The proposed study is a competitive renewal of our currently funded project that is investigating how epidemiological factors, clinical and pathological characteristics, and tumor marker expression influence the risk of second primary invasive contralateral breast cancer among survivors of a first primary invasive breast cancer. Here we propose to expand this work by evaluating factors that are related to risk of second primary breast cancers among ductal carcinoma in situ (DCIS) survivors. Incidence rates of DCIS have increased 7.2- fold from 1980 to 2001 in the United States, largely as a result of widespread breast cancer screening. DCIS lesions are very responsive to available therapies, and five-year disease-specific survival rates are close to 100%. However, DCIS survivors have a 3.4 to 8.6-fold higher risk of developing a second breast cancer compared to the risk that women in the general population have of developing a first breast cancer. The recent rapid rise in DCIS incidence rates has translated into a large and growing population of DCIS survivors who are particularly susceptible to developing a second breast cancer. Not all DCIS patients will go on to develop a second breast cancer, so certain surgical and adjuvant therapy combinations for DCIS constitute over- treatment for those at low risk of a second breast cancer, while others constitute under-treatment for those at high risk. At present, however, there is a lack of meaningful prognosticators to indicate which DCIS survivors are at high or low risk of developing a second breast cancer. Such prognosticators could be important guides to help these patients and their clinicians choose the most appropriate course of therapy and subsequent follow-up care. We propose to investigate how epidemiological, clinical, and histopathological characteristics of DCIS impact the risk of second primary breast cancers among DCIS survivors. We will recruit 515 patients diagnosed with DCIS and a verified subsequent second primary in situ or invasive breast cancer, and a control group consisting of 1,030 patients diagnosed only with DCIS to address the following specific aims: 1) How do epidemiological risk factors for breast cancer, including reproductive characteristics, anthropometric measures, use of exogenous hormones, mammographic density, and family history of breast cancer, influence the risks of second primary breast cancer overall, contralateral second primary breast cancer, and ipsilateral second primary breast cancer among DCIS survivors?;and 2) How do the clinical and histopathological features of DCIS, including treatments, tumor grade, and histological subtype impact risks of second primary breast cancer overall, contralateral second primary breast cancer, and ipsilateral second primary breast cancer among DCIS survivors? The proposed study will provide important information to the rapidly growing population of DCIS survivors as its results may help modulate their risk of developing a second primary breast cancer and inform their decision-making regarding DCIS treatments and subsequent breast cancer screening.

Public Health Relevance

In the United States about 20% of all breast cancers diagnosed are of a type called ductal carcinoma in situ (DCIS). DCIS patients have a very high survival rate but also have a high risk of developing a second breast cancer, and little is known about which DCIS survivors will and will not go on to develop second breast cancers. The primary goal of this study is to identify epidemiological, clinical, and histopathological characteristics that may be associated with risk of second breast cancers that can help DCIS survivors make decisions regarding their treatment and follow-up.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA097271-10
Application #
8597519
Study Section
Special Emphasis Panel (ZRG1-PSE-B (03))
Program Officer
Shelburne, Nonniekaye F
Project Start
2002-07-01
Project End
2014-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
10
Fiscal Year
2014
Total Cost
$514,603
Indirect Cost
$222,215
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
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
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
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