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

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Female breast cancer in the elderly; Optimizing Clinical guidelines

USing clinico-pathological and molecular data

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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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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

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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• 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

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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 10902Preoperative chemotherapy

EORTC 10801BCT vs Mastectomy

EORTC 10854Perioperative chemotherapy

EORTC 22881

TEAM data

Pooled datasetn=5500 (>65 years)

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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

e.bastiaannet@lumc.nl

071-5265818