Grand Challenges in Cancer Endocrinology: Endocrine Related Cancers, an Expanding Concept

classically includes a group of sex steroid responsive cancers, such as cancers of the breast, endometrium, prostate, and testis, but also other cancers such as thyroid and ovary cancers that are responsive to pituitary hormones (1). Based on this widely accepted concept, at least 35–40% of newly diagnosed cancers fall into this definition (2). This concept has been useful for its clinical implications, and has lead to the use of anti-estrogenic/anti-androgenic treatments for sex hormone responsive cancers, as well as to thyroid-stimulating hormone (TSH) suppressive therapy with l-thyroxine (l-T4) for differentiated thyroid cancer. Moreover, several studies have tried to identify physiological conditions, such as early menarche, late menopause, age of first pregnancy, and number of pregnancies, prolonged lactation, and obesity, that may all affect sex steroids availability/exposure and modulate cancer risk. Another series of studies have identified germline polymorphisms, which are linked to the modulation of cancer risk through the genetic control of serum hormone levels or target tissue responses (3). Finally, other studies have addressed the possible effects of the exposure to exogenous sex hormones, such as estroprogestins (4) or postmenopausal estrogen replacing therapy (5) or endocrine disruptors (6). While all these studies have provided useful information for cancer prevention and treatment, our understanding of how genetic traits relevant to hormone action, control and interaction with physiological conditions, hormonal supplementations, and environmental factors is still limited. Another grand challenge is represented by the possibility to achieve effective and risk-free chemoprevention for subjects predisposed to individual endocrine related cancers, as exemplified by the use of tamoxifen and other agents in breast cancer predisposed subjects (6). In recent years, several studies have challenged this classical view of endocrine related cancer. We now summarize recent data, which should be taken into account to reformulate the term “endocrine related cancer” in a more expanded way.