National Surgical Adjuvant Study of Breast Cancer(N-SAS BC) 07 [RESPECT]

This study is a randomized, comparative trial of postoperative adjuvant therapies in women with HER2 (human epidermal growth factor receptor type-2)-positive primary breast cancer who are ≥70 years of age that will compare trastuzumab (Herceptin®) monotherapy (H group) and trastuzumab in combination with chemotherapy (H+CT group).

The objectives of this study are as follows.

• To verify the clinical positioning of trastuzumab monotherapy and combined trastuzumab and chemotherapy as postoperative adjuvant therapies for the treatment of HER2-positive primary breast cancer patients who are ≥70 years of age.
• To evaluate the safety of trastuzumab monotherapy and combined trastuzumab and chemotherapy in patients who are ≥70 years of age. In particular, to evaluate cardiac disorders that are a characteristic adverse drug reaction of trastuzumab as well as geriatric-related concerns including lipid metabolism, cerebral infarction and cognitive disorders.
• To evaluate overall survival in patients who are ≥70 years of age using trastuzumab monotherapy or combined trastuzumab and chemotherapy.
• To evaluate health-related quality of life (HRQOL), cost-effectiveness (utility), and conduct a comprehensive geriatric assessment (CGA) in patients who are ≥70 years of age and using trastuzumab monotherapy or combined trastuzumab and chemotherapy.
• To establish and expand information networks by the participation of practitioners in clinical trials that are involved in general clinical practice and breast cancer.

Inclusion criteria

• Histologically diagnosed as invasive breast cancer and received curative operation for primary breast cancer.
• Stage: 1 (tumor size [pT] > 0.5 cm), 2A, 2B or 3A/ M0
• Female between 70 and 80 years old
• Primary region is HER 2 positive: either 3+ overexpression by IHC or positive by FISH
• Baseline left ventricular ejection fraction (LVEF) is ≥55% measured by echocardiography or MUGA scan within 4 weeks before registration.
• PS: 0-1 (ECOG)
• Sufficient organ function meeting following criteria within 4 weeks before registration:

• Leukocyte ≥2500 mm3
• Neutrophil ≥1500 mm3
• Platelet ≥100 000 mm3
• Serum total bilirubin ≤2.0 x upper limit of normal (ULN)
• ALT (GPT) or AST (GOT) ≤2.5 x ULN
• Serum creatinine ≤2.0 x ULN
• ALP ≤2.5 x ULN
• No previous endocrine therapy or chemotherapy for breast cancer
• Signed written informed consent

Exclusion criteria

• Active multiple primary cancer (synchronous multiple primary cancer and invasive cancer of other organs)
• Postoperative histological axillary lymph node metastasis ≥4
• Axillary lymph node is not histologically evaluated
• Histologically confirmed positive margin in breast conservation surgery (evaluation of margin status is based on policy of site)
• History of drug-related allergy which could hinder planned treatment
• Any history or complication of following cardiac disorders

• History of congestive heart failure, cardiac infarction
• Complication requires treatment such as: ischemic cardiac disorder, arrhythmia, valvular heart disease
• Poorly controlled hypertension (ex. Systolic arterial pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg)
• Poorly controlled diabetes
• Continuous visit to a medial institution is considered difficult due to deterioration of activity of daily living (ADL)
• Difficult to participate in the trial because of psychiatric disorder or psychiatric symptoms
• Ineligible to the trial based on decision of an investigator