Grant Number:	5R01CA097271-03 Interpret this number
Primary Investigator:	Li, Christopher
Organization:	Fred Hutchinson Cancer Research Center
Project Title:	Tamoxifen & Second Breast Cancer: Epidemiology/Pathology
Fiscal Year:	2005

DESCRIPTION (provided by applicant): 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?




Alcohol consumption, smoking, and invasive breast cancer risk after ductal carcinoma in situ.
Authors: Jordahl K.M. , Malone K.E. , Baglia M.L. , Flanagan M.R. , Tang M.C. , Porter P.L. , Li C.I. .
Source: Breast Cancer Research And Treatment, 2022-03-27 00:00:00.0; , .
EPub date: 2022-03-27 00:00:00.0.
PMID: 35347551
Related Citations

Association between antidepressant use and second breast cancer event after ductal carcinoma in situ diagnosis: a nested case-control study.
Authors: Mansi E.T. , Malone K.E. , Tang M.T. , Loroña N.C. , Li C.I. .
Source: Cancer Causes & Control : Ccc, 2022-01-21 00:00:00.0; , .
EPub date: 2022-01-21 00:00:00.0.
PMID: 35061141
Related Citations

Bisphosphonate Use and Breast Cancer Risk among Women with Ductal Carcinoma In Situ.
Authors: Li C.I. , Flanagan M.R. , Tang M.C. , Porter P.L. , Malone K.E. .
Source: Cancer Research, 2021-05-15 00:00:00.0; 81(10), p. 2799-2802.
EPub date: 2021-03-24 00:00:00.0.
PMID: 33762354
Related Citations

Reproductive and menopausal factors and risk of second primary breast cancer after in situ breast carcinoma.
Authors: Baglia M.L. , Tang M.C. , Malone K.E. , Porter P. , Li C.I. .
Source: Cancer Causes & Control : Ccc, 2019 Jan; 30(1), p. 113-120.
EPub date: 2018-12-11 00:00:00.0.
PMID: 30539315
Related Citations

Family History and Risk of Second Primary Breast Cancer after In Situ Breast Carcinoma.
Authors: Baglia M.L. , Tang M.C. , Malone K.E. , Porter P. , Li C.I. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2018-01-16 00:00:00.0; , .
EPub date: 2018-01-16 00:00:00.0.
PMID: 29339357
Related Citations

Use of Antihypertensive Medications Not Associated with Risk of Contralateral Breast Cancer among Women Diagnosed with Estrogen Receptor-Positive Invasive Breast Cancer.
Authors: Chen L. , Malone K.E. , Li C.I. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Sep; 24(9), p. 1423-6.
PMID: 26084603
Related Citations

Bisphosphonate use after estrogen receptor-positive breast cancer and risk of contralateral breast cancer.
Authors: Monsees G.M. , Malone K.E. , Tang M.T. , Newcomb P.A. , Li C.I. .
Source: Journal Of The National Cancer Institute, 2011-12-07 00:00:00.0; 103(23), p. 1752-60.
EPub date: 2011-12-07 00:00:00.0.
PMID: 22021667
Related Citations

Relationship between diabetes and risk of second primary contralateral breast cancer.
Authors: Li C.I. , Daling J.R. , Tang M.T. , Malone K.E. .
Source: Breast Cancer Research And Treatment, 2011 Jan; 125(2), p. 545-51.
PMID: 20625814
Related Citations

Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users.
Authors: Pitteri S.J. , Amon L.M. , Busald Buson T. , Zhang Y. , Johnson M.M. , Chin A. , Kennedy J. , Wong C.H. , Zhang Q. , Wang H. , et al. .
Source: Cancer Research, 2010-11-01 00:00:00.0; 70(21), p. 8598-606.
EPub date: 2010-11-01 00:00:00.0.
PMID: 20959476
Related Citations

Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor-positive invasive breast cancer.
Authors: Li C.I. , Daling J.R. , Porter P.L. , Tang M.T. , Malone K.E. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2009-11-10 00:00:00.0; 27(32), p. 5312-8.
EPub date: 2009-11-10 00:00:00.0.
PMID: 19738113
Related Citations

Adjuvant hormonal therapy for breast cancer and risk of hormone receptor-specific subtypes of contralateral breast cancer.
Authors: Li C.I. , Daling J.R. , Porter P.L. , Tang M.T. , Malone K.E. .
Source: Cancer Research, 2009-09-01 00:00:00.0; 69(17), p. 6865-70.
EPub date: 2009-09-01 00:00:00.0.
PMID: 19706753
Related Citations