FileNewTemplatePrecancerous Lesions: Timing and Biology
Victoria Seewaldt, M.D.
Early detection/prevention cancers w/ aggressive biology
18FDG PET
- 53% European American
- 29% Hispanic American
PART 1 - One-size-all screening
PART 2 - If you don’t know what’s broke – its hard to fix it.
PART 3 – Prevention needs to make the whole body healthy
PART 1 - One-size-all screening fails
Failure of one-size-fits-all cancer screening
ER+ breast cancer Calcifications - 79% HER2+ breast cancers Calcifications - 71%
Need to use the right tool for the job
Triple-negative breast cancers Low frequency calcs - 15% No findings - 30% Mass/Focal asymmetry - 32%
Thinking about mammography anatomy1.gif (GIF Image, 355 × 273 pixels) http://www.breastdiagnostic.com/images/anatomy1.gif
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Mammary Fat
Lactiferous Duct
S. Riley
T1N0
- 269 Caucasian
48 mos observation, 51 breast cancers - 22 Focal / Age shifted
- 29 Non-focal / Accelerated
09/2010
NL
tissue
02/2011
Age Shifted Accelerated (Interval TNBC BRCA1) Genomic instability
TNBC
Node +
CHEMO
TNBC
Node +
CHEMO
PALPABLE
Multi-Focal
Metastasis
PART 2 - If you don’t know what’s broke – its hard to fix it. – Dad
Alternative trial design with surrogate endpoint
R A N D O M I Z E
YES AGENT
ATYPIA
Compare Signaling
U01CA189283: City of Hope, Duke, Ohio State, U. Tennessee, U.
Wisconsin, Emory - Combined MRI/proteomic profiling
Combined Cohort n=2,1070; Preliminary Data Duke n=1,241/year
MRI in 12 months Abnormal Biopsy
(2% n= 24)
Normal MRI
67-71 women/yr
Interval Cancer
U01
Cohort
U01+
NCOR
Core biopsy – FFPE
proteomic profiling stroma/epithelium
RPPA (40-60 proteins)
WBC DNA
Genetic analysis
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M L
U. Tennessee, U. Wisconsin, Emory
Dietze, Seewaldt Nature Reviews, 2015
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PART 3 – Prevention needs to make the whole body healthy
From 1992 - 2006 female mortality increased in >50%
of US counties vs. 3% counties for men - David Kindig and Erika Cheng, University of Wisconsin
- Chris Murray, University of Washington
Obesity and insulin resistance Diabetes occurs when the pancreas “burns out”
2 hr Healthy – HgbA1C = 5.3
glucose
Insulin
glucose
Insulin
glucose
Insulin
At risk breast tissue Increased insulin sensitivity
+ +
Insulin stimulates signaling pathways that promotes the
aggressive behavior of TNBC
cancer initiation.
healthier.
Gail + density 0.64 0.643 0.68 0.624
Density 0.55 - 0.67 0.571
- only populations
GREEN LINE=
[Cecchini et al. Boyd Can. Prev. Res. 5(11), 1321-9, 2012]
Mammographic Density and Individual Risk