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Models of Breast Cancer Growth and Investigations of Adjuvant Surgical Oophorectomy

From the Department of Surgery, University of Wisconsin School of Medicine, Madison, Wisconsin.

Correspondence: Address correspondence and reprint requests to: Richard R. Love, MD, Department of Medicine (RRL) and Surgery (JEN), University of Wisconsin School of Medicine, 610 Walnut St., 256 WARF Bldg., Madison, WI 53726–2397; Fax: 608-263-4497; E-mail: rrlove{at}facstaff.wisc.edu

ABSTRACT

Clinical observations of the natural history of breast cancer and its response to a variety of therapeutic interventions have contributed to changing concepts about the growth and metastatic spread of this disease. Increased attention has been given to tumor cell dormancy and the occurrence of greatly delayed metastatic disease development, which has been important to rethinking therapy. Although gene profiling of breast tumors recently has highlighted the importance of individual tumor characteristics in patients’ prognosis, considerable data also support the concept of breast cancer as a problem of macro- and microenvironmental regulatory imbalance and dynamic chaos. Observations of unexpectedly large survival benefits from adjuvant surgical oophorectomy done in the luteal phase of the menstrual cycle in premenopausal women are consistent with an interpretation that extratumoral interactions in the host environment are important in prognosis. These observations also suggest that a treatment paradigm shift from an exclusive focus on cell kill and specific tumor cell molecular targets to one focused also on broad host regulatory control may be useful. Clinical trials and laboratory mechanistic investigations based on these data and observations can determine the potential impact of therapeutic interventions targeting host system macro and micro tumor cell environments.

Key Words: Oophorectomy • Breast cancer • Host • Regulation

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