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Molecular pathoepidemiology of contralateral breast cancer

Award Number: R01CA206464
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2017
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Molecular pathoepidemiology of contralateral breast cancer - ABSTRACT Survivors of first primary breast cancer (BC) have a 2- to 5-fold increased risk of developing a second primary in the opposite breast. The high incidence and improved survival for BC has resulted in increasing numbers (currently nearly 3 million in U.S.) of women at risk of contralateral breast cancer (CBC). Studies to date have identified environmental, genetic, and treatment-related risk factors for CBC. However, despite advances in characterizing the etiology of CBC, a large fraction of CBC incidence remains unexplained, hindering the development of effective risk stratification or risk prediction tools which will be pivotal in developing effective CBC prevention, surveillance, and therapeutic strategies for BC survivors. In the context of CBC risk, first primary tumors reflect the joint effects of environmental exposures and host features, including those that are known and measurable as well as those that are unidentified and/or unmeasurable. Molecular features of first primary tumors could be powerful complementary indicators of risk of CBC. In a strategy designed to advance risk stratification capacity, we will use cutting edge genomic technologies to interrogate first primary tumors in the context of CBC risk. We will also assess the concordance of molecular features in paired first and second primary tumors to elucidate insights into the biology of CBC and potentially shared etiologic mechanisms. The proposed research builds on the unique resources of the large multi-center WECARE Study of CBC with features including: population-based ascertainment of CBC cases and controls (women with unilateral breast cancer (UBC)); detailed clinical data including treatment of first primary BCs from medical record reviews; extensive risk factor data; germline genetic data from an ongoing GWAS; and mammographic density data. We will obtain tumor blocks for first primary breast tumors of >500 UBC controls and first primary tumors plus contralateral tumors from > 500 CBC cases. Laboratory work will include: pathology reviews; transcriptome-wide molecular profiling of tumors; IHC analyses; and replication analyses. Our Primary Aim is to identify molecular biomarkers in first primary breast tumors associated with risk of developing a subsequent CBC. We will conduct: RNA-sequencing on first primary tumors; identify the most informative markers; develop a molecular signature associated with CBC and evaluate it jointly with treatment and lifestyle/personal/medical/germline genetic risk factors; and replicate with similar risk factors in an independent sample of > 400 CBC cases and > 400 UBC controls. Our Secondary Aims are to: (1) examine the risk signature in first primary tumors (established in the Primary Aim) in relation to CBC subtype-specific risk; and (2) assess the concordance of gene/transcript expression or alterations and subtypes in paired first primary and contralateral tumors and determine the extent to which lifestyle/personal/medical/germline genetic risk factors and treatment affect the development of marker-concordant CBC.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	6	4/1/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	6	2/22/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $1,297,113 )
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	002	6	6/11/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,297,113
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	006	6	8/26/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$430,194
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	003	6	7/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	5	3/11/2022	NON-COMPETING CONTINUATION	$0
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	005	5	8/26/2022	NON-COMPETING CONTINUATION	-$1
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	001	5	6/11/2022	NON-COMPETING CONTINUATION	$0
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	004	4	8/26/2022	NON-COMPETING CONTINUATION	-$430,193
														Subtotal = $1,297,113

Issue Date FY: 2021 ( Subtotal = $1 )
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	5	6/11/2021	NON-COMPETING CONTINUATION	$1
														Subtotal = $1

Issue Date FY: 2020 ( Subtotal = $2,016,169 )
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	4	6/10/2020	NON-COMPETING CONTINUATION	$2,016,169
														Subtotal = $2,016,169

Issue Date FY: 2019 ( Subtotal = $414,309 )
2019	2019	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	3	4/1/2019	NON-COMPETING CONTINUATION	$414,309
														Subtotal = $414,309

Issue Date FY: 2018 ( Subtotal = $1,850,931 )
2018	2018	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	2	3/30/2018	NON-COMPETING CONTINUATION	$1,850,931
														Subtotal = $1,850,931

Issue Date FY: 2017 ( Subtotal = $1,438,154 )
2017	2017	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	001	1	7/11/2017	NEW	$3
2017	2017	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	1	2/17/2017	NEW	$1,438,151
														Subtotal = $1,438,154

Grand Total All Awards = $7,016,677

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Molecular pathoepidemiology of contralateral breast cancer

Award Number: R01CA206464

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2017

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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