22. may 2008, SM 1

The Clinical database of DBCG

(Danish Breast Cancer Cooperative Group)

1977-2008

Susanne Møller

DBCG secretariate

Copenhagen University Hospital

22. may 2008, SM 2

Number of patients with invasive

breast cancer 1977-2007

(n=84833)

0

500

1000

1500

2000

2500

3000

3500

4000

1977

1980

1983

1986

1989

1992

1995

1998

2001

2004

2007

DBCG 07

DBCG 04

DBCG 01

DBCG 99

DBCG 89

DBCG 82

DBCG 77

22. may 2008, SM 3

In situ carcinoma,DCIS LCIS

1982-2006, n=3228

0

50

100

150

200

250

1982 1985 1988 1991 1994 1997 2000 2003 2006

in situ

22. may 2008, SM 4

Hereditary Breast and Ovarian

Cancer Registry (HBOC)

1999-2006 , 3121 families

0

100

200

300

400

500

600

700

1999 2000 2001 2002 2003 2004 2005 2006

families

22. may 2008, SM 5

Restrictions of the database

• Only one record of each patient , primary key of the database is the unique civil personal registration number (CPR)

– If bilaterel breast cancer, only one side

– If new breast cancer during follow-up or after 10 years, only the first event can be recorded

• Data reported just from clinical centers in charge of breast cancer patients.

– If no surgery, greater risk of no registration

22. may 2008, SM 6

Completeness :

Number of patients with primary invasive

breast cancer in DBCG vs CR vs Patobank

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

1977

1980

1983

1986

1989

1992

1995

1998

2001

2004

2007

DBCG

CR

Patobank

22. may 2008, SM 7

Registrations of individual

patient data in DBGC

• All units involved in diagnosis and treatment

contributes

– Demographic data

– Histo-pathological variables

– Type of surgery

– Systemic therapy (chemo-, endocrine- and biological-)

– Radiation therapy

– Follow-up until 10 years

– Death

22. may 2008, SM 8

Histo-pathology CRF

A

Højre Kommunikation mellem aksil- og mammakavitet Ja Nej Biopsidato:

Side:

Venstre Suspekte mikroforkalkninger efterladt Ja Nej

Øvre lateral Papil fjernet Ja Nej Lumpek-tomidato:

Øvre medial Bundfascie på præparat Ja Nej

Biopsitype: Nedre lateral Palpabel tumor Ja Nej

Excision Nål-cytologi Nedre medial Nålemarkeret proces Ja Nej

Incision Nål-histologi

Lokali-sation

(evt. flere afkryds-ninger):

Central Klinisk Mb. Paget Ja Nej

22. may 2008, SM 9

Type of surgery by year

0

500

1000

1500

2000

2500

3000

3500

4000

1977

1980

1983

1986

1989

1992

1995

1998

2001

2004

2007

biopsy only

BCS

mastectomy

22. may 2008, SM 10

Mamma –CRF: Definition of risk groups according

to demographic and histopathological variables

C: DBCG GRUPPE – UDFYLDES AF KIRURGISK AFDELING.

Alder Tumor størrelse

Positive lymfeknuder

Type og malign. grad

Receptor status HER-2 status

TOP2A status

DBCG gruppe

Normal/ukendt I Negativ/ ukendt Abnorm II

Positiv/ Ukendt

Medulær(neg) Positiv II

Duktal I, ?

Lobulær I-II, ? Anden type

Negativ II

0

Duktal II-III Lobulær III

II

< 20 mm

> 1 II

> 35 år

> 20 mm II

< 35 år II

22. may 2008, SM 11

Mamma –CRF: Protocol allocation D: POSTOPERATIV BEHANDLING– UDFYLDES AF ONKOLOGISK AFDELING.

DBCG gruppe Alder Receptor status

HER-2 status

Standard behandling *)

Behandlingsprogram **) Protokol

I Ingen 2007 – a

Positiv KT, ET, T 2007 – b,t FACE(postmen.) Positiv / ? Negativ / ? KT, ET 2007 – b FACE(postmen.)

Positiv KT, T 2007 – d,t

< 60 år

Negativ Negativ / ? KT 2007 – d

Positiv / ? ET 2007 – c FACE

Positiv KT, T 2007 – d,t

II

> 60 år Negativ Negativ / ? KT 2007 – d

*) KT (kemoterapi) = EC x 3 ? Doc x 3. ET (endokrin terapi) = for præ (på diagnosetidspunkt): TAM i 5 år for post (på diagnosetidspunkt): TAM i 2½ år ? aromatasehæmmer i 2½ år. T = trastuzumab.

**) Patienter med et eller flere af følgende kriterier indgår ikke i DBCG’s behandlingsprogrammer for inv. c. m. Sæt evt. flere kryds.

Patienter med en eller flere af følgende kriterier bør følges og indberettes i henhold til DBCG’ behandlingsprogrammer. Afvigelser fra standardbehandling angives på Flow Sheet:

Fjernmetastaser Tidl. malign. incl. c. mam. (undt. c. cutis & c. colli ut. in situ)

Sarkom/phyllodes Bilateral c. mammae

DCIS, LCIS, PDN (udfyld In situ skema) Kontraindikation for standard behandling

Andet: Teknisk inoperabel

Ikke opereret iflg. DBCG’s kirurgiske procedure

22. may 2008, SM 12

Definition of Patient population

• Patients with invasive breast cancer,

surgery according to DBCG 95.4%

• No surgery (biopsi only) 4.2%

• Other diagnoses 0.4%

– Sarcoma

– Padget

– Fibroadenoma

22. may 2008, SM 13

Patients ineligible to DBCG programmes

• Due to diagnosis 5.9%– Distant metastasis 1.5%

– Previous malignancy 2.1%

– Bilateral breast cancer 1.7%

– Other reasons 0.6%

• Due to noneligibility for systemic therapy 24.3%– Contra indication due to medical condition incl. age 15.3%

– Inflammatory breast cancer 0.2%

– Surgery not according to DBGC guidelines 1.8%

– Patient do not want to participate 1.1%

– Protocol violation (misclassified or not treated according DBCG) 2.2%

– Unknown 3.8%

22. may 2008, SM 14

Protocol allocation in DBGC

programmes

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

dbcg

77

dbcg

82

dbcg

89

dbcg

99

dbcg

01

dbcg

04

high risk

low risk

ineligible

22. may 2008, SM 15

Follow-up of enrolled patients during treatment

and after treatment for 10 years

(currently 30.000 patients)

• Systemic therapy – Chemotherapy (type, dose, number of series,18-48 weeks )

– Endocrine therapy (type, dose, 1-5 years, + extended)

– Trastuzumab (1 year)

• Radiotherapy (target, dose, number of fractions )

• Adverse events, targeted dependent on treatment

• Recurrence – loco-regional, distant, contralateral breast, other malignancy

– death as first event

• Death for all patients (by linkage to CPR)

22. may 2008, SM 16

Events in DBGC programmes

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

dbcg 77 dbcg 82 dbcg 89 dbcg 99 dbcg 01 dbcg 04

On study

End of follow up without event

event - Dead (1. event)

event - othen malignancy

event - recurrence

22. may 2008, SM 17

Reasons for withdrawal without

event in DBGC programmes

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

dbcg

77

dbcg

82

dbcg

89

dbcg

99

dbcg

01

dbcg

04

10 years follow up completed

Programme violation (excl. Crit.)

Not treated according to

allocation

Lost to follow up

Lack of capacity

Patients condition

Voluntary withdrawal

22. may 2008, SM 18

IT systems

• Oracle database , many tables

• Programming language : SQL

• Data entry

– in the secretariate: Forms6

– From the clinical units: on-line system

• Statistical analyses language: SAS and R

• Mirror of the database in SAS-files

– Historic samples

22. may 2008, SM 19

Data validation

• At data entry:

– validating values of individual variables

– consistency of data from the same CRF

– check of protocol allocation

• Daily validation of

– double entry

– consistency of data between CRFs

• Regular check for missing CRFs

– Gap in the flow of CRFs

– Too long time since last follow-up

22. may 2008, SM 20

Clinical quality database

• 11 indicators of clincal quality are defined for breast

cancer treatment (june 2005).

• Yearly reports : mean values by units and time trend

• Example: Indicator no 4

– Rate of node negative patients,

– suitable for SN methods,

– whose nodal status is determind by SN.

– Reference value was 95%

– 2005-6 the numbers were: 1659 / 1975, rate=84 %

22. may 2008, SM 21

Rate of node negative patients, suitable for SN methods,

whose nodal status is determind by SN for each unit.

22. may 2008, SM 22

Rate of node negative patients, suitable for SN methods,

whose nodal status is determind by SN for a single unit vs.

total mean for the same units according to time.

22. may 2008, SM 23

Rate of node negative patients, suitable for SN methods,

whose nodal status is determind by SN

for a single unit vs. nationwide means according to time.

22. may 2008, SM 24

Achievements from the DBCG database

The establishment of the multidisciplinary breast cancer group with its associated database has provided the opportunity to

• improve the quality of the diagnostic and therapeutic aspects of breast cancer (guidelines)

• run trials, national or in international collaboration.

• the clinical data combined with the availability of tumour tissue has provided the ideal conditions for translational research.

22. may 2008, SM 25

Achievements from the DBCG database

• Clinical trials, nationwide, international.

• Translational reseach, connection to tumor tissue.

• Supply data as well as statistical expertise for specificresearch.

• Epidemiological research.

• Guidelines.

• Quality control, nationwide, international (EBCTCG)

• International collaboration- early warning

• Tools for information and education, professional- and public-

22. may 2008, SM 26

SLUT