Stromal contributions to breast carcinogenesis

Active Project Grant Awarded Last action

Award ID
R01CA277817
Recipient
Awarding agency
Obligated
$3,548,931

Award facts

Assistance listing
93.394 Cancer Detection and Diagnosis Research
Completion date 67% complete
Place of performance
Gainesville, FL 32611, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The human breast is a highly organized, complex organ that consists of an epithelial tissue surrounded by stroma that regulates its proliferation, differentiation, and survival. Stroma is responsible for sustaining normal breast tissue structure and function via a variety of signaling mechanisms that control and regulate normal processes and suppress malignant transformation. The role of stroma in breast tumor initiation, progression, and responsiveness to treatment as well as potential utility for targeted therapies has been widely discussed in recent reviews. While cancer tissue stroma has been widely explored, the evidence of stromal contributions to early stages of carcinogenesis is extremely limited. To fill these gaps, we propose a conceptually and methodologically novel investigation that will focus on benign breast disease (BBD) and high mammographic breast density (MBD), strong risk factors both independently associated with increased breast cancer (BCA) risk, which presents a unique opportunity for studying early changes in the breast and elucidating underlying molecular mechanisms. The study will be conducted by an interdisciplinary team of experts in BCA epidemiology, breast pathology/image analysis, BCA biology, and biostatistics, with a history of long and productive collaboration. We will use data and breast biopsy samples from three established prospective cohorts (nurses' health study, nurses' health study II, and women's health repository) to address the following aims: (1) prospectively examine associations of reproductive risk factors (e.g., parity, age at first birth) with expression of stromal markers (asma, FAP, MMP14, TNC, and S100A6) in benign biopsy samples from cancer-free women (N~1,350); (2) examine associations of stromal markers with MBD (N~1,350); and (3) examine associations of stromal markers in women with a previous benign biopsy and the risk of subsequent BCA in a nested case-control design (~400 cases/~975 controls). This proposal leverages established tissue resources, use of validated multiplex immunoflourence for stromal markers, and automated image analysis for MBD assessment. Understanding the associations of BCA risk factors with stromal markers will advance our knowledge on its role in breast carcinogenesis in epidemiologic studies. We will generate the first comprehensive data on the stromal markers' expression in non-cancer breast and will identify markers that could significantly advance future risk prediction. Stromal activity is potentially modifiable via a variety of targeted therapies; if our project successfully demonstrates an association between stromal markers in benign breast tissue and increased BCA risk and/or high MBD, these findings could eventually translate into pharmaceutical interventions aimed at primary BCA prevention in high-risk women with high MBD and/or BBD. Importantly, these findings would apply to a large segment of women undergoing routine biopsies and those with high MBD in whom novel prevention strategies, improved risk prediction, and tailored clinical management are urgently needed.

Transactions

Action Obligated Date
Amendment $685,520
Amendment $688,712
Amendment $657,613
Amendment $758,543
Original award $758,543

Subawards

Subrecipient Amount Awarded
H. Lee Moffitt Cancer Center And Research Institute Hospital, Inc. For this proposed plan, Dr. Heine's lab will perform the quality control checks on the study mammograms, generate the automated breast density features, and… $47,044
Cornell University Rulla Tamimi, ScD, MPI and Site Principal Investigator, has worked with the Nurses' Health Studies (NHS) for over 15 years. She is very familiar with the… $120,121
The Washington University The team at Wash U will be led by Dr. Colditz who will work with Drs. Tamimi and Yaghjyan to provide input on the final methods and samples being identified,… $370,618
Brigham & Womens Physician Organization, Inc. Dr. Bernard Rosner has expertise in statistical methods and approaches. He has worked closely with the study MPIs, Drs. Colditz, Tamimi and Yaghjyan for over 12… $166,028
Beth Israel Deaconess Medical Center, Inc. Dr. Yu Jing Jan Heng at Beth Israel Deaconess Medical Center (BIDMC) will oversee the logistics and digitization of slides from the Nurses’ Health Studies (NHS)… $81,882
The Washington University The team at Wash U will be led by Dr. Colditz who will work with Drs. Tamimi and Yaghjyan to provide input on the final methods and samples being identified,… $110,996
Cornell University Rulla Tamimi, ScD, MPI and Site Principal Investigator, has worked with the Nurses' Health Studies (NHS) for over 15 years. She is very familiar with the… $118,330
H. Lee Moffitt Cancer Center And Research Institute Hospital, Inc. For this proposed plan, Dr. Heine's lab will perform the quality control checks on the study mammograms, generate the automated breast density features, and… $47,045
Brigham & Womens Physician Organization, Inc. Dr. Bernard Rosner has expertise in statistical methods and approaches. He has worked closely with the study MPIs, Drs. Colditz, Tamimi and Yaghjyan for over 12… $147,393
Cornell University Rulla Tamimi, ScD, MPI and Site Principal Investigator, has worked with the Nurses' Health Studies (NHS) for over 15 years. She is very familiar with the… $137,618
Beth Israel Deaconess Medical Center, Inc. Dr. Yu Jing Jan Heng at Beth Israel Deaconess Medical Center (BIDMC) will oversee the logistics and digitization of slides from the Nurses’ Health… $195,167
The Washington University The team at Wash U will be led by Dr. Colditz who will work with Drs. Tamimi and Yaghjyan to provide input on the final methods and samples being identified,… $228,674
H. Lee Moffitt Cancer Center And Research Institute Hospital, Inc. For this proposed plan, Dr. Heine's lab will perform the quality control checks on the study mammograms, generate the automated breast density features, and… $91,666
Brigham & Womens Physician Organization, Inc. Dr. Bernard Rosner has expertise in statistical methods and approaches. He has worked closely with the study MPIs, Drs. Colditz, Tamimi and Yaghjyan for over 12… $203,690
Beth Israel Deaconess Medical Center, Inc. Dr. Yu Jing Jan Heng at Beth Israel Deaconess Medical Center (BIDMC) will oversee the logistics and digitization of slides from the Nurses’ Health… $100,086
Cornell University Rulla Tamimi, ScD, MPI and Site Principal Investigator, has worked with the Nurses' Health Studies (NHS) for over 15 years. She is very familiar with the… $70,401
Show all 16

Quick answers

Who received award R01CA277817?

R01CA277817 was awarded to University Of Florida by National Cancer Institute (National Institutes of Health) on July 3, 2023.

How much is award R01CA277817 worth?

$3,548,931 has been obligated on R01CA277817.

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