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1. Association between tumor-infiltrating lymphocytes and survival in patients with metastatic breast cancer receiving first-line chemotherapy: analysis of CALGB 40502.

Author

Stover, Daniel, Salgado, Roberto, Savenkov, Oleksander, Ballman, Karla, Mayer, Erica, Magbanua, Mark, Loi, Sherene, Vater, Mark, Glover, Kristyn, Watson, Mark, Wen, Yujia, Symmans, W, Perou, Charles, Carey, Lisa, Partridge, Ann, and Rugo, Hope

Abstract

Association of stromal tumor-infiltrating lymphocytes (sTILs) with survival outcomes among patients with metastatic breast cancer (MBC) remains unclear. The primary objective was to evaluate the association of sTILs with progression-free survival in randomized phase III trial CALGB 40502. sTILs were associated with progression-free and overall survival in chemotherapy-treated MBC when controlling for treatment arm; however, this effect did not remain significant after additional adjustment for hormone receptor status. CALGB is now part of the Alliance for Clinical Trials in Oncology. Trial Registration: ClinicalTrials.gov: NCT00785291.

Published
2024

3. B-cells and regulatory T-cells in the microenvironment of HER2+ breast cancer are associated with decreased survival: a real-world analysis of women with HER2+ metastatic breast cancer.

Author

Steenbruggen, Tessa, Wolf, Denise, Campbell, Michael, Sanders, Joyce, Cornelissen, Sten, Thijssen, Bram, Salgado, Roberto, Yau, Christina, O-Grady, Nick, Basu, Amrita, Bhaskaran, Rajith, Mittempergher, Lorenza, Hirst, Gillian, Coppe, Jean-Philippe, Kok, Marleen, Sonke, Gabe, van t Veer, Laura, and Horlings, Hugo

Subjects
Gene expression, HER2-positive, Metastatic breast cancer, Multiplex immunofluorescence, Spatial composition, Tumor immune microenvironment
Abstract

BACKGROUND: Despite major improvements in treatment of HER2-positive metastatic breast cancer (MBC), only few patients achieve complete remission and remain progression free for a prolonged time. The tumor immune microenvironment plays an important role in the response to treatment in HER2-positive breast cancer and could contain valuable prognostic information. Detailed information on the cancer-immune cell interactions in HER2-positive MBC is however still lacking. By characterizing the tumor immune microenvironment in patients with HER2-positive MBC, we aimed to get a better understanding why overall survival (OS) differs so widely and which alternative treatment approaches may improve outcome. METHODS: We included all patients with HER2-positive MBC who were treated with trastuzumab-based palliative therapy in the Netherlands Cancer Institute between 2000 and 2014 and for whom pre-treatment tissue from the primary tumor or from metastases was available. Infiltrating immune cells and their spatial relationships to one another and to tumor cells were characterized by immunohistochemistry and multiplex immunofluorescence. We also evaluated immune signatures and other key pathways using next-generation RNA-sequencing data. With nine years median follow-up from initial diagnosis of MBC, we investigated the association between tumor and immune characteristics and outcome. RESULTS: A total of 124 patients with 147 samples were included and evaluated. The different technologies showed high correlations between each other. T-cells were less prevalent in metastases compared to primary tumors, whereas B-cells and regulatory T-cells (Tregs) were comparable between primary tumors and metastases. Stromal tumor-infiltrating lymphocytes in general were not associated with OS. The infiltration of B-cells and Tregs in the primary tumor was associated with unfavorable OS. Four signatures classifying the extracellular matrix of primary tumors showed differential survival in the population as a whole. CONCLUSIONS: In a real-world cohort of 124 patients with HER2-positive MBC, B-cells, and Tregs in primary tumors are associated with unfavorable survival. With this paper, we provide a comprehensive insight in the tumor immune microenvironment that could guide further research into development of novel immunomodulatory strategies.

Published
2023

7. Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status

Author

Wang, Yuwei, Dackus, Gwen M. H. E., Rosenberg, Efraim H., Cornelissen, Sten, de Boo, Leonora W., Broeks, Annegien, Brugman, Wim, Chan, Terry W. S., van Diest, Paul J., Hauptmann, Michael, ter Hoeve, Natalie D., Isaeva, Olga I., de Jong, Vincent M. T., Jóźwiak, Katarzyna, Kluin, Roelof J. C., Kok, Marleen, Koop, Esther, Nederlof, Petra M., Opdam, Mark, Schouten, Philip C., Siesling, Sabine, van Steenis, Charlaine, Voogd, Adri C., Vreuls, Willem, Salgado, Roberto F., Linn, Sabine C., and Schmidt, Marjanka K.

Published
2024
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8. Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M., Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L., Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S., Grigoriadis, Kristiana, Moore, David A., Black, James R. M., Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas B. K., Naceur-Lombardelli, Cristina, Cook, Daniel E., Salgado, Roberto, Wilson, Gareth A., Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martínez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G., Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M., Naidu, Babu, Middleton, Gary, Blyth, Kevin G., Fennell, Dean A., Forster, Martin D., Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J., Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G., Lester, Jason F., Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M., Lawrence, David, Navani, Neal, Janes, Sam M., Dive, Caroline, Blackhall, Fiona H., Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A., Peggs, Karl S., Schwarz, Roland F., Van Loo, Peter, Miedema, Daniël M., Birkbak, Nicolai J., Hiley, Crispin T., Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2024
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9. Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study

Author

Acs, Balazs, Leung, Samuel CY, Kidwell, Kelley M, Arun, Indu, Augulis, Renaldas, Badve, Sunil S, Bai, Yalai, Bane, Anita L, Bartlett, John MS, Bayani, Jane, Bigras, Gilbert, Blank, Annika, Buikema, Henk, Chang, Martin C, Dietz, Robin L, Dodson, Andrew, Fineberg, Susan, Focke, Cornelia M, Gao, Dongxia, Gown, Allen M, Gutierrez, Carolina, Hartman, Johan, Kos, Zuzana, Lænkholm, Anne-Vibeke, Laurinavicius, Arvydas, Levenson, Richard M, Mahboubi-Ardakani, Rustin, Mastropasqua, Mauro G, Nofech-Mozes, Sharon, Osborne, C Kent, Penault-Llorca, Frédérique M, Piper, Tammy, Quintayo, Mary Anne, Rau, Tilman T, Reinhard, Stefan, Robertson, Stephanie, Salgado, Roberto, Sugie, Tomoharu, van der Vegt, Bert, Viale, Giuseppe, Zabaglo, Lila A, Hayes, Daniel F, Dowsett, Mitch, Nielsen, Torsten O, and Rimm, David L

Subjects
Cancer, Clinical Research, Breast Cancer, Biomarkers, Tumor, Biopsy, Breast Neoplasms, Female, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Ki-67 Antigen, Receptors, Estrogen, International Ki67 in Breast Cancer Working Group of the Breast International Group and North American Breast Cancer Group, Medical and Health Sciences, Pathology
Abstract

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error (p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections (p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor.

Published
2022

12. Author Correction: Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial

Author

Buisseret, Laurence, Loirat, Delphine, Aftimos, Philippe, Maurer, Christian, Punie, Kevin, Debien, Véronique, Kristanto, Paulus, Eiger, Daniel, Goncalves, Anthony, Ghiringhelli, François, Taylor, Donatienne, Clatot, Florent, Van den Mooter, Tom, Ferrero, Jean-Marc, Bonnefoi, Hervé, Canon, Jean-Luc, Duhoux, Francois P., Mansi, Laura, Poncin, Renaud, Barthélémy, Philippe, Isambert, Nicolas, Denis, Zoë, Catteau, Xavier, Salgado, Roberto, Agostinetto, Elisa, de Azambuja, Evandro, Rothé, Françoise, Craciun, Ligia, Venet, David, Romano, Emanuela, Stagg, John, Paesmans, Marianne, Larsimont, Denis, Sotiriou, Christos, Ignatiadis, Michail, and Piccart-Gebhart, Martine

Published
2023
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13. Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials

Author

Rediti, Mattia, Fernandez-Martinez, Aranzazu, Venet, David, Rothé, Françoise, Hoadley, Katherine A., Parker, Joel S., Singh, Baljit, Campbell, Jordan D., Ballman, Karla V., Hillman, David W., Winer, Eric P., El-Abed, Sarra, Piccart, Martine, Di Cosimo, Serena, Symmans, William Fraser, Krop, Ian E., Salgado, Roberto, Loi, Sherene, Pusztai, Lajos, Perou, Charles M., Carey, Lisa A., and Sotiriou, Christos

Published
2023
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14. Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial

Author

Buisseret, Laurence, Loirat, Delphine, Aftimos, Philippe, Maurer, Christian, Punie, Kevin, Debien, Véronique, Kristanto, Paulus, Eiger, Daniel, Goncalves, Anthony, Ghiringhelli, François, Taylor, Donatienne, Clatot, Florent, Van den Mooter, Tom, Ferrero, Jean-Marc, Bonnefoi, Hervé, Canon, Jean-Luc, Duhoux, Francois P., Mansi, Laura, Poncin, Renaud, Barthélémy, Philippe, Isambert, Nicolas, Denis, Zoë, Catteau, Xavier, Salgado, Roberto, Agostinetto, Elisa, de Azambuja, Evandro, Rothé, Françoise, Craciun, Ligia, Venet, David, Romano, Emanuela, Stagg, John, Paesmans, Marianne, Larsimont, Denis, Sotiriou, Christos, Ignatiadis, Michail, and Piccart-Gebhart, Martine

Published
2023
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15. Tumour Infiltrating Lymphocytes (TILs) and immune composition in breast cancer patients from Kenya: Spatial distributions and associations with risk factors and tumour characteristics

Author

Sayed, Shahin, Koka, Hela, Abubakar, Mustapha, Gardner, Kevin, Salgado, Roberto, Moloo, Zahir, Caban-Ureña, Ambar Beatriz, Rosen, Daniel, Castro, Patricia, Saleh, Mansoor, Shaikh, Asim Jamal, Shah, Jasmit, Figueroa, Jonine, Makokha, Francis, Ha, Hien Khanh, Wang, Zhong, Magangane, Pumza, Naidoo, Richard, Ngundo, Veronica, Yang, Xiaohong Rose, and Govender, Dhirendra

Published
2023
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17. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Author

El Bairi, Khalid, Haynes, Harry R, Blackley, Elizabeth, Fineberg, Susan, Shear, Jeffrey, Turner, Sophia, de Freitas, Juliana Ribeiro, Sur, Daniel, Amendola, Luis Claudio, Gharib, Masoumeh, Kallala, Amine, Arun, Indu, Azmoudeh-Ardalan, Farid, Fujimoto, Luciana, Sua, Luz F, Liu, Shi-Wei, Lien, Huang-Chun, Kirtani, Pawan, Balancin, Marcelo, El Attar, Hicham, Guleria, Prerna, Yang, Wenxian, Shash, Emad, Chen, I-Chun, Bautista, Veronica, Do Prado Moura, Jose Fernando, Rapoport, Bernardo L, Castaneda, Carlos, Spengler, Eunice, Acosta-Haab, Gabriela, Frahm, Isabel, Sanchez, Joselyn, Castillo, Miluska, Bouchmaa, Najat, Md Zin, Reena R, Shui, Ruohong, Onyuma, Timothy, Yang, Wentao, Husain, Zaheed, Willard-Gallo, Karen, Coosemans, An, Perez, Edith A, Provenzano, Elena, Ericsson, Paula Gonzalez, Richardet, Eduardo, Mehrotra, Ravi, Sarancone, Sandra, Ehinger, Anna, Rimm, David L, Bartlett, John MS, Viale, Giuseppe, Denkert, Carsten, Hida, Akira I, Sotiriou, Christos, Loibl, Sibylle, Hewitt, Stephen M, Badve, Sunil, Symmans, William Fraser, Kim, Rim S, Pruneri, Giancarlo, Goel, Shom, Francis, Prudence A, Inurrigarro, Gloria, Yamaguchi, Rin, Garcia-Rivello, Hernan, Horlings, Hugo, Afqir, Said, Salgado, Roberto, Adams, Sylvia, Kok, Marleen, Dieci, Maria Vittoria, Michiels, Stefan, Demaria, Sandra, and Loi, Sherene

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Breast Cancer, Cancer, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, International Immuno-Oncology Biomarker Working Group, Clinical sciences, Oncology and carcinogenesis, Epidemiology
Abstract

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Published
2021

18. Automated Scoring of Nuclear Pleomorphism Spectrum with Pathologist-level Performance in Breast Cancer

Author

Mercan, Caner, Balkenhol, Maschenka, Salgado, Roberto, Sherman, Mark, Vielh, Philippe, Vreuls, Willem, Polonia, Antonio, Horlings, Hugo M., Weichert, Wilko, Carter, Jodi M., Bult, Peter, Christgen, Matthias, Denkert, Carsten, van de Vijver, Koen, van der Laak, Jeroen, and Ciompi, Francesco

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Nuclear pleomorphism, defined herein as the extent of abnormalities in the overall appearance of tumor nuclei, is one of the components of the three-tiered breast cancer grading. Given that nuclear pleomorphism reflects a continuous spectrum of variation, we trained a deep neural network on a large variety of tumor regions from the collective knowledge of several pathologists, without constraining the network to the traditional three-category classification. We also motivate an additional approach in which we discuss the additional benefit of normal epithelium as baseline, following the routine clinical practice where pathologists are trained to score nuclear pleomorphism in tumor, having the normal breast epithelium for comparison. In multiple experiments, our fully-automated approach could achieve top pathologist-level performance in select regions of interest as well as at whole slide images, compared to ten and four pathologists, respectively., Comment: 16 pages, 11 figures

Published
2020

19. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Author

Ng, Kevin W., Boumelha, Jesse, Enfield, Katey S. S., Almagro, Jorge, Cha, Hongui, Pich, Oriol, Karasaki, Takahiro, Moore, David A., Salgado, Roberto, Sivakumar, Monica, Young, George, Molina-Arcas, Miriam, de Carné Trécesson, Sophie, Anastasiou, Panayiotis, Fendler, Annika, Au, Lewis, Shepherd, Scott T. C., Martínez-Ruiz, Carlos, Puttick, Clare, Black, James R. M., Watkins, Thomas B. K., Kim, Hyemin, Shim, Seohee, Faulkner, Nikhil, Attig, Jan, Veeriah, Selvaraju, Magno, Neil, Ward, Sophia, Frankell, Alexander M., Al Bakir, Maise, Lim, Emilia L., Hill, Mark S., Wilson, Gareth A., Cook, Daniel E., Birkbak, Nicolai J., Behrens, Axel, Yousaf, Nadia, Popat, Sanjay, Hackshaw, Allan, Hiley, Crispin T., Litchfield, Kevin, McGranahan, Nicholas, Jamal-Hanjani, Mariam, Larkin, James, Lee, Se-Hoon, Turajlic, Samra, Swanton, Charles, Downward, Julian, and Kassiotis, George

Published
2023
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20. The evolution of non-small cell lung cancer metastases in TRACERx

Author

Al Bakir, Maise, Huebner, Ariana, Martínez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas B. K., Pich, Oriol, Moore, David A., Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander M., Bunkum, Abigail, Lim, Emilia L., Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T., Hill, Mark S., Cook, Daniel E., Wilson, Gareth A., Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A., Price, Gillian, Kerr, Keith M., Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R., Blackhall, Fiona H., Cave, Judith, Blyth, Kevin G., Nair, Arjun, Ahmed, Asia, Taylor, Magali N., Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M., Janes, Sam M., Papadatos-Pastos, Dionysis, Forster, Martin D., Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J., Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2023
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21. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M., Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L., Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S., Grigoriadis, Kristiana, Moore, David A., Black, James R. M., Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas B. K., Naceur-Lombardelli, Cristina, Cook, Daniel E., Salgado, Roberto, Wilson, Gareth A., Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martínez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G., Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M., Naidu, Babu, Middleton, Gary, Blyth, Kevin G., Fennell, Dean A., Forster, Martin D., Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J., Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G., Lester, Jason F., Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M., Lawrence, David, Navani, Neal, Janes, Sam M., Dive, Caroline, Blackhall, Fiona H., Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A., Peggs, Karl S., Schwarz, Roland F., Van Loo, Peter, Miedema, Daniël M., Birkbak, Nicolai J., Hiley, Crispin T., Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2023
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22. Genomic–transcriptomic evolution in lung cancer and metastasis

Author

Martínez-Ruiz, Carlos, Black, James R. M., Puttick, Clare, Hill, Mark S., Demeulemeester, Jonas, Larose Cadieux, Elizabeth, Thol, Kerstin, Jones, Thomas P., Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Prymas, Paulina, Rowan, Andrew, Ward, Sophia, Cubitt, Laura, Athanasopoulou, Foteini, Pich, Oriol, Karasaki, Takahiro, Moore, David A., Salgado, Roberto, Colliver, Emma, Castignani, Carla, Dietzen, Michelle, Huebner, Ariana, Al Bakir, Maise, Tanić, Miljana, Watkins, Thomas B. K., Lim, Emilia L., Al-Rashed, Ali M., Lang, Danny, Clements, James, Cook, Daniel E., Rosenthal, Rachel, Wilson, Gareth A., Frankell, Alexander M., de Carné Trécesson, Sophie, East, Philip, Kanu, Nnennaya, Litchfield, Kevin, Birkbak, Nicolai J., Hackshaw, Allan, Beck, Stephan, Van Loo, Peter, Jamal-Hanjani, Mariam, Swanton, Charles, and McGranahan, Nicholas

Published
2023
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23. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author

Karasaki, Takahiro, Moore, David A., Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Bakir, Maise Al, Watkins, Thomas B. K., Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S., Frankell, Alexander M., Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L., Martínez-Ruiz, Carlos, Black, James R. M., Biswas, Dhruva, Campbell, Brittany B., Lee, Claudia, Colliver, Emma, Enfield, Katey S. S., Hessey, Sonya, Hiley, Crispin T., Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J., Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad S., Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R., Rekhtman, Natasha, Travis, William D., Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G., McGranahan, Nicholas, Swanton, Charles, and Jamal-Hanjani, Mariam

Published
2023
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24. Body composition and lung cancer-associated cachexia in TRACERx

Author

Al-Sawaf, Othman, Weiss, Jakob, Skrzypski, Marcin, Lam, Jie Min, Karasaki, Takahiro, Zambrana, Francisco, Kidd, Andrew C., Frankell, Alexander M., Watkins, Thomas B. K., Martínez-Ruiz, Carlos, Puttick, Clare, Black, James R. M., Huebner, Ariana, Bakir, Maise Al, Sokač, Mateo, Collins, Susie, Veeriah, Selvaraju, Magno, Neil, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Ward, Sophia, Jayanth, Nick, Salgado, Roberto, Bridge, Christopher P., Christiani, David C., Mak, Raymond H., Bay, Camden, Rosenthal, Michael, Sattar, Naveed, Welsh, Paul, Liu, Ying, Perrimon, Norbert, Popuri, Karteek, Beg, Mirza Faisal, McGranahan, Nicholas, Hackshaw, Allan, Breen, Danna M., O’Rahilly, Stephen, Birkbak, Nicolai J., Aerts, Hugo J. W. L., Jamal-Hanjani, Mariam, and Swanton, Charles

Published
2023
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25. PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial

Author

Voorwerk, Leonie, Isaeva, Olga I., Horlings, Hugo M., Balduzzi, Sara, Chelushkin, Maksim, Bakker, Noor A. M., Champanhet, Elisa, Garner, Hannah, Sikorska, Karolina, Loo, Claudette E., Kemper, Inge, Mandjes, Ingrid A. M., de Maaker, Michiel, van Geel, Jasper J. L., Boers, Jorianne, de Boer, Maaike, Salgado, Roberto, van Dongen, Marloes G. J., Sonke, Gabe S., de Visser, Karin E., Schumacher, Ton N., Blank, Christian U., Wessels, Lodewyk F. A., Jager, Agnes, Tjan-Heijnen, Vivianne C. G., Schröder, Carolien P., Linn, Sabine C., and Kok, Marleen

Published
2023
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28. A Pathologist-Annotated Dataset for Validating Artificial Intelligence: A Project Description and Pilot Study

Author

Dudgeon, Sarah N, Wen, Si, Hanna, Matthew G, Gupta, Rajarsi, Amgad, Mohamed, Sheth, Manasi, Marble, Hetal, Huang, Richard, Herrmann, Markus D, Szu, Clifford H., Tong, Darick, Werness, Bruce, Szu, Evan, Larsimont, Denis, Madabhushi, Anant, Hytopoulos, Evangelos, Chen, Weijie, Singh, Rajendra, Hart, Steven N., Saltz, Joel, Salgado, Roberto, and Gallas, Brandon D

Subjects
Quantitative Biology - Quantitative Methods, Electrical Engineering and Systems Science - Image and Video Processing
Abstract

Purpose: In this work, we present a collaboration to create a validation dataset of pathologist annotations for algorithms that process whole slide images (WSIs). We focus on data collection and evaluation of algorithm performance in the context of estimating the density of stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. Methods: We digitized 64 glass slides of hematoxylin- and eosin-stained ductal carcinoma core biopsies prepared at a single clinical site. We created training materials and workflows to crowdsource pathologist image annotations on two modes: an optical microscope and two digital platforms. The workflows collect the ROI type, a decision on whether the ROI is appropriate for estimating the density of sTILs, and if appropriate, the sTIL density value for that ROI. Results: The pilot study yielded an abundant number of cases with nominal sTIL infiltration. Furthermore, we found that the sTIL densities are correlated within a case, and there is notable pathologist variability. Consequently, we outline plans to improve our ROI and case sampling methods. We also outline statistical methods to account for ROI correlations within a case and pathologist variability when validating an algorithm. Conclusion: We have built workflows for efficient data collection and tested them in a pilot study. As we prepare for pivotal studies, we will consider what it will take for the dataset to be fit for a regulatory purpose: study size, patient population, and pathologist training and qualifications. To this end, we will elicit feedback from the FDA via the Medical Device Development Tool program and from the broader digital pathology and AI community. Ultimately, we intend to share the dataset, statistical methods, and lessons learned., Comment: 26 pages, 4 figures, 2 tables Submitted to the Journal of Pathology Informatics Project web page: https://ncihub.org/groups/eedapstudies

Published
2020
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29. Self-Supervised Nuclei Segmentation in Histopathological Images Using Attention

Author

Sahasrabudhe, Mihir, Christodoulidis, Stergios, Salgado, Roberto, Michiels, Stefan, Loi, Sherene, André, Fabrice, Paragios, Nikos, and Vakalopoulou, Maria

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Segmentation and accurate localization of nuclei in histopathological images is a very challenging problem, with most existing approaches adopting a supervised strategy. These methods usually rely on manual annotations that require a lot of time and effort from medical experts. In this study, we present a self-supervised approach for segmentation of nuclei for whole slide histopathology images. Our method works on the assumption that the size and texture of nuclei can determine the magnification at which a patch is extracted. We show that the identification of the magnification level for tiles can generate a preliminary self-supervision signal to locate nuclei. We further show that by appropriately constraining our model it is possible to retrieve meaningful segmentation maps as an auxiliary output to the primary magnification identification task. Our experiments show that with standard post-processing, our method can outperform other unsupervised nuclei segmentation approaches and report similar performance with supervised ones on the publicly available MoNuSeg dataset. Our code and models are available online to facilitate further research., Comment: 10 pages. Code available online at https://github.com/msahasrabudhe/miccai2020_self_sup_nuclei_seg

Published
2020

30. 1511 Pan-tumor harmonization of pathologic response assessment for standardized data collection in neoadjuvant IO trials (PATHdata): Interim analysis of a multi-institutional reproducibility study

Author

Xiaowei Xu, Hao Wang, Michael Tetzlaff, James Ziai, Sabina Signoretti, Ashley Cimino-Mathews, Tricia Cottrell, Janis M Taube, Annikka Weissferdt, Richard A Scolyer, Pierre-Olivier Fiset, Jaime Rodriguez-Canales, Lynette M Sholl, Julie S Deutsch, Krista Chen, Carlos E de Andrea, Christine Orr, Salgado Roberto, Christian Schurch, Raja Seethala, and Alexander S Baras

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
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32. Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials

Author

Taylor, Carolyn, Dodwell, David, McGale, Paul, Hills, Robert K, Berry, Richard, Bradley, Rosie, Braybrooke, Jeremy, Clarke, Mike, Gray, Richard, Holt, Francesca, Liu, Zulian, Pan, Hongchao, Peto, Richard, Straiton, Ewan, Coles, Charlotte, Duane, Fran, Hennequin, Christophe, Jones, Glenn, Kühn, Thorsten, Oliveros, Sileida, Overgaard, Jens, Pritchard, Kathy I, Suh, Chang-Ok, Beake, Graham, Boddington, Clare, Davies, Christina, Davies, Lucy, Evans, Vaughan, Gay, Jo, Gettins, Lucy, Godwin, Jon, James, Sam, Kerr, Amanda, Liu, Hui, MacKinnon, Elizabeth, Mannu, Gurdeep, McHugh, Theresa, Morris, Philip, Nakahara, Mariko, Read, Simon, Taylor, Hannah, Ferguson, John, Scheurlen, Hans, Zurrida, Stefano, Galimberti, Viviana, Ingle, James, Valagussa, Pinuccia, Veronesi, Umberto, Anderson, Stewart, Tang, Gong, Fisher, Bernard, Fossa, Sophie, Valborg Reinertsen, Kristin, Host, Herman, Muss, Hyman, Holli, Kaija, Albain, Kathy, Arriagada, Rodrigo, Bartlett, John, Bergsten-Nordström, Elizabeth, Bliss, Judith, Brain, Etienne, Carey, Lisa, Coleman, Robert, Cuzick, Jack, Davidson, Nancy, Del Mastro, Lucia, Di Leo, Angelo, Dignam, James, Dowsett, Mitch, Ejlertsen, Bent, Francis, Prue, García-Sáenz, José Angel, Gelber, Rich, Gnant, Michael, Goetz, Matthew, Goodwin, Pam, Halpin-Murphy, Pat, Hayes, Dan, Hill, Catherine, Jagsi, Reshma, Janni, Wolfgang, Loibl, Sibylle, Mamounas, Eleftherios, Martín, Miguel, McIntosh, Stuart, Mukai, Hirofumi, Nekljudova, Valentina, Norton, Larry, Ohashi, Yasuo, Piccart, Martine, Pierce, Lori, Raina, Vinod, Rea, Daniel, Regan, Meredith, Robertson, John, Rutgers, Emiel, Salgado, Roberto, Slamon, Dennis, Spanic, Tanja, Sparano, Joseph, Steger, Guenther, Toi, Masakazu, Tutt, Andrew, Viale, Giuseppe, Wang, Xiang, Wilcken, Nicholas, Wolmark, Norman, Yu, Ke-Da, Cameron, David, Bergh, Jonas, Swain, Sandra, Whelan, Tim, and Poortmans, Philip

Published
2023
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34. Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer.

Author

Axelrod, Margaret L, Nixon, Mellissa J, Gonzalez-Ericsson, Paula I, Bergman, Riley E, Pilkinton, Mark A, McDonnell, Wyatt J, Sanchez, Violeta, Opalenik, Susan R, Loi, Sherene, Zhou, Jing, Mackay, Sean, Rexer, Brent N, Abramson, Vandana G, Jansen, Valerie M, Mallal, Simon, Donaldson, Joshua, Tolaney, Sara M, Krop, Ian E, Garrido-Castro, Ana C, Marotti, Jonathan D, Shee, Kevin, Miller, Todd W, Sanders, Melinda E, Mayer, Ingrid A, Salgado, Roberto, and Balko, Justin M

Subjects
CD8-Positive T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Humans, Neoplasm Recurrence, Local, Paclitaxel, Albumins, Neoplasm Proteins, Antineoplastic Combined Chemotherapy Protocols, Prognosis, Treatment Outcome, Neoadjuvant Therapy, Gene Expression Regulation, Neoplastic, Adult, Aged, Middle Aged, Female, Tumor Microenvironment, Programmed Cell Death 1 Receptor, Triple Negative Breast Neoplasms, B7-H1 Antigen, Progression-Free Survival, Clinical Research, Genetics, Breast Cancer, Cancer, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeThe recent approval of anti-programmed death-ligand 1 immunotherapy in combination with nab-paclitaxel for metastatic triple-negative breast cancer (TNBC) highlights the need to understand the role of chemotherapy in modulating the tumor immune microenvironment (TIME).Experimental designWe examined immune-related gene expression patterns before and after neoadjuvant chemotherapy (NAC) in a series of 83 breast tumors, including 44 TNBCs, from patients with residual disease (RD). Changes in gene expression patterns in the TIME were tested for association with recurrence-free (RFS) and overall survival (OS). In addition, we sought to characterize the systemic effects of NAC through single-cell analysis (RNAseq and cytokine secretion) of programmed death-1-high (PD-1HI) CD8+ peripheral T cells and examination of a cytolytic gene signature in whole blood.ResultsIn non-TNBC, no change in expression of any single gene was associated with RFS or OS, while in TNBC upregulation of multiple immune-related genes and gene sets were associated with improved long-term outcome. High cytotoxic T-cell signatures present in the peripheral blood of patients with breast cancer at surgery were associated with persistent disease and recurrence, suggesting active antitumor immunity that may indicate ongoing disease burden.ConclusionsWe have characterized the effects of NAC on the TIME, finding that TNBC is uniquely sensitive to the immunologic effects of NAC, and local increases in immune genes/sets are associated with improved outcomes. However, expression of cytotoxic genes in the peripheral blood, as opposed to the TIME, may be a minimally invasive biomarker of persistent micrometastatic disease ultimately leading to recurrence.

Published
2020

35. Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials

Author

Braybrooke, Jeremy, Bradley, Rosie, Gray, Richard, Hills, Robert K, Pan, Hongchao, Peto, Richard, Dodwell, David, McGale, Paul, Taylor, Carolyn, Aihara, Tomohiko, Anderson, Stewart, Blum, Joanne, Cardoso, Fatima, Chen, Xiaosong, Crown, John P, Ejlertsen, Bent, Friedl, Thomas W P, Harbeck, Nadia, Janni, Wolfgang, Jensen, Maj-Britt, Mamounas, Eleftherios, Narui, Kazutaka, Nitz, Ulrike, Norton, Larry, O'Shaughnessy, Joyce, Piccart, Martine, Robert, Nicholas, Shao, Zhi-Ming, Slamon, Dennis, Sparano, Joseph, Watanabe, Toru, Yothers, Greg, Yu, Ke-Da, Berry, Richard, Boddington, Clare, Clarke, Mike, Davies, Christina, Davies, Lucy, Duane, Fran, Evans, Vaughan, Gay, Jo, Gettins, Lucy, Godwin, Jon, James, Sam, Lui, Hui, Lui, Zulian, MacKinnon, Elizabeth, Mannu, Gurdeep, McHugh, Theresa, Morris, Philip, Read, Simon, Straiton, Ewan, Buzdar, Aman, Suman, Vera J, Hunt, Kelly K, Leonard, Robert C F, Mansi, Janine, Delbaldo, Catherine, Piedbois, Pascal, Quinaux, Emmanuel, Fesl, Christian, Gnant, Michael, Sölkner, Lidija, Steger, Guenther, Eikesdal, Hans Petter, Lønning, Per Eystein, Bee, Valerie, Fung, Helena, Mackey, John, Martin, Miguel, Press, Michael, De Azambuja, Evandro, Gelber, Richard, Regan, Meredith, Di Leo, Angelo, Van Dooren, Veerle, Nogaret, Jean Marie, Bartlett, John, Chen, Bingshu E, Gelmon, Karen, Goss, Paul E, Levine, Mark N, Parulekar, Wendy, Pritchard, Kathleen I, Shepherd, Lois, Berry, Donald, Cirrincione, Constance, Shulman, Lawrence N, Winer, Eric, Gelman, Rebecca S, Harris, Jay R, Henderson, Craig, Shapiro, Charles L, Christiansen, Peer, Ewertz, Marianne, Mouridsen, Henning T, Van Leeuwen, Elise, Linn, Sabine, Van Rossum, Annelot G J, Van Tinteren, Harm, Van Werkhoven, Erik, Goldstein, Lori, Gray, Robert, Eiermann, Wolfgang, Gianni, Luca, Valagussa, Pinuccia, Bogaerts, Jan, Bonnefoi, Herve, Poncet, Coralie, Huovinen, Riikka, Joensuu, Heikki, Bonneterre, Jacques, Fargeot, Pierre, Fumoleau, Pierre, Kerbrat, Pierre, Luporsi, Elisabeth, Namer, Moïse, Carrasco, Eva M, Segui, Miguel Angel, Meisner, Christoph, Loibl, Sibylle, Nekljudova, Valentina, Thomssen, Christoph, Von Minckwitz, Gunter, Kümmel, Sherko, Lopez, Massimo, Vici, Patrizia, Fountzilas, George, Koliou, Georgia, Mavroudis, Dimitrios, Saloustros, Emmanouil, Brain, Etienne, Delaloge, Suzette, Michiels, Stefan, Mathoulin-Pelissier, Simone, Bines, Jose, Sarmento, Roberta M B, Bonadonna, Gianni, Brambilla, Cristina, Rossi, Anna, Bliss, Judith, Coombes, Raoul Charles, Kilburn, Lucy, Marty, Michel, Amadori, Dino, Boccardo, Francesco, Nanni, Oriana, Rubagotti, Alessandra, Scarpi, Emanuela, Masuda, Norikazu, Toi, Masakazu, Ueno, Takayuki, Ishikawa, Takashi, Matsumoto, Koji, Takao, Shintaro, Sommer, Harald, Foroglou, Pericles, Giokas, George, Kondylis, D, Lissaios, Byron, Reinisch, Mattea, Lee, Keun Seok, Nam, Byung-Ho, Ro, Jung Sil, De Matteis, Andrea, Perrone, Francesco, Tang, Gong, Wolmark, Norman, Hozumi, Yasuo, Nomura, Yasuo, Earl, Helena, Hiller, Louise, Vallier, Anne-Laure, De Mastro, Lucia, Venturini, Macro, Delozier, Thierry, Lemonnier, Jerome, Martin, Anne-Laure, Roché, Henri, Spielmann, Marc, Chen, Xiasong, Shen, Kunwei, Albain, Kathy, Barlow, William, Budd, George T, Gralow, Julie, Hayes, Dan, Bartlett-Lee, Peter, Ellis, Paul, Bianco, Angelo Raffaele, De Laurentiis, Michelino, De Placido, Sabino, Wildiers, Hans, Hsu, Limin, Eremin, Oleg, Walker, Leslie G, Ahlgren, Johan, Blomqvist, Carl, Holmberg, Lars, Lindman, Henrik, Asmar, Lina, Jones, Stephen E, Gluz, Oleg, Liedtke, Cornelia, Arriagada, Rodrigo, Bergsten-Nordström, Elizabeth, Carey, Lisa, Coleman, Robert, Cuzick, Jack, Davidson, Nancy, Dignam, James, Dowsett, Mitch, Francis, Prudence A, Goetz, Matthew P, Goodwin, Pam, Halpin-Murphy, Pat, Hill, Catherine, Jagsi, Reshma, Mukai, Hirofumi, Ohashi, Yasuo, Pierce, Lori, Poortmans, Philip, Raina, Vinod, Rea, Daniel, Robertson, John, Rutgers, Emiel, Salgado, Roberto, Spanic, Tanja, Tutt, Andrew, Viale, Giuseppe, Wang, Xiang, Whelan, Tim, Wilcken, Nicholas, Cameron, David, Bergh, Jonas, and Swain, Sandra M

Published
2023
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36. DCIS AI-TIL: Ductal Carcinoma In Situ Tumour Infiltrating Lymphocyte Scoring Using Artificial Intelligence

Author

Hagos, Yeman Brhane, Sobhani, Faranak, Castillo, Simon P., Hall, Allison H., AbdulJabbar, Khalid, Salgado, Roberto, Harmon, Bryan, Gallagher, Kristalyn, Kilgore, Mark, King, Lorraine M., Marks, Jeffrey R., Maley, Carlo, Horlings, Hugo M., West, Robert, Hwang, E. Shelley, Yuan, Yinyin, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Kakileti, Siva Teja, editor, Gabrani, Maria, editor, Manjunath, Geetha, editor, Rosen-Zvi, Michal, editor, Braman, Nathaniel, editor, Schwartz, Robert G., editor, Frangi, Alejandro F., editor, Chung, Pau-Choo, editor, Weight, Christopher, editor, and Jagadish, Vekataraman, editor

Published
2022
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39. NeoTRACT: Phase II trial of neoadjuvant tumor infiltrating lymphocyte- and response-adapted chemoimmunotherapy for triple-negative breast cancer (TNBC).

Author

Stecklein, Shane R., primary, Aripoli, Allison, additional, Salgado, Roberto, additional, O'Dea, Anne, additional, Nye, Lauren Elizabeth, additional, Larson, Kelsey E., additional, Satelli, Deepti, additional, Rader, Ryan, additional, Madan, Rashna, additional, Yoder, Rachel, additional, Staley, Joshua M., additional, Fernandez, India, additional, Heinrich, Adam, additional, Wagner, Jamie L., additional, Balanoff, Christa, additional, Kilgore, Lyndsey, additional, Bantis, Leonidas, additional, Godwin, Andrew K., additional, Khan, Qamar J., additional, and Sharma, Priyanka, additional

Published
2024
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40. Data from Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy

Author

Martín, Miguel, primary, Yoder, Rachel, primary, Salgado, Roberto, primary, del Monte-Millán, María, primary, Álvarez, Enrique L., primary, Echavarría, Isabel, primary, Staley, Joshua M., primary, O'Dea, Anne P., primary, Nye, Lauren E., primary, Stecklein, Shane R., primary, Bueno, Coralia, primary, Jerez, Yolanda, primary, Cebollero, María, primary, Bueno, Oscar, primary, García Saenz, José Ángel, primary, Moreno, Fernando, primary, Bohn, Uriel, primary, Gómez, Henry, primary, Massarrah, Tatiana, primary, Khan, Qamar J., primary, Godwin, Andrew K., primary, López-Tarruella, Sara, primary, and Sharma, Priyanka, primary

Published
2024
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43. Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer

Author

Loi, Sherene, Salgado, Roberto, Adams, Sylvia, Pruneri, Giancarlo, Francis, Prudence A., Lacroix-Triki, Magali, Joensuu, Heikki, Dieci, Maria Vittoria, Badve, Sunil, Demaria, Sandra, Gray, Robert, Munzone, Elisabetta, Drubay, Damien, Lemonnier, Jerome, Sotiriou, Christos, Kellokumpu-Lehtinen, Pirkko Liisa, Vingiani, Andrea, Gray, Kathryn, André, Fabrice, Denkert, Carsten, Piccart, Martine, Roblin, Elvire, and Michiels, Stefan

Published
2022
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44. Development of a deep‐learning model tailored for HER2 detection in breast cancer to aid pathologists in interpreting HER2‐low cases.

Author

Bannier, Pierre‐Antoine, Broeckx, Glenn, Herpin, Loïc, Dubois, Rémy, Van Praet, Lydwine, Maussion, Charles, Deman, Frederik, Amonoo, Ellen, Mera, Anca, Timbres, Jasmine, Gillett, Cheryl, Sawyer, Elinor, Gazińska, Patrycja, Ziolkowski, Piotr, Lacroix‐Triki, Magali, Salgado, Roberto, and Irshad, Sheeba

Subjects
FLUORESCENCE in situ hybridization, BREAST cancer, DEEP learning, ARTIFICIAL intelligence, LYMPHOCYTE count, BREAST
Abstract

Aims: Over 50% of breast cancer cases are "Human epidermal growth factor receptor 2 (HER2) low breast cancer (BC)", characterized by HER2 immunohistochemistry (IHC) scores of 1+ or 2+ alongside no amplification on fluorescence in situ hybridization (FISH) testing. The development of new anti‐HER2 antibody‐drug conjugates (ADCs) for treating HER2‐low breast cancers illustrates the importance of accurately assessing HER2 status, particularly HER2‐low breast cancer. In this study we evaluated the performance of a deep‐learning (DL) model for the assessment of HER2, including an assessment of the causes of discordances of HER2‐Null between a pathologist and the DL model. We specifically focussed on aligning the DL model rules with the ASCO/CAP guidelines, including stained cells' staining intensity and completeness of membrane staining. Methods and Results: We trained a DL model on a multicentric cohort of breast cancer cases with HER2‐IHC scores (n = 299). The model was validated on two independent multicentric validation cohorts (n = 369 and n = 92), with all cases reviewed by three senior breast pathologists. All cases underwent a thorough review by three senior breast pathologists, with the ground truth determined by a majority consensus on the final HER2 score among the pathologists. In total, 760 breast cancer cases were utilized throughout the training and validation phases of the study. The model's concordance with the ground truth (ICC = 0.77 [0.68–0.83]; Fisher P = 1.32e‐10) is higher than the average agreement among the three senior pathologists (ICC = 0.45 [0.17–0.65]; Fisher P = 2e‐3). In the two validation cohorts, the DL model identifies 95% [93% ‐ 98%] and 97% [91% ‐ 100%] of HER2‐low and HER2‐positive tumours, respectively. Discordant results were characterized by morphological features such as extended fibrosis, a high number of tumour‐infiltrating lymphocytes, and necrosis, whilst some artefacts such as nonspecific background cytoplasmic stain in the cytoplasm of tumour cells also cause discrepancy. Conclusion: Deep learning can support pathologists' interpretation of difficult HER2‐low cases. Morphological variables and some specific artefacts can cause discrepant HER2‐scores between the pathologist and the DL model. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Tumor-Infiltrating Lymphocytes in Patients With Stage I Triple-Negative Breast Cancer Untreated With Chemotherapy.

Author

Geurts, Veerle C. M., Balduzzi, Sara, Steenbruggen, Tessa G., Linn, Sabine C., Siesling, Sabine, Badve, Sunil S., DeMichele, Angela, Ignatiadis, Michail, Leon-Ferre, Roberto A., Goetz, Matthew P., Wolff, Antonio C., Klar, Natalie, Michiels, Stefan, Loi, Sherene, Adams, Sylvia, Horlings, Hugo M., Sonke, Gabe S., Salgado, Roberto, and Kok, Marleen

Published
2024
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50. Microtubule targeting agents influence the clinical benefit of immune response in early breast cancer.

Author

Jose, Vinu, primary, Venet, David, additional, Rothé, Françoise, additional, Majjaj, Samira, additional, Vincent, Delphine, additional, Buisseret, Laurence, additional, Salgado, Roberto, additional, Sirtaine, Nicolas, additional, Michiels, Stefan, additional, Loi, Sherene, additional, Joensuu, Heikki, additional, and Sotiriou, Christos, additional

Published
2024
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