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Advances in Breast Cancer Detection and Management

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. DISCLOSURE.

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Advances in Breast Cancer Detection and Management

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  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 Women’s 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 YES CEE (Conjugated equine estrogens) 0.625 mg/d 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 (N=331), CEE+MPA, or Placebo WHI Writing JAMA 2002; 288: 321 Chlebowski JAMA 2003; 289: 3253

  5. Available online @ http://jama.ama-assn.org/

  6. Clinical Trial: Sensitivity Analysis CEE+MPA vs. Placebo Breast Cancer Risk During Intervention and Postintervention HR=1.62 (1.10, 2.39) HR=1.26 (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

  7. 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

  8. 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 Conclusions

  9. 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

  10. 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

  11. 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

  12. Breast MRI: Screening Saslow et al CA Cancer J Clin 2007;57:75-89

  13. San Antonio Breast Cancer Symposium Update

  14. Trial ABCSG-12: Endocrine Therapy With or Without Zoledronic Acid ABCSG-12: 1801 patients, stage I/II < 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 Surgery + RT Goserelin 3.6 mg q28d 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)

  15. ABCSG-12 Trial of Endocrine TherapyWith or Without Zoledronic Acid:First Efficacy Results Gnant et al. ASCO 2008; abstract LBA4.

  16. 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

  17. Kaplain Meier Plot for Time to Progression (TTP)

  18. d

  19. A G O 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

  20. ypTis No ypT0 No Treatment Group EffectsUse of Trastuzumab in Patients with HER2-Positive Tumors P<0.001 N=736 N=671 * excluding patients with HER2 negative or HER2 unknown tumors

  21. 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 antibody=3.5 1. Beeram M., et al. J Clin Oncol. 2008; 26 (May 20 suppl; abstr 1028).

  22. Prior Chemotherapy and Anti-HER2 Therapy

  23. Analysis of Efficacy: Antitumor Activity Median follow-up, 4.4 mo (19 weeks) ORR=Objective response rate * Because of limited follow-up, 19 patients have only had 1 post-baseline tumor assessment † PR+CR ‡ Confirmed Objective response: Complete or partial response determined on two consecutive occasions 4 weeks apart

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