Protocol amendment 1 included the following changes: • General abolition of capecitabine for all study patients and all corresponding chapters and mentions were removed • The dose of docetaxel was increased from 75 mg/m2 to 100 mg/m2: Patients with a HER2-positive or a HER2-negative tumors and a partial or complete remission will receive thereafter 4 cycles of docetaxel 100 mg/m², day 1 q day 21 (as part of setting I or III) • Supportive treatment for lapatinib was updated • Definition of pathological response: No microscopic evidence of residual viable invasive tumor cells in all resected specimens of the breast and no microscopic evidence of residual viable tumor cells in axillary nodes

Protocol amendment 2 included the following changes: • Information on Anthracycline combined with Taxanes, Trastuzumab, Bevacizumab and Taxanes, and RAD001 and Paclitaxel treatments were updated • Information on expected toxicities for RAD001 and lapatinib was updated. The dose of lapatinib was reduced from 1250 mg daily to 1000 mg daily • Rationale of the GeparQuinto Trial was updated: The MRT-PREDICT substudy will compare the molecular changes with changes revealed by MR imaging • To examine and compare pre-specified molecular markers such as Ki-67, phospho-mTOR, YB-1, COX-2, HuR, phospho-p70 S6K, p65 NF kappa B, PTEN, PI3-K, Akt, SOX-10 (a marker for stem cell like breast cancers), and biomarkers from the GeparQuattro Herceptin resistance project, Neo-PREDICT, and other ongoing translational research projects on core biopsy before and after end of chemotherapy • Biomaterial collection: Patient has consented to the biomaterial collection and the paraffin-embedded tumor tissue block of diagnostic core has been sent to central biomaterial banks • Text editing of inclusion criteria No 7 and exclusion criteria No 9 • Update of exclusion criteria No 22: Concurrent treatment with: a) oral chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (<=10 mg methylprednisolone or equivalent) were not allowed; b) oral contraception and hormone replacement therapy prior treatment had to be stopped before study entry • Supportive treatment with pegfilgrastim and loperamide was updated • Toxicities (Clinically relevant cardiac events) at Follow-up evaluation had to be reported • Sample Size Determination: settings will be completed independently from each other. If setting I is completed before setting II then patients pretreated with EC outside of this trial and without interim response can be randomized

Protocol amendment 3 included the following changes: • Follow-up evaluation: After chemotherapy, all patients will be followed up until end of study for the occurrence of local or distant recurrence and death. Every 6 months a visit at the trial site should be performed and documented. The site of recurrence as well as the cause of death should be documented. After the end of study no study specific treatment or investigation is planned. However information on health status of the patients might be collected either based on yearly chart reviews at the sites or based on information deriving from the GBG registry of previous study participants • End of study definition and analysis after breast surgery: End of study (EOS) will be when 379 events occurred in setting I and 120 events occoured in setting III, resp. The log-rank test will then have 80% power to detect the hazard ratio (HR) of 0.75 for disease-free survival to the significance level of α=0.05. The analysis in setting II will be performed at the same time (HR=0.6).