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Female breast cancer in the elderly; Optimizing Clinical guidelines
USing clinico-pathological and molecular data
Departments
Department of Surgery
- Surgery
Prof. dr. C.J.H. van de Velde
- Gerontology and Geriatrics
Dr. G.J. Liefers
Department of Gerontology & Geriatrics
Prof. dr. R.G.J. Westendorp
Dr. A.J.M. de Craen
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
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Giordano et al. JCO2005;4:783-91
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
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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
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Three parts
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Observational study design
• Integraal Kankercentrum West
• Landelijk
• Eurocare
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Comprehensive Cancer Centre West
Selection
- Female patients with breast cancer
- 1999-2001
- 65 years and older
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Registration form
• Histopathology
• Complications
• Morfology, size, grade, TNM, etc
•Surgery
• Receptors
•Radiotherapy
•Chemotherapy (CTC)
•Detection (screening / patient
detected)
•Hormone therapy
• Treatment
Comorbidity
•Charlson
•Smoking
• Surgery
• Follow-up
•BMI
• Status
•Results from the blood
test
• Recurrence
•Geriatric parameters
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• Treatment
recurrence
• Radiotherapy
• Adjuvant treatment
• Unplanned change
CT
• Palliative treatment
Observational study design
• IKW “documentatie studie”
• Landelijk
• Eurocare
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Landelijke data 1994-2005
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Observational study design
• IKW “documentatie studie”
• Landelijk
• Eurocare: data uit Europa
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Three parts
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Data from clinical trials
EORTC 10902
Preoperative chemotherapy
EORTC 10801
BCT vs Mastectomy
EORTC 10854
Perioperative chemotherapy
EORTC 22881
TEAM data
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Pooled dataset
n=5500 (>65 years)
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)
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Three parts
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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
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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
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Methods
DNA SNP array
• Infinium SNP array Illumina
mRNA Expression array
 Human WG6 expression array Illumina
Protein Immunohistochemical staining on Tissue Micro Array
(TMA)
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Three parts
Prospective study
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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
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More information
Esther Bastiaannet
Heelkunde / Ouderengeneeskunde
[email protected]
071-5265818
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