Obesity-associated changes in molecular biology of primary breast cancer
Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using da...
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| creator | Nguyen, Ha-Linh Geukens, Tatjana Maetens, Marion Aparicio, Samuel Bassez, Ayse Borg, Ake Brock, Jane Broeks, Annegien Caldas, Carlos Cardoso, Fatima De Schepper, Maxim Delorenzi, Mauro Drukker, Caroline A Glas, Annuska M Green, Andrew R Isnaldi, Edoardo Eyfjörð, Jórunn Khout, Hazem Knappskog, Stian Krishnamurthy, Savitri Lakhani, Sunil R Langerød, Anita Martens, John W. M McCart Reed, Amy E Murphy, Leigh Naulaerts, Stefan Nik-Zainal, Serena Nevelsteen, Ines Neven, Patrick Piccart, Martine Poncet, Coralie Punie, Kevin Purdie, Colin Rakha, Emad A Richardson, Andrea Rutgers, Emiel Vincent-Salomon, Anne Simpson, Peter T Schmidt, Marjanka K Sotiriou, Christos Span, Paul N Tan, Kiat Tee Benita Thompson, Alastair Tommasi, Stefania Van Baelen, Karen Van de Vijver, Marc Van Laere, Steven van’t Veer, Laura Viale, Giuseppe Viari, Alain Vos, Hanne Witteveen, Anke T Wildiers, Hans Floris, Giuseppe Garg, Abhishek D Smeets, Ann Lambrechts, Diether Biganzoli, Elia Richard, François Desmedt, Christine |
| description | Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring. |
| format | Article |
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M ; McCart Reed, Amy E ; Murphy, Leigh ; Naulaerts, Stefan ; Nik-Zainal, Serena ; Nevelsteen, Ines ; Neven, Patrick ; Piccart, Martine ; Poncet, Coralie ; Punie, Kevin ; Purdie, Colin ; Rakha, Emad A ; Richardson, Andrea ; Rutgers, Emiel ; Vincent-Salomon, Anne ; Simpson, Peter T ; Schmidt, Marjanka K ; Sotiriou, Christos ; Span, Paul N ; Tan, Kiat Tee Benita ; Thompson, Alastair ; Tommasi, Stefania ; Van Baelen, Karen ; Van de Vijver, Marc ; Van Laere, Steven ; van’t Veer, Laura ; Viale, Giuseppe ; Viari, Alain ; Vos, Hanne ; Witteveen, Anke T ; Wildiers, Hans ; Floris, Giuseppe ; Garg, Abhishek D ; Smeets, Ann ; Lambrechts, Diether ; Biganzoli, Elia ; Richard, François ; Desmedt, Christine</creator><creatorcontrib>Nguyen, Ha-Linh ; Geukens, Tatjana ; Maetens, Marion ; Aparicio, Samuel ; Bassez, Ayse ; Borg, Ake ; Brock, Jane ; Broeks, Annegien ; Caldas, Carlos ; Cardoso, Fatima ; De Schepper, Maxim ; Delorenzi, Mauro ; Drukker, Caroline A ; Glas, Annuska M ; Green, Andrew R ; Isnaldi, Edoardo ; Eyfjörð, Jórunn ; Khout, Hazem ; Knappskog, Stian ; Krishnamurthy, Savitri ; Lakhani, Sunil R ; Langerød, Anita ; Martens, John W. M ; McCart Reed, Amy E ; Murphy, Leigh ; Naulaerts, Stefan ; Nik-Zainal, Serena ; Nevelsteen, Ines ; Neven, Patrick ; Piccart, Martine ; Poncet, Coralie ; Punie, Kevin ; Purdie, Colin ; Rakha, Emad A ; Richardson, Andrea ; Rutgers, Emiel ; Vincent-Salomon, Anne ; Simpson, Peter T ; Schmidt, Marjanka K ; Sotiriou, Christos ; Span, Paul N ; Tan, Kiat Tee Benita ; Thompson, Alastair ; Tommasi, Stefania ; Van Baelen, Karen ; Van de Vijver, Marc ; Van Laere, Steven ; van’t Veer, Laura ; Viale, Giuseppe ; Viari, Alain ; Vos, Hanne ; Witteveen, Anke T ; Wildiers, Hans ; Floris, Giuseppe ; Garg, Abhishek D ; Smeets, Ann ; Lambrechts, Diether ; Biganzoli, Elia ; Richard, François ; Desmedt, Christine</creatorcontrib><description>Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. 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This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.</abstract><pub>Nature</pub><oa>free_for_read</oa></addata></record> |
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| title | Obesity-associated changes in molecular biology of primary breast cancer |
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