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315 citation(s) found for "Vachon, CM".

Abstract P6-05-38: Breast Density Notification: Impact on anxiety, breast cancer worry, and self-perceived risk among Latinas at a federally qualified medical center
Ghosh, Karthik, Jenkins, Sarah M. , Rhodes, Deborah J. , Ramos, Edna P., Jewett, Matt, Gonzalez, Crystal, Hernandez, Valentina, Vachon, Celine M. , Ridgeway, Jennifer L. , Austin, Jessica D. , Borah, Bijan J. , Patel, Bhavika , Norman, Aaron D. , Singh, Davinder , Suman, Vera J. , Vachon, Celine M.

Cancer Research | March 2, 2023 | Volume: 83 | Issue: 5_Supplement | Pages: P6-05-38-P6-05-38

10.1158/1538-7445.sabcs22-p6-05-38 Get It

Abstract Mammographic breast density (MBD) has been shown to be a strong, independent risk factor for breast cancer (BC) irrespective of race/ethnicity. Given the risk association of MBD and its potential to mask tumors on a mammogram, state and federal laws have mandated that women receive information regarding their personal MBD in their mammography reports. However, concerns have been raised regarding the impact of MBD notification on patient anxiety, especially written information for women who experience health disparities such as racial/ethnic minorities, lower health literacy, limited English proficiency and lower socioeconomic status. We performed a randomized controlled clinical trial to examine the impact of three different written and interpersonal approaches to MBD notification on patient anxiety, BC worry, and self-perceived BC risk, among Latinas receiving routine mammography screening at a federally qualified medical center (FQHC). We hypothesized that interpersonal education would reduce anxiety and worry, relative to the written notifications alone. The study was performed at the Baseline Clinic of Mountain Park Health Center, a FQHC in Phoenix, AZ. Women between ages 40 and 74 years presenting for screening mammogram were eligible. After providing signed informed consent, participants were randomized equally to usual care (UC- mailed notification letter); enhanced care (notification letter and MBD educational brochure designed for this study): interpersonal care (notification letter, brochure, promotora education via telephone). A stratified block randomization procedure was used with age > 50 years (yes vs no), ethnicity (Hispanic vs non-Hispanic), and language preference (Spanish vs. English) as strata. Study participants completed surveys at the time of enrollment/pre-intervention (T0), at two weeks to six months after intervention was delivered (T1), and about one year after randomization (T2). Anxiety state was measured using the state anxiety subscale of the State-Trait Anxiety Inventory scale (STAI-S) (range from 20-80). BC worry was probed using the question: “How frequently do you worry about getting breast cancer someday”. The self-perceived lifetime risk of BC was rated between 0% (no chance of BC) to 100% (definitely will get BC). The proportion of participants with an increase or persistence of higher level for each outcome between time points was compared between the three study groups. The study was approved by the Mayo Clinic Institutional Review Board. 1332 Latina women were enrolled and randomized between October 2016 and October 2019. All completed the baseline (T0) survey, 928 completed T1, 632 completed T2, and 516 completed both T1 and T2 surveys. At study entry, majority of the participants were young (64.1% between age 40-49 years), had no family history of breast cancer (81.0%), had less than high school education (68.8%), and were married or partnered (67.8%). At T0, the mean (SD) anxiety STAI score was 32.5 (11.1); 51.8% with moderate or severe anxiety (score > 30). With regard to BC worry, 41.3% reported worrying “sometimes”, “often”, or “almost all the time”. Further, 25.4% reported a self-perceived lifetime risk of developing BC of >10% while only 6.6% had a Gail model estimated lifetime risk score of >10%. There was no significant difference in changes in anxiety, BC worry or self-perceived risk from T0 to either T1 or T2 surveys between the intervention groups. In summary, this study found high levels of baseline anxiety and BC worry (despite the majority being 40-49 years old and having no family history of BC) which persisted regardless of how notification and education were delivered. Future work is needed to improve the understanding of factors that could lower anxiety and BC worry and improve risk perception in this population. Citation Format: Karthik Ghosh, Sarah Jenkins, Jennifer Ridgeway, Jessica D. Austin, Bijan Borah, Bhavika K. Patel, Deborah Rhodes, Aaron Norman, Edna P. Ramos, Matt Jewett, Crystal Gonzalez, Valentina Hernandez, Davinder Singh, Vera Suman, Celine Vachon. Breast Density Notification: Impact on anxiety, breast cancer worry, and self-perceived risk among Latinas at a federally qualified medical center. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-38.
Abstract GS4-06: Radiomic phenotypes of breast texture and association with breast cancer risk and masking
Pantalone, Lauren , Jensen, Matthew L. , Cohen, Eric A. , Brandt, Kathleen R. , Vachon, Celine M. , Winham, Stacey J. , McCarthy, Anne Marie , Gastounioti, Aimilia , Scott, Christopher G. , Norman, Aaron D. , Mankowski, Walter C. , Jensen, Matthew, Horng, Hannah , Conant, Emily F. , Kerlikowske, Karla , Kontos, Despina , Vachon, Celine M.

Cancer Research | March 2, 2023 | Volume: 83 | Issue: 5_Supplement | Pages: GS4-06-GS4-06

10.1158/1538-7445.sabcs22-gs4-06 Get It

Abstract Breast parenchymal patterns on radiologic images are associated with breast cancer risk. Radiomic features have been proposed as quantitative measures of parenchymal patterns. We defined intrinsic imaging phenotypes of breast parenchymal patterns based on radiomic features extracted from full field digital mammography (FFDM) in breast screening populations and assessed whether these phenotypes are associated with breast cancer risk and masking. We selected 30,000 women with 4-view FFDM exams from Hologic machines from three institutions (Hospital of the University of Pennsylvania, Mayo Clinic, and San Francisco Mammography Registry), randomly split into a training (20,000 women) and test set (10,000 women). In total, 390 radiomic features were automatically extracted from each image using a validated software pipeline, standardized, and adjusted for site differences using ComBat. We used two methods, hierarchical clustering and Principal Components (PCs) analysis, to classify significant variation among the features in the training set and replicate among the test set. Next, we applied the replicated clusters and PCs to an independent nested case-control set [1082 invasive breast cancer (BC) cases (of which 151 were Black and 893 White women, 38 other race) matched to 2837 controls (411 Black and 2345 White women, 81 other race) on age, race, timing of images, and site]. We examined associations of the clusters and PCs with invasive breast cancer risk, as well as masking [defined as a false-negative (FN) screen (124 cases and 319 matched controls) and additionally the subset with symptomatic interval cancer (IC) within 12 months of negative screen (88 cases and 223 matched controls)] using conditional logistic regression. We evaluated their association with breast cancer alone, and with adjustment for age, body mass index (BMI) and breast density assessed by Breast Imaging Reporting and Data System (BI-RADS) using likelihood ratio tests. We estimated discrimination using area under the curve (AUC) and compared AUCs for models that included the radiomic clusters and PCs with the model that included only age, BMI and density. We also stratified analyses by race (Black/White). From hierarchical clustering, we defined six statistically significant phenotype clusters (each of at least 1000 women) in the training set which were replicated in the test set. For PC Analysis, we identified six PCs in the training set, explaining 85% of the variation in texture features and reproduced these in the test set. The six radiomic phenotype clusters (P< 0.001) and six PCs (P< 0.001) were both associated with invasive BC, including after adjusting for age, BMI, and density (cluster P=0.004; PCs P< 0.001). Improvements in discrimination of invasive BC with inclusion of PCs or clusters were more pronounced among Black women (Table). Further, the PCs (P< 0.001) and clusters (P< 0.001) were significantly associated with FN overall and for symptomatic IC (PCs P< 0.001; clusters P=0.001), but only PCs remained significant after adjusting for age, BMI and density (PCs P=0.004 for FN; PCs P=0.007 for symptomatic IC). Discrimination of masking also improved with inclusion of both clusters and PCs (Table). We identified reproducible radiomic phenotypes that are associated with invasive BC risk, above and beyond breast density with the strongest associations for invasive BC among Black women and symptomatic interval cancers. Citation Format: Stacey Winham, Anne Marie McCarthy, Aimilia Gastounioti, Christopher Scott, Aaron Norman, Walter C. Mankowski, Lauren Pantalone, Matthew Jensen, Eric A. Cohen, Hannah Horng, Kathleen Brandt, Emily F. Conant, Karla Kerlikowske, Despina Kontos, Celine Vachon. Radiomic phenotypes of breast texture and association with breast cancer risk and masking [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-06.
Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival
Morra, Anna , Andrulis, Irene L. , Beckmann, Matthias W. , Bolla, Manjeet K. , Camp, Nicola J. , Cessna, Melissa H., Chang‐Claude, Jenny , Collaborators, NBCS, Daly, Mary B., Easton, Douglas F. , Eccles, Diana M., Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, García‐Closas, Montserrat , Gündert, Melanie , Hahnen, Eric , Haiman, Christopher A. , Hamann, Ute, Harrington, Patricia, Hoppe, Reiner , Howell, Anthony , Investigators, ABCTB, Investigators, kConFab, Janni, Wolfgang, Johnson, Nichola , Kristensen, Vessela N. , Lindblom, Annika , Mannermaa, Arto , Mavroudis, Dimitrios, Nevelsteen, Ines, Neven, Patrick , Obi, Nadia , Offit, Kenneth , Park‐Simon, Tjoung‐Won , Patel, Alpa V. , Phillips, Kelly‐Anne , Plaseska-Karanfilska, Dijana, Rack, Brigitte , Rhenius, Valerie , Sawyer, Elinor J. , Schmutzler, Rita K. , Schuetze, Sabine, Shah, Mitul , Smichkoska, Snezhana , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Vachon, Celine M. , Veen, Elke M. van , Wang, Qin , Wendt, Camilla, Wildiers, Hans , Adank, Muriel A. , Hooning, Maartje J. , Eccles, Diana , Plaseska‐Karanfilska, Dijana , Eccles, Diana , Evans, D Gareth , García-Closas, Montserrat , Phillips, Kelly-Anne , Wildiers, Hans , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Schreurs, Maartje A. C. , Anton‐Culver, Hoda , Augustinsson, Annelie , Behrens, Sabine , Bojesen, Stig E. , Brauch, Hiltrud , Broeks, Annegien , Buys, Saundra S. , Castelao, Jose E. , Chung, Wendy K. , Colonna, Sarah V. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Dennis, Joe , Devilee, Peter , Dörk, Thilo , Dunning, Alison M. , Dwek, Miriam , Eriksson, Mikael , Fehm, Tanja , Figueroa, Jonine D. , Gabrielson, Marike , Gago-Domínguez, Manuela , García-Sáenz, José Á. , Genkinger, Jeanine M. , Graßmann, Felix , Hartikainen, Jaana M. , Hopper, John L. , Houlston, Richard S. , Jakubowska, Anna , Jernström, Helena , John, Esther M. , Jones, Michael E. , Kurian, Allison W. , Lambrechts, Diether , Marchand, Loı̈c Le , Lubiński, Jan , Lux, Michael P. , Mulligan, Anna Marie , Muranen, Taru , Nevanlinna, Heli , Newman, William G. , Olshan, Andrew F. , Peterlongo, Paolo , Polley, Eric C. , Presneau, Nadège , Pylkäs, Katri , Radice, Paolo , Rashid, Muhammad Usman , Robson, Mark E. , Romero, Atocha , Saloustros, Emmanouil , Scott, Christopher, Southey, Melissa C. , Tapper, William , Teras, Lauren R. , Tomczyk, Katarzyna , Troester, Melissa A. , Vachon, Celine M. , Winqvist, Robert , Ziogas, Argyrios , Hall, Per N , Pharoah, Paul D.P. , Hollestelle, Antoinette , Schmidt, Marjanka K.

No container title available | February 13, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-2569372/v1 | PMID 36824750 Get It

Abstract Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR(95%CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR(95%CI) :1.30 (1.09–1.56)]. In conclusion, systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. (Main MS: 3201 words)
Abstract P070: Volumetric parenchymal pattern analysis for breast cancer risk estimation
Cohen, Eric A. , Pantalone, Lauren , Mankowski, Walter C. , Nguyen, Alex Anh-Tu, Vachon, Celine M, Mankowski, Walter C , Maghsoudi, Omid Haji , Acciavatti, Raymond J. , Scott, Christopher G. , Winham, Stacey J. , Maidment, Andrew D. A. , McCarthy, Anne Marie , Conant, Emily F. , Kontos, Despina

Cancer Prevention Research | January 4, 2023 | Volume: 16 | Issue: 1_Supplement | Pages: P070-P070

10.1158/1940-6215.precprev22-p070 Get It

Abstract Introduction: Mammographic breast density is among the strongest risk factors for breast cancer. However, breast density is typically assessed subjectively by the radiologist according to the Breast Imaging Reporting and Data System (BI-RADS) based on 2 dimensional (2D) digital mammography (DM) images. Digital breast tomosynthesis (DBT) is quickly replacing DM and allows more detailed volumetric imaging of the breast. Advances in radiomics, the high-throughput extraction of radiologic features, has enabled characterization of breast parenchymal complexity beyond breast density alone. The purpose of this study was to compare the performance of volumetric parenchymal pattern analysis from DBT and DM with conventional breast density measurement with respect to breast cancer risk estimation. Methods: We performed a case control study among women with concurrent DM and DBT screening (Selenia Dimensions, Hologic Inc.) at our institution between 3/2011-12/2014. Cases were diagnosed with breast cancer within 1 year of screening; controls were confirmed negative or benign at 1 year follow-up, matched on race (Black, White, other/unknown) and age (5-year bins). After exclusions for imaging artifacts, craniocaudal (CC) and mediolateral oblique (MLO) views for 187 cases and 737 controls, in six image formats were assessed: 1) raw (“FOR PROCESSING”) DM; 2) processed (“FOR PRESENTATION”) DM; 3) raw DBT central projection; 4) processed DBT central projection; 5) DBT central reconstructed slice; and 6) DBT reconstructed stack. For cases, we analyzed the breast contralateral to cancer diagnosis; for controls the same breast as the matched case. We extracted radiomic features using a lattice-based approach with the publicly available CaPTk software, averaging features for each breast over CC and MLO views. We examined 3 lattice window sizes (6.4, 12.8, and 25.6 mm) and 23 resolutions for image resampling (0.075 - 2mm). We performed PCA on the resulting 487 features for each combination of window size and resolution and built conditional logistic regression models to assess the association of the first 7 principal components with breast cancer, with models including age, BMI, and BI-RADS density. For each image type we calculated the model C-statistic at all window sizes and resolutions, for a total of 2304 experimental conditions. Results: Features from reconstructed DBT scans had on average higher C-statistics across all experimental conditions. A model using only age, BMI, and BI-RADS density had a C-statistic of 0.61. Models using radiomic features plus age, BMI, and BI-RADS density had mean C-statistic of 0.68 (IQR 0.68, 0.69) for reconstructed DBT scans; for all other image types, the mean C-statistic ranged from 0.64 to 0.66. Conclusions: Incorporating volumetric breast parenchymal patterns from DBT improves breast cancer risk estimation beyond markers derived from DM and beyond conventional BI-RADS density. Citation Format: Eric A. Cohen, Omid Haji Maghsoudi, Raymond Acciavatti, Lauren Pantalone, Walter Mankowski, Alex A Nguyen, Christopher G. Scott, Stacey Winham, Andrew D. Maidment, Anne Marie McCarthy, Celine M Vachon, Emily F Conant, Despina Kontos. Volumetric parenchymal pattern analysis for breast cancer risk estimation. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P070.
Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort
Sherman, Mark E. , Vierkant, Robert A. , Masters, Matthew , Radisky, Derek C. , Winham, Stacey J. , Degnim, Amy C. , Vachon, Celine M. , Patel, Alpa V. , Teras, Lauren R. , Winham, Stacey J , Degnim, Amy C , Vierkant, Robert A , Teras, Lauren R , Sherman, Mark E , Radisky, Derek C , Vachon, Celine M.

Cancer Prevention Research | January 3, 2023 | Volume: 16 | Issue: 3 | Pages: 175-184

10.1158/1940-6207.capr-22-0403 | PMID 36596665 Get It

Abstract Nonsteroidal anti-inflammatory agents (NSAID) are associated with modest inconsistent reductions in breast cancer risk in population-based cohorts, whereas two focused studies of patients with benign breast disease (BBD) have found lower risk with NSAID use. Given that BBD includes fibroinflammatory lesions linked to elevated breast cancer risk, we assessed whether NSAID use was associated with lower breast cancer risk among patients with BBD. Participants were postmenopausal women in the Cancer Prevention Study-II (CPS-II), a prospective study of cancer incidence and mortality, who completed follow-up surveys in 1997 with follow-up through June 30, 2015. History of BBD, NSAID use, and covariate data were updated biennially. This analysis included 23,615 patients with BBD and 36,751 patients with non-BBD, including 3,896 incident breast cancers over an average of 12.72 years of follow-up among participants. NSAID use, overall and by formulation, recency, duration, and pills per month was analyzed versus breast cancer risk overall and by BBD status using multivariable-adjusted Cox models; BBD status and NSAID use were modeled as time-dependent exposures. Patients with BBD who reported using NSAIDs experienced lower breast cancer risk (HR, 0.87; 95% CI, 0.78–0.97), with similar effects for estrogen receptor (ER)-positive breast cancers [HR, 0.85; 95% confidence interval (CI), 0.74–0.97] and ER-negative breast cancers (HR, 0.87; 95% CI, 0.59–1.29); among women without BBD, NSAID use was unrelated to risk (HR, 1.02; 95% CI, 0.92–1.13; Pinteraction = 0.04). Associations stratified by age, obesity, menopausal hormone use, and cardiovascular disease were similar. Among patients with BBD, NSAID use appears linked to lower breast cancer risk. Further studies to assess the value of NSAID use among patients with BBD are warranted. Prevention Relevance: We examined whether NSAID use, a modifiable exposure, is associated with breast cancer risk in postmenopausal women from the Cancer Prevention Study-II with self-reported benign breast disease, an often inflammatory condition associated with higher rates of breast cancer.
Abstract A003: Risks of ductal carcinoma in situ of the breast associated with pathogenic variants in cancer predisposition genes
Couch, Ronan E. , LaDuca, Holly , Goldgar, David E. , Pesaran, Tina , Dolinsky, Jill S. , Teras, Lauren R., Patel, Alpa V. , Ruddy, Kathryn J. , Vachon, Celine M. , Yao, Song, Huang, Huaizhi , Yadav, Siddhartha , Polley, Eric C. , Boddicker, Nicholas , Na, Jie , Gnanaolivu, Rohan , Hart, Steven N. , Palmer, Julie R. , Teras, Lauren R. , Olson, Janet E. , Vachon, Celine M. , Kraft, Peter , Yao, Song , Trentham‐Dietz, Amy , Nathanson, Katherine L. , Weitzel, Jeffrey N. , Domchek, Susan M. , Couch, Fergus J. , Hu, Chunling

Cancer Prevention Research | December 1, 2022 | Volume: 15 | Issue: 12_Supplement_1 | Pages: A003-A003

10.1158/1940-6215.dcis22-a003 Get It

Abstract Introduction: The relationship between germline pathogenic variants (PVs) in cancer predisposition genes and ductal carcinoma in situ (DCIS) is not well established. The objective of this study is to determine the risks of DCIS and contralateral breast cancer among women with DCIS associated with germline PVs in cancer predisposition genes. Methods: Associations between pathogenic variants in 11 cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MSH6, PALB2, RAD51C, and RAD51D) and DCIS were determined in case control analyses of a population-based cohort of 3876 women with DCIS and age-matched unaffected women, and in a clinical cohort of 9887 DCIS cases undergoing clinical genetic testing at Ambry Genetics and unaffected reference controls. The incidence of contralateral breast cancer risk in BRCA1, BRCA2, and PALB2 PV carriers with DCIS was also evaluated in a time-to-event analysis. Results: The mean age at diagnosis of DCIS was 50 years in the clinical testing cohort and 59 years in the population-based cohort. The frequency of PVs in 11 predisposition genes among DCIS cases was 6.9% in the clinical testing cohort and 4.9% in the population-based cohort. PVs in ATM, BRCA1, BRCA2, CHEK2, MSH6, PALB2, and RAD51D were associated with significantly increased risks (Odds Ratio (OR) >2) of DCIS in the clinical testing cohort whereas only PVs in BRCA1, CHEK2, PALB2, and ATM were associated with significantly increased risks of DCIS in the population-based cohort. The cumulative incidence of contralateral breast cancer among BRCA1, BRCA2, and PALB2 PV carriers with DCIS was 11% in 5-years and 20% in 15-years. Conclusions: This study provides new insights into PVs that predispose to DCIS. In addition, it establishes an increased risk of contralateral breast cancer risk among women with DCIS who are carriers of PVs in BRCA1, BRCA2, or PALB2. These findings will guide surveillance and risk reducing strategies in germline PV carriers with DCIS. Citation Format: Huaizhi Huang, Ronan E. Couch, Holly LaDuca, Siddhartha Yadav, Eric C. Polley, Nicholas J. Boddicker, Jie Na, Rohan D. Gnanaolivu, David E. Goldgar, Tina Pesaran, Steven N. Hart, Jill S. Dolinsky, Julie R. Palmer, Lauren Teras, Alpa V. Patel, Kathryn J. Ruddy, Janet E. Olson, Celine M. Vachon, Peter Kraft, Song Yao, Amy Trentham-Dietz, Katherine L. Nathanson, Jeffrey N. Weitzel, Susan M. Domchek, Fergus J. Couch, Chunling Hu. Risks of ductal carcinoma in situ of the breast associated with pathogenic variants in cancer predisposition genes [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A003.
A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk
Dicanio, Marco, Giaccherini, Matteo , Clay‐Gilmour, Alyssa , Macauda, Angelica , Sáinz, Juan , Machiela, Mitchell J. , Rybicka‐Ramos, Malwina, Barington, Torben , Kumar, Shaji , Bhatti, Parveen , Brown, Elizabeth E. , Haastrup, Eva, Orlowski, Robert Z. , Dudziński, Marek , García‐Sánz, Ramón , Kruszewski, Marcin , Martínez‐López, Joaquín , Beider, Katia , Iskierka‐Jazdzewska, Elżbieta , Pelosini, Matteo , Berndt, Sonja I. , Raźny, Małgorzata , Collado, Pilar, Petrini, Mario , Butrym, Aleksandra , Ziv, Elad , Andersen, Niels Frost, Mazur, Grzegorz , Wątek, Marzena , Zawirska, Daria , Ebbesen, Lene Hyldahl, Gemignani, Federica , Várkonyi, Judit , Buda, Gabriele , Nagler, Arnon, Druzd‐Sitek, Agnieszka , Wu, Xifeng , Kádár, Katalin , Camp, Nicola J. , Grząśko, Norbert , Waller, Rosalie, Vachon, Celine M. , Campa, Daniele , Martinez-Lopez, Joaquin , Waller, Rosalie G. , Griffin, R. L. , Beider, Katia , Lesueur, Fabienne , Hildebrandt, Michelle A T , Vachon, Celine, Campa, Daniele , Orlowski, Robert Z. , Martinez-Lopez, Joaquin , Butrym, Aleksandra , Garcia-Sanz, Ramon , Bhatti, Parveen , Ziv, Elad , Waller, Rosalie G , Machiela, Mitchell J , Sainz, Juan , Watek, Marzena , Iskierka-Jazdzewska, Elżbieta , Martinez-Lopez, Joaquin , Mazur, Grzegorz , Giaccherini, Matteo , Griffin, Rosalie , Norman, Aaron D. , Tyczyńska, Agata , Chanock, Stephen Jacob , Cozen, Wendy , Suska, Anna , Jamroziak, Krzysztof , Rajkumar, S. Vincent , Jurczyszyn, Artur , Vangsted, Annette Juul , Collado, Pilar Garrido, Vogel, Ulla , Hofmann, Jonathan N. , Slager, Susan L. , Subocz, Edyta , Giles, Graham G. , Lesueur, Fabienne , Hildebrandt, Michelle A.T. , Marques, Herlander , Dumontet, Charles , Nagler, Arnon , Vachon, Celine M. , Canzian, Federico

International Journal of Cancer | September 9, 2022 | Volume: 152 | Issue: 2 | Pages: 239-248

10.1002/ijc.34278 | PMID 36082445 Get It

AbstractPleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome‐wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10−8) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4‐rs34517439‐A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13‐1.32, P = 4.81 × 10−7). rs34517439‐A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA‐binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4‐rs34517439 as a potentially novel MM risk locus.
Progression and survival of MBL: a screening study of 10 139 individuals
Slager, Susan L. , Parikh, Sameer A. , Achenbach, Sara J., Rabe, Kari G. , Boddicker, Nicholas , Kleinstern, Geffen , Lesnick, Connie , Call, Timothy G. , Vachon, Celine M. , Braggio, Esteban , Hanson, Curtis A. , Shanafelt, Tait D. , Chaffee, Kari G. , Boddicker, Nicholas J , Lesnick, Connie E, Cerhan, James R , Vachon, Celine M. , Kay, Neil E , Braggio, Esteban , Parikh, Sameer A , Shanafelt, Tait D , Slager, Susan L , Norman, Aaron D. , Olson, Janet E. , Cerhan, James R. , Kay, Neil E.

Blood | August 15, 2022 | Volume: 140 | Issue: 15 | Pages: 1702-1709

10.1182/blood.2022016279 | PMID 35969843 Get It

Abstract Monoclonal B-cell lymphocytosis (MBL) is a common hematological premalignant condition that is understudied in screening cohorts. MBL can be classified into low-count (LC) and high-count (HC) types based on the size of the B-cell clone. Using the Mayo Clinic Biobank, we screened for MBL and evaluated its association with future hematologic malignancy and overall survival (OS). We had a two-stage study design including discovery and validation cohorts. We screened for MBL using an eight-color flow-cytometry assay. Medical records were abstracted for hematological cancers and death. We used Cox regression to evaluate associations and estimate hazard ratios and 95% confidence intervals (CIs), adjusting for age and sex. We identified 1712 (17%) individuals with MBL (95% LC-MBL), and the median follow-up time for OS was 34.4 months with 621 individuals who died. We did not observe an association with OS among individuals with LC-MBL (P = .78) but did among HC-MBL (hazard ratio, 1.8; 95% CI, 1.1-3.1; P = .03). Among the discovery cohort with a median of 10.0 years follow-up, 31 individuals developed hematological cancers with two-thirds being lymphoid malignancies. MBL was associated with 3.6-fold risk of hematological cancer compared to controls (95% CI, 1.7-7.7; P &lt; .001) and 7.7-fold increased risk for lymphoid malignancies (95% CI:3.1-19.2; P &lt; .001). LC-MBL was associated with 4.3-fold risk of lymphoid malignancies (95% CI, 1.4-12.7; P = .009); HC-MBL had a 74-fold increased risk (95% CI, 22-246; P &lt; .001). In this large screening cohort, we observed similar survival among individuals with and without LC-MBL, yet individuals with LC-MBL have a fourfold increased risk of lymphoid malignancies. Accumulating evidence indicates that there are clinical consequences to LC-MBL, a condition that affects 8 to 10 million adults in the United States.
Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies
Jung, Audrey , Ahearn, Thomas U. , Behrens, Sabine , Middha, Pooja , Bolla, Manjeet K. , Wang, Qin , Arndt, Volker , Aronson, Kristan J. , Brenner, Hermann , Eriksson, Mikael , Evans, D. Gareth , Hadjisavvas, Andreas , Haiman, Christopher A. , Håkansson, Niclas , Hamann, Ute , Hoppe, Reiner , Howell, Anthony , Hunter, David J. , Kosma, Veli‐Matti , Lissowska, Jolanta , Loizidou, Maria A. , Mannermaa, Arto , Maurer, Tabea, Olsson, Håkan , Patel, Alpa V , Perou, Charles M. , Shibli, Rana , Stone, Jennifer , Vachon, Celine M. , Wang, Sophia , Wu, Anna H. , Yang, Xiaohong R. , Zheng, Wei , Easton, Douglas F. , Chatterjee, Nilanjan , García‐Closas, Montserrat , Chang‐Claude, Jenny , Olsson, Håkan , Jung, Audrey Y , Becher, Heiko , Brenner, Hermann , Canzian, Federico , Czene, Kamila , Eliassen, A Heather , Figueroa, Jonine D , Fritschi, Lin , Gabrielson, Marike , Giles, Graham G , Guénel, Pascal , Hadjisavvas, Andreas , Håkansson, Niclas , Hall, Per N , Hüsing, Anika , Koutros, Stella , Kraft, Peter , Marchand, Loïc Le , Lissowska, Jolanta , Loizidou, Maria A , Mannermaa, Arto , Murphy, Rachel A , Olsson, Håkan , Patel, Alpa V , Perou, Charles M , Shu, Xiao-Ou , Southey, Melissa C , Stone, Jennifer , Tamimi, Rulla M , Vachon, Celine M. , Wolk, Alicja , Dunning, Alison M , Pharoah, Paul D P , Easton, Doug , Milne, Roger L , Schmidt, Marjanka K , García-Closas, Montserrat , Chang-Claude, Jenny , Behrens, Sabine , Evans, D Gareth , Arndt, Volker , Kapoor, Pooja Middha , Zheng, Wei , Eriksson, Mikael , Wang, Sophia S , Wang, Qin , Augustinsson, Annelie , Freeman, Laura E. Beane , Becher, Heiko , Canzian, Federico , Carey, Lisa A. , Czene, Kamila , Eliassen, A. Heather , Figueroa, Jonine D. , Fritschi, Lin , Gabrielson, Marike , Giles, Graham G. , Guénel, Pascal , Hopper, John L. , Hüsing, Anika , Kaaks, Rudolf , Koutros, Stella , Kraft, Peter , Lacey, James V. , Marchand, Loı̈c Le , Murphy, Rachel A. , Olshan, Andrew F. , Rennert, Gad , Shu, Xiao‐Ou , Southey, Melissa C. , Tamimi, Rulla M. , Teras, Lauren R. , Troester, Melissa A. , Truong, Thérèse , Wolk, Alicja , Dunning, Alison M. , Pharoah, Paul D.P. , Milne, Roger L. , Schmidt, Marjanka K.

JNCI: Journal of the National Cancer Institute | June 20, 2022 | Volume: 114 | Issue: 12 | Pages: 1706-1719

10.1093/jnci/djac117 | PMID 35723569 Get It

AbstractBackgroundReproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.MethodsAnalyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2–like, HER2-enriched–like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided.ResultsCompared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2–like, and HER2-enriched–like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity &lt; .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity &lt; .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.ConclusionsThis large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.
Abstract 5256: Incidence of squamous cell carcinoma (SCC) in a large screening cohort of monoclonal B-cell lymphocytosis (MBL)
Ansari, Ahmed Nadeem, Achenbach, Sara J., Kleinstern, Geffen , Lesnick, Connie , Call, Timothy G., Vachon, Celine M. , Hanson, Curtis A. , Baum, Christian L. , Parikh, Sameer A. , Norman, Aaron D. , Rabe, Kari G. , Olson, Janet E. , Cerhan, James R. , Kay, Neil E. , Vachon, Celine M. , Braggio, Esteban , Shanafelt, Tait D. , Slager, Susan L.

Cancer Research | June 15, 2022 | Volume: 82 | Issue: 12_Supplement | Pages: 5256-5256

10.1158/1538-7445.am2022-5256 Get It

Abstract MBL is a common pre-malignant condition characterized by circulating clonal B-cells with an absolute B-cell count &lt;5x109/L and no lymphadenopathy, organomegaly, or cytopenias. MBL is the precursor to CLL. The incidence of cutaneous SCC in CLL is significantly higher compared to controls. The incidence of SCC in MBLs has not yet been determined. Study participants from the Mayo Clinic Biobank who had no prior history of hematologic malignancy, were 40 years or older, and were Olmsted County residents completed a health questionnaire and provided blood samples between 7/2009 and 12/2020. Stored peripheral blood mononuclear cells were screened for MBL using flow cytometry. We defined three MBL immunophenotypes: CLL-like MBL (CD5+, CD20dim), atypical MBL (CD5+, CD20+), and non-CLL-like MBL (CD5-, CD20+). MBL individuals were also classified by cell count into low-count MBL (LC-MBL) and high-count MBL (HC-MBL), with HC-MBL having a percent clonal B-cell count ≥85%. Data on newly diagnosed SCC was abstracted from the medical records, and prior history of skin cancer before sample collection was ascertained from patient questionnaires. Individuals were followed from sample date to the earliest of SCC, death, loss to follow-up, progression, or 12/31/2020. Cumulative SCC incidence was adjusted for competing risk of death. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age and sex. A total of 5,470 participants were screened for MBL and included 949 (17%) with LC-MBL, 63 (1%) with HC-MBL, and 4,458 (81%) controls (negative for MBL). Individuals with HC-MBL (median age 75 years) or LC-MBL (median age 73 years) were significantly older (P&lt;0.001) than controls (median age 66 years). There were 41 (65%) males among HC-MBL, 447 (47%) among LC-MBL, and 1,551 (35%) among controls. Prior skin cancer history was highest among HC-MBLs (N=17, 27%) or LC-MBLs (N=236, 25%) compared to controls (N=767, 17%). After a median follow-up of 18 months (range 0-138), 154 of the 5,470 individuals were identified to have incident SCC following MBL screening. At least one SCC was observed in 3 individuals with HC-MBL, 33 individuals with LC-MBL, and 118 controls. The 5- and 10-year cumulative incidence of SCC in individuals with MBLs was 7% and 16%, respectively; control estimates were 4% and 8%, respectively. However, after adjusting for age and sex, we observed no evidence of an association between MBL and risk of incident SCC (HR=0.95, CI=0.65-1.40, P=0.80), nor when we stratified individuals by age or by sex (all P&gt;0.05). In the largest MBL screening cohort to date, individuals with MBL do not have an increased risk of incident SCC compared to controls. In contrast to individuals with CLL, these individuals with screening MBL do not need increased dermatologic examination for skin cancer, which is important given the high prevalence of MBL (18% of the population above age 40). Citation Format: Ahmed Nadeem Ansari, Sara J. Achenbach, Sameer A. Parikh, Geffen Kleinstern, Aaron D. Norman, Kari G. Rabe, Connie E. Lesnick, Timothy G. Call, Janet E. Olson, James R. Cerhan, Neil E. Kay, Celine M. Vachon, Esteban Braggio, Curtis A. Hanson, Tait D. Shanafelt, Christian L. Baum, Susan L. Slager. Incidence of squamous cell carcinoma (SCC) in a large screening cohort of monoclonal B-cell lymphocytosis (MBL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5256.