Abstract

Introduction

What is a Herceptin (Trastuzumab) ?

Herceptin (Trastuzumab) is an monoclonal antibody ,it is an example of targeted therapy an agent that is directed against a specific change in the cancer cell. Herceptin is approved for the adjuvant treatment of HER2-overexpressing, node-positive or node-negative (ER/PR-negative or with one high-risk feature) breast cancer.

__________________________

Methods

Results

Results Results

Conclusion The combination of Herceptin and chemotherapy decreased the death rate by 23 percent compared with chemotherapy alone. After a median follow-up period of 29 months, women treated with a combination of either Herceptin plus doxorubicin (or epirubicin) and cyclophosphamide (AC therapy), or Herceptin plus paclitaxel (Taxol) survived on average more than five months longer than those treated with the chemotherapy drugs alone (25.4 months vs. 20.3 months). Quality-of-Life Increases With Herceptin Use. Cardiac toxicity in the trial was 4.1 percent for those taking trastuzumab vs. 0.8 percent for those on standard chemotherapy The most common adverse reactions in patients receiving Herceptin are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity 2 years herceptin administration showed no better results in OS versa 1 year herceptin administration.

Corresponding author and co-authors;

Gani Oruqaj; g_oruqaj@yahoo.com, mob; +377 44 23 77 42

Learta Pervizaj ; learta1@hotmail.com,

Lavdim Ibrahimi; filas_med@hotmail.com

Fig.no.1

Normal HER2 expression

HER2 amplification leads to HER2 overexpression

HER2 overexpression leads totumour proliferation

Treatment with Herceptin

r

Extracellular targetingHerceptin , Omnitarg,

cetuximabSignal

transductionto nucleus

Intracellular targeting

TarcevaT, gefitinib

Nuclear targetingantisense

oligonucleotides, ribozymes

Gene activation CELLDIVISION HER2/neu (also known as

ErbB-2, ERBB2) stands for "Human Epidermal growth factor Receptor 2" and is a protein giving higher aggressiveness in breast cancers. It is a member of the ErbB protein family, more commonly known as the epidermal growth factor receptor family. HER2/neu has also been designated as CD340 (cluster of differentiation 340) and p185.

An increased amount of HER2 is a marker for a very aggressive form of breast cancer. Approximately 30 percent of all breast cancers overexpress HER2.

The oncogene neu is so-named because it was derived from a cell line in rat. HER2 is named because it has similar structure to human epidermal growth factor receptor, or HER1. ErbB2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFR

Targeting the HER receptor

1. Extracellular targeting

2. Intracellular targeting

• Aim of research; • Trastuzumab q3w after standard adjuvant therapy• 1 vs 2 years of treatment• Adverse side events that often encounter during treatment• Crossover permitted after 1st interim efficacy analysis• Trial ;medical records of patients treated at the Cancer Clinic-

ONKOMED

IHC 3+ or FISH+ Node-positiveand high-risknode-negative EBC

Observation

1-year trastuzumab

2-year trastuzumab

8 mg/kg loading dose 6 mg/kg

q3w

Surgery + standard

predefined (neo)adjuvant

CT + RT

Trial design

AC, doxorubicin 60 mg/m2 or epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2

HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry, MBC;metastatic breast cancer

HER2-positive MBC (IHC 3 + or 2+)No prior chemotherapy for MBC

AC q3w x 6 cycles(n=138)

AC q3w x 6 cycles + trastuzumab 4 mg/kg loading, then 2 mg/kg qw until disease progression (n=143)

Paclitaxel 175 mg/m2

q3w x 6 cycles (n=96)

Paclitaxel 175 mg/m2 q3w x 6 cycles + trastuzumab 4 mg/kg loading, then 2 mg/kg qw until disease progression (n=92)

Prior adjuvant anthracyclines

(n 42)

No prior anthracyclines

(n 42)

-OS, overall survival

Probability of survival

17.9 24.8+40%

Trastuzumab + paclitaxel Paclitaxel

05 1

015

20 2

5

30

35

40

45

6.9 months

1.0

0.6

0.8

0.4

0.2

0.0

Trial : OS (IHC 3+ taxane subgroup)

-Patients progressing on docetaxel alone could cross over to receive trastuzumab-FISH, fluorescence in situ hybridisation; -LVEF, left ventricular ejection fraction-Patients show a better outcome in overall survival rate in the regimen docetaxel + trastuzumab ,8.5 months compared to paclitaxel + trastuzumab, 6.9 months

HER2-positive MBC (IHC 3+ and / or FISH+)No prior chemotherapy for MBCBaseline LVEF >50%

Docetaxel 100 mg/m2

q3w x 6 cycles( n 42)

Docetaxel 100 mg/m2

q3w x 6 cycles +trastuzumab 4 mg/kg loading, then 2 mg/kg qw until disease progression( n 42)

•Twice as many patients receiving trastuzumab survived 3 years (33% vs 16%)

Trastuzumab + docetaxel (n=92)Docetaxel alone (n=94)

Patients alive (%)

22.7 31.20

20

40

60

80

100

0 5 10 15 20 25 30 35 5040 45

+37%Time (months)8.5 months

OS (IHC 3+ / FISH+)

aBased on pretreatment blood counts only SAE, serious adverse event; H, trastuzumab; Diff, difference

SAE, %

Fever

Heart failure

Leucopeniaa

Febrile neutropenia

Alopecia

Alone(n=95)

1

1

5

-

26

H(n=91)

2

2

6

-

26

Diff

1

1

1

0

Alone(n=94)

1

0

15

17

6

H (n=92)

1

1

20

23

10

Diff

0

1

5

6

4

Paclitaxel Docetaxel

Effect of adding trastuzumab to chemotherapy: SAEs

BREAST CANCER -HERCEPTIN IMPACT AND SUCCESS IN PATIENTS WITH AGGRESSIVE BREAST CANCER AND HER 2+ PROVED BY IHC OR FISH

Gani Oruqaj, Learta Pervizaj, Lavdim Ibrahimi Armend Spahiu, MD, internist and medical oncologist

KOSOVO, University of Prishtina-Prishtina, Medical Faculty, Cancer Care Clinic –ONKO-MED-Prizren,Kosovo

FISH

Patient tumour sample

Herceptin®

therapy

+–2+

3+

1+0

+–

FISH

IHC

Herceptin®

therapy

Herceptin®

therapy

Interceptors of HER signalling

HER2 testing algorithm

Methods and Material used in

the trial to find out the HER 2

positivity in women with MBC.

IHC and FISH confirm

Patients alive (%)

22.7 31.20

20

40

60

80

100

0 5 10 15 20 25 30 35 5040 45

+37%

8.5 months

1 year Trastuzumab trial2 years Trastuzumab trial

Acknowledgements ; Cancer Care Clinic –ONKO-MED, Prizren-Kosovo ,Armend Spahiu , MD, medical oncologist,

ONKO-MED