Signed Informed Consent Form
 Age  18 years at time of signing the Informed Consent Form
 Ability to comply with the study protocol
 Histologically confirmed invasive breast carcinoma
 Clinical stage at presentation (as per American Joint Committee on Cancer [AJCC]
Cancer Staging Manual, 8th edition): cT4/anyN/M0, any cT/N2–3/M0, or
cT1-3/N0-1/M0 (patients with cT1mi/T1a/T1b/N0 are not eligible) including the
following requirements:
- Patients with cT1-3/N0-1/M0 disease at presentation (patients with
cT1mi/T1a/T1b/N0 are not eligible) must have pathologic evidence of residual
invasive carcinoma in axillary lymph node(s) at surgery (with or without residual
invasive disease in the breast)
- Patients with cT4/anyN/M0 or any cT/N2–3/M0 disease at presentation must
have pathologic evidence of residual invasive carcinoma in the breast and/or
axillary lymph node(s) at surgery
 Diagnosis of HER2-positive breast cancer with assessment of known hormone
receptor (ER positive or negative/PgR positive or negative) and known PD-L1
status (positive or negative), as documented through central testing of a
representative tumor tissue specimen from a pretreatment (prior to neoadjuvant
therapy) biopsy. The tumor tissue specimen must be submitted prior to study
enrollment.

Stage IV (metastatic) breast cancer
 Inadequate excision (as described in Section 4.1.1)
 An overall response of disease progression according to the investigator at the
conclusion of preoperative systemic therapy
 Patients for whom radiotherapy would be recommended for breast cancer treatment
but for whom it is contraindicated because of medical reasons (e.g., connective
tissue disorder or prior ipsilateral breast radiation)
 History of other malignancy within 5 years prior to screening, except for
appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,
Stage I uterine cancer, or DCIS
 History of exposure to the following cumulative doses of anthracyclines:
- Doxorubicin  240 mg/m2
- Epirubicin or liposomal doxorubicin-hydrochloride (Myocet)  480 mg/m2
- For other anthracyclines, exposure equivalent to doxorubicin  240 mg/m2
 Prior treatment with atezolizumab
 Prior treatment with trastuzumab emtansine in the neoadjuvant setting or relapse
to trastuzumab emtansine in the adjuvant setting
 Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
including anticytotoxic T lymphocyte-associated protein-4, antiPD-1, and
antiPD-L1 therapeutic antibodies
 Current NCI CTCAE v5.0 Grade  2 peripheral neuropathy
 Dyspnea at rest
 Cardiopulmonary dysfunction as defined by any of the following:
- History of NCI CTCAE v5.0 Grade  3 symptomatic heart failure or New York
Heart Association (NYHA) criteria Class  II
- Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia
not controlled by adequate medication, severe conduction abnormality, or
clinically significant valvular disease
Atezolizumab and Trastuzumab Emtansine—F. Hoffmann-La Roche Ltd
73/Protocol WO42633, Version 2
- High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart
rate  100/min at rest, significant ventricular arrhythmia (ventricular
tachycardia) or higher-grade atrioventricular (AV)-block (second-degree
AV-block Type 2 [Mobitz 2] or third degree AV-block)
- Significant symptoms (Grade  2) relating to left ventricular dysfunction, cardiac
arrhythmia, or cardiac ischemia while or since receiving preoperative therapy
- History of a decrease in LVEF to  40% during prior trastuzumab treatment
(e.g., during preoperative therapy)
- Myocardial infarction within 12 months prior to randomization
- Uncontrolled hypertension (systolic blood pressure 180 mmHg and/or diastolic
blood pressure 100 mmHg)
- Evidence of transmural infarction on ECG
- Requirement for continuous oxygen therapy
 Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré
syndrome, or multiple sclerosis (see Appendix 9 for a more comprehensive list of
autoimmune diseases and immune deficiencies), with the following exceptions:
- Patients with a history of autoimmune-related hypothyroidism who are on a
stable dose of thyroid-replacement hormone are eligible for the study.
- Patients with controlled type 1 diabetes mellitus who are on a stable insulin
regimen are eligible for the study.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are met:
o Rash must cover  10% of body surface area
o Disease is well controlled at baseline and requires only low-potency
topical corticosteroids.
o No occurrence of acute exacerbations of the underlying condition
requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids,
biologic agents, oral calcineurin inhibitors, or high-potency or oral
corticosteroids within the previous 12 months.
 History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis
- History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
 Active tuberculosis