1. IBCSG 22-00: Objective To evaluate the efficacy of a low- dose chemotherapy regimen, hypothesized to have anti- angiogenic activity, administered following a standard chemotherapy program, in patients whose tumors are not endocrine therapy-responsive.

2. IBCSG 22-00: Angiogenesis inhibition for pre and postmenopausal hormone non-responsive tumors Stratify Menop.status Institution Induction CT SURGERYSURGERY Randomize before induction CT or any time prior to day 56 of last induction CT cycle ≦ 8 weeks A B Induction CT CM x 12 months

3. IBCSG 22-00: Eligibility Pre- or postmenopausal ER- and PgR receptors negative (<10%) Resection margins free of tumor Axillary staging performed SNB positive: axillary dissection done SNB micrometastasis only: randomize to trial 23-01

4. IBCSG 22-00: Eligibility

5. IBCSG 22-00: approved induction regimens AC/EC x 4 CMF x 6 AC/EC x 4 followed by CMF x 3 or T x 4 CEF/CAF 1,8 x 6 FEC 100 Iv FAC x 6 A x 4 followed by iv CMF x 4 Dose dense ACT x 4 FEC 100 x 3 followed by T x 3 TAC x 6 A x 3 followed by T x 3 followed by classical CMF x 3

6. IBCSG 22-00: Concomitant treatments Radiotherapy to the conserved breast is mandatory Herceptin for Her2+ disease is allowed

7. IBCSG 22-00: Randomization 1 Verify eligibility. Obtain written informed consent Complete Confirmation of Registration Form (A). Complete the pre-randomization Quality of Life (QL) core and module forms. Telephone or fax your Randomization Center.*

8. IBCSG 22-00: Randomization 2 All GOCCHI investigators will contact the GOCCHI Coordinating Center to randomize patients: Phone: 56-2-2330798 Fax: 56-2-2310983 Email: datacenter@gocchi.cldatacenter@gocchi.cl

9. IBCSG 22-00: CRF completion Documentation: 3 part paper CRF‘s Submit white original and yellow copy

10. IBCSG 22-00: QL timepoints Revised per amendment 4

11. IBCSG 22-00: Forms completion AE form No AE forms during induction CT 1 AE form per CMM form Submit every 3 months