Second primary or contralateral breast cancer (CBC) is an issue of growing importance given that breast cancer incidence and survival rates are increasing. Treatment with tamoxifen decreases risk of CBC by 47 percent. However, it is only recommended for women with estrogen receptor-positive (ER+) breast cancer, as it has no effect on estrogen receptor-negative (ER-) tumors. Unfortunately, half of all ER+ first breast cancers fail to respond to tamoxifen, and most that do respond eventually develop tamoxifen resistance. Preliminary data suggest that tamoxifen users may develop more ER- CBC's than expected. Thus, one of our objectives is to test the hypothesis that tamoxifen use increases risk of ER- CBC. Additionally, while tamoxifen reduces a woman's risk of ER+ CBC, many women treated with tamoxifen nonetheless do develop it. Mechanisms by which tamoxifen inhibits the development of some ER+ CBC's, but not all, may be related to altered expression of ER or factors downstream of the ER resulting in altered interaction with tamoxifen in some tumors. Thus, a second objective of this study is to evaluate how tamoxifen affects the expression of selected tamoxifen resistance-associated factors. Findings related to these factors may point toward additional mechanisms by which resistance may unfold and improve our ability to tailor treatments. We propose to conduct a population-based nested case-control study of 400 women aged 40-79 who have been diagnosed with CBC and 800 matched controls diagnosed with a first but never a CBC. The specific questions to be evaluated are: (1) Does tamoxifen therapy for a first breast cancer influence risk of ER- and ER+ CBC? (2) How does tamoxifen therapy for a first breast cancer alter the expression of tumor markers involved in pathways leading to tamoxifen resistance in CBC? (3) Do the expression of these tumor markers by first breast cancers or other patient characteristics predict which women have increased or decreased risks of developing CBC if they use tamoxifen? (4) Among the CBC cases, how does tamoxifen alter the expression of these tumor markers in first compared to contralateral cancers?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA097271-04
Application #
7061342
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Kasten-Sportes, Carol H
Project Start
2003-06-06
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
4
Fiscal Year
2006
Total Cost
$713,769
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Baglia, Michelle L; Tang, Mei-Tzu C; Malone, Kathleen E et al. (2018) Family History and Risk of Second Primary Breast Cancer after In Situ Breast Carcinoma. Cancer Epidemiol Biomarkers Prev 27:315-320
Chen, Lu; Malone, Kathleen E; Li, Christopher I (2015) Use of Antihypertensive Medications Not Associated with Risk of Contralateral Breast Cancer among Women Diagnosed with Estrogen Receptor-Positive Invasive Breast Cancer. Cancer Epidemiol Biomarkers Prev 24:1423-6
Monsees, Genevieve M; Malone, Kathleen E; Tang, Mei-Tzu C et al. (2011) Bisphosphonate use after estrogen receptor-positive breast cancer and risk of contralateral breast cancer. J Natl Cancer Inst 103:1752-60
Li, Christopher I; Daling, Janet R; Tang, Mei-Tzu C et al. (2011) Relationship between diabetes and risk of second primary contralateral breast cancer. Breast Cancer Res Treat 125:545-51
Pitteri, Sharon J; Amon, Lynn M; Busald Buson, Tina et al. (2010) Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users. Cancer Res 70:8598-606
Li, Christopher I; Daling, Janet R; Porter, Peggy L et al. (2009) Adjuvant hormonal therapy for breast cancer and risk of hormone receptor-specific subtypes of contralateral breast cancer. Cancer Res 69:6865-70
Li, Christopher I; Daling, Janet R; Porter, Peggy L et al. (2009) Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor-positive invasive breast cancer. J Clin Oncol 27:5312-8