A Prospective, Randomized, Open, Multicentre Phase III-study to Assess the Efficacy of Secondary Adjuvant Endocrine Anastrozole Therapy for 2 Further Yrs vs 5 Further Yrs in Patients With HR +ve Breast Cancer After 5-yr Primary Adjuvant Endocrine Therapy
Phase: PHASE3
Conditions: Breast Cancer
Sponsor: AstraZeneca

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Clinical Study Protocol Amendment Number 1 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
2(12) 
Old text: 
Inclusion criteria: 
1. 
Postmenopausal patients with histologically verified invasive or minimally invasive 
breast cancer that has been radically treated locally with or without previous 
chemotherapy and/or radiotherapy 
2. 
Aged 80 years  
3. 
No distant metastasis at randomisation  
4. 
No recurrence at randomisation  
5. 
TNM-classification at the time of diagnosis: T1-3, N0-1, M0 
6. 
Oestrogen and/or progesterone receptor-positive before the start of primary  
endocrine therapy  
7. 
Endocrine therapy for 5 years (maximum deviation ± 12 months) 
8. 
Therapy break (from the preliminary therapy) maximum 12 months  
9. 
At the time of randomisation, the results of the following tests must be available: 
a) Medical history and clinical examination (within one month prior to randomisation) 
b) Gynaecological examination (within one month prior to randomisation)  
c) Chest x-ray or CT scan (within one year prior to randomisation) 
d) Bilateral mammogram (within one year prior to randomisation) – exception are 
women with mastectomy (unilateral) 
f) Ultrasound of the abdomen or abdominal CT (within one year prior to randomisation) 
e) Laboratory parameters (within 3 months prior to randomisation) 
- Adequate liver function (GOT or GPT >d 2.5 x ULN; total bilirubin < 2 x ULN, 
AP < 2 x ULN) 
- Serum creatinine d 1.5 x ULN 
10. Informed consent prior to randomisation 
Amended text: 
Inclusion criteria: 
1. 
Postmenopausal patients with histologically verified invasive or minimally invasive 
breast cancer that has been radically treated locally with or without previous 
chemotherapy and/or radiotherapy 
2. 
Aged 80 years  
3. 
No distant metastasis at randomisation 1 
4. 
No recurrence at randomisation 1 
5. 
TNM-classification at the time of diagnosis: T1-3, N0-1, M0 
6. 
Oestrogen and/or progesterone receptor-positive before the start of primary  
endocrine therapy  
7. 
Endocrine therapy for 5 years (maximum deviation ± 12 months) 
8. 
Therapy break (from the preliminary therapy) maximum 12 months  
9. 
Informed consent prior to randomisation 
                                                 
1 See section 5.4 

Clinical Study Protocol Amendment Number 1 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
3(12) 
Old text: 
Exclusion criteria:  
1. 
Premenopausal patients or patients with non-determinable menopausal status at 
randomisation 
2. 
Manifest secondary malignancy or status post secondary malignancy between the time 
of initial diagnosis and randomisation  
3. 
General contraindications and/or hypersensitivity to anastrozole  
4. 
Carcinoma in situ of any size with or without Paget's disease of the nipple or T4 
tumours at the time of initial diagnosis  
5. 
Receptor determination unknown or negative at the time of diagnosis or at the start of 
the primary endocrine therapy 
6. 
Age > 80 years  
7. 
Performance index > 3 as per WHO 
8. 
Regular use of hormone products and hormone replacement therapy (HRT) for more 
than 6 months since the primary breast cancer surgery 
9. 
Serious concomitant disease preventing implementation of adjuvant therapy in line with 
the protocol and/or controlled follow-up 
10. Lack of patient cooperation 
11. Legal incapacity and/or other circumstances preventing the patient from understanding 
the nature, significance and implications of the clinical trial 
12. Existing psychiatric disease as per ICD at study enrolment (especially alcohol dependency) 
Amended text: 
Exclusion criteria:  
1. 
Premenopausal patients or patients with non-determinable menopausal status at 
randomisation 
2. 
Manifest secondary malignancy or status post secondary malignancy  
3. 
General contraindications and/or hypersensitivity to anastrozole  
4. 
Carcinoma in situ of any size with or without Paget's disease of the nipple or T4 
tumours at the time of initial diagnosis  
5. 
Receptor determination unknown or negative at the time of diagnosis or at the start of 
the primary endocrine therapy 
6. 
Age > 80 years  
7. 
Known hepatic and/or renal impairment 
8. 
Performance index >2 as per WHO 
9. 
Regular use of hormone products and hormone replacement therapy (HRT) for more 
than 6 months since the primary breast cancer surgery 
10. Serious concomitant disease preventing implementation of adjuvant therapy in line with 
the protocol and/or controlled follow-up 
11. Lack of patient cooperation 
12. Legal incapacity and/or other circumstances preventing the patient from understanding 
the nature, significance and implications of the clinical trial 
13. Existing psychiatric disease as per ICD at study enrolment (especially alcohol dependency) 

Clinical Study Protocol Amendment Number 1 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
4(12) 
Affected protocol point: 
Amendment of the text under point 1 "Patient population – exclusion criteria" or addition  
as a separate item under point 5 "Study population": 5.4. Diagnosis 
New text:  
Distant metastasis and local recurrence at the time of randomisation are ruled out in any  
case using the following examinations at the least, or using methods regarded as equivalent 
or better according the current state of scientific knowledge: 
a) Medical history within one month prior to randomisation 
b) Gynaecological examination including ultrasound within six months  
prior to randomisation (exceptions are women with a hysterectomy) 
c) Chest x-ray or CT scan within one year prior to randomisation 
d) Bilateral mammogram within one year prior to randomisation – exception  
are women with mastectomy (unilateral) 
e) Ultrasound of the abdomen or abdominal CT within one year prior to randomisation 
Affected protocol point: 
5.4. Premature termination of the clinical study (page 23) 
Old text: 
5.4.  
Premature termination of the clinical study 
5.4.1.  Premature termination in an individual case 
Reasons leading to study discontinuation are: 
- 
Withdrawal of patient consent 
- 
Occurrence of intolerable adverse events 
- 
Occurrence of relapse, secondary cancer or death of the patient 
- 
Lack of compliance or cooperation of the patient 
- 
Serious protocol violation 
- 
Other personal reasons for the patient (e.g. change of location); there is usually  
the possibility of ongoing care at another ABCSG study site 
- 
Patient no longer attends (lost to follow-up): the maximum time frame for this is  
- 
In the therapy phase: +6 months calculated from the scheduled visit  
date (see 6.5.) 
- 
In the follow-up phase: +12 months from the scheduled visit date  
The investigator must make every effort to establish contact with the patient.  
5.4.2.  Discontinuation of the entire study 
5.4.3.  Closure of an individual site 

Clinical Study Protocol Amendment Number 1 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
5(12) 
Amended text: 
5.5.  
Premature termination of the clinical study 
5.5.1.  Premature termination in an individual case 
Reasons leading to study discontinuation are: 
- 
Withdrawal of patient consent 
- 
Occurrence of intolerable adverse events 
- 
Occurrence of relapse, secondary cancer or death of the patient 
- 
Lack of compliance or cooperation of the patient 
- 
Serious protocol violation 
- 
Other personal reasons for the patient (e.g. change of location); there is usually  
the possibility of ongoing care at another ABCSG study site 
- 
Patient no longer attends (lost to follow-up): the maximum time frame for this is  
- 
In the therapy phase: +6 months calculated from the scheduled visit date  
(see 6.5.) 
- 
In the follow-up phase: +12 months from the scheduled visit date  
The investigator must make every effort to establish contact with the patient. 
- 
Development of hepatic, renal insufficiency 
5.5.2.  Discontinuation of the entire study 
5.5.3.  Closure of an individual site 

Clinical Study Protocol Amendment Number 1 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
6(12) 
Affected protocol point: 
7. Implementation 
7.1. Examination parameters before study start (page 27) 
Old text: 
7.1.  
Examination parameters before study start 
1. 
Medical history, e.g. histological findings, HR status findings, WHO status (within one 
month prior to randomisation) 
2. 
Clinical examinations (within one month prior to randomisation): 
x 
Clinical examination  
x 
Gynaecological examination  
3. 
Radiological investigations (within one year prior to randomisation): 
x 
Sonography of the abdomen or abdominal CT  
x 
Chest x-ray or CT  
x 
Bilateral mammogram (unilateral mammogram in the case of mastectomy) 
x 
Bone density measurement (optional) 
4. 
Laboratory parameters (within 3 months prior to randomisation): 
x 
LFP (GOT, GPT, total bilirubin, AP) 
x 
RFP (serum creatinine)  
x 
Optional tumour markers: CEA, CA 15-3 
Amended text: 
7.1.  
Examination parameters before study start 
1. 
Medical history, e.g. histological findings, HR status findings (within one month prior to 
randomisation) 
2. 
Physical examinations, medical history, WHO status (within one month prior to 
randomisation) 
3. 
Gynaecological examination (including ultrasound) (within 6 months prior to 
randomisation) 
4. 
Radiological investigations (within one year prior to randomisation): 
x 
Sonography of the abdomen or abdominal CT  
x 
Chest x-ray or CT  
x 
Bilateral mammogram (unilateral mammogram in the case of mastectomy) 
x 
Bone density measurement (optional) 
5. 
Query known hepatic, renal insufficiency 
6. 
Optional tumour markers: CEA, CA 15-3 

Clinical Study Protocol Amendment Number 1 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
7(12) 
Affected protocol point: 
7. Implementation  
7.2. Examination parameters during the study (page 27) 
Old text: 
7.2.2.  After 12 and 24 months (Arm A and B) 
1. 
Clinical examination  
2. 
Survey of fracture rate 
3. 
Adverse events leading to discontinuation of therapy 
4. 
Serious adverse events 
5. 
Laboratory parameters: 
x 
LFP (GOT, GPT, total bilirubin, AP) 
x 
RFP (serum creatinine) 
x 
Optional TU marker: CEA, CA 15-3  
6. 
Gynaecological examination 
7. 
Radiological examinations  
x 
Sonography of the abdomen or abdominal CT  
x 
Chest x-ray or CT 
x 
Bilateral mammogram (unilateral mammogram in the case of 
x 
mastectomy) 
6. 
Bone density measurement (optional) 
Amended text: 
7.2.2.  After 12, 24, 36, 48 and 60 months 
1. 
Physical examination 
2. 
Survey of fracture rate 
3. 
Adverse events leading to discontinuation of therapy 
4. 
Serious adverse events 
5. 
Development of hepatic, renal insufficiency 
6. 
Optional TU marker: CEA, CA 15-3  
7. 
Gynaecological examination 
8. 
Radiological examinations  
x 
Sonography of the abdomen or abdominal CT  
x 
Chest x-ray or CT 
x 
Bilateral mammogram (unilateral mammogram in the case of 
x 
mastectomy) 
9. 
Bone density measurement (optional) 

Clinical Study Protocol Amendment Number 1 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
8(12) 
Affected protocol point: 
7. Implementation  
7.3. Follow-up (page 28) 
Old text: 
7.3.  
Follow-up 
After the therapy is complete, follow-up examinations are carried out at yearly intervals (+/- 6 
months) for a period of 8 years in Arm A and 5 years in Arm B. 
1. 
Clinical examinations 
2. 
Bilateral mammogram (unilateral mammogram in the case of mastectomy) 
3. 
Serious adverse events (see 9.1 and 9.2.4) 
Amended text: 
7.3.  
Follow-up 
After the therapy is complete, follow-up examinations are carried out at 36, 48 and 60 months 
in Arm A analogously to the therapy examinations in the Arm B. After the 60th monthly visits, 
the standardised follow-up examinations are carried out at yearly intervals (+/- 6 months) 
over a period of 5 years for both arms. 
1. 
Physical examination 
2. 
Bilateral mammogram (unilateral mammogram in the case of mastectomy) 
3. 
Serious adverse events (see 9.1 and 9.2.4) 
Affected protocol point: 
1.2. Flow chart (page 12) 
Old text: 
1. Separate specification for patient history and clinical examination 
2. No detailed information for gynaecological examination 
Amended text: 
1. Change to physical examination 
2. Gynaecological examination with asterisk * in screening: * Including ultrasound 
(exception: status post hysterectomy) or ** at the therapy visits: ** "Follow-up 
examination in accordance with the current state of scientific knowledge" 

Clinical Study Protocol Amendment Number 1 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
11(12) 
 
Agreement for Protocol Amendment No. 1 
Title: 
A Prospective, Randomised, Open, Multicentre Phase III Study to Assess the 
Efficacy of Secondary Adjuvant Endocrine Anastrozole Therapy for 2 Further 
Yrs vs 5 Further Yrs in Patients With HR +ve Breast Cancer After 5-yr 
Primary Adjuvant Endocrine Therapy 
Study no.: 
1033AU/0003 
Version: 
Final version 1.0 dated 21/03/2005 
I agree with the contents of this protocol amendment. 
 
 . . . . . . . . . . . . .  
 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Date 
   
 
 
 
 
Responsible statistician 
Special Facility for Medical Statistics and Information Technology 
 
Institute of Clinical Biometrics 
 
Medical University of Vienna 
 
Spitalgasse 23 
1090 Vienna, Austria 
 
 

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A.  
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
2(15) 
Old text: 
Inclusion criteria: 
1. 
Postmenopausal patients with histologically verified invasive or minimally invasive 
breast cancer that has been radically treated locally with or without previous 
chemotherapy and/or radiotherapy 
2. 
Aged 80 years  
3. 
No distant metastasis at randomisation  
4. 
No recurrence at randomisation  
5. 
TNM-classification at the time of diagnosis: T1-3, N0-1, M0 
6. 
Oestrogen and/or progesterone receptor-positive before the start of primary 
endocrine therapy  
7. 
Endocrine therapy for 5 years (maximum deviation ± 12 months) 
8. 
Therapy break (from the preliminary therapy) maximum 12 months  
9. 
Informed consent prior to randomisation 
Amended text: 
Inclusion criteria: 
1. 
Postmenopausal patients with histologically verified invasive or minimally invasive 
breast cancer that has been radically treated locally with or without previous 
chemotherapy and/or radiotherapy 
2. 
No distant metastasis at randomisation  
3. 
No recurrence at randomisation  
4. 
TNM-classification at the time of diagnosis: T1-3, N0 and N+, M0 
5. 
Oestrogen and/or progesterone receptor-positive before the start of primary 
endocrine therapy  
6. 
Endocrine therapy for 5 years (maximum deviation ± 12 months) 
7. 
Therapy break (from the preliminary therapy) maximum 12 months  
8. 
Informed consent prior to randomisation 
Old text: 
Exclusion criteria:  
1. 
Premenopausal patients or patients with non-determinable menopausal status at 
randomisation 
2. 
Manifest secondary malignancy or status post secondary malignancy  
3. 
General contraindications and/or hypersensitivity to anastrozole  
4. 
Carcinoma in situ of any size with or without Paget's disease of the nipple or T4 
tumours at the time of initial diagnosis  
5. 
Receptor determination unknown or negative at the time of diagnosis or at the start 
of the primary endocrine therapy 
6. 
Age > 80 years  
7. 
Known hepatic and/or renal impairment 
8. 
Performance index >2 as per WHO 
9. 
Regular use of hormone products and hormone replacement therapy (HRT) for 
more than 6 months since the primary breast cancer surgery 
10. Serious concomitant disease preventing implementation of adjuvant therapy in line 
with the protocol and/or controlled follow-up 
11. Lack of patient cooperation 

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A.  
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
3(15) 
12. Legal 
incapacity 
and/or 
other 
circumstances 
preventing 
the 
patient  
from understanding the nature, significance and implications of the clinical trial 
13. Existing psychiatric disease as per ICD at study enrolment (especially alcohol 
dependency) 
Amended text: 
Exclusion criteria:  
1. 
Premenopausal patients or patients with non-determinable menopausal status at 
randomisation 
2. 
Manifest secondary malignancy or status post secondary malignancy (exceptions: 
simultaneous bilateral breast cancer, oestrogen and/or progesterone 
receptor-positive on both sides, at the time of diagnosis; cervical carcinoma 
in situ and basal cell skin cancer)  
3. 
General contraindications and/or hypersensitivity to anastrozole  
4. 
Carcinoma in situ of any size with or without Paget's disease of the nipple or T4 
tumours at the time of initial diagnosis  
5. 
Receptor determination unknown or negative at the time of diagnosis or at the start 
of the primary endocrine therapy 
6. 
Known hepatic and/or renal impairment 
7. 
Performance index >2 as per WHO 
8. 
Regular use of hormone products and hormone replacement therapy (HRT) for 
more than 6 months since the primary breast cancer surgery 
9. 
Serious concomitant disease preventing implementation of adjuvant therapy in line 
with the protocol and/or controlled follow-up 
10. Lack of patient cooperation 
11. Legal incapacity and/or other circumstances preventing the patient from 
understanding the nature, significance and implications of the clinical trial 
12. Existing psychiatric disease as per ICD at study enrolment (especially alcohol 
dependency) 
Affected protocol point: 
Point 1.1. Study summary/study schedule (protocol, page 11) and point 4. Design 
(protocol, page 21.) 
Old text: 
Planned recruitment end: 
 
 
 
 
December 2008 
Planned end of the maximum treatment phase: 
 
December 2013 
Planned end of follow-up: 
 
 
 
 
December 2018 
Amended text: 
Planned recruitment end: 
 
 
 
 
December 2009 
Planned end of the maximum treatment phase: 
 
December 2014 
Planned end of follow-up: 
 
 
 
 
December 2019 
Affected protocol point: 
Point 1.2. Flow chart (protocol, page 12)

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A.  
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
4(15) 
Old flow chart 
 
1.2. 
Flow chart 
 
Parameter 
Screening 
6 months 
12 
months 
24 
months 
36 
months 
48 
months 
60 
months 
6 years 
7 years 8 years 
9 years 
10 years 
Verification of 
inclusion and 
exclusion criteria 
x 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
x 
 
 
 
 
 
 
 
 
 
 
 
Clinical examination 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Gynaecological 
examination 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
Ultrasound or  
CT of abdomen 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
Chest x-ray or CT 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
Bilateral or unilateral 
mammogram 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Measurement of bone 
density (optional) 
x 
 
x 
x 
x**** 
x**** 
x**** 
 
 
 
 
 
Survey of fracture rate 
 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
LFP* 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
RFP** 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
TU marker*** 
(optional) 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
SAE/AE  
 
See point 9 
See point 9 
 
Legend: * LFP: GOT,GPT, AP, total bilirubin;** RFP: Serum creatinine; *** TU marker: CEA, CA 15-3;****only for patients in Arm B (5 years of anastrozole) 

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A.  
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
5(15) 
New flow chart 
 
1.2. 
Flow chart 
 
 
Legend: *   
Including assessment of general status to record WHO status 
**  Including ultrasound 
***  Follow-up examination according to the current state of scientific knowledge 
 
****  TU marker: CEA, CA 15-3 
 
 
Parameter 
Screening 
6 
months 
12 
months 
24 
months 
36 
months 
48 
months 
60 
months 
6 
years 
7 
years 
8 
years 
9 
years 
10 
years 
Verification of inclusion and 
exclusion criteria 
x 
 
 
 
 
 
 
 
 
 
 
 
Physical examination * 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Gynaecological examination 
x** 
 
x*** 
x*** 
x*** 
x*** 
x*** 
 
 
 
 
 
Ultrasound or CT of abdomen 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
Chest x-ray or CT 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
Bilateral or unilateral mammogram 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Measurement of bone density 
(optional) (thoracic/lumbar spine) 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
Survey of fracture rate 
 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
TU marker**** (optional) 
x 
 
x 
x 
x 
x 
x 
 
 
 
 
 
SAE/AE  
 
See Chapter 9 of the protocol 
See Chapter 9 of the protocol 

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A.  
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
7(15) 
11.2. Data collection / documentation sheets 
 
11.2.1. Documentation 
At the study sites, all data required by the study protocol as well as objective and 
subjective information must be entered directly into the relevant medical files/original 
patient documentation before documentation in the CRF. 
All data collected during the study is entered into the designated documentation forms 
(CRFs) by the investigator or a person who has previously been authorised in writing. 
These provide a mirror image of the requirements according to the protocol.  
 
If an examination has not been completed, this will be indicated with "n.d.". If information 
is not available, this will be documented with "n.a.". 
 
The IntTrial® system allows the investigator to document study data electronically  
("on-screen"; "e-CRF") or conventionally on a paper CRF. The study CRF is made 
available on CD-ROM. The CD-ROM contains all CRF pages both in the form of fillable 
PDF documents (e-CRF) and as a print version, which can be printed out and completed 
by hand. 
After completion on computer, the CRF pages are sent to Data Management by email. 
Alternatively, the pages can also be printed out and either faxed or sent by mail. A copy  
of each page sent is kept at the site, either in electronic or paper form. 
In the case of conventional documentation, the print template of the CRF is used. Fully 
completed pages are sent by post or faxed to Data Management. All entries must be 
made in permanent black or blue ballpoint pen to ensure the legibility of all copies.  
It is important that documentation is completed soon after therapy. Documentation should 
therefore be completed and sent to Data Management within 7 days of a visit. 
The completed CRF pages are sent to: 
ABCSG Data Management 
FAO 
 
Theresiengasse 32 
1180 Vienna, Austria 
Study fax: 
 
 
Study email: 
 

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A.  
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
8(15) 
11.2.2. Subsequent corrections to documentation 
Once a CRF page has been completed on the computer and forwarded to Data 
Management, the page can no longer be corrected by the investigator and resubmitted to 
Data Management. The CRF page is entered into the preliminary database and further 
adjustments may only be carried out again during SDV.  
If a CRF page is accidentally sent to Data Management twice, the second page will not be 
input, but simply archived. SDV is performed on the first version of the respective CRF 
page. 
The same rules apply to paper CRFs. Since in this case, entries are made by hand, 
corrections made during documentation are made in accordance with the usual rules. An 
incorrect entry is crossed out, however, the deleted entry must remain recognisable. The 
corrected value should be written next to it. The date of the change and signature/initials 
of the investigator or authorised person must be added to each correction. The use of 
correction fluid is prohibited. 
11.3. Data acquisition 
 
Data acquisition is carried out by the person responsible for data management. Data entry 
takes place on an ongoing basis, in parallel with the clinical trial. 
11.3.1. Data entry / obvious corrections / queries 
CRFs received by Data Management are included in the preliminary study database. A 
system consisting of the Cardiff Teleform Reader, the Teleform Verifier and MS-SQL is 
used for the input process with IntTrial®. The input process is divided into automatic data 
acquisition, followed by a manual check by the data entry staff, with each value being 
checked subsequently. 
A copy of each CRF page is automatically archived in electronic format as an indexed 
PDF. Corrections of obvious mistakes in the documentation (obvious corrections) are 
made immediately during input by the input staff and the changes are logged in the 
database. Missing, contradictory or illegible entries are also logged as queries in the 
database. 
11.3.2. Creating an electronic copy of CRFs for source data verification (SDV) 
To enable the study data to be monitored, the data from each CRF page included in the 
preliminary study database is exported into a blank CRF form. The obvious corrections 
made as well as the queries logged in the database are exported into the form. 
These CRF pages are then made available to the competent monitor for source data 
adjustment. During SDV, queries already listed are processed and the CRF page is 
signed by the investigator after any corrections are made. A copy of the signed CRF 
remains at the site and the original is given to the monitor. 

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A.  
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
9(15) 
11.3.3. Data entry / database validation / database lock 
The signed CRF pages are forwarded by the monitor to Data Management and then 
entered into the database again from there. This data is then validated by a final query 
process, based on checks for validity, consistency and plausibility. 
Query forms to clarify any queries are passed on to the investigator for processing  
via the monitor. After processing, these are sent back to Data Management, and  
a copy is retained at the site. 
After clarification of all possible queries using query forms, the database is closed. The 
analysis and statistical analysis is carried out using SAS® (Statistical Analysis Software) 
version 8. 
11.4.  Original data in the CRF 
 
All data collected within this protocol must be available as original data in the respective 
medical history. Direct entries in the CRF are not considered to be source data. 
 
11.5.  Storage of CRFs 
 
Once the study is completed, the documentation remains with the ABCSG. The originals 
of all central study documents including the documentation sheets are stored at the study 
site for at least 15 years after the end of the study. CRFs can also be stored on image 
carriers or other data storage devices.  
 
During the study, one copy of the CRF remains with the respective investigator. The 
investigator also retains the administrative documents produced (correspondence with the 
Ethics Committee, BUMI, AstraZeneca, study site etc.), the patient identification list, 
signed informed consent forms, copies of documentation sheets and the general study 
documentation (protocol, amendments) for the period of time stated above. 
Original data on study patients (medical files) must be stored in accordance with the 
archiving term applicable to the study sites, however, for a minimum of 15 years. 
 
If the investigator does not stay at the study site for whatever reason (e.g. retirement, 
appointment elsewhere), the retention of the documents must be handed over to a 
successor, who consequently takes on the responsibility, and this must be documented in 
writing. Both AstraZeneca and the ABCSG must be informed of such a transfer in writing. 

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A.  
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
10(15) 
Amended text: 
11.  DATA MANAGEMENT 
 
Data is managed by the ABCSG using the "Macro" (InferMED) data management system 
via the "DATAPORT" web portal. "MACRO" is a piece of software developed for use in 
controlled single or multi-centre clinical studies of all phases (I-IV). Documentation is web-
based (eCRF) and is supported by active online support. 
System compliance with the requirements of international guidelines such as "ICH Good 
Clinical Practice" and "FDA 21 CFR Part 11" is essential for "MACRO". An audit trail is 
created for the entire course of the study, which shows any changes e.g. in terms of the 
data entered, the date and time of entry and the added comments. 
"MACRO" also provides the possibility for easy detection of discrepancies in the individual 
data sets (e.g.implausibilities selected by Edit Check programming, missing values etc.) 
through the use of various marks (icons). This allows the employees from Monitoring and 
Data Management to generate queries (=discrepancies) quickly, which in turn can be 
processed by the investigator in a timely manner. Through automatic assignment of 
specific "marks" (icons) by the system, the processing status of the queries  
(= discrepancies) is visible and can be tracked up to final completion. 
Employees from Monitoring also have the option to use other "marks" (= icons) to indicate 
the status of source data verification (SDV) (e.g. planned, completed, pending, 
discontinued). 
Due to the web-based processing, all entries, changes, queries etc. are visible to 
authorised persons immediately after implementation. This reduces the processing time 
and means that all data is available more quickly for statistical evaluation. 
 
11.1. Patient identification list 
 
 
All patient-related data will be recorded in anonymous form. Each patient is assigned a 
patient number at randomisation that uniquely identifies them together with their initials. 
The investigator will keep a confidential patient list, in which the identifying data is linked 
to the patients’ full name and optionally the insurance number. 
 
11.2. Data collection / documentation sheets 
 
11.2.1. Documentation 
At the study sites, all data required by the study protocol as well as objective and 
subjective information must be entered directly into the relevant medical files/original 
patient documentation before documentation in the web-based CRF (eCRF). 

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A.  
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
11(15) 
Patient data that is relevant for the study is collected in the "MACRO" data management 
system via the "DATAPORT" web portal directly at the site by the investigator or by study 
personnel with documentation authorisation. Only in exceptional cases will a hard-copy 
CRF be provided for the site. In this case, entries must be made in block letters or in 
easily legible script using a black or blue pen. The data documented on hard-copy CRFs 
is recorded in "MACRO" by data entry staff from the ABCSG using "double data entry". 
Correct collection and input of data is checked by the competent monitor via the Internet 
and is marked accordingly in the system using a designated icon. Any queries 
(=discrepancies) are generated by the monitor via the internet and are immediately visible 
to both the investigator and Data Management as soon as they are created on the system. 
 
11.3. Data management (data review) 
The eForms marked as source data verified by Monitoring are checked for consistency 
and plausibility by Data Management. Any queries (=discrepancies) are generated via the 
Internet and are therefore visible to both the investigator and monitor as soon as they are 
created in the system by means of "marks" (icons). Data Management locks all eForms 
that it finds to be fully correct, meaning they are protected from further processing. 
"Marks" indicate this processing status. 
The individual working steps carried out by Data Management are specified in SOPs (= 
standard operating procedures) and WIs (= working instructions). 
Justification for the amendment:  
- 
The age limit in the inclusion and exclusion criteria is being raised (reason: there 
are a number of sprightly patients who will tolerate the study follow-up phase well 
and can remain compliant. The primary objective of the study will not be affected 
by a potential increase in the incidence of deaths that are not breast cancer 
related.) 
- 
Correction of the permitted N-stages of the tumour from N1 to N+ (reason: it is 
expected that all patients, regardless of their N-stage at the time of diagnosis will 
benefit from extending the therapy with anastrozole beyond 5 years)  
- 
Addition to the exclusion criterion: "Manifest secondary malignancy or status post 
secondary malignancy" with the following exceptions: a) simultaneous bilateral 
breast cancer, oestrogen and/or progesterone receptor-positive on both sides at 
the time of diagnosis (reason: because of the simultaneity of the tumour 
occurrence, such a carcinoma is interpreted as a multi-centric carcinoma); b) in-
situ carcinoma of the cervix and basal cell carcinoma of the skin, is a correction of 
the data in the CRF and protocol, as these exceptions were defined in the CRF 
(reason: the probability of relapse in these carcinomas is minimal.) 
- 
Extension of the recruitment phase for 1 year (reason: the annual recruitment rate 
was overestimated in the study planning phase.)  

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
14(15) 
 
Agreement for Protocol Amendment No. 2 
Title: 
A Prospective, Randomised, Open, Multicentre Phase III Study to Assess 
the Efficacy of Secondary Adjuvant Endocrine Anastrozole Therapy for 2 
Further Yrs vs 5 Further Yrs in Patients With HR +ve Breast Cancer After 
5-yr Primary Adjuvant Endocrine Therapy 
Study no.: 
1033AU/0003 
Version: 
Final version dated 30/10/2008 
I agree with the contents of this protocol amendment. 
 
 . . . . . . . . . . . . .   
 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Date 
   Assoc. Univ. 
 
 
 
 
Responsible statistician 
Special Facility for Medical Statistics and Information Technology 
Institute of Clinical Biometrics 
Medical University of Vienna 
Spitalgasse 23 
1090 Vienna, Austria 
 

Clinical Study Protocol Amendment Number 2 
Study Code 1033AU/0003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
15(15) 
 
Agreement for Protocol Amendment No. 2 
Title: 
A Prospective, Randomised, Open, Multicentre Phase III Study to Assess 
the Efficacy of Secondary Adjuvant Endocrine Anastrozole Therapy for 2 
Further Yrs vs 5 Further Yrs in Patients With HR +ve Breast Cancer After 
5-yr Primary Adjuvant Endocrine Therapy 
Study no.: 
1033AU/0003 
Version: 
Final Version dated 30/10/2008 
I agree with the contents of this protocol amendment. 
 
 . . . . . . . . . . . . .   
 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Date 
  
 
 
 
Medical Director at AstraZeneca Österreich  
Schwarzenbergplatz 7 
1037 Vienna, Austria 
 

Clinical Study Protocol Amendment Number 3 
Study Code: 1033AU/003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
4(5) 
 
Agreement for Protocol Amendment No. 3 
Title: 
A Prospective, Randomised, Open, Multicentre Phase III Study to Assess 
the Efficacy of Secondary Adjuvant Endocrine Anastrozole Therapy for 2 
Further Yrs vs 5 Further Yrs in Patients With HR +ve Breast Cancer After 
5-yr Primary Adjuvant Endocrine Therapy 
Study no.: 
1033AU/0003 
Version: 
Final version dated 27/11/2009 
I agree with the contents of this protocol amendment. 
 
 . . . . . . . . . . . . .   
 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Date 
   
 
 
 
, 
ABCSG statistician 
Austrian Breast and Colorectal Cancer Study Group 
Nußdorfer Platz 8 
1190 Vienna, Austria 

Clinical Study Protocol Amendment Number 3 
Study Code: 1033AU/003, 
ABCSG Protocol 16, S.A.L.S.A. 
SOP-00008-G T02 Clinical Study Protocol Amendment Template 
Version 6, Date: 1 May 2004 
5(5) 
 
Agreement for Protocol Amendment No. 3 
Title: 
A Prospective, Randomised, Open, Multicentre Phase III Study to Assess 
the Efficacy of Secondary Adjuvant Endocrine Anastrozole Therapy for 2 
Further Yrs vs 5 Further Yrs in Patients With HR +ve Breast Cancer After 
5-yr Primary Adjuvant Endocrine Therapy 
Study no.: 
1033AU/0003 
Version: 
Final version dated 27/11/2009 
I agree with the contents of this protocol amendment. 
 
 . . . . . . . . . . . . .   
 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   
Date 
  
 
 
 
Medical Director 
AstraZeneca Österreich GmbH 
Schwarzenbergplatz 7 
1037 Vienna, Austria