It must be remembered that the following are a collection of newer references that inform you what’s new with cancer of the uterus. They have appeared in recent medical publications and are relevant regarding future treatment or give further insights into what I have already discussed.
Certainly, physicians use tamoxifen in the treatment of estrogen receptor positive breast cancer to prevent recurrences of cancer. Researchers could show that tamoxifen improved survival rates in women with breast cancer. Unfortunately, at the same time one of the side-effects is the development of uterine cancer (=endometrial cancer).
To clarify, a chlorinated tamoxifen analogue, called toremifene, has a different metabolism and did not result in endometrial proliferation or cancer formation (Ref. 5). In brief, 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.
Less estrogen receptor uterine cancer more aggressive
Notably, estrogen receptor negative uterine cancer is similar in behavior to estrogen receptor negative breast cancer (Ref. 6). Indeed, researchers found previously that there is an over-expression of a specific protein kinase with hormone independent breast cancer. In particular, they also found this in tamoxifen induced uterine cancers. For this reason, they postulated that both conditions have a common cause, namely an over-expression of a specific protein kinase, which leads to a low estrogen receptor.
Clinical proof that estrogen receptor expression is important for uterine cancer
Moreover, 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 invasive the tumor is. Specifically, a pathologist can test for this specific protein kinase expression in tissue samples. For this reason, this information is useful to predict whether a patient will have a good or a bad outlook (=prognosis).
Tackling the more difficult to treat stage III uterine cancer
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. Particularly, the researchers examined various parameters to find out especially whether or not they would be predictive of survival outcome.
Notably, they found that the following parameters influenced survival independently. First, the age of the patient; second, the depth of tumor invasion into the uterus and third, confinement of local metastases to only pelvic lymph nodes, but not beyond were the factors that were important. On the other hand, there was no relationship to the grade of the tumor, histology type or whether or not paraaortic lymph gland metastases were present. 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. In this case 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%.
Stage III C uterine cancer treated with surgery, radiotherapy and chemotherapy
In Ref. 8 researchers followed another group of 21 patients with stage III C disease (like in the previous study). All patients had surgery with dissection of pelvic and paraaortic lymph nodes. Depending on the microscopic finding a staged combination therapy was given with more aggressive disease getting all of surgery, radiotherapy and chemotherapy.
In other words, 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. In this case, this approach is very similar to ovarian cancer, where cytoreductive surgery has led to impressive improvements of survival rates. This link takes you there.
Italian Tamoxifen Prevention study
The Italian Tamoxifen Prevention study, which is summarized in Ref. 9, has provided some new insights into breast cancer prevention. Significantly, hormone replacement therapy (=HRT) was introduced originally to treat menopausal symptoms. This was several decades ago with only estrogen as a hormone replacement. However, 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. Specifically, 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). Indeed, as mentioned above, the newer anti-estrogen medication toremifene might improve this further.
Nutritional factors are important for development of uterine cancer
What nutritional factors are important for development of uterine cancer? Expressly, Ref. 10 asked exactly this question. 56,837 women were followed through the National Breast Screening Study where 221 patients developed uterine cancer (adenocarcinoma). Surprisingly, 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. In this case an effective way to reduce the BMI would be to follow the zone diet of Dr.Sears (Ref.3), a Mediterranean diet or the South Beach diet.
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).
For example, lycopene (a substance found in tomatoes) and saturated fat showed some reduction of risk. In general, this fits in with the observation by Dr. Sears that an increased BMI causes the syndrome of insulin resistance, meaning that the insulin level shows a permanent elevation. On the contrary, 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).
Balanced hormone replacement allows longer survivals with uterine cancer
Truly, perhaps the most important observation by several anti-aging physicians is the fact that women who have a balanced hormone replacement with bio-identical estrogen and progesterone hormones enjoy longer lives with no development of breast, uterine, colon and other cancers. It is important to realize that this fact has been published in the anti-aging literature between 2000 and 2008. For one thing, Dr. Lee pointed out that saliva hormone tests are the only reliable test that reflects the tissue levels of hormones (Ref.13). In fact, blood tests are often misleading in that hormone levels are often reported to be low (when tissue levels can be high) prompting the physician to overdose with hormone replacement.
Saliva hormone tests more accurate for progesterone levels
However, using saliva tests to monitor for hormone levels and keeping the estrogen to progesterone levels at a ratio of 1:200 (level of progesterone 200-fold higher or more than the estrogen level) will keep estrogen under control and prevent the development of breast cancer or uterine cancer (Ref.13 and 14). In short, using bio-identical hormone replacement in menopause (and in andropause for the male) will likely add 10 to 15 years of cancer-free, productive life to most people’s life expectancy.
1. Cancer: Principles &Practice of Oncology.4th edition. Edited by Vincent T. DeVita, Jr. et al. Lippincott, Philadelphia,PA, 1993. Vol. 1. Chapter on gynecological tumors.
2. Cancer: Principles&Practice of Oncology. 5th edition, volume 1. Edited by Vincent T. DeVita, Jr. et al. Lippincott-Raven Publ., Philadelphia,PA, 1997. Chapter on gynecological tumors.
3. B. Sears: “The age-free zone”. Regan Books, Harper Collins, 2000.
4. E Weiderpass et al. Cancer Causes Control 2000 Feb;11(2):185-192.
5. S Shibutani et al. Cancer Res 2001 May 15;61(10):3925-3931.
6. DB Fournier et al. Gynecol Oncol 2001 Jun;81(3):366-372.
7. DS McMeekin et al. Gynecol Oncol 2001 May;81(2):273-278.
8. LA Katz et al. Am J Obstet Gynecol 2001 May;184(6):1071-1073.
9. B Bonanni et al. Breast J 2000 Oct;6(5):317-323.
10. MG Jain et al. Eur J Epidemiol 2000;16(10):899-905.
11. Conn’s Current Therapy 2004, 56th ed., Copyright © 2004 Elsevier
12. Ferri: Ferri’s Clinical Advisor: Instant Diagnosis and Treatment, 2004 ed., Copyright © 2004 Mosby, Inc
13. Dr. John R. Lee and Virginia Hopkins: “Hormone Balance Made Simple – The Essential How-to Guide to Symptoms, Dosage, Timing, and More”. Wellness Central, NY, 2006
14. Dr. John R. Lee, David Zava and Virginia Hopkins: “What your doctor may not tell you about breast cancer – How hormone balance can help save your life”, Wellness Central, Hachette Book Group USA, 2005. Page 29 – 38 (Chapter 2): Risk factors for breast cancer. Page 360 to 374 explains about xenohormones and how they cause estrogen dominance. Pages 221 to 234 (chapter 12) explains why Tamoxifen is not recommended and bio-identical progesterone is more powerful in preventing breast and uterine cancer.