Breast Cancer and Hormones: Still More Questions Than Answers - PowerPoint PPT Presentation

Loading...

PPT – Breast Cancer and Hormones: Still More Questions Than Answers PowerPoint presentation | free to view - id: fe5b-ODU3O



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Breast Cancer and Hormones: Still More Questions Than Answers

Description:

Breast Cancer and Hormones: Still More Questions Than Answers. Susan M Love MD MBA ... Prolonged estrogen withdrawal in breast cancer cells results in a ... – PowerPoint PPT presentation

Number of Views:118
Avg rating:3.0/5.0
Slides: 21
Provided by: susan45
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Breast Cancer and Hormones: Still More Questions Than Answers


1
Breast Cancer and Hormones Still More Questions
Than Answers
  • Susan M Love MD MBA
  • President of the Susan Love MD Breast Cancer
    Foundation

2
Why doesnt ERT/HRT cause more breast cancer?
50-300 pg/ml
100 pg/ml
4-12 pg/ml
Post- menopause
Standard ERT
Pre- menopause
3
Clinical Paradoxes
  • HRT vs Tamoxifen in women with proliferative
    disease
  • HRT plus Tamoxifen for prevention
  • Breast cancer in women taking HRT
  • HRT after breast cancer
  • Treatment of metastatic disease

4
HRT/ERT in Women with Atypical Hyperplasia
5
Tamoxifen in Women with Proliferative Disease
  • There was an 88 reduction in risk of breast
    cancer in women with atypical hyperplasia who
    took tamoxifen for four years.

6
Tamoxifen plus ERT/HRT for Prevention
7
Mortality in breast cancer patients with a
history of previous ERT/HRT
8
Mortality in Breast Cancer Patients with previous
ERT/HRT
9
Studies of Women with Breast Cancer on ERT/HRT
10
OCP and HRT
11
Does adding a progestin increase risk of breast
cancer?
  • Progestin increases mitotic activity
  • PEPI EP causes higher breast density than E
    alone
  • Two observational studies EP associated with
    greater risk than E alone.

12
Or the people who take it?
  • Women who take E plus P all still have their
    uterus
  • Women on E alone have undergone a hysterectomy
    usually premenopausally which reduces the risk of
    breast cancer even when ERT is taken.

13
Treatment of Metastatic Disease
  • 6 randomized controlled studies comparing DES and
    Tam
  • 2 comparing ethinyl estradiol to Tam
  • 5 comparing megestrol acetate to Tam
  • 5 comparing medroxyprogesterone acetate to Tam
  • no difference in response rate, duration or
    survival.

14
Biological Observations
  • Safety of low dose
  • Systemic versus local hormones
  • Other hormones

15
Is low dose really safer?
  • Cell lines exhibit a biphasic response to
    estrogens
  • Low doses increase cell proliferation
  • High does inhibit cell proliferation Lippman
    1976
  • Prolonged estrogen withdrawal in breast cancer
    cells results in a hypersensitivity to estrogen
    Santen 2002

16
Systemic versus local
  • E2 and E1 concentrations in premenopausal women
    are 10x and 20x greater in NAF than serum
  • E2 and E1 concentrations in postmenopausal women
    not on HRT are 50x and 35x greater in NAF than
    serum. Ernster 1987
  • Breast tissue has both aromatase and sulfatase
    necessary to produce its own estrogen Chetrite
    2000
  • Different ducts within the same breast have
    different levels of estrogen Elia AACR 2002

17
How does it work?
  • Paracrine
  • Autocrine
  • Stromal
  • Intraductal macrophages

18
Breast Cancer and the Biosystem
Breast cells
Uterine Life
GONADOSTAT
Hypothalamus
Prenatal Influence
Growth Factors
Maternal and Placental Steroid Hormones
Pituitary
Ovaries
(-)
Target cells Luminal mammary Epithelial cells S
HR (-) and SHR ()
Puberty- Adolescence
Mitogenic and Differentiation Signals
Menstrual Cycle
Mitogenic Microenviroment
Estrogens Progestins Androgens

Pregnancy
Exogenous Sex Hormones
Differentiation
Cell Proliferation

Menopause
Diet-Lifestyle
Accumulation of Genomic Damage
Apoptosis/Atrophy
Cancer
19
Research Priorities
  • Beyond formulations and delivery routes
  • Physiology of the non lactating breast
  • What is concentrated and what is absorbed
  • Effect of exogenous hormones on intraductal
    levels
  • Effects of other hormones, growth factors and
    inhibitors locally and systemically
  • Physiology of the high risk breast and the
    breast cancer breast

20
  • We must beware of thinking we understand the
    connections between hormones and the breast.
  • We have only just begun..
About PowerShow.com