In recent years, new technologies have allowed us to better characterize the heterogeneity of breast cancer and to identify a number of biological subtypes based on their molecular profiles. Consequently, molecular classification of tumors is increasingly being used to guide treatment selection and new treatment development, in evaluating prognosis, and in studies of etiology. One molecular classification, the """"""""intrinsic subtype"""""""", which distinguishes among breast cancers based on either their cell type of origin (luminal A/B or basal) or whether the tumor is HER2-positive, has been used to identify biologically and clinically distinct subtypes of breast cancer. The primary goal of this proposal is to examine the effects of intrinsic subtypes and their relationship to breast cancer risk factors and short and long-term prognosis in two ongoing cohort studies of breast cancer survivors (N=4177) being conducted within the Kaiser Permanente of Northern California (KPNC) Medical Care program. The first study, the Life After Cancer Epidemiology (LACE) cohort, a population-based cohort of 2,288 women diagnosed with Stage I>1 cm, II, or IIIa breast cancer, was established in 2000- 2002 to examine behavioral factors and breast cancer prognosis. These data will be combined with 1890 additional cases of similar stage from the Pathways cohort, a study of short term breast cancer survivors which began in January 2006. Given the inconsistency observed to date in findings between energy related factors and prognosis and the suggestion that effects may vary by tumor characteristics such as hormone receptor status, a secondary goal of this proposal is to examine whether specific behaviors related to energy balance may be related to prognosis among breast cancer patients in general or primarily among women with certain intrinsic subtypes Since most studies have only reported on effects of energy related factors on short term prognosis, another secondary goal of this proposal is to continue to follow women in the LACE cohort up until 15 year post-diagnosis and to examine the relationship of energy related lifestyle factors with long-term prognosis. Data on weight, weight change, physical activity and diet were collected at multiple time points post diagnosis. Women are followed annually for recurrence and death by self report and verified by medical record and death certificates. During the proposed new funding period, archived tumor blocks will be retrieved and, using immunohistochemical assays (IHC), breast cancers will be classified into intrinsic subtypes. This study will achieve tremendous cost savings by examining the proposed questions within two existing cohort of cancer survivors for whom post diagnosis data on behavior are already available and by retrieving tumor specimens within a cohort where close to 90% the women belong to the KPNC, an HMO, where tumor specimens are readily accessible. Our proposal addresses a range of issues that are emerging priority areas in cancer survivorship research which will have both clinical and public health impact.

Public Health Relevance

A limited number of studies with relatively small samples or short-term follow-up have classified tumors into intrinsic subtypes and examined their association with clinical tumor characteristics or survival. An even smaller number have looked at breast cancer risk factors. The combined LACE and Pathways cohorts, as proposed in this study constitutes one of the largest resources on breast cancer survivors with already collected clinical data from medical charts and lifestyle and other factors from self- administered questionnaires. The addition of the proposed intrinsic subtype (IHC) molecular markers to this resource provides an innovative and cost-efficient method for classifying breast cancer subtypes (IHC assays can be done on archived tumor tissue) that will improve our understanding of variation in prognosis, and also allows for the unique combination of molecular and behavioral information to help better understand which women are most likely to benefit from changes in lifestyle after a breast cancer diagnosis, information of both clinical and public health significance. This population-based cohort is uniquely positioned to address several important gaps in our knowledge about cancer survivorship.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Schully, Sheri D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Kaiser Foundation Research Institute
United States
Zip Code
Nelson, Sandahl H; Marinac, Catherine R; Patterson, Ruth E et al. (2016) Impact of very low physical activity, BMI, and comorbidities on mortality among breast cancer survivors. Breast Cancer Res Treat 155:551-7
Vigen, Cheryl; Kwan, Marilyn L; John, Esther M et al. (2016) Validation of self-reported comorbidity status of breast cancer patients with medical records: the California Breast Cancer Survivorship Consortium (CBCSC). Cancer Causes Control 27:391-401
Jones, Lee W; Habel, Laurel A; Weltzien, Erin et al. (2016) Exercise and Risk of Cardiovascular Events in Women With Nonmetastatic Breast Cancer. J Clin Oncol 34:2743-9
Sposto, Richard; Keegan, Theresa H M; Vigen, Cheryl et al. (2016) The Effect of Patient and Contextual Characteristics on Racial/Ethnic Disparity in Breast Cancer Mortality. Cancer Epidemiol Biomarkers Prev 25:1064-72
Jones, Lee W; Kwan, Marilyn L; Weltzien, Erin et al. (2016) Exercise and Prognosis on the Basis of Clinicopathologic and Molecular Features in Early-Stage Breast Cancer: The LACE and Pathways Studies. Cancer Res 76:5415-22
Kwan, Marilyn L; Bernard, Philip S; Kroenke, Candyce H et al. (2015) Breastfeeding, PAM50 tumor subtype, and breast cancer prognosis and survival. J Natl Cancer Inst 107:
Cheng, Iona; Shariff-Marco, Salma; Koo, Jocelyn et al. (2015) Contribution of the neighborhood environment and obesity to breast cancer survival: the California Breast Cancer Survivorship Consortium. Cancer Epidemiol Biomarkers Prev 24:1282-90
Kwan, Marilyn L; Kroenke, Candyce H; Sweeney, Carol et al. (2015) Association of high obesity with PAM50 breast cancer intrinsic subtypes and gene expression. BMC Cancer 15:278
Colonna, Sarah; Halwani, Ahmad; Ying, Jian et al. (2015) Women with breast cancer in the Veterans Health Administration: demographics, breast cancer characteristics, and trends. Med Care 53:S149-55
Wu, Anna H; Kurian, Allison W; Kwan, Marilyn L et al. (2015) Diabetes and other comorbidities in breast cancer survival by race/ethnicity: the California Breast Cancer Survivorship Consortium (CBCSC). Cancer Epidemiol Biomarkers Prev 24:361-8

Showing the most recent 10 out of 34 publications