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The Oncologist, Vol. 11, No. suppl_1, 1-3, September 2006; doi:10.1634/theoncologist.11-90001-1
© 2006 AlphaMed Press

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Introduction

What Are the Current Standards of Care and Recent Developments in the Management of Breast Cancer?

David Camerona, Richard Bellb, Matti Aaproc, Christoph Zielinskid

a Western General Hospital, Edinburgh, United Kingdom; b The Andrew Love Cancer Centre, Geelong, Victoria, Australia; c Clinique de Genolier, Genolier, Switzerland; d University Hospital Vienna, Vienna, Austria

Correspondence: Matti Aapro, M.D., Clinique de Genolier, 1 Route du Muids, Genolier VD CH-1272, Switzerland. Telephone: +41-22-366-91-36; Fax: +41-22-366-91-31; e-mail: maapro{at}genolier.net

Received June 12, 2006; accepted for publication June 21, 2006.

This series of articles reports proceedings of a meeting held in Vienna, Austria, in February 2006 entitled "International Breast Cancer Expert Forum: Milestones in Management, Confidence in Care." Over the course of 2 days, this international conference brought together a distinguished group of breast cancer specialists with the aim of exploring current treatment options for women diagnosed with early breast cancer (EBC) or advanced and metastatic breast cancer (MBC), discussing recent treatment advances in these settings and reviewing the latest clinical trial data for four important agents: trastuzumab (Herceptin®; F. Hoffmann-La Roche Ltd., Basel, Switzerland), capecitabine (Xeloda®; F. Hoffmann-La Roche Ltd.), bevacizumab (Avastin®; F. Hoffmann-La Roche Ltd.), and ibandronate (Bondronat®; F. Hoffmann-La Roche Ltd.).

The key challenge of treatment for EBC is to improve the likelihood of a cure and, over the past 10 years, several therapeutic advances have made a significant impact on survival in women with EBC. While better screening and diagnostic techniques have resulted in increased detection of early-stage tumors, the reduction in breast cancer mortality has in large part been a result of the widespread adoption of adjuvant endocrine treatment and adjuvant chemotherapy, particularly anthracycline-containing and, more recently, taxane-containing combination regimens [1–3]. Clinical trials are continuing to build on this success through the introduction of new agents into the adjuvant setting, with the goal of providing more effective treatment to patients that will, when adopted in the clinic, ultimately prolong survival.

Recent interim efficacy and safety analyses from five studies of adjuvant trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER-2), consistently demonstrated significantly longer disease-free survival in women with HER-2-positive EBC [4–7]. In addition, one analysis with a median follow-up of 2 years has, at this early time point, already demonstrated a significant improvement in overall survival [5]. More recently, since the date of this meeting, the Herceptin® Adjuvant (HERA) trial has also demonstrated a significant survival benefit at 2 years’ median follow-up [8]. Adjuvant use of trastuzumab in EBC has been approved in the European Union (May 22, 2006), and the overwhelming positive data have already resulted in routine use of trastuzumab in this setting in several countries.

Based on the high efficacy and survival benefit of the capecitabine–docetaxel combination in MBC, oral capecitabine is being integrated into the treatment of women with EBC [9, 10]. Capecitabine itself has a favorable safety profile, with minimal myelosuppression and alopecia [11], which, together with its efficacy, make it an ideal agent to further improve outcomes. A broad clinical program is investigating capecitabine both alone and in combination in the neoadjuvant and adjuvant settings. Early data indicate that capecitabine combinations are highly effective and well tolerated in the primary treatment of breast cancer.

The potential benefit of bisphosphonates in EBC was discussed. Oral clodronate has recently shown a survival benefit for EBC patients [12]. Similarly, decreasing tumor burden, reducing skeletal complications, and ultimately improving overall survival are key outcomes that are currently being explored through clinical trials of ibandronate in the adjuvant setting. In particular, the oral formulation of ibandronate may play an important role in the future therapy of EBC because it offers patients the flexibility of at-home, simple, once-daily dosing with a low incidence of side effects.

In the advanced/MBC setting, the newer therapies docetaxel, trastuzumab, and capecitabine have significantly improved survival. Nonetheless, MBC remains incurable and there is still a need for better, rationally designed treatment options. The effective management of tumor-related adverse events and pain is also an important goal for clinicians, as well as continuing to establish the best sequencing of therapies to halt progression and prolong survival [13].

Both trastuzumab and capecitabine have demonstrated overall survival benefits as first-line therapy in combination with docetaxel in women with MBC [9, 10, 14, 15]. Novel combinations of trastuzumab with chemotherapeutic agents such as capecitabine, vinorelbine, and gemcitabine have also yielded promising phase II data in HER-2-positive disease. In HER-2-negative disease, single-agent capecitabine and combinations of capecitabine with paclitaxel, vinorelbine, and bevacizumab have demonstrated good efficacy with favorable safety profiles [16–22]. The novel combination of capecitabine, docetaxel, and bevacizumab is under investigation, and early results suggest a feasible combination (Perez, personal communication, 2006).

Bone metastases are particularly prevalent in MBC, occurring in up to 80% of patients, and can cause severe pain and skeletal morbidity [23]. Both the oral and i.v. formulations of ibandronate demonstrate comparable efficacy in women with MBC, preventing skeletal events and providing long-term relief of metastatic bone pain, while maintaining quality of life [24–27]. Furthermore, because of its favorable renal safety profile, i.v. ibandronate can be administered in an intensive loading-dose schedule that provides rapid and effective relief of metastatic bone pain within days [28].

The agents discussed in this supplement (trastuzumab, capecitabine, and ibandronate) are important in the first-line treatment and supportive care of MBC. In EBC, trastuzumab is becoming the foundation of care in the adjuvant treatment of women with HER-2-positive disease. Capecitabine has shown promising initial data and is being further investigated in this setting. The potential benefits of ibandronate in the adjuvant treatment of breast cancer are also under investigation.


   DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
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M. A. has acted as a consultant for, performed contract work for, and received financial support within the last two years from Roche and sanofiaventis. C. Z. has acted as a consultant and performed contract work within the last two years for Roche.


   ACKNOWLEDGMENT
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The authors would like to thank Diana James for medical writing support during the preparation of this manuscript.


   REFERENCES
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 References
 

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