1. Optimizing Treatment for Her 2 Positive Metastatic Breast Cancer Patients Sunil Verma MD, MSEd, FRCPC Medical Oncologist Chair, Breast Medical Oncology Sunnybrook Odette Cancer Centre Associate Professor, University of Toronto

2. Her 2 Story Poor Prognostic Marker

3. Outline First Line Treatment Second Line Treatment and Beyond Individualized Approach An Algorithm and Concluding Remarks

4. Outline First Line Treatment Second Line Treatment and Beyond Individualized Approach An Algorithm and Concluding Remarks

5. OS was a secondary endpoint in the study Chemotherapy = either doxorubicin or epirubicin + cyclophosphamide or paclitaxel OS, overall survival; RR, relative risk of death Adapted from Slamon DJ, et al. N Engl J Med 2001; 344:783–792. Trastuzumab prolongs overall survival in HER2-positive MBC Chemotherapy (n = 234) Chemotherapy + trastuzumab (n = 235) Overall survival (%) Time (months after enrolment) RR = 0.80 (95% CI = 0.64,1.00) p = 0.046 Median OS: 20.3 months Median OS: 25.1 months 0 20 40 60 80 100 5152535450

6. First Line Treatment Approach (2001- 2011) A number of effective options with chemo and anti-her2 –Taxanes and Herceptin –Vinorelbine and Herceptin –Capecitabine and Anti-Her2 –Doublet chemo with Her 2 generally not used Select group of patients may benefit from an anti-Her2 and anti-estrogen approach

7. Recent Achievements in Her 2 positive MBC First Line –MA.31 Taxane + H vs. Taxane + L –CLEOPATRA Chemo + H vs. Chemo +H+P 7

8. Gelmon et. al ASCO 2012 8

9. 9

10. CLEOPATRA study design 10 HER2, human epidermal growth factor receptor 2; MBC, metastatic breast cancer; PD, progressive disease Patients with HER2-positive MBC centrally confirmed (N=808) Placebo + trastuzumab 1:1 Randomization was stratified by geographic region and prior treatment status (neo/adjuvant chemotherapy received or not) Docetaxel ≥6 cycles recommended n=406 n=402 Pertuzumab + trastuzumab Docetaxel ≥6 cycles recommended PD Swain et al. SABCS 2012 Poster P5-18-26.

11. CLEOPATRA: Significantly higher response rate with pertuzumab and trastuzumab Patients, n (%) HT (n = 336) PHT (n = 343) Independently reviewed objective response rate Difference in response rates (95% CI) 233 (69.3)275 (80.2) 10.8% points (4.2, 17.5) p = 0.001 Complete response rate14 (4.2)19 (5.5) Partial response rate219 (65.2)256 (74.6) Stable disease70 (20.8)50 (14.6) Progressive disease28 (8.3)13 (3.8) Unable to assess or no assessment5 (1.5) H, trastuzumab; P, pertuzumab; T, docetaxel Adapted from Baselga J, et al. N Engl J Med 2012; 366:109–119.

12. Updated Kaplan-Meier curves of investigator-assessed PFS 12 D, docetaxel; PFS, progression-free survival; Pla, placebo; Ptz, pertuzumab; T, trastuzumab 0510152025303540 0 10 20 30 40 50 60 70 80 90 100 Time (months) Progression-free survival (%) 4550 0 0 0 0 8 8 34 26 67 42 108 72 178 110 218 148 284 223 341 329 402 406 Ptz + T + D: median 18.7 months Pla + T + D: median 12.4 months HR=0.69 95% CI 0.58−0.81 ∆=6.3 months n at risk Ptz + T + D Pla + T + D Swain et al. SABCS 2012 Poster P5-18-26.

13. Kaplan-Meier curves of the confirmatory overall survival analysis 13 Stopping boundary for concluding statistical significance at this second interim analysis was p≤0.0138 D, docetaxel; Pla, placebo; Ptz, pertuzumab; T, trastuzumab 0510152025303540 0 10 20 30 40 50 60 70 80 90 100 n at risk 0Ptz + T + D 0Pla + T + D Time (months) Overall survival (%) 455055 0 0 9 4 33 22 84 67 143 128 230 198 317 285 342 324 371 350 387 383 402 406 89% 94% 1 year 2 years 69% 81% 3 years 66% 50% Ptz + T + D: 113 events; median not reached Pla + T + D: 154 events; median 37.6 months HR=0.66 95% CI 0.52−0.84 p=0.0008 Swain et al. SABCS 2012 Poster P5-18-26.

14. Breast cancer therapies following discontinuation of study treatment in patients who had withdrawn from study treatment 14 n (%) Placebo + trastuzumab + docetaxel (n=338) Pertuzumab + trastuzumab + docetaxel (n=298) Any260 (76.9)225 (75.5) In patients receiving subsequent breast cancer treatment n=260n=225 Any HER2-targeted treatment178 (68.5)160 (71.1) Trastuzumab104 (40.0)106 (47.1) Lapatinib114 (43.8)93 (41.3) Trastuzumab emtansine26 (10.0)21 (9.3) Capecitabine140 (53.8)113 (50.2) Vinorelbine70 (26.9)51 (22.7) Cyclophosphamide43 (16.5)30 (13.3) Doxorubicin46 (17.7)29 (12.9) Paclitaxel32 (12.3)21 (9.3) Docetaxel11 (4.2)13 (5.8) Swain et al. SABCS 2012 Poster P5-18-26.

15. Adverse events (all grades) with ≥25% incidence or ≥5% difference between arms 15 Highlighted are adverse events with ≥5% higher incidence n (%) Placebo + trastuzumab + docetaxel (n=396) Pertuzumab + trastuzumab + docetaxel (n=408) Diarrhea191 (48.2)278 (68.1) Alopecia240 (60.6)248 (60.8) Neutropenia197 (49.7)216 (52.9) Nausea168 (42.4)179 (43.9) Fatigue148 (37.4)155 (38.0) Rash95 (24.0)149 (36.5) Decreased appetite105 (26.5)121 (29.7) Mucosal inflammation79 (19.9)112 (27.5) Asthenia121 (30.6)110 (27.0) Vomiting97 (24.5)104 (25.5) Peripheral edema122 (30.8)101 (24.8) Pruritus40 (10.1)68 (16.7) Constipation101 (25.5)63 (15.4) Febrile neutropenia30 (7.6)56 (13.7) Dry skin23 (5.8)44 (10.8) Swain et al. SABCS 2012 Poster P5-18-26.

16. Cardiac adverse events 16 * In patients with post-baseline assessment LVEF, left ventricular ejection fraction; LVSD, left ventricular systolic dysfunction n (%) Placebo + trastuzumab + docetaxel Pertuzumab + trastuzumab + docetaxel Data cutoff dateMay 2011 (n=397) May 2012 (n=396) May 2011 (n=407) May 2012 (n=408) LVSD (all grades)33 (8.3)34 (8.6)18 (4.4)22 (5.4) Symptomatic LVSD7 (1.8) 4 (1.0)5 (1.2) LVEF decline to <50% and by ≥10% points from baseline* 25/379 (6.6)28/378 (7.4)15/393 (3.8)18/394 (4.6) LVEF recovery to ≥50%*18/25 (72.0)25/28 (89.3)13/15 (86.7)16/18 (88.9) Swain et al. SABCS 2012 Poster P5-18-26.

17. KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugate consisting of HERCEPTIN, a humanized anti-HER2 IgG1 monoclonal antibody DM1, a cytotoxic microtubule inhibitor derived from maytansine −on average, KADCYLA has 3.5 DM1 molecules per antibody MCC, a stable thioether linker, covalently linking HERCEPTIN to DM1 T-DM1 Mechanism of Action Antibody (HERCEPTIN) Stable linker Cytotoxic agent (DM1) Emtansine DM: derivative of maytansine MCC: 4-[N-maleimidomethyl] cyclohexane-1- carboxylate KADCYLA Product Monograph. Hoffmann-La Roche Limited. September 11, 2013. Swanton C, Johnston SR, editors. Handbook of Metastatic Breast Cancer, 2 nd ed. Informa Healthcare, New York, 2012.

18. In vitro studies in human breast cancer cells that overexpress HER2 have shown that, like HERCEPTIN, KADCYLA Binds subdomain IV of the HER2 extracellular domain Inhibits HER2 signaling Mediates antibody-dependent cell-mediated cytotoxicity (ADCC) Inhibits shedding of the HER2 extracellular domain T-DM1 Retains Activity of Herceptinf KADCYLA Product Monograph. Hoffmann-La Roche Limited. September 11, 2013.

19. KADCYLA has the additional MOA of DM1. Upon binding to HER2, KADCYLA undergoes Receptor-mediated internalization Subsequent lysosomal degradation Intracellular release of DM1-containing cytotoxic catabolites DM1 binding to tubulin, disrupting microtubule networks in the cell, resulting in cell cycle arrest and apoptotic cell death T-DM1 Intracellular Delivery of DM1 HER2 Lysosomal degradation DM1 release* Internalization Inhibition of tubulin polymerizatio n KADCYLA *The primary DM1-containing cytotoxic catabolite released is lysine-MCC-DM1. KADCYLA Product Monograph. Hoffmann-La Roche Limited. September 11, 2013. LoRousso PM, et al. Clin Cancer Res 2011.

20. PHASE II STUDY T-DM1 vs. Docetaxel and Trastuzumab 1:1 HER2-positive, recurrent locally advanced breast cancer or MBC (N=137) Trastuzumab 8 mg/kg loading dose; 6 mg/kg q3w IV + Docetaxel 75 or 100 mg/m 2 q3w (n=70) Crossover to T-DM1 (optional) PD a T-DM1 3.6 mg/kg q3w IV (n=67) PD a Hurvitz, et al., JCO, 2013

21. Objective Response by Investigator Patients With Measurable Disease at Baseline Trastuzumab + docetaxel (n=69) a T-DM1 (n=67) Patients with an objective response, b n (%)40 (58.0)43 (64.2) 95% CI45.5–69.251.8–74.8 Objective responses, n (%) Complete response3 (4.3)7 (10.4) Partial response37 (53.6)36 (53.7) Stable disease23 (33.3)13 (19.4) Progressive disease4 (5.8)8 (11.9) Unable to evaluate or missing2 (2.9)3 (4.5) Patients with clinical benefit, c n (%)56 (81.2)50 (74.6) 95% CI70.7–89.163.2–84.2 a One patient was not included in the efficacy analysis due to study site withdrawal. b Defined as complete or partial response based on RECIST 1.0 determined on 2 consecutive tumor assessments at least 4 weeks apart. c Defined as objective response any time during the study or maintained stable disease for at least 6 months from randomization. Hurvitz SA, et al. Abstract 5.001. ESMO 2011. Hurvitz, et al., JCO, 2013

22. This presentation contains non-licensed product information and may be subject to local affiliate compliance and / or legal approval before onward internal distribution. This information is for internal use only and must not be distributed externally Time (months) Progression-Free Survival by Investigator Randomized Patients Proportion progression-free 1.0 0.8 0.6 0.4 0.2 0.0 02468101214161820 Number of patients at risk T+D706663534327124220 T-DM16760514642352215630 Hazard ratio and log-rank P value were from stratified analysis. Trastuzumab + docetaxel (n=70) T-DM1 (n=67) Median PFS, mos Hazard ratio95% CI Log-rank P value 9.2 14.2 0.59 0.36 – 0.97 0.035 Hurvitz, et al., JCO, 2013

23. Figure adapted from: http://clinicaltrials.gov/ct2/show/NCT01120184; Roche. Data on file MARIANNE: A clinical trial of pertuzumab and T-DM1 in first-line metastatic breast cancer HER2-positive, progressive or recurrent, locally advanced or untreated MBC (N = 1092) Pertuzumab + T-DM1 Trastuzumab + taxane (docetaxel or paclitaxel) R Placebo + T-DM1 20102011–20122013 First patient in July 2010 Last patient in Q2 2012 T-DM1 ± pertuzumab: blinded, placebo-controlled Trastuzumab + taxane: open-label

24. Summary First Line The standard of care should consist of pertuzumab and trastuzumab along with docetaxel (?other taxane alternative) T-DM1 looks very promising in the first line and may be suited for selected patients –Not candidates for chemotherapy –DFI < 6 months –Contraindication to taxanes 24

25. Future Questions First Line Can we combine Pertuzumab and Herceptin with other partners –Other taxanes –Other chemotherapies (Vinorelbine/Capecitabine) –Other biologics – T-DM1/Bevacizumab Developing effective drugs that can target brain metastases Duration of targeted therapy for those responding 25

26. Outline First Line Treatment Second Line Treatment and Beyond Individualized Approach An Algorithm and Concluding Remarks

27. Second Line (2006-2010) There is continued benefit of trastuzumab beyond progression –Capecitabine and Trastuzumab There is benefit of Lapatinib in combination with Capecitabine upon progression on Trastuzumab

28. Recent Achievements in Her 2 positive MBC Second Line and Beyond –EGF 104900 L+ H vs L alone –EMILIA T-DM1 vs Cape + L –Bolero-3 Vinorelbine + H + Everolimus vs. Vinorelbine + H 28

29. Trastuzumab and Lapatinib

30. Trastuzumab and Lapatinib Overall Survival

31. EMILIA Study Design 1:1 HER2-positive LABC or MBC (N=980) Prior taxane and trastuzumab Progression on metastatic treatment or within 6 months of adjuvant treatment PD T-DM1 3.6 mg/kg q3w IV Capecitabine 1000 mg/m 2 PO bid, days 1–14, q3w + Lapatinib 1250 mg/day PO qd PD Verma et al NEJM 2012

33. EMILIA: Overall Survival

34. EMILIA Adverse Events Verma et al NEJM 2012 34

35. 2 T-DM1 c (optional crossover) TH3RESA Study Schema Stratification factors: World region, number of prior regimens for advanced BC, d presence of visceral disease Co-primary endpoints: PFS by investigator and OS Key secondary endpoints: ORR by investigator and safety PD T-DM1 3.6 mg/kg q3w IV (n=400) Treatment of physician’s choice (TPC) b (n=200) HER2-positive (central) advanced BC a (N=600) ≥2 prior HER2-directed therapies for advanced BC Prior treatment with trastuzumab, lapatinib, and a taxane a Advanced BC includes MBC and unresectable locally advanced/recurrent BC. b TPC could have been single-agent chemotherapy, hormonal therapy, or HER2-directed therapy, or a combination of a HER2-directed therapy with a chemotherapy, hormonal therapy, or other HER2-directed therapy. c First patient in: Sep 2011. Study amended Sep 2012 (following EMILIA 2nd interim OS results) to allow patients in the TPC arm to receive T-DM1 after documented PD. d Excluding single-agent hormonal therapy. BC, breast cancer; IV, intravenous; ORR, objective response rate; PD, progressive disease; q3w, every 3 weeks. 1 Wildiers H, et al. ECC 2013; Abstract 15LBA..

36. PFS by Investigator Assessment Median follow-up: TPC, 6.5 months; T-DM1, 7.2 months. Unstratified HR=0.521 (P<0.0001). 198120622813610 4043342411146627120 TPC T-DM1 No. at risk: Time (months) 1412108642 0.0 0.2 0.4 0.6 0.8 1.0 0 Proportion progression-free TPC (n=198) T-DM1 (n=404) Median (months)3.36.2 No. of events129219 Stratified HR=0.528 (95% CI, 0.422, 0.661) P<0.0001 Wildiers H, et al. ECC 2013; Abstract 15LBA..

37. First Interim OS Analysis 198 404 169 381 125 316 80 207 51 127 30 65 9 30 0 0 TPC T-DM1 No. at risk: 3 7 Time (months) 44 patients in the TPC arm received crossover T-DM1 treatment after documented progression. Unstratified HR=0.57 (P=0.004). 1612108642 0.0 0.2 0.4 0.6 0.8 1.0 Proportion surviving 014 Observed 21% of targeted events TPC (n=198) T-DM1 (n=404) Median (months)14.9NE No. of events4461 Stratified HR=0.552 (95% CI, 0.369, 0.826); P=0.0034 Efficacy stopping boundary HR<0.363 or P<0.0000013 Wildiers H, et al. ECC 2013; Abstract 15LBA..

38. The PI3K pathway and Breast Cancer Constitutive activation of the PI3K pathway is frequent. PI3K pathway activation conveys malignant transformation, cell growth and invasion, tumor neoangiogensis and resistance towards anti- cancer treatments. Known mechanisms of PI3K pathway activation include activating mutations of RTKs, gain-of-function mutation of the PIK3CA gene, and loss-of- function mutations of PTEN. Ras 4EBP1 Raf Erk Rsk PI3K TORC1 S6K Rheb S6 PIP 3 Tuberin PTEN TORC2 MEK Akt PDK1 HER2/HER3 Tuberin

39. O’Regan R, et al. ASCO 2013; Abstract 505. Not for distribution. O Regan ASCO 2013 39

40. O’Regan R, et al. ASCO 2013; Abstract 505. Not for distribution. O Regan ASCO 2013 40

41. Summary Second Line and Beyond T-DM1 offers significant clinical benefit and superior toxicity profile and is very effective for second line Her 2 + treatment Patients progressing on T-DM1 still may derive a benefit from ongoing systemic tx with chemo with anti-Her 2 approaches The role of Lapatinib has evolved and now is generally considered in third or later lines of treatment. One may consider earlier use if: –Progressive brain metastases despite radiation –Lack of response to first/second line of herceptin –? Biomarkers – p95 still needs to be validated 41

42. Future Questions Is there a benefit of Pertuzumab or T-DM1 (along with other partners) beyond progression? What is the effect on tumor biology once patients progress on Pertuzumab/T-DM1? –What are potential targeted agents that may help overcome resistance? What will be the role of PI3K inhibitors in second line + treatment? Who are the ideal patients for dual targeted treatment alone? 42

43. Outline First Line Treatment Second Line Treatment and Beyond Individualized Approach An Algorithm and Concluding Remarks

44. Personalized Factors to Consider Hormone Receptor Status Prior Adjuvant Trastuzumab CNS Metastases Biomarkers

45. CLEOPATRA Overall survival in predefined subgroups 45 ER, estrogen receptor; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; PgR, progesterone receptor 8080.660.52 ‒ 0.84 4320.660.47 ‒ 0.93 3760.660.46 ‒ 0.94 3060.720.48 ‒ 1.07 1350.680.36 ‒ 1.28 1140.550.31 ‒ 0.98 2530.640.41 ‒ 1.00 6810.700.53 ‒ 0.91 1270.510.27 ‒ 0.95 7890.660.52 ‒ 0.85 190.720.15 ‒ 3.50 4800.700.51 ‒ 0.95 300.520.14 ‒ 1.91 2610.660.43 ‒ 1.03 370.290.06 ‒ 1.43 6300.570.44 ‒ 0.74 1781.420.71 ‒ 2.84 3880.730.50 ‒ 1.06 4080.570.41 ‒ 0.79 7210.660.51 ‒ 0.85 7670.670.52 ‒ 0.86 nHR95% CI All No Yes Europe North America South America Asia <65 years ≥65 years <75 years ≥75 years White Black Asian Other Visceral disease Non-visceral disease Positive Negative IHC 3+ FISH-positive 01 ER/PgR status Disease type Race Age group Region HER2 status Prior (neo)adjuvant chemotherapy 2345 Favors placebo Favors pertuzumab Swain et al. SABCS 2012 Poster P5-18-26. Hormone Receptor Status

46. Cap + LapT-DM1 Baseline characteristic Total n Median (mos) HR (95% CI) T-DM1 Better Cap + Lap Better All patients99125.130.90.70 (0.56, 0.87) Age group <65 years853 24.630.90.66 (0.52, 0.83) 65–74 years 113 27.1NR0.74 (0.37, 1.47) ≥75 years25 NR11.13.45 (0.94, 12.65) ER and PR status ER+ and/or PR+54525.331.90.62 (0.46, 0.85) ER– and PR–426 23.7 27.10.75 (0.54, 1.03) Line of therapy a First-line11827.9NR0.61 (0.32, 1.16) Second-line361NR27.10.88 (0.61, 1.27) Third- and later-line51223.333.90.62 (0.46, 0.84) EMILIA Overall Survival Subgroup Analyses Hazard ratio 0.20.5125 a Defined as any systemic therapy including endocrine and chemotherapy. NR, not reached. From confirmatory OS analysis; data cut-off July 31, 2012. Verma et al. ESMO 2012; Oral Abstract #LBA12 Hormone Receptor Status

47. CI, confidence interval; PFS, progression-free survival CLEOPATRA: Independently assessed PFS by prior trastuzumab therapy in patients with (neo)adjuvant therapy HT Median PFS, months PHT Median PFS, months Hazard ratio (CI) Prior (neo)adjuvant trastuzumab treatment (n = 88) 10.416.9 0.62 (0.35, 1.07) No prior (neo)adjuvant trastuzumab treatment (n = 288) 12.621.6 0.60 (0.43, 0.83) Adapted from Baselga J, et al. N Engl J Med 2012; 366:109–119. Prior Trastuzumab

48. CLEOPATRA:Overall survival subgroup analyses An exploratory subgroup analysis was performed for patients who had received prior neoadjuvant and/or adjuvant trastuzumab therapy (88 patients). –The observed hazard ratio of 0.68 (95% CI 0.30−1.55) indicates overall survival benefit in the pertuzumab arm 48 Swain et al. SABCS 2012 Poster P5-18-26. Prior Trastuzumab

49. EMILIA: Progression-Free Survival Subgroup Analyses ER and PR status 9.0 10.3 0.72 (0.58, 0.91) 0.56 (0.44, 0.72) 7.1 5.6 545 426 ER+ and/or PR+ ER− and PR− 10.8 9.6 9.0 0.51 (0.30, 0.85) 0.69 (0.53, 0.91) 0.69 (0.55, 0.86) 5.7 6.8 6.5 118 361 512 Line of therapy a First Second Third Age 9.8 7.0 0.62 (0.52, 0.74) 1.06 (0.68, 1.66) 6.0 8.1 853 138 <65 yrs ≥65 yrs Median, mos HR (95% CI) Median, mos Total n Baseline characteristic T-DM1 better Cap + Lap better 0.20.5125 9.60.66 (0.56, 0.78) 6.4991 All pts HRs were from unstratified analysis. a Defined as any systemic therapy, including endocrine or chemotherapy. T-DM1Cap + Lap Hazard ratio Verma et al. N Eng J Med 2012 (incl. supplementary appendix) Blackwell et al. ASCO 2012; Abst #LBA1 Data cut-off Jan 14, 2012 Prior Trastuzumab

50. Cap + LapT-DM1 Baseline characteristic Total n Median (mos) HR (95% CI) T-DM1 Better Cap + Lap Better All patients99125.130.90.70 (0.56, 0.87) Age group <65 years853 24.630.90.66 (0.52, 0.83) 65–74 years 113 27.1NR0.74 (0.37, 1.47) ≥75 years25 NR11.13.45 (0.94, 12.65) ER and PR status ER+ and/or PR+54525.331.90.62 (0.46, 0.85) ER– and PR–426 23.7 27.10.75 (0.54, 1.03) Line of therapy a First-line11827.9NR0.61 (0.32, 1.16) Second-line361NR27.10.88 (0.61, 1.27) Third- and later-line51223.333.90.62 (0.46, 0.84) EMILIA: Overall Survival Subgroup Analyses Hazard ratio 0.20.5125 a Defined as any systemic therapy including endocrine and chemotherapy. NR, not reached. From confirmatory OS analysis; data cut-off July 31, 2012. Verma et al. ESMO 2012; Oral Abstract #LBA12 Prior Trastuzumab

51. EMILIA CNS metastases at baseline and Progression 51 CNS Metastases

52. EMILIA OS Analysis for Patients with CNS mets at baseline 52 CNS Metastases

53. Outline First Line Treatment Second Line Treatment and Beyond Individualized Approach An Algorithm and Concluding Remarks

54. HISTORY – 30 YEARS IN THE MAKING

55. Milestones in the Management of HER2-positive MBC Overall Survival Verma et. al The Oncologist 2013 Abbreviations: Ana, anastrozole; Cape, capecitabine; CT, chemotherapy; Doc, docetaxel; Lap, lapatinib; Let, letrozole; OS, overall survival; Pac, paclitaxel; Pert, pertuzumab; T-DM1, trastuzumab emtansine; Tras, trastuzumab. First Line Second Line +

56. An Algorithm to Manage Her 2 positive MBC Verma et. al The Oncologist 2013

57. An Algorithm to Manage Her 2 positive MBC Is there still activity of Trastuzumab/Lapatini b post T-DM1? Is there still activity of Trastuzumab/Lapatini b post T-DM1? Can we consider Pertuzumab for DFI 6m- 1year? Can we consider another taxane with P + H? Can we consider another taxane with P + H? Verma et. al The Oncologist 2013

58. Conclusion Raising the Bar The outcome of patients with Her 2 positive breast cancer has significantly improved in the past two decades Novel targeted drugs are improving survival and reducing toxicity for patients with advanced breast cancer The future looks quite bright as we can now envision a total targeted approach for some of these patients…..and an overall survival in excess of five years for some of our patients!