Amv Storniolo

A phase I, dose escalation study of lapatinib in combination with carboplatin, paclitaxel, with and without trastuzumab in patients with metastatic breast cancer.

Abstract #3121 Background : Lapatinib is a selective and highly potent dual, competitive inhibitor of erbB1 and erbB2 tyrosine kinases with clinical activity in erbB2-positive metastatic breast cancer (MBC). The combination of carboplatin, paclitaxel, and trastuzumab has been shown to have significant clinical activity in MBC as well as in the adjuvant setting. Given the synergy of dual inhibition with trastuzumab and lapatinib observed in both the preclinical and clinical settings, we assessed the feasibility, safety, and early clinical activity of paclitaxel, carboplatin, lapatinib with and without trastuzumab in patients (pts) with MBC.
 Methods : MBC pts previously untreated with trastuzumab or cytotoxic chemotherapy for metastatic or locally recurrent disease were enrolled into either Group (Grp) A (erbB2 positive) or B (erbB2 positive or negative). Escalating doses of lapatinib (planned range of 750-1500 mg/d) were administered in combination with (Grp A) or without (Grp B) trastuzumab (4 mg/kg followed by weekly 2 mg/kg infusions). Paclitaxel (80 mg/m 2 ) and carboplatin (AUC 2 mg/ml*min) were administered on days 1, 8, 15 with cycles repeated every 28 days. Starting doses of lapatinib were 750 mg in Grp A and 1000 mg in Grp B. A standard 3 + 3 Phase I design is being used until the optimally tolerated regimen (OTR) dose level is determined. An additional 14 - 17 pts will be enrolled into each grp at the OTR dose level to further assess safety and tolerability.
 Results : Fourteen pts (Grp A n=8, Grp B n=6) have been enrolled in the study (median age 42 yrs, range 27-66). A median of 5.5 cycles (range 4-17) in Grp A and 3.5 (range 1-7) in Grp B have been administered. All pts had at least one adverse event (AE). In Grp A, grade 3 toxicities include neutropenia (50%), diarrhea (38%), rash (25%), vomiting (13%), hypokalemia (13%), and syncope (13%). No grade 4 toxicities were reported. In Grp B, grade 3 toxicities include fatigue (33%), hyponatremia (17%), menorrhagia (17%), dermatitis (17%), and rash (17%). One pt (in Grp B) had grade 4 neutropenia. No febrile neutropenia was observed. In Grp A, there was one DLT (Gr 3 diarrhea) at lapatinib 1000 mg. In Grp B, one DLT (Gr 4 neutropenia) at lapatinib 1000 mg has been observed. Clinical activity to date includes 8/8 objective responses in Grp A, (1 CR, 7 PR) and 2/6 objective responses (2 PR) in Grp B (all pts in Grp B were erbB2 negative). Dose escalation continues in both grps.
 Conclusions : Lapatinib may be administered safely in combination with carboplatin, paclitaxel, with and without trastuzumab at known effective doses for each. Clinical activity has been observed. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3121.

An Exploratory Study of the Biological Activity of Sunitinib as a Component of Neoadjuvant Therapy for Breast Cancer.

Background: The neoadjuvant setting provides an ideal opportunity to explore the impact of sunitinib alone and in combination with paclitaxel on the functional status of tumor vasculature as indicated by changes in tumor interstitial pressure (IFP) and circulating progenitor cell (CPC) subsets.Methods: Patients(pts.) with newly diagnosed stage Ic-IIIc breast cancer were treated with sunitinib monotherapy (100 mg Day 1; 37.5 mg D2-14) prior to the initiation of paclitaxel (80 mg/M2 D1,8,15 every 28 days x 4 cycles) with sunitinib (25 mg/d). IFP and CPC subsets were assessed at baseline and after sunitinib monotherapy. IFP was measured in three separate areas of the tumor using a micropressure transducer catheter; mean and highest IFP recorded were analyzed. Improvements in poly-chromatic flow cytometry allowed distinction of pro-angiogenic (pCPC = Live/AC133+CD34bright/CD31+CD45dim\), from non-angiogenic (nCPC = Live/AC133-CD34bright/CD31+/CD45dim\), CPCs that cannot be quantified separately using previously reported protocols1. Baseline CPC subsets were also compared to age and gender matched healthy controls.Results: From July 2008 to May 2009, 14 pts were enrolled; baseline and post-sunitinib IFP and CPC data are available for 12 and 11 pts respectively. The median age was 48 (range 32-69). Mean pretreatment tumor diameter was 3.2 cm. Sunitinib monotherapy was generally well tolerated; two patients developed grade III toxicities including hypertension (n=1) and hand-foot syndrome (n=1). Sunitinib significantly decreased mean IFP (18.87 mmHg vs. 6.38 mmHg; p=0.002); similar results were obtained when only the maximum IFP was considered (22.32 mmHg vs. 8.36 mmHg; p=0.003). pCPC frequency was not different between pts and healthy controls (0.099% vs. 0.076%, p=0.24) but the p:nCPC ratio was significantly higher in pts compared to healthy controls (3.26 vs. 1.46; p=0.001) suggesting a shift toward vascular damage and/or active angiogenesis. Both pCPC frequency (0.099 vs. 0.022; p=0.001) and p:nCPC ratio (3.26 vs. 0.78; p=0.001) significantly decreased after sunitinib monotherapy. Analysis of paclitaxel + sunitinib is too early (n=4).Conclusion: Sunitinib, through its effects on VEGF-mediated vascular permeability, markedly reduces tumor IFP. In addition sunitinib profoundly reduces pCPCs that are thought to be important for angiogenesis in human cancers. Accrual is ongoing (planned N=40). Analysis of IFP and CPC subsets after paclitaxel + sunitinib as well as additional correlates will be presented.1 Duda et al. (2007). Nat. Protocol 2, 805-810. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 202.

Abstract P1-03-02: “Normal” tissue adjacent to breast cancer is not normal

Background: Gene expression data from pancreatic cancer, histologically normal tissue adjacent to the cancer and normal pancreas reveals that adjacent normal has already acquired a number of transcriptional alterations and is not, therefore, an appropriate baseline for comparison with cancers. (Gadaleta et al., 2011) The purpose of this study was to determine if this is also the case for breast cancer and, if so, to identify the differences in gene expression between adjacent normal and normal breast. Methods: RNA-Seq data from breast cancer and adjacent normal was downloaded from the TCGA (The Cancer Genome Atlas) data portal. The epithelia from 20 frozen tissue cores from healthy premenopausal donors to the Susan G. Komen for the the Cure® Tissue Bank at the IU Simon Cancer Center were microdissected and the RNA isolated. RNA-seqeuncing was carried out using the Life Technologies SOLiD Platform. RPKM gene expression values from TCGA and sequencing of the Komen normal tissues were merged, quantile normalized, and batch effect corrected. Normalization and differential gene expression was performed using Partek Genomics Suite. Results: Principal component analysis (PCA) reveals complete separation between adjacent normal and healthy normal breast tissue. Setting a maximum FDR (false discover rate) of 5%, 2239 genes are differentially expressed between adjacent normal and healthy normal. Ingenuity pathway analysis reveals that the Fos, Jun and TGFbeta pathways are active in the adjacent normal. Conclusions: Tissue adjacent to a primary breast cancer is not normal when using healthy breast tissue as a comparator. As RNA-Seq data is digital, it is possible to quantify the changes in gene expression starting from healthy normal to normal adjacent to tumor to tumor. Increasing and decreasing gene expression values provide clues to the fundamental molecular changes occurring in histologically normal appearing adjacent tissue. The differences in gene expression we have identified are some of the earliest changes in breast carcinogenesis and provide insight into the etiology of this disease and, potentially, its prevention. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-03-02.

P2-13-01: Gene Profiling of Whole Blood May Identify Patients with BRCA Mutations.

Background:The BRCA1 and the BRCA2 proteins play a role in DNA repair and confer genomic stability to the cell. Identifying BRCA mutation carriers has become an important tool for prevention as well as guiding therapy in cancer patients. We proposed to test the hypothesis that gene expression analysis of peripheral whole blood can reliably detect these mutations. Materials and methods: Following IRB approval, 10cc of blood was collected from 36 women (BRCA1 (n=8), BRCA2 (n=9), Hereditary breast cancer without BRCA (FAM) (n=7), sporadic breast cancer (SPO) (n=11)). 3 of BRCA1 and 5 of BRCA2 samples were from women without cancer. Following RNA extraction (using the method described by Beekman et al) and quality assessment, Illumina® Whole-Genome DASL™ microarray (Human Ref-8 BeadChips) analysis was performed. The raw data was normalized and analyzed using Partek® Genomic Suite. Differentially expressed genes were identified using ANOVA analysis. Geneset specific supervised analysis was performed to visualize the inherent similarities and differences in the gene expression amongst different groups for 1) DNA repair and 2) Immune-system-related genes. Ingenuity Pathway Analysis (IPA) was performed to interpret the data in the context of biological processes, pathways and networks. Results: Twenty-nine of the 87 immune-related genes were up-regulated in BRCA1 and BRCA2 groups compared to SPO or FAM groups; these included IL7R, CD53, CD2, CD48 and HLA-DRA. Twenty-five of the 79 DNA repair genes were up-regulated in BRCA1 and BRCA2; these included FANCC, RAD51L3, MSH2, MSH6 and PCNA. In IPA analysis, the comparison of BRCA1 vs. REST (BRCA2 + FAM + SPO) showed a strong immunologic signal, with the top altered biological processes including “Immunologic disease”, “Infection mechanism”, “Immune cell trafficking” and “cell-mediated immune response “. The top 5 canonical pathways also reflected a similar pattern and included “iCOS-iCOSL Signaling in T Helper Cells”, “OX40 Signaling Pathway”, “Calcium-induced T Lymphocyte”, “Apoptosis Regulation of IL-2 Expression in Activated and Anergic T Lymphocytes” and “Protein Ubiquitination Pathway”. When BRCA2 was compared with the REST (BRCA1 + FAM + SPO), a much weaker signal was noted with none of the canonical pathways being significantly altered. PAM analysis showed that a set of 16 genes could differentiate the BRCA patients from the rest with an error rate of 5%. Further validation of this geneset is being performed. Conclusion: Gene profiling in whole blood may offer an easy, reliable and inexpensive way to identify patients with BRCA mutation. Further studies are currently underway to validate our results in a larger patient population. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-01.

P5-05-02: Phenotypic Plasticity in the Normal Breast.

Background: The cell of origin of metaplastic carcinoma of the breast (MCB) is an enigma. MCB comprises less than 4% of all breast cancers, and is a member of the subtype of breast cancer referred to as Triple Negative Breast Cancer (TNBC). It is aggressive with a prognosis worse than that that for invasive ductal carcinoma NOS (not otherwise specified), as well as other TNBCs. Identification of the histogenesis of MCB is likely to provide clues to its oncogenesis. Differentiation along non-epithelial lineages is also observed in benign lesions of the breast. Adenomyoepitheliomas, thought to arise from myoepithelial cells, have been observed to contain areas of cartilaginous, sebaceous, squamous, and osseous differentiation. Methods: Healthy woman volunteers from central Indiana were invited to donate breast tissue to the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center. Starting from the 10 gauge tissue cores, 28 normal mammary epithelial (HME) and 33 normal stromal (HMS) cell lines were established using an organoid isolation method after digestion with enzymes for 24 hours. The HME cell lines were characterized by immunohistochemistry (IHC). Ploidy was determined by karyotype and Interphase FISH mapping with centromere probes for Chromosomes X and 17. Cellular morphology was observed both on two-dimensional and in three-dimensional culture systems. The HME cells were subjected to FACS analysis using multiple antibodies including CD24, CD44, Muc1, CD49f, and EpCAM. Results: 96.9% of early passage cells are diploid. The HME cells express vimentin, CK 5/6, p63, CD 10, CK 18, and HER-1 when grown on two dimensional plastic surfaces. Cells placed in the center of a sandwich of Matrigel® uniformly form spheres 37mm-325mm in diameter. Hematoxylin and eosin staining of the formalin-fixed and paraffin-embedded sections of these spheres reveal keratinized squamous differentiation. When the cells are grown on Laminin, Collagen IV, or Fibronectin surfaces multiple cell types are observed including osteoclasts, distinguished by the presence of Tartrate Resistant Acid Phospatase; and chondrocytes, confirmed by staining with Alcian Blue. Other cells with a spindle-shape and cytoplasmic vacuoles turn a dark reddish-brown color when stained with Oil Red O, characteristics of adipocytes. In other areas of the culture, the cells form a syncitium and they express the protein MyoD, a marker of immature muscle. Finally, there are numerous cells with long, dendritic processes. These cells express Nestin, a marker of neural stem cells; glial fibrillary acidic protein (GFAP), expressed by mature astrocytes; and beta-III tubulin produced by differentiated neurons. Using FACS, the HME cells were found to be CD49f positive and EpCAM negative. Multiple nucleoli were confirmed using anti-Nucleostemin IHC. Conclusions: Phenotypic plasticity is common to all the HME cell lines characterized to date. Differentiation into cells of mesodermal and ectodermal origin, CD49+/EpCAM- by FACS, and the presence of multiple nucleoli suggest that the isolated cells are a multipotent/stem cell residing in the normal adult breast. These cells, through a series of yet to be elucidated events, may be the cells of origin of MCB. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-05-02.

Abstract P2-14-02: A Pilot Study of Vascular Endothelial Growth Factor Inhibition with Pazopanib in Patients (pts) with Lymphedema Following Breast Cancer Treatment

Purpose: Lymphedema is a significant long-term complication of primary therapy for breast cancer. VEGF has a major impact on vascular permeability and lymphangiogenesis. In a prior case control study, we found a significant increase in serum VEGF-C (median 6895 vs. 5349 pg/mL, p=0.0016) in women with lymphedema compared to women without lymphedema suggesting inhibition of VEGF-C as a potential therapeutic strategy. Methods: Pts with significant unilateral lymphedema were treated with pazopanib 800 mg/day continuously. Baseline assessments include arm volume, interstitial fluid pressure (IFP), extracellular fluid volume by lymphometer (ECF), quality of life (QOL) and plasma VEGF-C,-D, and R3. IFP was measured serially for 24 hours after the first treatment; arm volume, ECF, QOL, and plasma VEGF-C/D/R3 are assessed every 4 weeks. Results: Ten pts were enrolled. Median duration of lymphedema was 3.5 years (0.7-8.2) Median time since surgery was 5.1 years (1.0-14.2); median time since radiation (n=9) was 4.7 years (0.4-8.8). Complete IFP data are available in 7 pts. Baseline IFP was significantly higher in the affected compared to unaffected arm (mean 5.73 vs. -1.78 mmHg; p=0.0005). Mean IFP in the affected arm decreased an average of 76% 24 hours after initiation of pazopanib (5.73 vs. 1.56 mmHg; p=0.0061). Toxicity was greater than anticipated with grade 3 fatigue (n=3), arthralgia (n=2), and anorexia (n=1); three pts discontinued therapy prior to the first post-treatment assessment. Five pts met the definition of response with a ≥25% reduction in excess arm volume four weeks after initiating treatment. ECF significantly (p=0.014) decreased as well though the mean difference in excess arm volume did not significantly change (p=0.06). Conclusions: Preliminary data supports the hypothesis that VEGF plays a role in the development and/or persistence of lymphedema after local therapy for breast cancer. Pazopanib acutely decreases IFP, leading to a decrease in ECF and modest improvement in arm volume but results in significant toxicity at the dose used on this study. Subsequent studies will explore a lower dose of pazopanib in this population. This study was supported by the Breast Cancer Research Foundation with pazopanib supplied by GSK. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-02.

Abstract PD01-08: Decoding the Transcriptional Landscape of Triple-Negative Breast Cancer Using Next-Generation Whole Transcriptome Sequencing

Indiana University-Purdue University Indianapolis (IUPUI)%%%%Triple-negative breast cancers (TNBCs) are negative for the expression of estrogen (ER), progesterone (PR), and HER-2 receptors. TNBC accounts for 15% of all breast cancers and results in disproportionally higher mortality compared to ER & HER2-positive tumours. Moreover, there is a paucity of therapies for this subtype of breast cancer resulting primarily from an inadequate understanding of the transcriptional differences that differentiate TNBC from normal breast. To this end, we embarked on a comprehensive examination of the transcriptomes of TNBCs and normal breast tissues using next-generation whole transcriptome sequencing (RNA-Seq). By comparing RNA-seq data from these tissues, we report the presence of differentially expressed coding and non-coding genes, novel transcribed regions, and mutations not previously reported in breast cancer. From these data we have identified two major themes. First, BRCA1 mutations are well known to be associated with development of TNBC. From these data we have identified many genes that work in concert with BRCA1 that are dysregulated suggesting a role of BRCA1 associated genes with sporadic TNBC. In addition, we observe a mutational profile in genes also associated with BRCA1 and DNA repair that lend more evidence to its role. Second, we demonstrate that using microdissected normal epithelium maybe an optimal comparator when searching for novel therapeutic targets for TNBC. Previous studies have used other controls such as reduction mammoplasties, adjacent normal tissue, or other breast cancer subtypes, which may be sub-optimal and have lead to identifying ineffective therapeutic targets. Our data suggests that the comparison of microdissected ductal epithelium to TNBC can identify potential therapeutic targets that may lead to be better clinical efficacy. In summation, with these data, we provide a detailed transcriptional landscape of TNBC and normal breast that we believe will lead to a better understanding of this complex disease.

Abstract P6-04-01: Next-Generation Transcriptome Sequencing of the Normal Breast

Background: Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established expressly to address and remedy this deficiency. The KTB acquires and banks normal breast tissue, that is, breast tissue from volunteer donors with no clinical evidence of breast malignancy. This tissue is NOT from reduction mammoplasties or from histologically normal tissue adjacent to a malignancy. The breast is one of the most complex genetic organs within the body. This is because the expression of its genes is under the control and influence of the hormonal milieu present in the circulating plasma, which changes as a function of age; for premenopausal women as a function of the menstrual cycle; and as a consequence of pregnancy. Therefore, there is unlikely to be a singular “normal” breast. We propose to produce a molecular encyclopedia of the normal breast which covers the entire spectrum of normal: puberty to menopause, low risk to high risk, nulliparous and parous. Materials and Methods: The epithelial compartment of fresh frozen tissue from 10 premenopausal donors to the KTB, 5 women who were in the follicular phase of the menstrual cycle and 5 who were in the luteal, was isolated using laser capture microdissection. Total RNA extracted from the cells was subsequently depleted for ribosomal RNA. RNA was sequenced on an Applied Biosystems SOLiD3 sequencer using 50bp runs. Reads were mapped to the human genome. Whole blood was collected at the time of tissue donation and uniformly processed into serum. Results: RNA sequencing of the 10 samples produced 596 million reads of which 386 million (62%) mapped to the human genome. Setting the p-value at Proliferating Cell Nuclear Antigen (PCNA), nucleosome assembly genes and genes involved with mitosis have greater expression during the luteal phase of the menstrual cycle. Genes associated with development, e.g., NOTCH2, PAX3, DKK3 and TWIST1, are more abundantly expressed during the follicular phase. Many of the differentially expressed genes have been implicated in breast oncogenesis. Conclusions: The Komen Tissue Bank has completed the first ever next-generation transcriptome sequencing of epithelial compartment of ten normal human breast specimens. This work has produced the most comprehensive catalog to date of the differences in the expression of protein encoding genes, pre-miRNAs, lincRNA exons, UCRs and novel transcribed regions as a function of the phase of the menstrual cycle. Additionally, this effort has identified a relatively significant number of genes whose expression is very likely under the control of estrogen. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-04-01.

Next-Generation Whole Transcriptome Sequencing of Triple-Negative Breast Tumors and Normal Tissues.

Background: Triple-negative breast cancer predominately affects pre-menopausal women and women of African-American descent and has been plagued by the absence of targeted therapies leading to poor survival. Using a new cutting edge technology, next-generation sequencing, we embarked on a study to analyze the whole transcriptomes of triple-negative tumors and normal tissues from pre-menopausal women in order to comprehensively identify new targets by analyzing all full length transcripts expressed in these tissues. This approach is independent of pre-determined gene selection as is common with microarrays, and allows for the analysis of RNA species that have not been previously profiled in breast cancer.Methods: cDNA libraries were created from RNA isolated from 8 triple-negative tumors and 2 normal breast tissues. Triple negative tumors were procured from Origene Technologies and normal breast tissues were procured from the Susan G. Komen for the Cure tissue bank at Indiana University. Normal samples were from healthy pre-menopausal volunteers with no history of disease. In order to eliminate bias from stromal tissue, normal samples were laser capture microdissected for ductal cells and RNA extracted from the excised tissue. cDNA libraries were prepared and subsequently sequenced on an Applied Biosystems (ABI) SOLiD3 sequencer using a 50bp fragment run. Mapping of whole reads to the human genome was performed using the SOLiD Analysis Pipeline Tool software (ABI) followed by a split-read alignment in order to map reads crossing exon-exon junctions. Gene expression profiles for each sample were then created and statistically compared to identify the most differentially expressed genes. In order to analyze for fusion genes, a split-read alignment of non-mapping reads to a composite transcriptome formed from previously mapped reads (clusters) was performed.Results: Sequencing of the 10 samples produced 513 million filtered reads equaling 25.66GB of data. Mapping of the reads to the genome revealed 1.14 million transcribed regions (exons). A preliminary analysis of gene expression shows 55.2% of the transcribed loci to have significant differential expression between tumor and normal. In a further analysis for gene fusions, several candidate fusions were bioinformatically detected. These are currently being reviewed and validated.Discussion: Herein we present a preliminary analysis of the transcriptomes of triple-negative breast cancers in comparison to normal tissues. A multitude of analyses are ongoing, including but not limited to: gene fusions, differentially expressed novel genes, novel transcripts, alternative splicing, intrinsic subtyping, and presence of viral genes. In addition 2 more triple-negative tumors and 8 normal samples will also be sequenced. In the current analysis, differentially expressed non-coding RNAs was highly pervasive among the samples indicating a major role of this RNA species in tumorigenesis. In addition, triple-negative breast cancers may contain fusion genes that could be “drivers” of this malignancy. Further validation of these differentially expressed RNAs and fusion genes in a larger set of samples with subsequent functional studies is planned. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6134.

P5-21-02: The Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center: The Source for Normal Breast Tissue and Biospecimens.

Background Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. This ignorance has been the consequence of the lack of access to richly annotated, high quality normal breast specimens. The Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB) was established expressly to remedy this deficiency. The KTB is a repository of specimens from volunteer donors with no clinical evidence of breast malignancy. The Bank9s mission is to make available specimens that will enable an understanding of the developmental biology of the normal breast, to provide insight into breast oncogenesis, and to provide a normal control for breast cancer research. The purpose of this presentation is to increase the awareness of this unique and rich research resource and to actively solicit the use of its specimens. Methods: The KTB has been prospectively banking fresh frozen breast tissue since mid-2006. Coincident with the tissue donation two tubes of blood are obtained, which are processed for lymphocyte DNA, serum and plasma. These specimens are richly annotated with detailed information regarding the donors’ reproductive history, medical history, family history, and medications. Standard Operating Procedures have been constructed so as to control, limit and identify potential sources of bias. All of this information is recorded in an Oracle-based, searchable database. Results: As of June 2011, the KTB and its predecessor bank, Mary Ellen9s Bank, have available fresh frozen breast tissue (10 gauge cores) from 1469 donors; formalin-fixed, paraffin-embedded tissue from 1055; DNA from 7507; serum from 2382; and plasma from 3771 donors. The KTB has also established 28 epithelial and 33 stromal cell lines from the cores; 4 of the epithelial cell lines have been immortalized using hTERT. Donors range in age from 18–86 years of age. 9% of donors to the KTB describe themselves as Hispanic/Latino. 5.2% of donors are Black or African-American. Using the Gail Risk Model, there is a bimodal distribution of life-time breast cancer risk among the donors: the largest peak is at 10% and a smaller one at 18%. Conclusions: The KTB is a unique and invaluable research resource which is now open for business and accessible to researchers across the globe. We encourage researchers to avail themselves of this unique tissue resource and to also acquaint themselves with other sources of healthy breast tissue, i.e., the Love/Avon Army of Women [http://www.armyofwomen.org/]. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-21-02.