Herceptin (trastuzumab) should be offered to patients with HER2-positive locally advanced or inflammatory breast cancer alongside chemotherapy. This is the conclusion of an article in this week’s edition of The Lancet, written by Dr Luca Gianni, Fondazione, IRCCS Istituto Nazionale dei Tumori, Milan, Italy, and colleagues.

This new research looks specifically at the effect of herceptin on locally advanced and inflammatory breast cancers. Locally advanced breast cancer accounts for 6–10% of new cases of breast cancer and has a worse prognosis than does early operable disease, although patients with locally advanced disease have a better outlook than do those with distant metastases. Inflammatory breast cancer is a rare clinical and pathological subtype that follows an aggressive course and needs systemic therapy even when apparently localised.

Amplification or overexpression, or both, of human epidermal growth factor receptor-2 (HER2, also known as ERBB2), is present in around 22% of early breast cancers, 35% of locally advanced and metastatic tumours, and 40% of inflammatory breast cancers, and is associated with aggressive disease and poor prognosis. Patients with HER2-positive locally advanced or inflammatory breast cancer are therefore in particular need of effective treatment. In this study, the authors assessed event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of herceptin.

The authors compared 1 year of treatment with herceptin (given as neoadjuvant and adjuvant treatment; n=117) with no herceptin (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant* chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen. The primary endpoint was event-free survival.

Herceptin significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% with herceptin vs 56% without). Herceptin was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs.

The authors conclude: “The addition of neoadjuvant and adjuvant* trastuzumab (herceptin) to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival, survival, and clinical and pathological tumour responses.”

In an accompanying Comment, Dr Melanie D Seal, and Dr Stephen K Chia, Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada, say: “Almost all new systemic agents being studied in cancer are targeted agents. Understanding the target, and downstream and redundant effects, is essential if we truly are moving to personalised medicine. Adjuvant studies require thousands of women to show survival benefits, at high cost and often long follow-up. Studies such as NOAH illustrate the benefits and potential of neoadjuvant trials and should challenge the dogma of our current strategies of therapeutic trials in early-stage breast cancer.”