What is the HERA Trial?
The HERceptin® Adjuvant (HERA) Trial is a large-scale international clinical trial designed to determine if earlier use of the breast cancer drug Herceptin® (trastuzumab) can increase the length of survival without cancer recurrence in women whose early breast cancer has been diagnosed as HER2 positive.

HER2-positive breast cancer refers to a form of the disease that may grow faster and is less responsive to standard treatment when compared to HER2-negative disease, and tends to be less responsive to classical treatment. The Breast International Group (BIG)* and F. Hoffmann-La Roche (Roche) are collaborating to conduct the HERA Trial.

*Additional collaborative partners for the HERA Trial include: collaborative groups affiliated with BIG, plus non-affiliated collaborative groups, and independent sites.

Who was eligible?
In summary, to have been eligible to participate in the HERA Trial patients must have had a diagnosis of primary breast cancer, have previously completed a course of adjuvant chemotherapy (chemotherapy given before or after surgery) and been identified through testing as having strongly HER2-positive breast cancer. Patients were then referred to a trial centre by their surgeon or oncologist. The HERA Trial allowed for the use of a range of chemotherapy regimens, thus maximizing the number of patients who were able to take part in the study.

Criteria
To be eligible to participate in the trial patients must have:

	been diagnosed with primary breast cancer
	been diagnosed as strongly HER2 positive (e.g. IHC3+ and/or FISH+)
	completed a course of standard systemic chemotherapy (standard chemotherapy administered before or after surgery) prior to enrolment
	fulfilled other pre-defined standard eligibility criteria.

HER2 testing
Two diagnostic techniques – Immunohistochemistry (IHC) and Fluorescence in situ Hybridisation (FISH) – were used to assess HER2 status for the HERA trial. The IHC technique measures the HER2 protein levels at the cell surface. The FISH technique measures the gene levels within the cell. Both techniques can determine which patients are most likely to respond to Herceptin® treatment.

Herceptin® therapy is recommended for patients whose tumours test positive with the FISH test, or have HER2 overexpression at the 3+ level with IHC. Recent data has confirmed that patients who test HER2 IHC3+ are more likely to show a response to Herceptin® compared to patients with IHC2+.¹

Scale of trial
Approximately 5,100 patients with HER2-positive breast cancer were enrolled from 480 sites in 39 countries. The trial was enlarged in 2003 to compensate for a better than anticipated risk profile of the patients included.

Length of study
Recruitment for the HERA Trial began in December 2001 and was completed in 2004. Enrolment was completed in 2005. The final analysis of study results will take place approximately two years after the final patient has been entered into the study (pre-defined as after the 951^st event).

Aim of trial
The HERA Trial aims to assess improvements in survival of women with early-stage breast cancer when Herceptin® is given after standard chemotherapy.

Rationale
Herceptin® has proven survival and quality of life benefits in the treatment of HER2-positive metastatic (advanced) breast cancer.² Investigators hope that by using Herceptin® at an earlier stage of the disease, they can maximise treatment benefits associated with Herceptin®.

Overview of Herceptin®
Herceptin® (trastuzumab) is a unique type of treatment for breast cancer. It is a biologically engineered drug (a monoclonal antibody) designed to target and block the function of HER2, a protein associated with aggressive cancer cell growth. Approximately 20 to 30 percent of breast cancer patients have tumours that show high levels of HER2, known as HER2-positive breast cancer.³

Unlike conventional chemotherapy, Herceptin® does not destroy normal, healthy cells, which is the primary cause of unwanted side effects associated with chemotherapy.

The clinical use of Herceptin® alone and in combination with chemotherapy has resulted in significant improvements in survival, disease progression and quality of life. Results from pivotal studies of Herceptin® repeatedly showed that the addition of Herceptin® to standard chemotherapy can increase survival by as much as 38 percent in women who have HER2-positive metastatic (advanced) breast cancer.^{1, 4}

Herceptin® is available for the treatment of metastatic breast cancer in 90 countries worldwide. As of May 2006, Herceptin® has also been approved in the European Union as adjuvant therapy following standard chemotherapy for early-stage HER2-positive breast cancer.

Information on BIG and Roche

Breast International Group
The Breast International Group (BIG) was founded in 1996 by a group of leading European breast cancer specialists. BIG enables its members – co-operative groups based in Europe, Latin America, Canada, Australia / New Zealand and Japan that have affiliated centres around the world - to get together regularly to develop collaborations in clinical and translational research in order to reduce wasteful duplication of efforts and to achieve results more quickly. By accelerating the process that informs both clinicians and patients about their treatment choices, and by guarding the highest standards and principles of research, BIG hopes ultimately that this model of international collaboration in breast cancer research will better serve the women whose lives are affected by this disease. For further information on BIG, please consult the Internet website at www.breastinternationalgroup.org.

F. Hoffmann-La Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. Roche employs roughly 70,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. For further information on Roche, please consult the Internet website at www.roche.com.