Current Treatment Options for Patients with Breast Cancer
Ian E. Smith Royal Marsden Hospital, London
Improved Breast Cancer Survival
Peto et al Lancet 2000
Local Treatment of Breast Cancer
Local Treatment of Breast Cancer
Local Treatment of Breast Cancer
Local Treatment of Breast Cancer
Sentinel Node Biopsy
Local Treatment of Breast Cancer
Large cancers Multifocal BRCA1/2?
Local Treatment of Breast Cancer
Radiotherapy
Always after conservative surgery Sometimes after mastectomy
Treatment of Breast Cancer
Bone Marrow Aspirate
Adjuvant Medical Therapy:
Given after Surgery for Early Breast Cancer
The majority of patients with early breast cancer used to relapse sooner or later however intensive their local treatment
Options for Adjuvant Therapy
Endocrine Therapy – ER+ve (75%)
Tamoxifen Aromatase Inhibitors Ovarian Ablation
Chemotherapy -
Higher risk
Several options
Herceptin -
HER2+ (20%)
Endocrine Therapy
• Only for ER+ve or PgR+ve (75%)
• Low toxicity
• Long term 5years
• Aromatase Inhibitors slightly better than tamoxifen – much more expensive
• Around 10% survival gain after 10 years
Chemotherapy
• High toxicity
• Short term 3-6months
• Newer drugs slightly better (eg taxanes)– much more expensive • 1-25% survival gain after 10 years • Careful selection of patients!
Factors in Favour of Chemotherapy Benefit
• • • • • Node +ve ER-ve Larger size of cancer >2cm High Grade (esp III) Younger women
Neoadjuvant Therapy before Surgery
Neoadjuvant therapy: Tumour an in vivo measure of response
Adjuvant therapy ‘blind’
So What’s New?
So What’s New?
Chemotherapy
cyclophosphamide Taxol Navelbine methotrexate Capecitabine 5FU Gemcitabine Adriamycin Biologicals mitomycin C Clodronate vinblastine Pamidronate mitoxantrone Zoledronate epirubicin Herceptin cis/carboplatin Lapatinib? Avastin? Taxotere
Endocrine therapy
Estrogens Androgens Progestogens tamoxifen toremifene Zoladex anastrozole letrozole exemestane Faslodex
HER2 receptor and Herceptin
Growth factor
Blocking antibody
Plasma membrane Signal transduction to nucleus
Binding site
Cytoplasm
Nucleus
CELL DIVISION
Gene activation
Adjuvant Herceptin Trials: First Results
Recurrence 4yrs Recurrence 2yrs
33%
23%
15%
14%
CT
CT+H
CT
CT+H
USA Trials
HERA Trial
Should Treatment for BRCA1/2 Disease be any Different?
• So far generally no but-
• BRCA1 usually ER-ve
• Sensitivity to chemotherapy may be different eg Carboplatin. Trial just started • Prophylactic mastectomy
Conclusions
• Mortality from breast cancer is falling • An important reason is the widespread use of adjuvant medical therapy is addition to surgery + RT • Multidisciplinary teams required to plan treatment • New targeted therapies are emerging – Herceptin showing best breast cancer results ever