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DCIS 101
SHARE Cancer Support
October 2019
No Financial Disclosures
What Is DCIS?
• Malignant cell appearance
• Non-obligate precursor
• 15-50% progress to
invasive cancer
• ~20% upgrade rate
• ~15% autopsies
Wood JOP 2016 12;4;309-311
Cowell Mol Oncol 2013 7;5:859-869
• ~60,000 / year in U.S.
• Typical presentation is
calcifications on mgm
• Occasionally presents as
palpable mass
2009 NIH Consensus Conference
https://consensus.nih.gov/2009/dcisstatement.htm
DCIS Incidence and
Screening Mammography
Vernig et al 2009
http://www.ncbi.nlm.nih.gov/books/NBK32570/
Treatment
Recommendations
Estrogen / Progesterone (ER/PR)
Receptors
• Estrogen binds to the receptor (present inside the cell) and
signals cell growth
• ER+(positive):
• Cancer cells have receptor, can be stimulated by estrogen
• ER- (negative):
• Cancer cells have lost the receptor, no response to estrogen
Normal Cell ER+ Cancer Cell ER+ Cancer Cell ER-
Estrogen Estrogen
Hormone Blockade
• Normal breast cells can develop abnormal growth when
exposed to estrogen
• Growth of ER/PR+ cancer cells stimulated by estrogen
• Reducing estrogen levels decreases risk of recurrence
Cancer Cell ER+
Tamoxifen
Estrogen Fat Cell
Hormone precursors
Aromatase
EstrogenPremenopausal women: tamoxifen
blocks ER receptor
Postmenopausal women: estrogen made in fat cells
Aromatase inhibitors block estrogen production
• Tamoxifen
• Blocks the estrogen receptor
• Pre- or post-menopausal
• 5 years
• Potential side effects:
•Hot flashes
•Vaginal discharge, ovarian
cysts, irregular bleeding
•Blood clots
•Uterine cancer (~4%,
average risk ~2%)
• Aromatase Inhibitors
•Anastrozole (Arimidex)
•Letrozole (Femara)
•Exemestane (Aromasin)
• Blocks production of
estrogen in the fat cells
• Postmenopausal only
• 5 years
• Potential Side effects:
•Hot flashes
•Bone loss / osteoporosis
•Joint pains
Why the Confusion?
• Not one disease
• Don’t agree on endpoint
•Overall survival
•Breast cancer specific survival
•Invasive vs in-situ recurrence
• Breast cancer specific survival
approaches 100% regardless of
treatment choice
Moran December 2015 ASCO Post
How To Decide?
•Treatment decisions require tradeoffs
•What endpoint most important to patients
•Can’t predict disease course
•Van Nuys Prognostic Index
•Patient Prognostic Index
•MSKCC Nomogram
•Oncotype Dx DCIS
•PreludeDx
• US Alliance COMET
• UK LORIS
• EORTC LORD
Clinical Trials
DCISoptions.org
DCISprecision.org
DCIS411.com
• Imaging
• Core biopsy
• Biomarkers
• Tailored / precision
therapy
• No therapy for some
• Intraductal therapy
dattai@mednet.ucla.edu
@DrAttai

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Topic-Driven Round Table on DCIS: Endocrine Therapy

  • 1. DCIS 101 SHARE Cancer Support October 2019
  • 3. What Is DCIS? • Malignant cell appearance • Non-obligate precursor • 15-50% progress to invasive cancer • ~20% upgrade rate • ~15% autopsies Wood JOP 2016 12;4;309-311 Cowell Mol Oncol 2013 7;5:859-869
  • 4. • ~60,000 / year in U.S. • Typical presentation is calcifications on mgm • Occasionally presents as palpable mass 2009 NIH Consensus Conference https://consensus.nih.gov/2009/dcisstatement.htm
  • 5. DCIS Incidence and Screening Mammography Vernig et al 2009 http://www.ncbi.nlm.nih.gov/books/NBK32570/
  • 7. Estrogen / Progesterone (ER/PR) Receptors • Estrogen binds to the receptor (present inside the cell) and signals cell growth • ER+(positive): • Cancer cells have receptor, can be stimulated by estrogen • ER- (negative): • Cancer cells have lost the receptor, no response to estrogen Normal Cell ER+ Cancer Cell ER+ Cancer Cell ER- Estrogen Estrogen
  • 8. Hormone Blockade • Normal breast cells can develop abnormal growth when exposed to estrogen • Growth of ER/PR+ cancer cells stimulated by estrogen • Reducing estrogen levels decreases risk of recurrence Cancer Cell ER+ Tamoxifen Estrogen Fat Cell Hormone precursors Aromatase EstrogenPremenopausal women: tamoxifen blocks ER receptor Postmenopausal women: estrogen made in fat cells Aromatase inhibitors block estrogen production
  • 9. • Tamoxifen • Blocks the estrogen receptor • Pre- or post-menopausal • 5 years • Potential side effects: •Hot flashes •Vaginal discharge, ovarian cysts, irregular bleeding •Blood clots •Uterine cancer (~4%, average risk ~2%) • Aromatase Inhibitors •Anastrozole (Arimidex) •Letrozole (Femara) •Exemestane (Aromasin) • Blocks production of estrogen in the fat cells • Postmenopausal only • 5 years • Potential Side effects: •Hot flashes •Bone loss / osteoporosis •Joint pains
  • 10. Why the Confusion? • Not one disease • Don’t agree on endpoint •Overall survival •Breast cancer specific survival •Invasive vs in-situ recurrence • Breast cancer specific survival approaches 100% regardless of treatment choice Moran December 2015 ASCO Post
  • 11. How To Decide? •Treatment decisions require tradeoffs •What endpoint most important to patients •Can’t predict disease course
  • 12. •Van Nuys Prognostic Index •Patient Prognostic Index •MSKCC Nomogram •Oncotype Dx DCIS •PreludeDx
  • 13. • US Alliance COMET • UK LORIS • EORTC LORD Clinical Trials
  • 17. • Imaging • Core biopsy • Biomarkers • Tailored / precision therapy • No therapy for some • Intraductal therapy

Notas do Editor

  1. So clearly we have a range from indolent to aggressive behavior – DCIS is not one disease. It’s challenging because regardless of treatment, survival approaches 100%. It’s also challenging because we don’t all agree on the proper endpoint…
  2. Prospective trials
  3. Right now, we’re making assumptions based on the information we have – known biologic indicators such as grade and ER status, tumor size, patient age. But when we have a patient in front of us, we know we don’t have a crystal ball – we can’t predict if her indolent DCIS today will be the same in a few years. In the future, I expect that we will be acting on better biomarkers so we can get to that place of tailored or precision therapy for the individual patient