Updates in the Treatment of Breast cancer Mohammad Jahanzeb, MD, FACP Professor of Clinical Medicine, Hematology-Oncology Director, UM Sylvester Deerfield.

Updates in the Treatment of Breast cancer

Mohammad Jahanzeb, MD, FACPProfessor of Clinical Medicine, Hematology-Oncology

Director, UM Sylvester Deerfield CampusAssociate Center Director for Community Outreach

Sylvester Comprehensive Cancer CenterUniversity of Miami, Miller School of Medicine

Clinical Breast Cancer Subsets defined by IHC

All Breast Cancers

ER+65-75%

HER2+15-20%

Triple negative

15%

H Burstein and A Goldhirsch St Gallen 2007

HER2 Positive Disease

Milestones of HER2/anti-HER2 therapies in BC

EGFR discovery

Cohen

neu oncogene discovery Weinberg

EGFR MoAb inhibited growth

Mendelsohn

FDA approves trastuzumab in

adjuvant setting

1982 19851978 1984 1998 2006 2007 2010

Her2 amplification in breast cancer

Aaronson

FDA approves trastuzumab

alone for 2nd line and in with

paclitaxel for 1st line MBC

FDA approves lapatinib +

letrozole for MBC

FDA approves lapatinib +

capecitabine for MBC

1987

Her2/neu amplification

correlates with shorter survival

Slamon

MBC : metastatic breast cancer; MoAb : monoclonal antibody

Her2 cloned Ullrich and Coussens

1983 2012

FDA approves pertuzumab + trastuzumab + docetaxel for

MBC

2013

FDA approves trastuzumab

emtansine for MBC

Accelerated approval of pertuuzmab/

trastzumab as neoadjuvant

therapy

Expanding Options in HER2 Targeting

· Block heterodimerization

– Add pertuzumab

· Antibody-toxin conjugate

– TDM1

· Downstream pathway inhibition

– Block MTOR/PI3K?

· Oral panHER TKI

– Lapatinib, neratinib

· Alternate antibody-drug conjugate

– MM302

Optimal HER-2 Directed Therapy Sequencing for HER-2+ Advanced Breast Cancer

Verma S et al. The Oncologist 2013;18:1153-1166©2013 by AlphaMed Press

First results from the phase III ALTTO trial (BIG 02-06; NCCTG 063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (TL) or their combination (L + T) in the adjuvant treatment of HER2-positive early breast cancer (EBC)

Presented By Martine Piccart-Gebhart at 2014 ASCO Annual Meeting

Adjuvant Lapatinib (ALTTO) Scheman=8381 total/6281 analyzed

HER2+ESBC

+ Trastuzumab X 1 year

+ Lapatinib X 1 year

+ Trastuzumab+ Lapatinib X 1 year

+ Trastuzumab X 3 months → Lapatinib X 9 months

Chemotherapy

Piccart et al, ASCO 2014

Different treatment approaches

• Sequential anti-HER2 therapy after all chemo (N= 4,613)

• Concurrent anti-HER2 therapy after anthracycline-based chemo (N=3,337)

• Concurrent anti-HER2 therapy with non-anthracycline chemo (N=431)

DISEASE-FREE SURVIVAL (DFS) ANALYSIS


OVERALL SURVIVAL (OS) ANALYSIS


Take Home Message from ALTTO

· While there was doubling of pCR in the NEOALTTO study, it did not translate into improved survival outcomes in ALTTO at 4.5 years follow up

· There was increased toxicity noted with lapatinib: diarrhea, rash or erythema

12

APHINITY ADJUVANT TRIAL

N=4805TCa x 6

TCa x 6

TCa = 6 cycles of docetaxel and carboplatin

Completed recruitment on 31-Aug-2013

I-SPY 2 Trial Neratinib Arm HER2(+) Subset (n = 66 v 22 control)

Park et al AACR 2014

Signature Estimated pCR rate Probability Neratinib is Superior to

Control

Predicted Probability of

Success in Phase 3Neratinib Concurrent

Controls

HER2+/HR- 56% 33% 95% 79%

HER2+/HR+ 30% 17% 91% 65%Neratinib is an oral dual HER2 and EGFR tyrosine kinase inhibitor

Phase III Trials· Neratinib

– Extending adjuvant therapy – Nala trial

· Neratinib/capecitabine vs lapatinib/capecitabine

· > 2 lines of HER2 targeted regimens for MBC

– ISPY3· Neoadjuvant trial to follow ISPY2

· Afatinib– Lux trial

· Vinorelbine/afatinib vs vinorelbine/trastuzumab· Progression on one line of trastuzumab rx

Can HER2 PET Predict Response to Anti-HER2 therapy?

THE ZEPHIR TRIAL

Presented By Geraldine Gebhart at 2014 ASCO Annual Meeting

Slide 9

Presented By Geraldine Gebhart at 2014 ASCO Annual Meeting

Conclusions· Absence of HER2 target per HER2 PET predicts

treatment failure

· Imaging early treatment response with FDG PET predicts treatment success

· Combining both imaging modalities improves predictive accuracy – HER PET+/FDG decline – 100% PPV– HER2 PET-/No FDG decline- 100% NPV

Hormone Receptor Positive Disease

Current Standard Options for Adjuvant Endocrine Therapy

Menopausal Status at Diagnosis

Initial Therapy Extended Therapy

Pre / peri-menopausal

Tamoxifen5 Tamoxifen5

Tamoxifen5 AI5 (*if post-menopausal)

Postmenopausal AI5

Tamoxifen2-3 AI2-3

Tamoxifen5 AI5

Tamoxifen5 Tamoxifen5

Adapted from ASCO Guidelines 2014. Available at: www.asco.org

What about ovarian suppression?

What about AI + OFS in premenopausal women?

There are insufficient data currently to recommend AI for > 5 years

SOFT/TEXT· SOFT: SUPPRESSION OF OVARIAN FUNCTION TRIAL · TEXT: TAMOXIFEN AND EXEMESTANE TRIAL (at NYU)· Both Phase III Trials; Exemestane Plus gonadotrophin-releasing hormone

(GnRH) Analogue as adjuvant therapy for premenopausal women with hormone receptor positive breast cancer

· Question: is temporary ovarian function suppression with GnRH analogues (ovarian ablation permanent with surgery or radiation) useful when combined with AI or TAM.

· Goserelin (zoladex 3.6 sc monthly), leuprorelin (lupron 3.75 im monthly), buserelin, triptorelin (3.75 im monthly)

· DFS event rate much lower than anticipated combined analysis (4690 patients)

TEXT & SOFTTamoxifen + OFS vs. Exemestane + OFS

Tamoxifen 20 mg/day+ OFS* (n = 1338)Premenopausal, HR+ BC

≤ 12 wks after surgery

N = 2672

Stratified by trial, use of chemotherapy, nodal status

*OFS TEXT: triptorelin 3.75 mg IM every 28 days for 6-8 weeks prior to initiation of

HT or concurrently with chemotherapy. SOFT: triptorelin, bilateral oophorectomy or Ovarian irradiation

TEXT

Exemestane 25 mg/day+ OFS* (n = 1021)

Tamoxifen 20 mg/day

• Premenopausal HR+ BC≤ 12 wks after surgery

(if no chemo) or

• ≤ 8 mos after chemo if

premen status confirmed

• N = 3066

SOFT

Tamoxifen + OFS*

Tamoxifen 20 mg/day+ OFS* (n = 1024)

N = 2346

Exemestane 25 mg/day+ OFS* (n = 1334)

Joint Analysis

Median follow up: 68 months

42% N+

Neo/Adjuvant chemotherapy: 58%

Pagani O, et al. NEJM July 2014.

N = 2344

Exemestane+ OFS*

SOFT/TEXT: Exemestane + OFS better DFS

Median f/u 5.7 years

SOFT/TEXT: selected AEs

QOL not differentEarly cessation of treatment 16 vs 11%

SOFT/TEXT: take home message

Low event rates

Exemestane with ovarian function suppression is a new evidence based treatment option for premenopausal women with HR+ early breast cancer

Important question from SOFT (tamoxifen+OFS vs tamoxifen) will be answered end of 2014

Some premenopausal women diagnosed with HR+ breast cancer have an excellent prognosis with highly-effective endocrine therapy alone (>97% BC free at 5 yrs)

Need longer f/u, esp OS

ABCSG-12: Study Design· Key endpoints

– Primary: DFS at 5 yrs– Secondary: relapse-free survival, OS, BMD, safety

TAM 20 mg/day

ANA 1 mg/day

1803 premenopausal pts with stage I/II BC

• 80% > 40 yrs• N+ 30%

• OFS: Goserelin Q 28 days• OFS started concurrently

with endocrine therapy • Only 5% received

Chemotherapy

Treatment 3 yrs(median follow-up: 62 mos)

TAM + ZA 4 mg q6m

ANA + ZA 4 mg q6m

R

Long-term monitoring for 5 yrs

for recurrence

and survival

(DFS, OS)

3-yrBMD

5-yrBMD

Gnant M, et al. N Engl J Med. 2009, Lancet 2011

DFS

ABCSG-12 (84 Months)ET + Zometa Vs ET

100

80

60

40

20

0

DF

S (

%)

0 12 24 36 48 60 72 84 96 108

Mos Since RandomizationPatients at Risk, nNo ZAZA

903900

858862

833841

807822

758788

653674

521544

405419

191208

OS100

80

60

40

20

0

OS

(%

)

0 12 24 36 48 60 72 84 96 108

Mos Since RandomizationPatients at Risk, nNo ZAZA

903900

864868

856858

839849

811818

706708

576587

456454

215232

Gnant M, et al. Lancet 2011.

88% vs 92 % p=0.009 95% vs 97% p=0.09

ABCSG-12 (84 Months): DFSTamoxifen vs AI

Conclusions· Highly effective endocrine therapy alone offers

excellent prognosis for some premenopausal women with HR+ BC– 95% 5 year OS in all three studies.

· Role of OFS: Await data on Tam vs Tam + OFS · Side effects of OFS should not be

underestimated. · I am not ready to use AI + OFS in

premenopausal women yet.

Targeted Therapies for ER+ MBC· CDK 4/6 regulates

cell cycle progression

• Palbociclib is an oral, potent inhibitor of CDK4/6

• PALOMA-1:– Palbo + Letrozole is superior

to Letrozole in 1st line ER+ MBC (median PFS 20.2 vs. 10.2 mo, HR 0.49, p=0.0004)

CDK4/6 inhibitor summary· Palbociclib improves PFS with letrozole

– Confirmatory phase III trials ongoing– Watch for maturing data in combination with fulvestrant or paclitaxel

· Several other CDK4/6 inhibitors in development, such as abemaciclib and LEE011

· Many remaining questions:– Is there an optimal endocrine, chemotherapy or targeted therapy

partner?– How do we sequence these relative to everolimus?– What are mechanisms of resistance?

Presented by: Tiffany A. Traina, MD

Next?

· Palbociclib: accelerated FDA submission expected

· PALOMA 2 (Letrozole +/-)· PALOMA 3 (Faslodex +/-)· Novartis: Monaleesa (Let +/-)· Lilly: RTC · Others?

Triple Negative Disease

TNBC patients have a worse prognosis

NTN stage I

TN stage INon TN stage II

TN stage II

Non TN stage III

TN stage III

Bauer et al Cancer May 2007

Triple-negative phenotype and molecular sybtypes.

Carey L A The Oncologist 2010;15:49-56

TNBC Shares Clinical and Pathologic Features With BRCA1-Related Breast

CancersCharacteristics Hereditary BRCA1 Triple Negative/Basal-like[1-3]

ER/PR/HER2 status Negative Negative

TP53 status Mutant Mutant

BRCA1 status Mutational inactivation* Diminished expression*

Gene-expression pattern Basal-like Basal-like

Tumor histologyPoorly differentiated

(high grade)Poorly differentiated

(high grade)

Chemosensitivity to DNA-damaging agents

Highly sensitive Highly sensitive

*BRCA1 dysfunction due to germline mutations, promoter methylation, or overexpression of HMG or ID4 [4]

1. Perou CM, et al. Nature. 2000; 406:747-752.2. Cleator S, et al. Lancet Oncol. 2007;8:235-44.3. Sorlie T, et al. Proc Natl Acad Sci U S A. 2001;98:10869-10874.4. Miyoshi Y, et al. Int J Clin Oncol. 2008;13:395-400.

Platinum Agents in TNBC

Trial Population Results

Control arm BALI-1 (CDDP) Sporadic TNBC 10% RR

Control arm phase III iniparib (gem/carbo) Sporadic TNBC 30% RR

TBCRC 001 (cetuximab/carbo) Sporadic TNBC 17% RR

14-pt trials neoadj CDDP (Byrski + Silver) BRCA1+ 86% pCR

24-pt trial neoadjuvant CDDP (Silver) Sporadic TNBC 15% pCR

Baselga J, et al. Ann Oncol. 2010;21(Suppl 8). Abstract 274O. O’Shaughnessy J, et al. J Clin Oncol. 2011;29(Suppl). Abstract 1007. Carey L, et al. 2008;26(Suppl). Abstract 1009. Byrski T, et al. J Clin Oncol. 2010;28:375-379. Silver DP, et al. J Clin Oncol. 2010;28:1145-1153.

Good preclinical rationale, particularly in BRCA-associatedClinical data:

Clinical role of platinums less clear: promising in BRCA+

CALGB 40603 and other trials designed to clarify

Neoadjuvant Carboplatin for TNBC

von Minckwitz, Lancet Oncol 2014; 15: 747–56; Sikov, SABCS 2013; Rugo SABCS 2013; Alba, BCRT, 2012 (136)

Summary of recent randomized trials

Study Design NpCR

Control Platinum

GeparSixto nplDox/Pac/Bev+/- wCb (AUC1.5) X 18 wks

315 42.7% 53.2%

ALLIANCE 406032x2 design

wPac +/- Cb (AUC 6) +/- bev AC X 4

433 41% 54%

GEICAM/2006-03 ECX4D +/-Cb AUC6 X 4 94 30% 30%

ISPY2 wPac+/-Cb/veliparib ACx4 71 26%(est) 52%(est)

Both GeparSixto and CALGB 40603 included Bev along with Cb and I spy included PARPi

Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide /

epirubicin / 5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer.

Kenji Tamura, Jun Hashimoto, Hitoshi Tsuda, Masayuki Yoshida, Hideko Yamauchi, Kenjiro Aogi, Satoru Shimizu, Hiroji Iwata, Norikazu Masuda, Naohito

Yamamoto, Kenichi Inoue, Shinji Ohno, Katsumasa Kuroi, Tamie Sukigara, Yasuhiro Fujiwara, Masashi Andoh

Abstract 1017

Aims• Compare pCR in HER2 Negative tumors with

paclitaxel +/- carbo followed by CEF (note: ER+ and TNBC combined)

• Evaluate pretreatment biomarkers Ki-67, EGFR, Cytokeratin (CK) 5/6, BRCA1, vimentin, ERCC1 and ZEB1 by IHC

Study Schema

CarboplatinAUC5

q3wks x 4

Paclitaxel 80 mg/m2 qwk x 12

CP-CEF

P-CEF

HER2 (-) BCStage II/IIIA18-70 years

PS 0/1Good Organ

functionWritten IC

S U

R G

E R

Y

CEF 500/100/500 mg/m2

q3wks x 4

R

CEF 500/100/500 mg/m2

q3wks x 4

Paclitaxel 80 mg/m2 qwk x 12

Enrolled 181 ptsN= 75 for TNBC56% Node positive

pCR rates

CP-CEF P-CEF0

20

40

60

80

100

32%17%

All patients

pC

R r

ate

(%)

CP-CEF P-CEF0

20

40

60

80

100

62%

26%

TNBC patients

pC

R r

ate

(%)

Primary Endpoint

P =0.04

pCR rates by EGFR

expression

EGFR- EGFR+

p=0.010

(%)

0All AllCP CPP P

11.518.2

6.7

45.0

63.6

22.220

40

60

80

p=0.040

p= N.S.

pC

R r

ate

Results

Mechanisms of Synthetic Lethality-PARP-1

42Image from: Iglehart JD, Silver DP. Synthetic Lethality-A new direction in cancer-drug development. NEJM 2009; 361 (2) ; 189-191. 2009 Massachusetts Medical Society.

All rights reserved. Permission requested.

Paclitaxel + Trastuzumab* +

New Agent A

Paclitaxel + New Agent C

Patient is on Study

Paclitaxel+ Trastuzumab


New Agent B

Paclitaxel

Paclitaxel + New Agent E

AC

ACHER 2 (+)

HER 2(–)

Randomize

Randomize

Surgery

Surgery

Learn and adapt from each patient as

we go along

Paclitaxel + New Agent F


New Agent C

Paclitaxel + New Agent DPaclitaxel +

New Agent GH


New Agent F

MRI

Residual

Disease

(Pathology)

Key

43

I-SPY 2 TRIAL:

Learn, Drop, Graduate, and Replace Agents Over Time

The I-SPY 2 Bayesian model estimates the probability distribution

of pCR rates in each signature

Actual pCR rates are biased by the adaptive randomization and are

not calculated

Rugo et. al. SABCS 2013

Veliparib/Carboplatin GRADUATES

in the Triple Negative Signature

SIGNATURE

Estimated pCR Rate(95% probability interval) Probability

Veliparib +Carbo is

Superior to Control

Predictive Probability of

Success in Phase 3

Veliparib/Carbo

ConcurrentControl

All HER2- 33% (22-43%)

22% (10-35%)

92% 55%

HR+/HER2- 14% (4-27%)

19% (6-35%)

28% 9%

HR-/HER2- 52% (35-69%)

26% (11-40%) 99% 90%

Rugo et. al. SABCS 2013

PARP Inhibitors in Development

• Olaparib (Astra Zeneca) PO• Veliparib (ABT888 - Abbvie) PO• BMN-673 (Biomarin) PO• Niraparib (MK-4827) PO• CEP 9722 (Cephalon) PO• GPI 21016 (MGI Pharma) PO• Iniparib (BSI 201 – Sanofi-Aventis) IV• Rucaparib aka AGO 14699 (Pfizer) IV• INO 1001 (Inotek – Genentech/Roche) IV

• Others?

TNBC: potential therapeutic targets

Mayer I A et al. Clin Cancer Res 2014;20:782-790

©2014 by American Association for Cancer Research

Novel Agents in Development for TNBC

· Met inhibitor: ARQ197, onartuzumab (Metmab), foretinib

· PI3K and/or inhibitor: BKM 120, temsirolimus (+ neratinib)

· HDAC inhibitors: entinostat, vorinosat· Demethylating agents: azacitidine

(+ entinostat)· PARP inhibitors: ABT-888, E7449,

Biomarin-BMN673, AZD2281, rucaparib

· Olaparib+ BKM120; · Angiogenesis inhibitor: cediranib

(+ olaparib), ramicurumab, IMC18F1, foretenib, sorafenib

· Hsp90 inhibitors: ganetespib · Aurora kinase inhibitors: ENMD 2076· Androgen Receptor Blockers:

enzalutamide

· EGF inhibitors: erlotinib (+ metformin), apatanib

· Lucitanib (FGFR+VEGF inhibitor)· Masitinib (C-Kit inhibitor)· MEK inhibitors: GSK1120212· Wnt inhibitor: LGK974· CDK inhibitor: dinaciclib, P276-00· FMS-Kit inhibitor: PLX3397 · Apoptosis inducer: LCL161

(deactivating inhibitor of apoptosis proteins)

· Immunotherapy: MUC1 vaccine, adoptive cellular therapy (DC-CIK)

· Cytotoxics: SN38 -NK012, AEZS-108 (LHRH-dox);

· Checkpoint inhibitors (anti PD-1, anti PDL-1)

Biologics in Breast Cancer: Bevacizumab

Antibody designed to normalizing the tumor blood vessels (antiangiogenic) and aid delivery of chemotherapy: Avastin (Bevacizumab)

E5103: addition of Bev to standard AC-T in women with high risk breast cancer· LN+ · LN – (TN>1cm, HR+ >5 cm or <5 cm with oncotype >11)

Bev at 15mg/kg given concurrently with chemo and +/- maintenance

In 2010 FDA rescinded Bev approval for metast BC

E5103: Bevacizumab2986 patients

No benefit from addition of Bev

Bevacizumab: take home message

No role for bevacizumab in breast cancer (FDA approval rescinded for metastatic disease and no benefit shown in earlier stages, including E5103)

Biospecimen bank with be utilized for predictors of toxicity and late relapse

SWOG Proposed Study

R

TNBC Post NAC PT1C or N+

N=400

Placebo x 1 year

MK3475 x 1 yearAnti-PD1 antibody

Primary endpoint:

DFS

A randomized, phase III trial to evaluate the efficacy and safety of MK-3475 as adjuvant therapy for triple receptor-negative breast cancer with >1 cm residual invasive cancer or any positive lymph nodes

(>pN1mic) after neoadjuvant chemotherapy

Slide 28

Presented By Melinda Telli at 2014 ASCO Annual Meeting

EA 1131A

RTNBC

Post NAC PT1C or N+

Placebo

Carboplatin X 4 cycles

Primary endpoint:

DFS

EA 1131A : A randomized, phase III trial to evaluate the efficacy of adjuvant carboplatin for triple receptor-negative breast cancer with

residual invasive cancer

427 Enrolled 407 MBC Bx 299 Genomics

195 Druggable Lesions55 Genomic-driven Rx

SAFIR 01 Molecular-Driven Study Flow

(13%)

Andre F, et al. Lancet Oncol 2014

Most Activating Mutations are Rare

SAFIR 01 Study

Outcomes

Andre F, et al. Lancet Oncol 2014

Targets addressed:

• PI3KCA mutation

• EGFR amplification

• AKT mutation

• FGFR amplification

• IGF-1R amplificationOverall Benefit Rate:12/407 (3%)Response Rate: 4/407 (1%)

17 Targeted Regimens

PREVENTION, SUPPORTIVE CARE & SURVIVORSHIP

Prevention of Early Menopause Study (POEMS)-S0230 Phase III trial of LHRH analog during chemotherapy to reduce ovarian failure in early stage, hormone receptor-negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance)

Presented By Halle Moore at 2014 ASCO Annual Meeting

Background


POEMS/S0230 Schema


Results· Ovarian failure at 2 years

– Standard chemotherapy: 15/69- 22%

– Standard chemotherapy + Goserelin: 5/66- 8%

· More women attempted and achieved successful pregnancies in the goserelin arm compared to the chemotherapy alone arm– 12/113 (12%) vs 22/105: (21%)

· Total number of babies: 12 vs 18

· Increased menopausal symptoms during treatment

· No negative impact on cancer outcomes

Take Home Message· Fertility preservation is an important issue

for young patients

· Current Options:- Ovarian Stimulation and embryo cryopreservation- Oocyte cryopreservation- Ovarian tissue cryopreservation (Experimental)- GnRH agonist during chemotherapy?

Vitamin d and breast cancer Background

Presented By Ana Elisa Lohmann at 2014 ASCO Annual Meeting

PROGNOSTIC ASSOCIATIONS OF 25OH VITAMIN D IN NCIC CTG MA.21 A PHASE III ADJUVANT RANDOMIZED CLINICAL TRIAL OF THREE CHEMOTHERAPY REGIMENS (CEF, EC/T, AC/T) IN HIGH RISK BREAST CANCER 

Presented By Ana Elisa Lohmann at 2014 ASCO Annual Meeting

Results· Sample size

– MA.21: N = 2104 patients

– Vit D sub-study: N = 934 patients

· Low VIT D level was not associated with recurrence free survival, breast cancer free survival or overall survival

· However,– Most patients had adequate VIT D levels at study entry (mean VIT D

level 27.9ng/ml), only 20% were deficient– One time point– Lack of data on VIT D supplementation– Analysis of a subset of patients not fully representative of the entire

population– Restrictive study population (white, young and with high risk BC)

Take Home Message· Link between VIT D and breast cancer

outcomes remains inconclusive

· Randomized trial desirable but not feasible

– Common use of VIT D and better VIT D levels– Patients with low level might not want to get

randomized to placebo

Effect of obesity in premenopausal ER+ early breast cancer:

· EΒCΤCG data on 80,000 patients in 70 trials· Independent prognostic factor (regardless of surgery type, tumor size,

grade, LN status, chemo, hormonal therapy)· Dose response: increasing BMI increasing BC mortality

Pan et. al.PASCO2014 abst # 503

Obesity confers worse outcomes in premenopausal ER+ BC

Pan et. al. PASCO2014 abst # 503

THANK YOU!

Updates in the Treatment of Breast cancer Mohammad Jahanzeb, MD, FACP Professor of Clinical Medicine, Hematology-Oncology Director, UM Sylvester Deerfield.

Documents

her2 amplification

her2 positive disease

her2 esbc trastuzumab

her2 therapies

erythema slide

year of antiher2 therapy

adjuvant treatment of

year lapatinib x