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Highlight Points
Breast Cancer and Hormones
from
Portuguese Menopause Society 2002 Proceedings
Menopause - Hormones and Cancer
Eds. Neves -e-Castro and B.G. Wren
(clic above to return to review)
compiled by
Timothy Bilash MD, MS, OBGYN
(June 2003)
www.DrTimDelivers.com
- There is no relationship between breast cancer and blood levels of Estrogen
-
the breast is capable of producing its own Estrogen, independent of circulating blood levels of Estradiol
- Estrogen Therapy is associated with a lower risk of dying from breast cancer in epidemiologic studies
- better survival is seen for current HRT users
- irrespective of tumor stage, hormone receptor status, and tumor detection mode
- breast cancer survival
- total survival
- tumor biology and short-term prognosis are more favorable in breast cancer patients who have used HRT prior to diagnosis
- no survival benefit beyond 10 years after stop HRT (past HRT use)
- family history and HRT exposure appear to be independent risk factors for breast cancer incidence
- Estrogen plus Progestin decreases breast cancer recurrence and death
- Progestin plus Estrogen added to Tamoxifen decreases breast cancer recurrence
- Proliferating normal breast cells do not contain receptors for either Estradiol or Progesterone, whereas proliferating breast cancer cells do
- Proliferation of breast epithelial cells is seen during the luteal menstrual phase in humans
- 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
- Genetic Factors in Breast Cancer
- the most frequent error found with breast cancer is in chromosome 17 (which has not been documented with estrogen treatment)
- chromosome 11 contains Loss of Heterogeneity (LOH) regions in breast and other organ cancers, with possible supressor gene dysfunction
- How Progestin affects on Breast Cells
- How Estrogen affects Breast Cells
- 2-MethoxyEstradiol, a major estradiol metabolite, inhibits breast cell growth
- catechol estrogen is thought to be the major breakdown product of estrogen, particularly 2-hydoxyestrogen, which is a very weak estrogen (1)
- methoxy derivatives are formed by methylation of the hydroxy ones, in small amounts
- 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.
- Phytoestrogens
- soy is at most slightly protective for breast cancer
- high soy doses increase invasiveness of breast cancer, soy metabolites are estrogenic
- soy may be beneficial early in life, protecting from breast carcinogens later in life
- a fiber and lignan diet seems protective for breast cancer
- enterolactone may be a good biomarker of decreased breast cancer risk, but the mechanism is unkown
- Detection of Breast Cancer by Mammogram
- there is no agreement on the correlation of Breast Density and Breast Cancer
- Breast Density may make diagnosis of breast tumors more difficult (increased density may hide tumors, decreasing mammogram sensitivity)
- 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
- IT SEEMS LIKELY THAT: dense breast tissue means more likely to have suspicious mammogram with increased density requiring biopsy. this would initially find more breast cancers in a group that is placed on or already on hormones (surveillance and detection bias: if 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]