Uterine cancer includes cancer of the inner lining (endometrium) as well as tumors involving the outer muscular margin of the uterus (uterine sarcomas). Uterine cancer of the inner lining of the uterus, called endometrial cancer, comprises about 95% of uterine cancers, and is the most common gynecologic cancer in the Western world (Bakkum-Gamez 2008; Plataniotis 2010; Llaurado 2012; Amant 2005; Rahaman 2003). American Cancer Society estimates for 2013 indicate that 49 560 women in the United States will develop endometrial cancer and 8190 will lose their lives to this disease (ACS 2013a). Most endometrial cancers appear in women between ages 60 and 70, but some occur before age 40 (A.D.A.M. 2012). Cancer of the uterus most frequently involves the endometrium; therefore, endometrial cancer will be the focus of this protocol (Acharya 2005; Amant 2005; A.D.A.M. 2012).
Endometrial cancer is a multifactorial disease, but one of the strongest risk factors is exposure to excess estrogen and/or a relative lack of progesterone (Amant 2005; Lee 2012; Carlson 2012). This is because estrogen stimulates rapid growth of endometrial cells, whereas progesterone counters this action. Long-term exposure to unopposed estrogen can lead to accelerated or abnormal growth of endometrial cells, and in some cases may lead to tumor formation. Numerous studies have shown that treatment with conventional hormone replacement therapy consisting of unopposed estrogen (estrogen without a progestogen) leads to an increased risk of developing endometrial cancer (Berstein 2002; Amant 2005; Woodruff 1994; Beral 2005). In addition to unopposed estrogen therapy, other risk factors that have been associated with endometrial cancer include obesity, diabetes, and diets high in sugar, animal fats, and cholesterol (Goodman, Hankin 1997; Hu 2003; Friberg 2011; Nakamura 2011; Fader 2009; McTiernan 2010).
Fortunately, the survival and cure rates for endometrial cancer are relatively high (Duong 2011; A.D.A.M. 2012). This is because abnormal vaginal bleeding is often among the first signs of endometrial cancer, prompting women to visit their gynecologist and typically receive an early diagnosis and treatment (Duong 2011, El-Sahwi 2012). Surgery to remove the uterus (hysterectomy) as well as the fallopian tubes and ovaries (bilateral salpingo-oophorectomy [BSO]) usually provides a good outcome for women with early stage cancer (A.D.A.M. 2012). Alternatively, for women with cellular overgrowth (hyperplasia) suggestive of pre-cancerous changes, a more conservative approach consisting of relatively high-dose progestogen therapy may be effective (Denschlag 2010; Baker 2007).
This protocol will outline the background and biology of endometrial cancer and discuss its conventional diagnosis and treatment. Several cutting-edge strategies that may improve patient outcomes will also be discussed. For example, intriguing evidence for potential synergism between progesterone, which is sometimes used in the treatment of some types of endometrial cancer, and vitamin D will be presented (Nguyen 2011; Montz 2002; Lotze 1982; Lee 2013), as will several novel diagnostic and therapeutic tools that may enhance the success rates of endometrial cancer care. You will also learn about some shortcomings of conventional hormone replacement therapy and how bioidentical hormone replacement may overcome some of these challenges.