Citations

Background and Purpose— Several angiographic factors of dural arteriovenous fistulas (dAVFs) are associated with aggressive presentation and poor natural history. We examined the association of magnetic resonance imaging T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) hyperintensity with aggressive presentation. Methods— A cohort of dAVF patients from 2 centers was retrospectively examined. T2/FLAIR hyperintensity was determined by blinded, de-identified review and compared with angiographic grade and presenting symptoms. Results— T2/FLAIR hyperintensity was only identified in dAVF patients with cortical venous drainage (CVD). Among patients with CVD, those with T2/FLAIR hyperintensity were more likely to present with aggressive symptoms (20/23, 87.0%) than those without (6/21, 28.5%), P <0.001. All cured dAVFs with symptom resolution and available post-treatment imaging had resolution of T2/FLAIR hyperintensity. Conclusions— T2/FLAIR hyperintensity strongly correlates with aggressive presentation and CVD in dAVF patients, and may identify a subset that would benefit from early treatment.

AbstractThe meniscal ossicle is observed in clinical practice, yet there currently is limited information on its potential clinical significance. The purpose of this study was to assess the clinical presentation, imaging findings, and clinical treatment and outcomes of a series of patients identified as having a meniscal ossicle. An institutional database was reviewed to identify knees with a meniscal ossicle. Clinical presentation, magnetic resonance imaging (MRI), treatment, and outcomes were analyzed. Radiographs were graded using Kellgren–Lawrence (KL) scores. MRIs were reviewed for the presence and location of meniscal ossicles and additional knee pathology. Knee arthroplasty rates were recorded with the remaining patients contacted to obtain final International Knee Documentation Committee (IKDC) and Tegner's scores. Failure was defined as conversion to arthroplasty or failing IKDC score (< 75.4). Forty-five meniscal ossicles in 45 patients (26 males and 19 females) with a mean age of 51 years (standard deviation [SD] = 19.0) were included. Pain was the most common presenting symptom (89%). Forty-two patients (93%) had an associated meniscus root tear on MRI. Eighteen percent of patients that did not have an ossicle on initial imaging subsequently developed an ossicle. Mean KL grades progressed significantly from baseline of 1.84 (SD = 1.0) to 2.55 (SD = 0.93 p < 0.01) on final follow-up. Thirty-nine percent of baseline radiographs showed KL grades of less than 2 compared with only 15% of follow-up radiographs (p = 0.04). Mean IKDC score obtained for patients ≤ 60 at an average follow-up of 3.1 years (SD = 3.2) was 65.2 (SD = 19.0). Eight out of 45 patients (18%) had progressed to total knee arthroplasty (TKA) by latest available follow-up. Sixty-two percent of patients met failure criteria at latest available follow-up. The meniscal ossicle is most commonly found in the posterior horn or root of the medial meniscus and is highly suggestive to be sequelae of a posterior root tear. Therefore, the presence of a meniscal ossicle should alert the orthopaedic surgeon to the high likelihood of the patient having a meniscus root tear. These patients have shown to have poor clinical outcomes and worsening arthritis.

Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in United States with a 5-year survival rate of only 8%. Inherited predisposition plays an important role in PDAC risk. Rare, moderately to highly penetrant mutations in hereditary cancer and pancreatitis genes, identified in families with a high incidence of disease, account for a small fraction of cases. At the other end of the spectrum, common risk variants of low penetrance have been discovered through genome-wide association studies (GWAS). Currently, over 20 common PDAC risk signals have been identified through GWAS in populations of European ancestry. However, these loci explain only a small fraction of genetic heritability for PDAC, and the causal genes for the large majority of these are unknown. Most susceptibility alleles discovered through GWAS are located in noncoding regions of the genome and are likely to function through allele specific regulation of gene expression. Transcriptome-wide association studies integrate expression quantitative trait loci (eQTL) with GWAS data to discover genes whose cis-regulated expression is associated with complex traits. To identify novel susceptibility loci and likely causal genes, we applied this approach to PDAC. Firstly, we used two reference datasets generated from histologically normal pancreatic tissue samples from individuals of European ancestry, the DCEG/LTG (n=95) and Genotype-Tissue Expression (GTEx v7, n=174), to build robust predictors for gene expression (n=2,872-5,906; r2&gt;0.01), using 5 different models (Top1, Lasso, Enet, Blup and Bslmm) in FUSION and PrediXcan. Gene expression predictors (n=2,043-21,422) were also generated by Enet in 48 different tissues (n=74-421 samples) from 608 individuals of European ancestry (GTEx). We then applied these predictor models to PDAC GWAS summary statistics from 9,040 PC cases and 12,496 controls. We discovered 24 genes whose genetically predicted expression is significantly associated with PDAC risk (FDR &lt; 0.05), including 13 candidate genes at 10 novel loci (CELA3B, SMC2, SMC2-AS1, RP11-80H5.9, SMUG1, BTBD6, RCCD1, PNMT, CDK12, PGAP3, SUPT4H1, RP11-888D10.3 and PGPEP1) and 11 at 5 known risk loci (TERT, CLPTM1L, ZDHHC11B, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, BCAR1 and TMEM170A). Pathway enrichment analysis for genes differentially expressed in the top vs. bottom quartile of CELA3B expression highlighted higher expression of inflammatory and immune response genes in both the DCEG/LTG and GTEx pancreatic transcriptome datasets, indicating that low expression of this gene may be associated with an inflammatory state in the pancreas. Our findings showcase the utility of integrating multiple datasets to generate hypotheses and provide novel clues for the genetic mechanisms underlying pancreatic cancer risk. Citation Format: Jun Zhong, Ashley Jermusyk, Lang Wu, Jason W. Hoskins, Irene Collins, Mingfeng Zhang, Song Lei, Charles C. Chung, Tongwu Zhang, Wenming Xiao, Rachael Stolzenberg-Solomon, Alison P. Klein, Brian M. Wolpin, Xiao-Ou Shu, Stephen J. Chanock, Sara Olson, Nilanjan Chatterjee, Jill Smith, Jianxin Shi, Peter Kraft, Gloria M. Petersen, Wei Zheng, Laufey T. Amundadottir. Large-scale transcriptome-wide association study (TWAS) identifies novel candidate susceptibility genes for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1591.

Purpose of review Single-organ vasculitis of the peripheral nervous system (PNS) is often designated nonsystemic vasculitic neuropathy (NSVN). Several variants or subtypes have been distinguished, including migratory sensory neuropathy, postsurgical inflammatory neuropathy, diabetic radiculoplexus neuropathies, skin-nerve vasculitides, and, arguably, neuralgic amyotrophy. NSVN often presents as nondiabetic lumbosacral radiculoplexus neuropathy (LRPN). This review updates classification, clinical features, epidemiology, and imaging of these disorders. Recent findings A recent study showed the annual incidence of LRPN in Olmstead County, Minnesota to be 4.16/100 000:2.79/100 000 diabetic and 1.27/100 000 nondiabetic. This study was the first to determine the incidence or prevalence of any vasculitic neuropathy. In NSVN, ultrasonography shows multifocal enlargement of proximal and distal nerves. In neuralgic amyotrophy, MRI and ultrasound reveal multifocal enlargements and focal constrictions in nerves derived from the brachial plexus. Histopathology of these chronic lesions shows inflammation and rare vasculitis. Diffusion tensor imaging of tibial nerves in NSVN revealed decreased fractional anisotropy in one study. Summary Single-organ PNS vasculitides are the most common inflammatory neuropathies. Neuralgic amyotrophy might result from PNS vasculitis, but further study is necessary. The usefulness of focal nerve enlargements or constrictions in understanding pathological mechanisms, directing biopsies, and monitoring disease activity in NSVN should be further investigated.

Significance Statement Targeting plasma cells to reduce the risk of antibody-mediated rejection and decreased allograft survival due to anti-HLA donor-specific antibodies has not been explored in transplantation. After sensitizing eight rhesus macaques with two sequential mismatched skin allografts, the authors desensitized four with daratumumab (anti-CD38 mAb) and plerixafor (anti-CXCR4) before transplant. Compared with controls, the daratumumab-treated animals had significantly reduced donor-specific antibody levels and prolonged renal graft survival; however, this reduction was not maintained. Two patients treated with daratumumab—one with therapy-resistant acute kidney antibody-mediated rejection and a highly sensitized heart transplant candidate—exhibited a significant decrease in class 1 and 2 donor-specific antibodies that led to clinical improvement of antibody-mediated rejection and heart graft access. These findings suggest daratumumab merits investigation as a potential therapeutic strategy, although further research is needed. Background Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production. Methods To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant. Results The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P <0.05) and prolonged renal graft survival (28.0 days versus 5.2 days; P <0.01). However, the reduction in donor-specific antibodies was not maintained because all recipients demonstrated rapid rebound of antibodies, with profound T cell–mediated rejection. In the two clinical patients, a combined heart and kidney transplant recipient with refractory antibody-mediated rejection and a highly sensitized heart transplant candidate, we also observed a significant decrease in class 1 and 2 donor-specific antibodies that led to clinical improvement of antibody-mediated rejection and to heart graft access. Conclusions Targeting CD38 with daratumumab significantly reduced anti-HLA antibodies and anti-HLA donor-specific antibodies in a nonhuman primate model and in two transplant clinical cases before and after transplant. This supports investigation of daratumumab as a potential therapeutic strategy; however, further research is needed regarding its use for both antibody-mediated rejection and desensitization.

554 Background: HER2+ breast cancer (BC) is particularly common in young women. Genomic features of HER2+ tumors before and after H-based therapy have not been described in a population of young women and may point to clinically targetable mechanisms of resistance. Methods: From a large prospective cohort of women diagnosed with BC age ≤40 years, we identified those with HER2+ BC and tumor tissue available for sequencing before and after chemo+H. Whole exome sequencing (WES) was performed on each tumor and on germline DNA from blood. Tumor-normal pairs were analyzed for mutations and copy number (CN) changes. Evolutionary analysis was performed for patients with both pre- and post-treatment (tx) samples. Results: 22 women had successful WES samples from at least one timepoint; 13 of these had paired sequencing results both before and after chemo+H. For the majority of women, post-tx sample was following neoadjuvant chemo + H, though post-tx timepoint for other women represented locoregional or distant metastasis (Table). TP53 was the only gene that was significantly recurrently mutated in both pre- and post-tx samples. Comparison of matched pre-tx and post-tx samples demonstrated that large changes in HER2 CN over the course of tx were uncommon, only 2/13 pts had > 2-fold change in HER2 CN. Other clonal and subclonal genomic alterations were found to be acquired in the post-tx sample compared to the pre-tx sample. One patient acquired a putative activating mutation in ERBB2. Another patient acquired a clonal hotpsot mutation in TP53. MYC gene amplification was observed in 4 post-tx tumors. NOTCH2 alterations were found in post-tx biopsies from 2 different patients, and mutations in STIL were also found in post-tx biopsies from 2 patients, though the function of these mutations is not known. Conclusions: HER2+ breast tumors in young women display genomic evolution following tx with chemo+H. HER2 CN changes are uncommon, but we identified several genes that warrant exploration as potential mechanisms of resistance to therapy in this population.[Table: see text]

Abstract Background Young women are more likely than older women to present with higher stage breast cancer (BC) and may benefit to a greater extent from downstaging with neoadjuvant systemic treatment (NST). Young age is also associated with greater likelihood of pathologic complete response (pCR). Using a large prospective cohort of young women with BC, we investigated response to neoadjuvant therapy, eligibility for breast conserving surgery (BCS) pre- and post-NST, and surgical treatment. Methods The Young Women's Breast Cancer Study (YWS) is a multi-center cohort of women diagnosed with BC at age ≤40, that enrolled 1302 patients from 2006 to 2016. Disease characteristics and treatment information were obtained through medical record and central pathology review. Surgical recommendation before and after NST, conversion from BCS borderline/ineligible to BCS eligible, surgery, documented reasons for choosing mastectomy (MTX) among BCS eligible women, and final pathologic response were independently reviewed. Results Among 1302 women enrolled in YWS, 801 (62%) presented with unilateral stage I-III breast cancer and 317(40%) received NST. Median age was 36 years old (22-40). Pre-NST, 85/317 (27%) were BCS eligible, 49 (15%) were borderline, and 169 (53%) were not eligible (16 inflammatory breast cancer (IBC), 88 large tumor size /cosmetic, 48 diffuse calcifications, and 83 multicentricity). Among the 218 patients who were BCS ineligible/borderline pre-NST, 82 (38%) became eligible for BCS after NST. 4 patients who were BCS eligible pre-NST became ineligible. Of all patients eligible for BCS post-NST (n=163), 80 (49%) attempted BCS, 74 (93%) of whom were successful, and 83 (51%) chose MTX. Reasons for choosing MTX included: patient preference (38/83 (46%)), BRCA or TP53 mutation (31 (37%)), family history (3 (4%)), unknown (11 (13%)). On final pathology, 75 (24%) patients had pCR. Among patients who achieved a pCR, 48 (64%) underwent MTX, fewer than half (21/48 (44%)) were for anatomic indications (IBC, large tumor at diagnosis, diffuse calcifications, multicentric disease). Conclusion While NST doubled the proportion of young women eligible for BCS, nearly half chose MTX regardless of response to NST, mostly for personal preference or high-risk preventative reasons. These data highlight that surgical decision making among young women with breast cancer is often driven by factors beyond extent of disease and clinical response to therapy. Table 1.Clinical-pathologic characteristicsCharacteristicsNumber%Pre NST surgical recommendation BCS eligible8526.8Borderline4915.5BCS ineligible16953.3Unknown144.4Clinical Response Complete20263.7Partial9229.0Stable30.9Progressing72.2Unknown134.1Pathologic Response pCR (No invasive or DCIS)7524No pCR24276Post NST Surgical recommendation BCS eligible16351.4BCS ineligible14445.4Unknown103.2Attempted surgery BCS8025.2MTX23674.1Unknown20.6Final Surgery BCS7423.3MTX24176unknown20.6 Citation Format: Kim HJ, Dominici L, Rosenberg S, Pak LM, Poorvu PD, Ruddy K, Tamimi R, Schapira L, Come S, Peppercorn J, Borges V, Warner E, Vardeh H, Collins L, King T, Partridge A. Surgical treatment after neoadjuvant systemic therapy in young women with breast cancer: Results from a prospective cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-01.

Abstract Background: Synchronous bilateral breast cancer is rare, with reported incidence from 0.3-12%; the incidence and pattern of bilateral breast cancer among younger women is unknown. Here we report the incidence and phenotypes of bilateral breast cancer in women ≤40 years of age enrolled in the Young Women's Study (YWS) cohort. Methods: The YWS is a multi-center, prospective cohort study that enrolled women with newly diagnosed breast cancer at age ≤40 years from 2006-2016. Those with synchronous bilateral breast cancer (in-situ and/or invasive) formed our study cohort. Disease characteristics and treatment were obtained by medical record review. Central pathology review was performed to capture histologic features and categorize the tumor phenotype as either luminal A (hormone receptor (HR)+, HER2-, grade 1 or 2), luminal B (HR+, HER2+, or HER2- and grade 3), HER2-type (HR-, HER2+), or triple negative (TNC; HR/HER2-). Tumor phenotypes of bilateral breast cancers were compared and evaluated for concordance. Results: Among 1302 patients enrolled in the YWS, 20 (1.5%) patients presented with bilateral disease, with median age of diagnosis of 38 years (range 18-40). The majority of patients (13 (65%)) presented with unilateral symptoms and contralateral disease was identified on subsequent imaging. 12 (60%) reported a positive family history of breast cancer and 17 (85%) underwent genetic testing; resulting in the identification of 6 mutation carriers (2 BRCA1, 3 BRCA2, 1 TP53). The majority of patients (15 (75%)) underwent bilateral mastectomy, 1 underwent unilateral mastectomy with contralateral lumpectomy, and 4 underwent bilateral lumpectomy. On pathology, 2 patients had bilateral in-situ disease, 5 had unilateral invasive and contralateral in-situ disease, and 13 had bilateral invasive disease. Of those with bilateral invasive disease, all had concordant tumor histology (92% ductal, 8% ductal and lobular), 10 (77%) patients had bilateral luminal tumors and when fully characterized 6 were of the same luminal type. Only one patient had bilateral basal-like breast cancer. Patient ID ERPRHer2 amplifiedGradePhenotype1Left++-2Luminal A Right++-3Luminal B3Left++-3Luminal B Right++-3Luminal B6Left++-3Luminal B Right++-3Luminal B9Left++-2Luminal A Right++-2Luminal A10Left+++3Luminal B Right++-2Luminal A12Left+--3Luminal B Right+--2Luminal A13Left---NABasal-like Right++-NALuminal A or B14Left+++2Luminal B Right++-3Luminal B15Left++-3Luminal B Right+++3Luminal B16Left+++3Luminal B Right--+NAHEr2-type17Left---3Basal-like Right---3Basal-like19Left++-2Luminal A Right++-3Luminal B20Left++-1Luminal A Right++-2Luminal A Conclusions: Among a large cohort of young women, only 20 (1.5%) had bilateral disease, and the majority of the invasive tumors were of the luminal phenotype, yet frequently differed by grade or HER2 status; supporting the need for thorough pathologic evaluation of bilateral disease to determine risk and tailor treatment. Overall the low incidence of bilateral disease and preponderance of the luminal phenotype in this population is reassuring. Citation Format: Pak LM, Rosenberg SM, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Snow C, Collins L, King TA, Partridge AH. Tumor phenotype and concordance in synchronous bilateral breast cancer in young women [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-22-03.

Abstract Background: The 21-gene Recurrence Score (RS) assay is prognostic among women with early-stage estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC) and is used to select patients for chemotherapy (CT). Young women (age &lt;40) have represented a minority in studies evaluating gene expression assays, including TAILORx, and additional data in young women are needed. Methods: In the Young Women's Breast Cancer Study, a prospective cohort study of women diagnosed with BC at age &lt;40 enrolling between 2006-2016 (N=1302), we identified those with stage I-III ER+/HER2- BC. Disease and treatment information were obtained through serial surveys and medical record review. The RS was performed on banked specimens for those not tested clinically. Distant recurrence free interval (DRFI), defined as distant recurrence or BC specific death, by risk group was assessed using Cox regression and Kaplan-Meier survival estimates. Outcomes by receipt of CT were explored in the RS 11-25 group, and due to small number of events, reported descriptively. Results: Among eligible women (N=577), 189 (33%) had undergone RS testing and 320 (56%) had banked specimens sufficient for testing. Median follow-up was 6 years. Median age at diagnosis was 37, most had N0 BC (300/509, 59%), and the majority had RS 11-25 (306/509, 60%). RS result was significantly associated with DRFI in N0 BC, with hazard ratio (HR) (95% CI) of 0.29 (0.07,1.30) and 0.21 (0.09,0.50) for RS&lt;11 and RS 11-25, respectively, relative to RS&gt;26 (and trended towards significance in N1 BC). Results were similar using conventional RS groups. Among women with N0 BC and RS 11-25, 44% received CT, with two events in the 86 receiving CT (2.3%) and 6 events in the 109 without CT (5.5%); 5/8 (63%) occurred in those with RS 20-25. Table 1 N0N1Total Cohort N%N%N% 3005916332509100Median Age37.137.537.2Tumor Stage T120869694229358T28227784817635T3103159357T4001151Grade I4716855711II16555794926652III8829754618536Not assessed 1 1 PR status by IHC Negative (&lt;1%)2071710398Positive (&gt;=1%)280931469047092Chemotherapy No1414712715430Yes159531519335570Ovarian Suppression No263881499145289Yes37121495711TAILORx RS Groups RS &lt;1133111495411RS 11-2519565885430660RS &gt;=267224613714929Conventional RS Groups RS &lt;1812742543319939RS 18-3012542694221142RS &gt;=31481640259919 Table 2 6-year freedom from distant recurrence or breast cancer deathDRFI HR (95% CI) N0N1N0N1TAILORx RS Groups RS &lt;1194.4%92.3%0.29 (0.07,1.30)0.21 (0.03,1.61)RS 11-2596.9%85.2%0.21 (0.09, 0.50)0.55 (0.27,1.12)RS &gt;=2685.1%71.3%RefRefConventional RS Groups RS &lt;1897.5%85.9%0.19 (0.06,0.59)0.31 (0.13,0.74)RS 18-3093.1%87.3%0.39 (0.16,1.00)0.32 (0.14,0.73)RS &gt;=3186.4%62.8%RefRef Conclusions: The RS is prognostic among young women with node-negative and node-positive BC, and is a valuable tool for risk stratification. Disease outcomes among young women with N0 disease and RS 11-25, a minority of whom received CT, are very good. Evaluation of the effect of ovarian suppression/CT-induced amenorrhea by RS/treatment strata is ongoing. Citation Format: Poorvu PD, Gelber SI, Rosenberg SM, Ruddy KJ, Tamimi RM, Collins LC, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Jakubowski DM, Russell C, Winer EP, Partridge AH. Prognostic impact of the 21-gene recurrence score assay among young women with node-negative and node-positive ER+/HER2- breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-07.

Abstract Background: This analysis aimed to determine if associations of prediagnostic mammographic percent breast density, absolute dense area, and absolute non-dense area and risk of breast cancer vary according to the subsequent breast tumors biomarker status. Methods: We included 1,154 postmenopausal women diagnosed with breast cancer between June 1, 1989, and June 30, 2004, and 2,078 matched controls from the Nurses' Health Study I and II. Percent breast density, absolute dense and non-dense areas were estimated from digitized film mammograms using computer assisted thresholding techniques. Density measures were modeled as quartiles. Information on estrogen receptor (ESR1 [ER]), progesterone receptor (PGR [PR]), and human epidermal growth factor receptor 2 (ERBB2 [HER2]) status was obtained from pathology reports and medical records, and if missing, from immunostains performed on paraffin sections of tumor tissue microarrays (TMAs). Other biomarkers assessed on TMAs were androgen receptor (AR), cytokines 5/6 (KRT5/KRT6 [CK5/6]), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGFA [VEGF]), and cyclooxygenase 2 (PTGS2 [COX2]). Information on breast cancer risk factors was obtained prospectively from biennial questionnaires before the date of cancer diagnosis for cases and matched controls. Polychotomous logistic regression was used to assess associations of the three breast density measures with tumor subtypes based on the status of selected tissue markers. Results: Breast cancer risk was positively associated with percent density and absolute dense area and inversely associated with absolute non-dense area (p for trend&lt;0.0001 for all). The associations of percent density with breast cancer risk did not statistically significantly differ by the status of any of the markers. However, we found stronger positive associations for absolute dense area and KRT5/KRT6- and EGFR- tumors as compared to respective marker-positive tumors (4th vs. 1st quartile: OR=2.99 for KRT5/KRT6- vs. OR=0.92 for KRT5/KRT6+ tumors, p-heterogeneity &lt;0.001; OR=3.06 for EGFR- vs. OR=1.08 for EGFR+ tumors, p-heterogeneity=0.001). Stronger inverse associations of absolute non-dense area with breast cancer risk were found for ESR1- as compared to ESR1+ tumors, and for AR+, KRT5/KRT6+, and EGFR+ tumors as compared to respective marker-negative tumors (4th vs. 1st quartile: OR=0.21 for ESR1- vs. OR=0.59 for ESR1+ tumors, p-heterogeneity &lt;0.0001; OR=0.22 for AR+ vs. OR=0.42 for AR- tumors, p-heterogeneity=0.04; OR=0.21 for KRT5/KRT6+ vs. OR=1.14 for KRT5/KRT6- tumors, p-heterogeneity&lt;0.01; OR=0.37 for EGFR+ vs. OR=1.11 for EGFR- tumors, p-heterogeneity&lt;0.01). There were no differences in associations of the density measures with breast cancer by status of other markers evaluated. Conclusions: The findings suggest that some mammographic density measures are differentially associated with the risk of subsequent breast tumor subtypes. Citation Format: Lusine Yaghjyan, Andreas Pettersson, Graham Colditz, Laura Collins, Stuart Schnitt, Andrew Beck, Bernard Rosner, Celine Vachon, Rulla Tamimi. Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to the status of selected tissue markers: A case-control study. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PR09.