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2. Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer

Author

Young Han, Chae, Bedia, Jacob S., Yang, Wei-Lei, Hawley, Sarah J., Bergan, Lindsay, Hopper, Marika, Celestino, Joseph, Guo, Jing, Gornet, Terrie G., Soosaipillai, Antoninus, Yang, Hailing, Doskocil, Samantha D., Lokshin, Anna E., Handy, Beverly C., Diamandis, Eleftherios P., Moore, Richard G., Lu, Karen H., Lu, Zhen, Anderson, Karen S., Drescher, Charles W., Skates, Steven J., and Bast, Jr, Robert C.

Published
2024
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6. Measuring ovarian toxicity in clinical trials: an American Society of Clinical Oncology research statement

Author

Cui, Wanda, Rocconi, Rodney P, Thota, Ramya, Anderson, Richard A, Bruinooge, Suanna S, Comstock, Ioanna A, Denduluri, Neelima, Gassman, Audrey, Gralow, Julie, Hutt, Karla J, Amiri-Kordestani, Laleh, Lambertini, Matteo, Leighton, John, Lu, Karen H, Mostoufi-Moab, Sogol, Pollastro, Teri, Pradhan, Shan, Saber, Haleh, Schenkel, Caroline, Spratt, Daniel, Wedam, Suparna, and Phillips, Kelly-Anne

Published
2023
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8. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author

Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V., Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia V., Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, Renée T., Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Høgdall, Estrid, Høgdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th., John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Lubiński, Jan, Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., Matsuno, Rayna Kim, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo I., Olson, Sara H., Olsson, Håkan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamariña, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.

Published
2022
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17. Clinical significance of homologous recombination deficiency score testing in endometrial Cancer

Author

Siedel, Jean H., Ring, Kari L., Hu, Wei, Dood, Robert L., Wang, Ying, Baggerly, Keith, Darcy, Kathleen M., Conrads, Thomas P., Gallagher, Shannon, Tshiaba, Placede, Neff, Chris, Timms, Kirsten M., Mangala, Selanere, Westin, Shannon N., Broaddus, Russell, Lopez-Berestein, Gabriel, Lu, Karen H., Coleman, Robert L., Maxwell, George L., and Sood, Anil K.

Published
2021
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18. Normal Risk Ovarian Screening Study: 21-Year Update.

Author

Han, Chae Young, Lu, Karen H., Corrigan, Gwen, Perez, Alexandra, Kohring, Sharlene D., Celestino, Joseph, Bedi, Deepak, Bedia, Enrique, Bevers, Therese, Boruta, David, Carlson, Matthew, Holman, Laura, Leeds, Leroy, Mathews, Cara, McCann, Georgia, Moore, Richard G., Schlumbrecht, Matthew, Slomovitz, Brian, Tobias, Dan, and Williams-Brown, Yvette

Published
2024
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19. Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum‐resistant ovarian cancer.

Author

Hinchcliff, Emily M., Knisely, Anne, Adjei, Naomi, Fellman, Bryan, Yuan, Ying, Patel, Ami, Xu, Cai, Westin, Shannon N., Sood, Anil K., Soliman, Pamela T., Shafer, Aaron, Fleming, Nicole D., Gershenson, David M., Vikram, Raghunandan, Bathala, Tharakeswara, Vining, David, Ganeshan, Dhakshina M., Lu, Karen H., Sun, Charlotte C., and Meyer, Larissa A.

Subjects
OVARIAN cancer, IMMUNE checkpoint inhibitors, IMMUNE checkpoint proteins, PROGRESSION-free survival, SALPINGECTOMY, CA 125 test
Abstract

Background: Single‐agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%–40% of patients achieve stable disease. The primary objective was to estimate progression‐free survival (PFS) after sequential versus combination cytotoxic T‐lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum‐resistant high‐grade serous ovarian cancer (HGSOC). Methods: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune‐related PFS (irPFS). Results: Sixty‐one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77–2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77–2.43 months) (p =.402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient‐reported outcomes were similar in both arms. Conclusions: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum‐resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described. There was no difference in the median progression‐free survival for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum‐resistant high‐grade serous ovarian cancer. The adverse event profile was consistent with that previously reported for immune checkpoint blockade, and patient‐reported outcomes were similar in both arms. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Molecular Analysis of Clinically Defined Subsets of High-Grade Serous Ovarian Cancer

Author

Lee, Sanghoon, Zhao, Li, Rojas, Christine, Bateman, Nicholas W., Yao, Hui, Lara, Olivia D., Celestino, Joseph, Morgan, Margaret B., Nguyen, Tri V., Conrads, Kelly A., Rangel, Kelly M., Dood, Robert L., Hajek, Richard A., Fawcett, Gloria L., Chu, Randy A., Wilson, Katlin, Loffredo, Jeremy L., Viollet, Coralie, Jazaeri, Amir A., Dalgard, Clifton L., Mao, Xizeng, Song, Xingzhi, Zhou, Ming, Hood, Brian L., Banskota, Nirad, Wilkerson, Matthew D., Te, Jerez, Soltis, Anthony R., Roman, Kristin, Dunn, Andrew, Cordover, David, Eterovic, Agda Karina, Liu, Jinsong, Burks, Jared K., Baggerly, Keith A., Fleming, Nicole D., Lu, Karen H., Westin, Shannon N., Coleman, Robert L., Mills, Gordon B., Casablanca, Yovanni, Zhang, Jianhua, Conrads, Thomas P., Maxwell, George L., Futreal, P. Andrew, and Sood, Anil K.

Published
2020
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21. Correction: Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author

Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V., Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia V., Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, Renée T., Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Høgdall, Estrid, Høgdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th., John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Lubiński, Jan, Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., Matsuno, Rayna Kim, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo I., Olson, Sara H., Olsson, Håkan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamariña, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.

Published
2022
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34. A practical guide for the safe implementation of early phase drug development and immunotherapy program in gynecologic oncology practice

Author

Jazaeri, Amir, Coleman, Robert L., Sood, Anil K., Frumovitz, Michael M., Soliman, Pamela T., Shafer, Aaron, Cutrera, Jeffry J., Klinger, Marlana, Sharafi, Sara E., Johnson, Cynae A.L., Villanueva, Valerie F., Hinchcliff, Emily M., Dickens, Andrea, Cain, Katherine E., Anderson, Jaime E., Lu, Karen H., and Westin, Shannon N.

Published
2018
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35. Molecular, Metabolic, and Subcellular Mapping of the Tumor Immune Microenvironment via 3D Targeted and Non-Targeted Multiplex Multi-Omics Analyses.

Author

Ferri-Borgogno, Sammy, Burks, Jared K., Seeley, Erin H., McKee, Trevor D., Stolley, Danielle L., Basi, Akshay V., Gomez, Javier A., Gamal, Basant T., Ayyadhury, Shamini, Lawson, Barrett C., Yates, Melinda S., Birrer, Michael J., Lu, Karen H., and Mok, Samuel C.

Subjects
CYTOLOGY, DIAGNOSTIC imaging, THREE-dimensional imaging, GENOMICS, PREDICTION models, RESEARCH funding, OVARIAN tumors, CELL physiology, TUMOR markers, IMMUNE system, ANALYTICAL biochemistry, FLUORESCENT antibody technique, CELL lines, HISTOLOGICAL techniques, MASS spectrometry, GENE expression profiling, PROTEOMICS, EXTRACELLULAR matrix, SURVIVAL analysis (Biometry), COLLECTION & preservation of biological specimens, DATA analysis software, MOLECULAR diagnosis
Abstract

Simple Summary: A tumor tissue is composed of not only cancer cells but also other cell types and microorganisms that communicate among themselves in a three-dimensional (3D) space to support cancer cell growth. Using two different gynecologic tumor tissue samples, we integrated multiple new techniques using a suite of newly developed analytical methods to simultaneously identify expression of genes, metabolites, and proteins in single tissue 'voxels'. These tissue voxels contain cells, genes from those cells and microorganisms, and the stromal context of proteins (collagen), glycans, metabolites, and peptides, all identified in the 3D space within a tumor tissue. We have successfully demonstrated different arrays of analytes expressed by cancer cells and their neighboring cells in different regions of the tumor tissue. Understanding how cancer cells communicate with other cell types in the 3D space of the tumor tissue will allow for the identification of new therapeutic targets for the treatment of these diseases. Most platforms used for the molecular reconstruction of the tumor–immune microenvironment (TIME) of a solid tumor fail to explore the spatial context of the three-dimensional (3D) space of the tumor at a single-cell resolution, and thus lack information about cell–cell or cell–extracellular matrix (ECM) interactions. To address this issue, a pipeline which integrated multiplex spatially resolved multi-omics platforms was developed to identify crosstalk signaling networks among various cell types and the ECM in the 3D TIME of two FFPE (formalin-fixed paraffin embedded) gynecologic tumor samples. These platforms include non-targeted mass spectrometry imaging (glycans, metabolites, and peptides) and Stereo-seq (spatial transcriptomics) and targeted seqIF (IHC proteomics). The spatially resolved imaging data in a two- and three-dimensional space demonstrated various cellular neighborhoods in both samples. The collection of spatially resolved analytes in a voxel (3D pixel) across serial sections of the tissue was also demonstrated. Data collected from this analytical pipeline were used to construct spatial 3D maps with single-cell resolution, which revealed cell identity, activation, and energized status. These maps will provide not only insights into the molecular basis of spatial cell heterogeneity in the TIME, but also novel predictive biomarkers and therapeutic targets, which can improve patient survival rates. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Limited Independent Follow-Up with Germline Testing of Variants Detected in BRCA1 and BRCA2 by Tumor-Only Sequencing.

Author

Nowlen, Carol J., Daniels, Molly, Uzunparmak, Burak, Dumbrava, Ecaterina E. Ileana, Ying Yuan, Pate, Keyur P., Rayes, Nadine, Harkenrider, Jacqueline, Wathoo, Chetna, Veazie, Jennifer, Luna, Krystle A., Wanlin Wang, Horombe, Chacha, Javle, Milind, Ahnert, Jordi Rodon, Yap, Timothy A., Arun, Banu, Lu, Karen H., and Meric-Bernstam, Funda

Subjects
BRCA genes, HEREDITARY cancer syndromes, CANCER treatment, CANCER diagnosis, CANCER patients
Abstract

Introduction: Genomic profiling is performed in patients with advanced or metastatic cancer, in order to direct cancer treatment, often sequencing tumor-only, without a matched germline comparator. However, because many of the genes analyzed on tumor profiling overlap with those known to be associated with hereditary cancer predisposition syndromes (HCPS), tumor-only profiling can unknowingly uncover germline pathogenic (P) and likely pathogenic variants (LPV). In this study, we evaluated the number of patients with P/LPVs identified in BRCA1 and BRCA2 (BRCA1/2) via tumor-only profiling, then determined the germline testing outcomes for those patients. Methods: A retrospective chart review was performed to identify patients with BRCA1/2 variants on tumor-only genomic profiling, and whether they had germline testing. Results: This study found that of 2923 patients with 36 tumor types who underwent tumor-only testing, 554 had a variant in BRCA1/2 (19.0%); 119 of the 554 patients (21.5%) had a P/LP BRCA1/2 variant, representing 4.1% of the overall population who underwent genomic profiling. Seventy-three (61.3%) of 119 patients with BRCA1/2 P/LPV on tumor-only testing did not undergo germline testing, 34 (28.6%) had already had germline testing before tumor-only testing, and 12 (10.1%) underwent germline testing after tumor-only testing. Twenty-eight germline BRCA1/2 P/LPVs were detected, 24 in those who had prior germline testing, and 4 among the 12 patients who had germline testing after tumor-only testing. Conclusion: Tumor-only testing is likely to identify P/LPVs in BRCA1/2. Efforts to improve follow-up germline testing is needed to improve identification of germline BRCA1/2 alterations. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Creation and Implementation of an Environmental Scan to Assess Cancer Genetics Services at Three Oncology Care Settings

Author

Bednar, Erica M., Walsh, Jr., Michael T., Baker, Ellen, Muse, Kimberly I., Oakley, Holly D., Krukenberg, Rebekah C., Dresbold, Cara S., Jenkinson, Sandra B., Eppolito, Amanda L., Teed, Kelly B., Klein, Molly H., Morman, Nichole A., Bowdish, Elizabeth C., Russ, Pauline, Wise, Emaline E., Cooper, Julia N., Method, Michael W., Henson, John W., Grainger, Andrew V., Arun, Banu K., and Lu, Karen H.

Published
2018
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