Highlights
Breast Cancer and Hormones

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1. No relationship between breast cancer and blood levels of estrogen is observed
   
   1. the breast is capable of producing its own estrogen, independent of circulating blood levels of estradiol
      
      
      
2. HRT is associated with a lower risk of dying from breast cancer
   
   1. better survival is seen for current HRT users
      
      1. irrespective of tumor stage, hormone receptor status, and tumor detection mode
         
   2. breast cancer survival
      
   3. total survival
      
   4. tumor biology and short-term prognosis are more favorable in breast cancer patients who have used HRT prior to diagnosis
      
   5. no survival benefit beyond 10 years after stop HRT (past HRT use)
      
   6. family history and HRT exposure appear to be independent risk factors for breast cancer incidence
   7. Progestin plus Estrogen added to Tamoxifen decreases breast cancer recurrence
      
   8. Estrogen plus Progestin decreases breast cancer recurrence and death
      
      
      
3. Proliferating normal breast cells do not contain receptors for either estradiol or progesterone, whereas proliferating breast cancer cells do
   
   1. Proliferation of breast epithelial cells is seen during the luteal menstrual phase in humans
      
   2. A low dose of estrogen equivalent to follicular phase levels induced some proliferation, but higher-dose luteal phase estrogen levels were necessary for a maximum induction of cell division; there were no obvious effects of progesterone on proliferation
      
      
      
4. Genetic Factors in Breast Cancer
   
   1. the most frequent error found with breast cancer is in chromosome 17 (which has not been documented with estrogen treatment)
      
   2. chromosome 11 contains Loss of Heterogeneity (LOH) regions in breast and other organ cancers, with possible supressor gene dysfunction
      
      
      
5. Mechanisms of Progestin on Breast Cells
   
   
   
6. Mechanisms of Estrogen on Breast Cells
   
   
   
7. 2-MethoxyEstradiol, a major estradiol metabolite, inhibits cell growth
   
   1. catechol estrogen is thought to be the major breakdown product of estrogen, particularly 2-hydoxyestrogen, which is a very weak estrogen (1)
   2. methoxy derivatives are formed by methylation of the hydroxy ones, in small amounts
   3. 16-hydroxy estrogens are also formed, with potent estrogenic effects. the ratio of 2-hydroxy to 16-hydroxy estrogens is altered with breast cancer, osteoporosis, and cognitive changes.
      
      
      
8. Phytoestrogens
   
   1. soy is at most slightly protective for breast cancer
      
   2. high soy doses increase invasiveness of breast cancer, soy metabolites are estrogenic
      
   3. soy may be beneficial early in life, protecting from breast carcinogens later in life
      
   4. a fiber and lignan diet seems protective for breast cancer
      
   5. enterolactone may be a good biomarker of decreased breast cancer risk, but the mechanism is unkown
      
      
      
9. Detection of Breast Cancer by Mammogram
   
   1. there is no agreement on the correlation of breast density and breast cancer
      
   2. breast density may make diagnosis of breast tumors more difficult (increased density hides tumors, decreasing sensitivity)
      
   3. increase in mammographic density appears to be an early event that occurs during the first few months of therapy and thereafter remains stable during long-term treatment
      
   4. IT SEEMS LIKELY THAT: dense breast tissue means more likely to have suspicious mammogram with increased density requiring biopsy. would initially find more breast cancers in a group that is already on hormones (surveillance and detection bias: do more biopsies, find more cancer that is already there)
      

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(1) Shoham Z and Kopernik G, Tools for making correct decisions regarding hormone therapy. Part I: Background and drugs, Fertility and Sterility 81(6):June2004, p1447-1457 [07.17.04]