Nearly 20% of all breast cancer cases are ductal PKC 412 carcinoma in situ (DCIS) with over 60 0 cases diagnosed each year. among the breast cancer community and has implications for both the patient (via adverse treatment-related effects as well as out-of-pocket costs) and society (via economic costs and the public health and environmental harms resulting from healthcare delivery). This paper discusses DCIS treatment pathways and their implications for patients and society and calls for further research to examine the factors that are leading to such wide variation in treatment decisions. Introduction In 2014 an estimated 232 0 new breast cancer cases will be diagnosed in the PKC 412 U.S. (1) of which approximately 20% will be ductal carcinoma in situ (DCIS) (2 3 DCIS is the earliest form of breast cancer; it is a non-invasive disease and estimates suggest that without treatment up to 70% of cases would never become clinically relevant (4-6). However clinicians cannot differentiate lesions that are likely to progress to invasive potentially lethal disease from those that could be spared treatment. A diagnosis of DCIS carries an excellent prognosis with a 15-year breast cancer mortality rate of 3% regardless of the treatment received (7 8 Treatment of DCIS varies widely in aggressiveness and may include some combination of breast conserving surgery (BCS) with or without radiation unilateral or bilateral total mastectomy contralateral prophylactic mastectomy breast reconstruction and anti-estrogen hormone therapy (9 10 Aggressive treatment may be an appropriate therapeutic approach in certain high-risk cases but an increasing number of studies have shown institutional regional and national-level variation in the use of mastectomy that PKC 412 exceeds the medical uncertainty pertaining to DCIS management (9 11 This variation has led to widespread concern in the medical community that DCIS is being overtreated (14). In many cases aggressive treatment may not be in the best long-term interest of the patient given potential Rabbit polyclonal to DDX6. treatment complications the adequate cancer control provided by less aggressive treatments and the increased risk of long term complications posed by PKC 412 some treatments. The objectives of this review are to discuss the range of impacts that may result from the overtreatment of DCIS and to call for further research to determine the factors that have led to the current wide variation in treatment decisions. DCIS treatment pathways and patient health outcomes About half of DCIS cases receive BCS with radiation (Figure 1) and approximately 40% of all patients regardless of surgical treatment pathway receive hormone therapy (e.g. Tamoxifen) as an adjuvant therapy for lesions that are estrogen receptor (ER)-positive (9 10 While these treatments result in a very high survival rate DCIS diagnosis and treatment in general has been associated with adverse health effects among patients. DCIS survivors report decreased physical activity high rates of weight gain and elevated use of anti-depressants following DCIS treatment (15) as well as reduction in social functioning mental health and vitality (16 17 Figure 1 Percent of DCIS cases receiving various treatments (9 10 Survivors who receive Tamoxifen as part of their treatment regimen PKC 412 for ER-positive lesions experience an increased risk of developing endometrial cancer and are more likely to experience thromboembolic and cerebrovascular events hot flashes irregular menses and vaginal discharge than those who do not receive this hormone therapy (18-23). Radiation therapy also has a number of associated side effects including an increased risk of cardiac toxicity secondary cancers pneumonitis and most commonly lymphedema and radiation-induced fatigue (22 24 Survivors who elect to undergo mastectomy report lower rates of physical activity than those who choose a less aggressive treatment (27). After mastectomy DCIS patients have reported lower body image and sexual functioning than those treated with BCS (28). Our preliminary data from the Wisconsin In Situ Cohort suggests that DCIS patients treated with BCS may have better physical function and fewer physical role limitations compared to women treated with mastectomy. These outcomes suggest that overly aggressive treatment of DCIS may have unnecessary long-term impacts on the health and well being of women. The PKC 412 question of overtreatment The medical community has responded to.