Editor’s Note
	A “functional cure” for metastatic breast cancer

In a prior issue of this audio series, Dr Kathy Miller discussed a 62-year-old woman treated in 1997 for pulmonary and hepatic metastases. After five years of treatment with chemotherapy and hormone therapy, the patient died of an unrelated stroke. During this time, she had minimal tumor-related symptoms and felt so well that she elected to have TRAM flap breast reconstruction and contralateral breast reduction for symmetry.

Aprolonged clinical course with metastatic breast cancer is becoming more common, and in this issue Dr Robert Carlson presents a woman from his practice who is about four years into therapy for metastatic disease to the mediastinum. The patient was initially managed with paclitaxel, followed by anastrozole, and is currently doing very well while receiving the estrogenreceptor downregulator, fulvestrant.

These two cases are reminders of the profound complexity of metastatic breast cancer. In the last decade, many new systemic agents have become available, making treatment decisions more difficult and effective communication between oncologists and patients even more essential.

One striking contrast between these two cases is that Dr Carlson’s patient — treated only a couple of years after Dr Miller’s patient — was able to receive fulvestrant, a novel endocrine intervention. This agent provides another relatively nontoxic alternative for our treatment armamentarium and, combined with the introduction of the aromatase inhibitors, has led to a dramatic decrease in the use of the older and more toxic agents, such as megestrol acetate, that were an integral component of breast cancer therapy in the past.

Fulvestrant’s unique mechanism of action has also taught us not to abandon new approaches to older tumor targets. In his interview, Dr Carlson voices optimism about combinations of targeted biologic interventions and endocrine agents now under active study. A previous interviewee in our series, Dr Dennis Slamon, was particularly interested in future clinical trials evaluating fulvestrant and trastuzumab.

Also in this issue, Dr Kathy Albain discusses the initial Phase II trial results with the tyrosine kinase inhibitor, gefitinib and her encouraging experience with patients experiencing relief of bone pain with this exciting new agent. It is apparent that in the next few years a number of new biologic interventions will join trastuzumab as an integral part of the breast cancer therapeutic armamentarium.

Dr Joyce O'Shaughnessy notes that perhaps the key to success for these new therapies will be the identification of molecular targets in the tumor that will aid in patient selection, in a manner similar to HER2 and trastuzumab.

Dr Monica Morrow notes that humoral factors controlling metastases are also important research considerations. She discusses an intriguing retrospective series, conducted with her surgical colleague, Dr Seema Kahn, suggesting that the removal of the primary lesion in women presenting with metastases may improve survival.

One wonders whether metastatic breast cancer will eventually mimic a chronic disease model like diabetes. Like Dr Miller’s patient, these women may eventually experience minimal disease-related morbidity and live long enough to die from other causes.

A number of research leaders interviewed for this audio series have noted that the disappointment with high-dose chemotherapy in the early 1990s led researchers away from the “infectious disease eradication” breast cancer model to a chronic disease model. It also seems likely that more informative molecular analyses may identify patients with potentially indolent tumors who would better fit into that model.

Another key issue in this chronic disease approach is the availability of minimally toxic interventions, such as the endocrine treatment that both Dr Miller’s and Dr Carlson’s patients received. Highly targeted therapies, such as biologic modulators and endocrine interventions, may offer the opportunity for women with metastatic breast cancer to be maintained in a prolonged asymptomatic state. If survival approaches that of age-matched controls without breast cancer, a “functional” cure can be attained with minimal treatmentrelated morbidity.

While this clinical research goal may be less appealing than the “magic bullet” we hoped for in the past, it also may be more attainable and would confer significant benefit to our patients.

— Neil Love, MD

Select publications

Long-term clinical complete remission of metastatic breast cancer

Ciatto S, Bonardi R. Is breast cancer ever cured? Follow-up study of 5623 breast cancer patients. Tumori 1991;77(6):465-7. Abstract

Greenberg PA et al. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996;14(8):2197-205. Abstract

Pierga JY et al. Response to chemotherapy is a major parameter influencing long-term survival of metastatic breast cancer patients. Ann Oncol 2001;12(2):231-7. Abstract

Tomiak E et al. Characterisation of complete responders to combination chemotherapy for advanced breast cancer: A retrospective EORTC Breast Group study. Eur J Cancer 1996;32A(11):1876-87. Abstract

Yamamoto N et al. Clinical characteristics of patients with metastatic breast cancer with complete remission following systemic treatment. Jpn J Clin Oncol 1998;28(6):368-73. Abstract

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