The availability of genetic testing for inherited mutations in the BRCA1 and BRCA2 genes provides potentially valuable information to women at high risk of breast or ovarian cancer. Unfortunately, carriers of these mutations have relatively few clinical management options to reduce their cancer risk. The investigators propose a study in response to the NCI's program announcement """"""""Clinical Epidemiology Studies in Hereditary Breast/Ovarian Cancer"""""""". They propose to evaluate the role of prophylactic surgery in reducing breast and ovarian cancer risk and mortality in BRCA1 and BRCA2 mutation carriers. Specifically, they propose: 1) to estimate the reduction in cancer risk following prophylactic surgery; 2) to estimate the reduction in cancer mortality following prophylactic surgery; 3) to evaluate differences in type of prophylactic mastectomy in breast cancer risk reduction; and 4) evaluate the psychosocial implications of prophylactic mastectomy or prophylactic oophorectomy, including measurement of mental health, satisfaction and quality of life. Two groups of women will be studied. Surgical subjects are those women who have undergone a bilateral prophylactic mastectomy (BPM) or prophylactic oophorectomy (BPO). Women will be followed-up over the course of this project to identify new occurrences of cancer surgery, or other relevant events. This follow-up will also yield longitudinal information about psychosocial adjustment to surgery including distress, depression, quality of life, satisfaction, and vulnerability to subsequent events. The risk of cancer in women who have undergone prophylactic surgery will be compared with cancer risk in controls that have no history of BPM or BPO. All study participants will carry documented disease-causing germline BRCA1/2 mutations. Analyses will be undertaken to specifically evaluate risk and mortality reduction following surgery. As recognized by this program announcement, women who have inherited germline BRCA1/2 mutations and are at extremely high risk of breast and ovarian cancer """"""""must make decisions about managing their cancer risk Ywith only limited scientific information about Ythe efficacy of prophylactic surgery"""""""". The announcement further recognizes that """"""""While prospective studies will eventually provide definitive answers to these question, there is an immediate need to address these issues through retrospective studies based on existing resources such as tissue banks and high-risk clinic registries and research projects"""""""". This proposal will address that immediate and important clinical need.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA083855-04
Application #
6653162
Study Section
Special Emphasis Panel (ZRG1-EDC-2 (03))
Program Officer
Arena, Jose Fernando
Project Start
2000-09-15
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
4
Fiscal Year
2003
Total Cost
$728,597
Indirect Cost
Name
University of Pennsylvania
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Walker, Logan C; Marquart, Louise; Pearson, John F et al. (2017) Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers. Eur J Hum Genet 25:432-438
Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B et al. (2017) Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3. Breast Cancer Res Treat 161:117-134
Rebbeck, Timothy R; Friebel, Tara M; Mitra, Nandita et al. (2016) Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women. Breast Cancer Res 18:112
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Shu, Catherine A; Pike, Malcolm C; Jotwani, Anjali R et al. (2016) Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations. JAMA Oncol 2:1434-1440
Zeng, Chenjie (see original citation for additional authors) (2016) Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. Breast Cancer Res 18:64
Blanco, Ignacio; Kuchenbaecker, Karoline; Cuadras, Daniel et al. (2015) Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. PLoS One 10:e0120020

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