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Team Project

Benign Breast Disease Team Project

•   BRCA1 (PC) •   p16 (PC) •   APC (PC) •   RASSF1A (PC) •   HIN1 (PC) •   EZH2 (JM) •   CEACAM6 (AG/JM, Poola) •   MMP1 (JM, Poola) •   TP53 (JM) •   HYAL1(JM, Poola) •   ALDH1 (JM) •   Periplakin, Epiplakin and Desmuslin (AG) •   Vitronectin and alpha-5-integrin (AG) •   IQGAP2 (AG) •   C5, C8G, C9 (AG) •   Mucin1 (AG) •   Glutathione S-transferase Mu1 and Mu3 (AG) •   ALDH16A1 (AG)
Other, Specify
Breast and Gynecologic Cancers Research

To identify women diagnosed with atypical ductal hyperplasia (ADH) who are at increased risk of developing invasive breast cancer (IBC) and who might benefit from risk reduction with the use of chemoprevention agents such as Tamoxifen. (Note: A companion protocol will study women with DCIS and their risk for invasive breast cancer.)

Biomarkers expressed in benign breast disease tissue of women who progresse to invasive breast cancer are quantitatively and/or qualitatively different from those expressed in tissue of matched women who do not progress to invasive breast cancer. A nested case-control design will be used to determine if available proteomic and methylation biomarkers predict risk for future invasive cancer (IBC). Women with ADH who are disease-free will be matched 2:1 to women with ADH who progress to IBC.
The performance of each biomarker tested will be undertaken in three steps: A.   Relative Risks Associated with Biomarker Values 1.    Cox regression will be used. Time measured from BBD diagnosis. 2.    Relative risks beyond those conferred by other predictors including age, family history, and histology will be examined. 3.    Separate models will be fit for ADH versus UH versus NP if there are sufficient numbers; Analyses will be combined with stratification if appropriate. B.   Capacity for Discrimination between Cases and Controls 1.   Primary comparison groups: subjects who developed invasive breast cancer by 7 years versus controls who are alive and without cancer at 7 years after BBD 2.   Secondary comparison groups: incident DCIS, invasive cancer after 7 years 3.   ROC curves will be used to compare cases with primary controls. Calculations are complicated because they must handle varying follow-up and the quota method of selecting non-cases 4.   Separate ROCs for BBD with and without atypia will be estimated if possible and compared. We will compare ROC curves for different biomarkers 5.   We will develop a combination biomarker score based on markers that appear to perform well using Cox regression. We will calculate its ROC curve and compare with ROC for best individual biomarker C.   Absolute Risk of IBC for Individual Decision Making 1.   Calculate individual risk of IBC .5-7.0 years after BBD with and without biomarker 2.   Compare risk distributions. How many people classified as high risk (>.75%X4.5) with and without the biomarker 3.   Calculate risk distributions for subjects who develop IBC by 7 years (cases) and for subjects alive without IBC by 7years (controls) 4.   Of subjects who develop IBC by 7 years, how many classified as high risk? This is the sensitivity (TPR) 5.   Of subjects who are alive without IBC by 7 years, how many classified as low risk? This is the specificity (1-FPR) 6.   Calculate the standardized net benefit that combines TPR and FPR into a single index 7.   Compare for different biomarkers and for the most discriminating biomarker combination

There are currently no biomarkers annotated for this protocol.

No datasets are currently associated with this protocol.


Appendix 2 BBD Forms
A set of CDE-based forms for Appendix 2 of the SOP for the Benign Breast Disease team project.
Standard Operating Procedure (SOP) For Selection of Archived FFPE Blocks to Support the Benign Breast Disease Project
To provide a standard operating procedure for identification, selection and retrieval of archived blocks in two large integrated community based health care systems, the Geisinger Health Care System in Pennsylvania and the Henry Ford Health System in Michigan. Processing of tissues from CVCs at Northwestern University, Duke University and Fox Chase Cancer Center for pre-validation studies will be undertaken with the same protocol described here for tissue processing.
2015 Steering Committee Meeting

The next EDRN Steering Committee Meeting will take place March 31st through April 2nd, 2015, in Atlanta, Georgia.

Announcement 02/12/2015

Please register for the 29th EDRN Steering Committee Meeting in Atlanta, GA from March 31-April 2, 2015. The registration page has information about booking hotel rooms and a draft agenda of the meeting.