Introduction. Approximately 20% of invasive breast cancers

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1 Introduction Approximately 2% of invasive breast cancers overexpress HER2 The current standard of care for neoadjuvant therapy is dual-targeted therapy with trastuzumab and pertuzumab plus chemotherapy how did we arrive here? Steinman S, et al. Ann Clin Lab Sci. 27;37:127-34; Swain SM, et al. ESMO 214. Abstract 35_PR; Nagayama A, et al. JNCI. 214;16. 1

2 NSABP B-18: 3 Things We Discovered About Neoadjuvant Therapy % A P =.99 Patients Events Postop Preop Year B P =.7 Events C P =.83 Deaths Of those requiring mastectomy at baseline, 27% converted to breastconserving surgery through neoadjuvant therapy. % D 1 8 pcr 4 pinv cpr P =.1 cnr Fisher B, et al. J Clin Oncol. 1998;16: Intrinsic Subtypes and Chemotherapy Sensitivity Pathologic CR to neoadjuvant anthracycline/taxane: Method of assessment T-FAC AC-T (N = 82) 1 (N = 17) 2 Gene expression microarray IHC proxy Luminal A/B 6% 7% Normal-like N/A HER2+/ER- 45% 36% Basal-like 45% 27% pcr rate in invasive lobular cancer: 4.2% 3 1. Rouzier R, et al. Clin Cancer Res. 25;11: ; 2. Carey LA, et al. Clin Cancer Res. 27;13: ; 3. Loibl S, et al. Breast Cancer Res Treat. 214;144:

3 NOAH Study: Addition of Neoadjuvant Trastuzumab to Chemotherapy Improves pcr Rate and Clinical Outcomes (cont.) Event-Free Survival Overall Survival Probability of Event-Free Survival.75.5 With trastuzumab Without trastuzumab Unadjusted Adjusted.25 Patients Events HR P Value HR P Value With trastuzumab Without trastuzumab No. at Risk With trastuzumab t Without trastuzumab Probability of Overall Survival With trastuzumab Without trastuzumab Patients Events HR P Value With trastuzumab Without trastuzumab No. at Risk With trastuzumab t Without trastuzumab Chemotherapy: AP x 3 Paclitaxel x 4 CMF x 3 A = doxorubicin 6 mg/m 2, P = paclitaxel 15 mg/m 2 (first 3 w, then 175 mg/m 2 ) Gianni L, et al. Lancet. 21;375: CLEOPATRA Progression-free survival in first-line 6 HER2-positive MBC Overall survival in first-line HER2-positive MBC A Independently Assessed Progression-Free Survival 1 9 Pertuzumab (median, 18.5 mo) 8 Control (median, 12.4 mo) 7 6 Hazard ratio,.62 5 (95% CI, ) 4 3 P < No. at Risk Months Pertuzumab Control n-free l % Progressio Surviva Hazard ratio,.64 5 (95% CI, ) 4 P = Pertuzumab, 69 events 1 Control, 96 events No. at Risk Months Pertuzumab Control al % Overall Surviva Baselga J, et al. N Engl J Med. 212;366:

4 NeoSphere: Efficacy Results by Breast and Lymph Nodal Status pcr in breast (ITT population) pcr in breast and node negative at surgery pcr in breast and N+ at surgery TD TDP TP DP (n = 17) (n = 17) (n = 17) (n = 96) 29.% 45.8% 16.8% 24.% 21.5% 39.3% 11.2% 17.7% 7.5% 6.5% 5.6% 6.3% The differences in pcr between the THP arm and other arms were statistically significant (P <.5 for all). T = trastuzumab D = docetaxel P = pertuzumab Gianni L, et al. Lancet Oncol. 212;13: TRYPHAENA Study: pcr by Hormone Receptor Status ER and PR negative ER and/or PR positive 65. pcr,,% FEC + D + P x 3 T + D + P x 3 (n = 73) FEC x 3 T + D + P x 3 (n = 75) TCD + P x 6 (n = 77) Schneeweiss A, et al. Ann Oncol. 213;24:

5 Response NeoALTTO Study Efficacy: pcr and tpcr pcr (no invasive cancer in the breast) Response L (N = 154) T (N = 149) L + T (N = 152) 24.7% 29.5% 51.3% P =.34 (L vs. T); P =.1 (L + T vs. T) L (N = 15) T (N = 145) L + T (N = 145) tpcr (no invasive cancer in the breast 2.% 27.6% 46.8% or LNs)* P =13(L.13 vs. T); P =.77 (L+Tvs vs. T) *Excludes 15 patients with nonevaluable nodal status. Lapatinib has not been approved for neoadjuvant therapy in HER2-positive breast cancer. Toxicity associated with the investigational arm of this study was acceptable and consistent with adverse events reported in other published reports with this agent. Baselga J, et al. Lancet. 212;379:

6 ALTTO: Disease-Free Survival Analysis 1% Free ct of Patients Alive and Disease Pc 8% 6% 4% L+T T L T **P.25 required for statistical significance. 2% 4-Yr. Hazard Ratio Arm No. Patients No. Events DFS Rate c.f. Tras* P-Value L+T 2, %.84 (.7, 1.2).48** T L2, %.96 (.8, 1.15).61 T 2, % *97.5% CI % Years Since Randomization L+T 2,93 1,938 1,832 1,672 1, T L 2,91 1,957 1,822 1,684 1, T 2,97 1,959 1,838 1,658 1, **P.25 required for statistical significance. Piccart-Gebhart M, et al. J Clin Oncol. 214;32:5s. Patient Selection for Neoadjuvant Chemotherapy Morphology Markers Approach Unicentric ER-, HER2+ Good High grade candidates Markers proliferation Unicentric Multicentric EIC ER+ low grade proliferation Any Consider endocrine Tx Require mastectomy CAVEAT: Patients with operable disease who desire mastectomy do not benefit from this approach. Caudle AS, et al. Breast Cancer Research. 212;14:R83; Oh JL, et al. J Clinic Oncol. 26;24:4971-5; Newman LA, et al. Sur Clin N Am. 27;87:

7 Assessing treatment response: Several studies report that MRI is superior to physical examination, mammography, or ultrasound in assessing NAC response Rosen, et al. AJR. 23; Wolmark N, et al. J Natl Can Inst Monogr. 21; Kim, et al. Acta Oncologica. 27; Prati, et al. Cancer. 29; Wasser, et al. Euro Rad. 23; Chen, et al. Cancer. 28; Chen, et al. J MRI. 28; Loo, et al. J Clin Onc. 211; McGuire, et al. ASCO. 21. Assessing the axilla after neoadjuvant chemotherapy: Post-core-biopsy MRI can lead to false positives Sentinel node biopsy difficult to follow response Ultrasound is optimal Axillary dissection unnecessary for clinically nodenegative patients Rosen, et al. AJR. 23; Wolmark N, et al. J Natl Can Inst Monogr. 21; Kim, et al. Acta Oncologica. 27; Prati, et al. Cancer. 29; Wasser, et al. Euro Rad. 23; Chen, et al. Cancer. 28; Chen, et al. J MRI. 28; Loo, et al. J Clin Onc. 211; McGuire, et al. ASCO

8 Patient Communication Tool We have developed a tool with several useful tips for communicating with your patients with breast cancer To access it and use it in your practice, please visit To receive credit, click the Get Credit tab at the bottom of the Webcast for access to the evaluation, attestation, and post-test. 215 Unless otherwise indicated, photographed subjects who appear within the content of this activity or on artwork associated with this activity are models; they are not actual patients or doctors. 8