Perioperative endocrine status and prognosis in early breast cancer

Although the relationship between breast cancer and hormones has been known for almost two centuries, it is only during the last 16 years that evidence suggesting the hormonal profile of the patient at the time of surgery can affect the outcome, came to light. A series of studies investigated the hypothesis that unopposed estrogen (observed during the follicular phase of the cycle) may adversely affect the overall and/or disease-free survival of women operated on at that time. The findings have been, at times, contradictory. The retrospective nature of the studies, poor recording of last menstrual period, small study size, and the possible effect of the timing of the diagnostic procedures (cytology or core biopsy) on the outcome may be responsible for the conflicting results. Despite this, more sophisticated studies based on pathological or hormonal observations/measurements, confirmed the relation of luteal phase surgery to better outcome. Estrogen-induced increased protease activity activates a cascade of proteolysis and allows the more discohesive tumor cells to gain access to the circulation. Moreover, disseminated cells might be able to proliferate easier because of several estrogen-dependent growth factors. Diminished immune function during the follicular phase, because of natural killer cell activity and mononuclear cell phagocytic activity down-regulation may also be implicated in the dissemination of viable tumor cells. Taken together these findings provide a framework for explaining the observation that luteal phase surgery can lead to an improved outcome. By altering the perioperative hormonal milieu it may be possible to reduce deaths from breast cancer in a simple and nontoxic manner.