Subtype switch between primary and recurrent breast cancer · 2020-04-21 · Subtype switch between...
Transcript of Subtype switch between primary and recurrent breast cancer · 2020-04-21 · Subtype switch between...
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Subtype switch between primary and recurrent breast cancer
the underlying molecular mechanism and therapeutic implications
Supervisors: Dr. Maya Dadiani Dr. Einav Gal Yam
Breast cancer translational research
Student: Inbar Eisenkot
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Breast cancer facts
Nature, Outlook Breast Cancer 2012
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1.7 million women worldwide are diagnosed with breast cancer each year
Nature, Outlook Breast Cancer 2012
Breast cancer facts
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Breast cancer subtypes
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Huge international efforts to profile Breast Cancer TCGA > 2800 tumors METABRIC > 2500 tumors Metastatic BC > 300 tumors
TCGA, Nature 490, 61–70, 2012
Genomic and transcriptomic landscape of breast cancer
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• Pathological Subtype:
• Molecular Subtype: Subtypes differ dramatically in terms of their gene expression pathways and regulators
Progesterone receptor (PR)
Estrogen receptor (ER) human epidermal
growth factor type 2 (HER2)
Sorlie Perou, PNAS, 2001
Subtypes Switch
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Clinical Question
Does a switch in ER/PR expression dictate a dramatic reprogramming of the
molecular signatures?
Subtype switch usually leads to a change in the subsequent treatment plan
The only remaining option is usually chemotherapy
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Study design
1st Aim
clinical and pathological characteristics of subtype switch
database and clinical records analysis
2nd Aim
MOLECULAR PROFILING OF MATCHED CASES
Primary
Recurrence
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n=2241 Patients in DB
n=220 Primary: Hormone Positive
n=182 Stable HR positive Matched samples
n=38 HR Positive to HR negative
patients
N=647 Patients with recurrence
n=68 Stable Hormonal Negative
patients
ER TN subtype switch rate in our cohort is 13% which aligns with the literature
N=288 Patients with known recurrence subtype
status
Database screening
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Clinical parameter ER TN ER ER TN TN
ER percentage
ER intensity
PR percentage
PR intensity
HER2
Age
Stage
Lymph nodes
Grade
KI 67
Recurrence location
Surgery type
Chemotherapy
Endocrine treatment
RFS
OS
The clinicopathological differences between the cohorts
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ER% in the primary tumor
P-value= 1.2x10−5
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Primary Tumor Recurrence
Pt
#1
Pt
#2
ER positive cells
Perliminary results
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Primary tumor Recurrent metastasis
Region 1: ER+++
Region 2: ER-
ER heterogeneity in the primary tumor: Multiple subtypes in the same tumor?
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770 breast cancer related genes
Molecular Profiling
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סיכום
2HER, פרוגסטרון, אסטרוגן: סוגי רצפטורים 3קבוצות לפי 3גידולי שד מסווגים ל •
גרורתיתמהגידולים משנים את הסיווג שלהם בעת חזרת מחלה 10-20%•
פחות אפשרויות טיפוליות –חשיבות קלינית משמעותית לאובדן ביטוי הרצפטורים •
?משנה גם את התנהגותו הקלינית והמולקולרית הרצפטוריהאם הגידול שעבר שינוי בסיווג : שאלת המחקר•
מאפיינים –אנליזה סטטיסטית ? מהם הפרמטרים הקליניים המאפיינים גידול ראשוני שנוטה לחזור בהיפוך הסיווג•
שונים בין הקבוצות
האם באותו גידול ראשוני ? האם חתימת הביטוי של הגידול בעת החזרה שונה מהגידול המקורי –מחקר מולקולרי •
?הגרורתיישנם מספר אזורים שונים ואיזה מהם דומה לגידול
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Acknowledgments
• Dr. Maya Dadiani
• Dr. Einav Gal Yam
• Gili Perry
• Dr. Nora Balint-Lahat