This open-label, randomized, multicenter study will evaluate participant preference for subcutaneous (SC) versus intravenous (IV) trastuzumab (Herceptin) in participants with HER2-positive metastatic breast cancer responding to first-line treatment with IV trastuzumab for at least 3 years. Participants will be randomized to receive either 3 cycles (cycle length = 21 days) of trastuzumab SC followed by 3 cycles of trastuzumab IV or 3 cycles of trastuzumab IV followed by 3 cycles of trastuzumab SC. All participants will receive trastuzumab SC for Cycles 7 to 18. Anticipated time on study treatment is 1 year or until disease progression or inacceptable toxicity occurs, whichever comes first.

Inclusion Criteria:

• Histologically or cytologically confirmed HER2-positive metastatic breast cancer
• On treatment with first-line trastuzumab IV and free of disease progression for at least 3 years
• Left ventricular ejection fraction (LVEF) of greater than or equal to (>/=) 50 percent (%)
• Hormonal therapy will be allowed
• Prior use of anti-HER2 therapy will be allowed

Exclusion Criteria:

• History of other malignancy, except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma and participants with other curatively treated malignancies who have been disease-free for at least 5 years; participants with previous ductal carcinoma in situ of the breast are also eligible
• Participants with severe dyspnea at rest or requiring supplementary oxygen therapy
• Serious cardiac illness or medical conditions that would preclude the use of trastuzumab
• Hepatitis B, hepatitis C or human immunodeficiency virus infection
• Pregnant or lactating women
• Concurrent enrollment in an other clinical trial using an investigational anti-cancer treatment, including hormonal therapy, biphosphonate therapy and immunotherapy, within 28 days prior to the first dose of study treatment
• Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin including hyaluronidase or the adhesive of the subcutaneous device, or a history of severe allergic or immunological reactions, for example, difficult to control asthma
• Central nervous system metastases, unless they have been treated and have been stable for at least 3 years
• Inadequate organ function