64
9
Conclusions
  • The increased breast cancer risk associated with
    combined estrogen plus progestin use declines
    markedly after therapy discontinuation and is
    unrelated to mammography utilization change
  • These findings support the hypothesis that the
    recent reduction in breast cancer incidence seen
    in the United States in certain age groups is
    predominantly related to a decrease in combined
    estrogen plus progestin use

10
Breast Cancer Screening
  • Early detection of breast cancer is accomplished
    through screening
  • Screening is undertaken to evaluate an
    asymptomatic population in order to detect
    unsuspected disease at a time when cure is still
    possible
  • Breast cancer screening involves mammography,
    ultrasound, MRI

11
Digital Mammography or Standard Testing
  • Women under 50 years of age
  • Women who were premenopausal or perimenopausal
  • Women classified as having heterogeneously dense
    or extremely dense breast tissue
  • Digital mammography performed significantly
    better in the detection of breast cancer

12
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16
Breast MRI Screening
  • 45 cancers
  • 22 seen on MRI only
  • 10 seen on MRI and mammography
  • 8 seen only on mammography
  • 4 interval cancers
  • 1 cancer detected on CBE only

Kriege et al NEJM July 2004
17
Breast MRI Screening
Saslow et al CA Cancer J Clin 20075775-89
18
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19
  • San Antonio Breast Cancer Symposium Update

20
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22
Trial ABCSG-12 Endocrine Therapy With or Without
Zoledronic Acid
ABCSG-12 1801 patients, stage I/II lt 10 nodes,
ER and/or PgR No adjuvant chemo Bone substudy
(N 404)
N 103
R A N D O M I Z E
Tamoxifen 20 mg/d
N 100
Tamoxifen 20 mg/d Zoledronic acid 4 mg q6m
Goserelin 3.6 mg q28d
Surgery RT
N 96
Anastrozole 1 mg/d
N 105
1533 centrally reviewed BMD measurements,
both trochanter and spine
Anastrozole 1 mg/d Zoledronic acid 4 mg q6m
Gnant M, et al. SABCS 2007 (Abstract 26)
23
ABCSG-12 Trial of Endocrine TherapyWith or
Without Zoledronic AcidFirst Efficacy Results
Tamoxifen (n 900) Anastrozole (n 903) HR P Value
Disease-Free Survival 65 events 72 events 1.096 .593
Recurrence-Free Survival 64 events 72 events 1.116 .529
Overall Survival 15 events 27 events 1.791 .065
ZA (n 899) No ZA (n 904) HR P Value
Disease-Free Survival 54 events 83 events 0.643 .011
Recurrence-Free Survival 54 events 82 events 0.653 .014
Overall Survival 16 events 26 events 0.595 .101
Gnant et al. ASCO 2008 abstract LBA4.
24
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26
FIRST (Fulvestrant fIRst-line Study Comparing
Endocrine Treatments)
  • Phase II, randomized, open-labeled, multi-center

Fulvestrant HD
(500 mg/mos plus 500 mg D14)
Advanced breast cancer ER
positive First line
Anastrozole 1 mg/d
Ellis et al SABCS 2008, Abst 6126
27
Kaplain Meier Plot for Time to Progression (TTP)
28
d
29
Integrated meta-analysis on 6634 patients with
early breast cancer receiving neoadjuvant
anthracycline-taxane /- trastuzumabcontaining
chemotherapyvon Minckwitz G, Kaufmann M, Kümmel
S, Fasching P, Eiermann W, Blohmer JU, Costa SD,
Loibl S, Mehta K, Untch Mfor the and
30
Treatment Group EffectsUse of Trastuzumab in
Patients with HER2-Positive Tumors
Plt0.001
N736
N671
excluding patients with HER2 negative or HER2
unknown tumors
31
A Phase II Study of Trastuzumab-DM1 (T-DM1), a
HER2 Antibody-Drug Conjugate, in Patients with
HER2-Positive Metastatic Breast Cancer (MBC)
Interim Results
  • DM1 is conjugated to trastuzumab via a
    non-reducible thioether bond to a linker molecule
    (MCC).1

Average number DM1 molecules/monoclonal
antibody3.5
1. Beeram M., et al. J Clin Oncol. 2008 26 (May
20 suppl abstr 1028).
32
Prior Chemotherapy and Anti-HER2 Therapy
Prior Therapy N112
Median number of chemotherapy agents for metastatic disease (range) 3 (112)
Prior anthracycline, n () 76 (67.9)
Median duration of prior trastuzumab therapy, weeks (range) 76.6 (3660)
Patients on prior lapatinib therapy, n () Median duration of lapatinib therapy, weeks (range) 62 (55.4) 26.3 (3106)
33
Analysis of Efficacy Antitumor Activity
Median follow-up, 4.4 mo (19 weeks)
Tumor Response as Assessed by Investigators N Overall ORRn () (95 CI) Confirmed ORRn () (95 CI)
All efficacy evaluable patients 107 42 (39.3) (30.0, 49.0) 29 (27.1) (19.4, 36.1)
Subset of patients with 6 months follow-up or have discontinued study treatment 76 33 (43.4) (32.6, 54.9) 29 (38.2) (27.3, 50.0)
ORRObjective response rate
Because of limited follow-up, 19 patients have
only had 1 post-baseline tumor assessment
PRCR Confirmed Objective response Complete or
partial response determined on two consecutive
occasions ?4 weeks apart
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