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Gender-affirming estrogen therapy and breast cancer treatment outcome

Award Number: R21CA267088
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/21/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Gender-affirming estrogen therapy and breast cancer treatment outcome - Project Summary Our overall objectives in this proposal are to establish a cross-sex mouse model for breast cancer (BC) and develop BC treatment strategies for transfeminine individuals receiving estrogen therapy (ET). Transfeminine individuals are assigned male at birth and a majority of them pursue ET to affirm their feminine identity. Exposing the male body to extremely high exogenous estrogen over extended periods in order to achieve levels comparable to cisgender women raises concerns about the adverse effects of ET. ET is essential for their wellbeing but it remains unclear how ET modulates their lifetime breast cancer (BC) risk and, if they are diagnosed with BC, how ET affects their BC prognosis. Other groups have established cross-sex hormone treatment mouse models to investigate the impact of gender affirming hormone therapy on bone and cardiovascular health. There is no animal model to investigate the link between cross-sex hormone treatment and cancer. This proposal will develop a cross-sex mouse model of feminization to determine the extent which ET affects BC treatment outcomes. We will transplant three types of breast tumors—Pik3camut, Brca1mut, or Tp53mut—into male mice receiving ET. We will compare tumor growth rates, breast histology, and treatment outcomes between male mice that continue and discontinue ET during BC treatment with alpelisib (for Pik3camut tumors), olaparib (for Brca mut tumors), or eribulin (for Tp53mut tumors). Our long-term goal is to establish BC treatment strategies for the transgender community. Our preclinical model can be utlilized to develop strategies to treat other BC subtypes as well as other hormone- dependent malignancies such as prostate cancer. Our work will not only have implications in reducing transgender cancer disparities; our findings will contribute to our understanding of sex hormone dependencies in BC thus improving treatment strategies for cisgender men and women with BC as well.


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	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	000	2	4/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $290,362 )
2023	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Trans-NIH Research Support	002	2	9/14/2023	SUPPLEMENT FOR EXPANSION	$89,920
2023	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	000	2	11/22/2022	NON-COMPETING CONTINUATION	$184,079
2023	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	001	2	3/22/2023	NON-COMPETING CONTINUATION	$16,363
														Subtotal = $290,362

Issue Date FY: 2022 ( Subtotal = $245,438 )
2022	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Cause and Prevention Research	000	1	12/21/2021	NEW	$245,438
														Subtotal = $245,438

Grand Total All Awards = $535,800

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Gender-affirming estrogen therapy and breast cancer treatment outcome

Award Number: R21CA267088

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/21/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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