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Multiregional imaging phenotypes and molecular correlates of aggressive versus indolent breast cancer

Award Number: R01CA222512
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2018
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Multiregional imaging phenotypes and molecular correlates of aggressive versus indolent breast cancer - ABSTRACT The goal of this research is to develop and validate prognostic imaging biomarkers for breast cancer. A major challenge in the management of breast cancer is distinguishing patients with indolent disease from those with aggressive lethal disease at diagnosis. Currently, there are no reliable biomarkers to distinguish these groups on an individual level. Consequently, all patients with breast cancer receive adjuvant therapies, but not all benefit equally. This one-size-fits-all approach causes overtreatment, leading to morbidity and mortality. The need for reliable biomarkers is highlighted by the randomized TAILORx trial, which identified a small group of low-risk breast cancer patients who had very low rates of recurrence without chemotherapy, based on the 21-gene Oncotype Dx assay. Unfortunately, a majority (67%) of patients fell in the intermediate-risk range according to the genomic assay, and uncertainty still remains regarding the need for chemotherapy among these patients. Clearly, better biomarkers are needed to improve prognostication and patient stratification in breast cancer. Built on extensive preliminary data, we hypothesize that imaging characteristics reflect underlying tumor pathophysiology, and that image-based phenotyping of both tumor and parenchyma will provide much improved accuracy for recurrence prediction. To test this hypothesis, we propose to: (1) develop and improve methods to explicitly quantify multiregional MRI phenotypes including those of intratumoral subregion and parenchyma, and systematically assess their reproducibility; (2) develop a prognostic imaging signature using a large retrospective cohort of >1000 patients curated by the Stanford Oncoshare Project, and validate it in the prospective multi-center I-SPY 1 cohort; (3) construct a radiogenomic signature to perform additional testing of its prognostic value in 13 public gene expression cohorts of >5000 breast cancer patients. To further improve prognostication, we will build a multifactorial model that integrates imaging with clinical and genomic markers. This research will advance the quantitative imaging field by moving beyond traditional gross-tumor features and incorporating additional parenchymal and intratumoral imaging characteristics. If successful, it will provide much needed, rigorously validated imaging biomarkers for breast cancer, which can be further tested for clinical utility in prospective trials. Ultimately, such biomarkers can be used to stratify patients and guide individualized therapy, by allowing clinicians to avoid overtreatment of indolent disease and intensify treatment in women with aggressive disease.


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 = -$8,410 )
2025	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	6	5/2/2025	NON-COMPETING CONTINUATION	-$8,410
														Subtotal = -$8,410

Issue Date FY: 2023 ( Subtotal = $438,028 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	001	6	3/21/2023	NON-COMPETING CONTINUATION	$35,756
2023	2023	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	6	12/23/2022	NON-COMPETING CONTINUATION	$402,272
														Subtotal = $438,028

Issue Date FY: 2022 ( Subtotal = $37,460 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	5	3/17/2022	NON-COMPETING CONTINUATION	$34,401
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	001	5	5/9/2022	NON-COMPETING CONTINUATION	$3,059
														Subtotal = $37,460

Issue Date FY: 2021 ( Subtotal = $485,193 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	4	1/22/2021	NON-COMPETING CONTINUATION	$485,193
														Subtotal = $485,193

Issue Date FY: 2020 ( Subtotal = $485,193 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	3	1/16/2020	NON-COMPETING CONTINUATION	$485,193
														Subtotal = $485,193

Issue Date FY: 2019 ( Subtotal = $470,637 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	2	1/30/2019	NON-COMPETING CONTINUATION	$470,637
														Subtotal = $470,637

Issue Date FY: 2018 ( Subtotal = $487,799 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Detection and Diagnosis Research	000	1	1/24/2018	NEW	$487,799
														Subtotal = $487,799

Grand Total All Awards = $2,395,900

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Multiregional imaging phenotypes and molecular correlates of aggressive versus indolent breast cancer

Award Number: R01CA222512

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2018

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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