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Departments
- Surgery
- Gerontology and Geriatrics
Department of Surgery Department of Gerontology & Geriatrics
Prof. dr. C.J.H. van de Velde Prof. dr. R.G.J. Westendorp
Dr. G.J. Liefers Dr. A.J.M. de Craen
FOCUS
Female breast cancer in the elderly; Optimizing Clinical guidelines
USing clinico-pathological and molecular data
FOCUS
The Netherlands
• Increase incidence breast cancer 2005-2025 18%
• 40-50% of these patients are 65 years and older
• 50-75% has comorbidity of any kind
• No internationally agreed recommendations
• Lack of clinical trial data
• Uncertainty treatment toxicity and benefits
• Interaction between therapy and comorbidity
• Competing risks of death
• New pathological and molecular variables
associated with outcome and response to therapy
• Lack of assessment tools to identify at-risk and frail elders in oncology
FOCUS
Several cohort studies
• Less aggressive therapy (corrected stage)
• Strongly decreased survival
(not only explained by therapy)
• Stage at diagnosis higher
• Tumor biology: increased hormone
receptor positive, less Her2/neu
overexpression, lower grades, lower
proliferative indices
Life expectancy is central issue
However
-Variability within age group is large (individualized treatment)
- Comorbidity
Risks / benefits treatment
Giordano et al. JCO2005;4:783-91
FOCUS
In conclusion
• Increasing incidence of breast cancer in elderly
However:
• Limited data
• No guidelines for individualized treatment
Female breast cancer in the elderly; Optimizing
clinical guidelines using clinico-pathological and
molecular data
FOCUS
FOCUS
Three parts
FOCUS
Observational study design
• Integraal Kankercentrum West
• Landelijk
• Eurocare
FOCUS
Comprehensive Cancer Centre West
Selection
- Female patients with breast cancer
- 1999-2001
- 65 years and older
FOCUS
Registration form
• Histopathology• Morfology, size, grade, TNM, etc
• Receptors
•Detection (screening / patient detected)
Comorbidity•Charlson
•Smoking
•BMI
•Results from the blood test
•Geriatric parameters
• Complications
•Surgery
•Radiotherapy
•Chemotherapy (CTC)
•Hormone therapy
• Treatment
• Surgery
• Radiotherapy
• Adjuvant treatment
• Unplanned change
CT
• Palliative treatment
• Follow-up
• Status
• Recurrence
• Treatment
recurrence
FOCUS
Observational study design
• IKW “documentatie studie”
• Landelijk
• Eurocare
FOCUS
Landelijke data 1994-2005
FOCUS
Observational study design
• IKW “documentatie studie”
• Landelijk
• Eurocare: data uit Europa
FOCUS
Three parts
FOCUS
Data from clinical trials
EORTC 10902Preoperative chemotherapy
EORTC 10801BCT vs Mastectomy
EORTC 10854Perioperative chemotherapy
EORTC 22881
TEAM data
Pooled datasetn=5500 (>65 years)
FOCUS
Trial data
1.Comparison of characteristics between the young and the elderly patients
Selection of the elderly
2. Multivariate analysis Survival (OS, DSS, DFS)
3. Risk factors for the elderly
- Morbidity
- Frequency of Adverse Events
- Treatment withdrawal
4. Age stratified analysis (65-74; 75-84 and 85 and older) within the elderly
patients (age-dependent prediction model)
FOCUS
Three parts
FOCUS
Gene expression analyis
• Recent studies no inclusion of elderly
Relevance of the signatures in elderly patients are unknown
• Which factors are significantly different between young and elderly
patients
• Are there different activated pathways in young vs. elderly breast
cancer patients
• Validate existing and/or find new prognostic/predictive factors for
elderly breast cancer patients
FOCUS
Central dogma of molecular biology
• DNA in nucleus
• Genes and non-coding
regions
• Gene: Introns and exons
• Transcriptie DNA RNA
Poly A tail, cap and
splicing mRNA
• mRNA translated into
protein in cytoplasm
FOCUS
Methods
DNA SNP array
• Infinium SNP array Illumina
mRNA Expression array
Human WG6 expression array Illumina
Protein Immunohistochemical staining on Tissue Micro Array
(TMA)
FOCUS
Three parts
Prospective study
FOCUS
Prospective study
Combination of all data
* Molecular data
* Trial data
* Data from cohorts
Risk model
- Recurrent disease
- (Breast cancer related) death
- Adverse events
- Patient and tumor characteristics
Evidence based, high quality care
Tailored treatment guidelines
FOCUS
More information
Esther Bastiaannet
Heelkunde / Ouderengeneeskunde
071-5265818