What's New With Uterine Cancer
The following are a collection of newer references that have appeared in recent medical publications and are relevant regarding future treatment or give further insights into what has been presented above.Tamoxifen is used in the treatment of estrogen receptor positive breast cancer to prevent recurrences of cancer. It has been shown to improve survival rates in women with breast cancer. Unfortunately, one of the side-effects is the development of uterine cancer (=endometrial cancer).
1. A chlorinated tamoxifen analogue, called toremifene, has a different metabolism and did not result in endometrial proliferation or cancer formation (Ref. 5). The authors feel that toremifene is a safer alternative to tamoxifen with the same breast cancer preventative effect, but not causing uterine cancer as a side effect.
2. Estrogen receptor negative uterine cancer is similar in behavior to estrogen receptor negative breast cancer according to the authors of Ref. 6. They found previously that there is an overexpression of a specific protein kinase with hormone independent breast cancer, which is also found in tamoxifen induced uterine cancers. They postulated that both conditions have a common cause , namely an overexpression of this specific protein kinase, which leads to a low estrogen receptor. The authors could prove on samples from 42 patients with uterine cancer that there was an inverse relationship between estrogen receptor expression and tumor depth invasion as well as expression of tumor grade. In other words, the less estrogen receptor there is, the more malignant and the more invasive the tumor is. Using tests of this specific protein kinase expression in tissue samples can therefore be used to predict whether a patient will have a good or a bad outlook (=prognosis).
3. As mentioned above stage III C uterine cancer, where pelvic and/or paraaortic lymph nodes are present, is particularly difficult to treat. Ref. 7 analyzed the records of 607 uterine cancer patients, of which 47 (=8%) had stage III C uterine cancer. Various parameters were examined to find out whether or not they would be predictive of survival outcome.
The findings were that age of the patient, depth of tumor invasion into the uterus and confinement of local metastases to only pelvic lymph nodes, but not beyond, were parameters that independently influenced survival. On the other hand there was no relationship to grade of tumor, histology type or whether or not paraaortic lymph glands were affected. 3-year survivals varied between 39% for the worst cases (with involvement of disease outside of the pelvic lymph glands) versus 93% for patients where the disease was confined to pelvic lymph glands only. Various treatment modalities were used to treat: surgery for all patients; radiation, chemotherapy and progestin therapy for selected patients. This brought the 3-year overall survival up to 77%.
4. In Ref. 8 another group of 21 patients with stage III C disease (like in the previous study) was followed. All patients had a surgery with dissection of pelvic and paraarotic lymph nodes. Depending on the microscopic finding a staged combination therapy was given with more agressive disease getting all of surgery, radiotherapy and chemotherapy.
Those patients with microscopic nodal disease got radiotherapy following the surgery. With macroscopic cancer lesions both radiotherapy and chemotherapy was given following the surgery. Overall survival for microscopic disease was more than 5 years, for macroscopic disease only 3 years. Both Ref. 7 and Ref. 8 indicate that survival rates can be much improved from the survival data given for stage III and IV,cited in the 5-year survival table before. It requires a rational approach as outlined in Ref. 8 by Katz et al. where the therapy is tailored to the findings during the surgical procedure. This approach is very similar to ovarian cancer, where cytoreductive surgery has led to impressive improvements of survival rates. This link takes you there.
5. The Italian Tamoxifen Prevention study, which is summarized in Ref. 9, has provided some new insights into breast cancer prevention. Originally, when hormone replacement therapy(=HRT) was introduced to treat menopausal symptoms several decades ago with only estrogen as a hormone replacement , it became apparent that side effects such as breast cancer and uterine cancer could occur in some patients.
The authors of Ref. 9 showed that it is possible to replace hormones with HRT and to give a reduced amount of tamoxifen at the same time, and this will reduce both uterine and breast cancer risk. The amount of tamoxifen was only 10 mg every second day. The HRT included progestins as other studies had shown that inclusion of his reduced the uterine cancer risk as well. Using this method it would be safe and effective to do HRT in menopause and at the same time do chemoprevention of breast cancer. Using this method side effects are cut down to a minimum as well, which had a positive effect on compliance (=women continued to take the medicine). As mentioned above, the newer anti-estrogen medication toremifene might improve this further.
6. What nutritional factors are important for development of uterine cancer? Ref. 10 asked exactly this question. 56,837 women were followed through the National Breast Screening Study where 221 patients developed uterine cancer (adenocarcinoma). The body mass index (=BMI) was the only positive finding that was extremely significant: a BMI of more than 25 carried with it a 2.7-fold risk for women to develop uterine cancer. An effective way to reduce the BMI would be to follow the zone diet of Dr.Sears (Ref.3).
7. Surprisingly other factors or lack of nutrient supplementation were not a significant risk (total dietary fiber, various types of fibers, vitamin C, E, A, folic acid, beta-carotene, lutein, or cryptoxanthin from coffee or tea). Lycopene (a substance found in tomatoes) and saturated fat showed some reduction of risk. This fits in with the observation by Dr. Sears that an increased BMI is associated with the syndrome of insulin resistance meaning that the insulin level is constantly elevated. Saturated fatty acids can bring insulin levels down to a certain extent, which in combination with calorie restriction will prevent cancer (Ref.3, p.126 and 127).
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