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Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

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Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment. / Morra, Anna; Escala-Garcia, Maria; Beesley, Jonathan; Keeman, Renske; Canisius, Sander; Ahearn, Thomas U; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Auer, Paul L; Augustinsson, Annelie; Beane Freeman, Laura E; Becher, Heiko; Beckmann, Matthias W; Behrens, Sabine; Bojesen, Stig E; Bolla, Manjeet K; Brenner, Hermann; Brüning, Thomas; Buys, Saundra S; Caan, Bette; Campa, Daniele; Canzian, Federico; Castelao, Jose E; Chang-Claude, Jenny; Chanock, Stephen J; Cheng, Ting-Yuan David; Clarke, Christine L; Colonna, Sarah V; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Daly, Mary B; Dennis, Joe; Dörk, Thilo; Dossus, Laure; Dunning, Alison M; Dwek, Miriam; Eccles, Diana M; Ekici, Arif B; Eliassen, A Heather; Eriksson, Mikael; Evans, D Gareth; Fasching, Peter A; Flyger, Henrik; Fritschi, Lin; Gago-Dominguez, Manuela; García-Sáenz, José A; Giles, Graham G; Grip, Mervi; Guénel, Pascal; Gündert, Melanie; Hahnen, Eric; Haiman, Christopher A; Håkansson, Niclas; Hall, Per; Hamann, Ute; Hart, Steven N; Hartikainen, Jaana M; Hartmann, Arndt; He, Wei; Hooning, Maartje J; Hoppe, Reiner; Hopper, John L; Howell, Anthony; Hunter, David J; Jager, Agnes; Jakubowska, Anna; Janni, Wolfgang; John, Esther M; Jung, Audrey Y; Kaaks, Rudolf; Keupers, Machteld; Kitahara, Cari M; Koutros, Stella; Kraft, Peter; Kristensen, Vessela N; Kurian, Allison W; Lacey, James V; Lambrechts, Diether; Le Marchand, Loic; Lindblom, Annika; Linet, Martha; Luben, Robert N; Lubiński, Jan; Lush, Michael; Mannermaa, Arto; Manoochehri, Mehdi; Margolin, Sara; Martens, John W M; Martinez, Maria Elena; Mavroudis, Dimitrios; Michailidou, Kyriaki; Milne, Roger L; Mulligan, Anna Marie; Muranen, Taru A; Nevanlinna, Heli; Newman, William G; Nielsen, Sune F; Nordestgaard, Børge G; Olshan, Andrew F; Olsson, Håkan; Orr, Nick; Park-Simon, Tjoung-Won; Patel, Alpa V; Peissel, Bernard; Peterlongo, Paolo; Plaseska-Karanfilska, Dijana; Prajzendanc, Karolina; Prentice, Ross; Presneau, Nadege; Rack, Brigitte; Rennert, Gad; Rennert, Hedy S; Rhenius, Valerie; Romero, Atocha; Roylance, Rebecca; Ruebner, Matthias; Saloustros, Emmanouil; Sawyer, Elinor J; Schmutzler, Rita K; Schneeweiss, Andreas; Scott, Christopher; Shah, Mitul; Smichkoska, Snezhana; Southey, Melissa C; Stone, Jennifer; Surowy, Harald; Swerdlow, Anthony J; Tamimi, Rulla M; Tapper, William J; Teras, Lauren R; Terry, Mary Beth; Tollenaar, Rob A E M; Tomlinson, Ian; Troester, Melissa A; Truong, Thérèse; Vachon, Celine M; Wang, Qin; Hurson, Amber N; Winqvist, Robert; Wolk, Alicja; Ziogas, Argyrios; Brauch, Hiltrud; García-Closas, Montserrat; Pharoah, Paul D P; Easton, Douglas F; Chenevix-Trench, Georgia; Schmidt, Marjanka K; NBCS Collaborators.

in: BREAST CANCER RES, Jahrgang 23, Nr. 1, 18.08.2021, S. 86.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Morra, A, Escala-Garcia, M, Beesley, J, Keeman, R, Canisius, S, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Arndt, V, Auer, PL, Augustinsson, A, Beane Freeman, LE, Becher, H, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brenner, H, Brüning, T, Buys, SS, Caan, B, Campa, D, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Cheng, T-YD, Clarke, CL, Colonna, SV, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Dörk, T, Dossus, L, Dunning, AM, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fritschi, L, Gago-Dominguez, M, García-Sáenz, JA, Giles, GG, Grip, M, Guénel, P, Gündert, M, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Hart, SN, Hartikainen, JM, Hartmann, A, He, W, Hooning, MJ, Hoppe, R, Hopper, JL, Howell, A, Hunter, DJ, Jager, A, Jakubowska, A, Janni, W, John, EM, Jung, AY, Kaaks, R, Keupers, M, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kurian, AW, Lacey, JV, Lambrechts, D, Le Marchand, L, Lindblom, A, Linet, M, Luben, RN, Lubiński, J, Lush, M, Mannermaa, A, Manoochehri, M, Margolin, S, Martens, JWM, Martinez, ME, Mavroudis, D, Michailidou, K, Milne, RL, Mulligan, AM, Muranen, TA, Nevanlinna, H, Newman, WG, Nielsen, SF, Nordestgaard, BG, Olshan, AF, Olsson, H, Orr, N, Park-Simon, T-W, Patel, AV, Peissel, B, Peterlongo, P, Plaseska-Karanfilska, D, Prajzendanc, K, Prentice, R, Presneau, N, Rack, B, Rennert, G, Rennert, HS, Rhenius, V, Romero, A, Roylance, R, Ruebner, M, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schneeweiss, A, Scott, C, Shah, M, Smichkoska, S, Southey, MC, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Teras, LR, Terry, MB, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, Wang, Q, Hurson, AN, Winqvist, R, Wolk, A, Ziogas, A, Brauch, H, García-Closas, M, Pharoah, PDP, Easton, DF, Chenevix-Trench, G, Schmidt, MK & NBCS Collaborators 2021, 'Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment', BREAST CANCER RES, Jg. 23, Nr. 1, S. 86. https://doi.org/10.1186/s13058-021-01450-7

APA

Morra, A., Escala-Garcia, M., Beesley, J., Keeman, R., Canisius, S., Ahearn, T. U., Andrulis, I. L., Anton-Culver, H., Arndt, V., Auer, P. L., Augustinsson, A., Beane Freeman, L. E., Becher, H., Beckmann, M. W., Behrens, S., Bojesen, S. E., Bolla, M. K., Brenner, H., Brüning, T., ... NBCS Collaborators (2021). Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment. BREAST CANCER RES, 23(1), 86. https://doi.org/10.1186/s13058-021-01450-7

Vancouver

Morra A, Escala-Garcia M, Beesley J, Keeman R, Canisius S, Ahearn TU et al. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment. BREAST CANCER RES. 2021 Aug 18;23(1):86. https://doi.org/10.1186/s13058-021-01450-7

Bibtex

@article{deeee56c93d94ff3a81f8ce3685a34da,
title = "Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment",
abstract = "BACKGROUND: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.METHODS: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15).RESULTS: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy.CONCLUSIONS: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.",
author = "Anna Morra and Maria Escala-Garcia and Jonathan Beesley and Renske Keeman and Sander Canisius and Ahearn, {Thomas U} and Andrulis, {Irene L} and Hoda Anton-Culver and Volker Arndt and Auer, {Paul L} and Annelie Augustinsson and {Beane Freeman}, {Laura E} and Heiko Becher and Beckmann, {Matthias W} and Sabine Behrens and Bojesen, {Stig E} and Bolla, {Manjeet K} and Hermann Brenner and Thomas Br{\"u}ning and Buys, {Saundra S} and Bette Caan and Daniele Campa and Federico Canzian and Castelao, {Jose E} and Jenny Chang-Claude and Chanock, {Stephen J} and Cheng, {Ting-Yuan David} and Clarke, {Christine L} and Colonna, {Sarah V} and Couch, {Fergus J} and Angela Cox and Cross, {Simon S} and Kamila Czene and Daly, {Mary B} and Joe Dennis and Thilo D{\"o}rk and Laure Dossus and Dunning, {Alison M} and Miriam Dwek and Eccles, {Diana M} and Ekici, {Arif B} and Eliassen, {A Heather} and Mikael Eriksson and Evans, {D Gareth} and Fasching, {Peter A} and Henrik Flyger and Lin Fritschi and Manuela Gago-Dominguez and Garc{\'i}a-S{\'a}enz, {Jos{\'e} A} and Giles, {Graham G} and Mervi Grip and Pascal Gu{\'e}nel and Melanie G{\"u}ndert and Eric Hahnen and Haiman, {Christopher A} and Niclas H{\aa}kansson and Per Hall and Ute Hamann and Hart, {Steven N} and Hartikainen, {Jaana M} and Arndt Hartmann and Wei He and Hooning, {Maartje J} and Reiner Hoppe and Hopper, {John L} and Anthony Howell and Hunter, {David J} and Agnes Jager and Anna Jakubowska and Wolfgang Janni and John, {Esther M} and Jung, {Audrey Y} and Rudolf Kaaks and Machteld Keupers and Kitahara, {Cari M} and Stella Koutros and Peter Kraft and Kristensen, {Vessela N} and Kurian, {Allison W} and Lacey, {James V} and Diether Lambrechts and {Le Marchand}, Loic and Annika Lindblom and Martha Linet and Luben, {Robert N} and Jan Lubi{\'n}ski and Michael Lush and Arto Mannermaa and Mehdi Manoochehri and Sara Margolin and Martens, {John W M} and Martinez, {Maria Elena} and Dimitrios Mavroudis and Kyriaki Michailidou and Milne, {Roger L} and Mulligan, {Anna Marie} and Muranen, {Taru A} and Heli Nevanlinna and Newman, {William G} and Nielsen, {Sune F} and Nordestgaard, {B{\o}rge G} and Olshan, {Andrew F} and H{\aa}kan Olsson and Nick Orr and Tjoung-Won Park-Simon and Patel, {Alpa V} and Bernard Peissel and Paolo Peterlongo and Dijana Plaseska-Karanfilska and Karolina Prajzendanc and Ross Prentice and Nadege Presneau and Brigitte Rack and Gad Rennert and Rennert, {Hedy S} and Valerie Rhenius and Atocha Romero and Rebecca Roylance and Matthias Ruebner and Emmanouil Saloustros and Sawyer, {Elinor J} and Schmutzler, {Rita K} and Andreas Schneeweiss and Christopher Scott and Mitul Shah and Snezhana Smichkoska and Southey, {Melissa C} and Jennifer Stone and Harald Surowy and Swerdlow, {Anthony J} and Tamimi, {Rulla M} and Tapper, {William J} and Teras, {Lauren R} and Terry, {Mary Beth} and Tollenaar, {Rob A E M} and Ian Tomlinson and Troester, {Melissa A} and Th{\'e}r{\`e}se Truong and Vachon, {Celine M} and Qin Wang and Hurson, {Amber N} and Robert Winqvist and Alicja Wolk and Argyrios Ziogas and Hiltrud Brauch and Montserrat Garc{\'i}a-Closas and Pharoah, {Paul D P} and Easton, {Douglas F} and Georgia Chenevix-Trench and Schmidt, {Marjanka K} and {NBCS Collaborators}",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
month = aug,
day = "18",
doi = "10.1186/s13058-021-01450-7",
language = "English",
volume = "23",
pages = "86",
journal = "BREAST CANCER RES",
issn = "1465-5411",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

AU - Morra, Anna

AU - Escala-Garcia, Maria

AU - Beesley, Jonathan

AU - Keeman, Renske

AU - Canisius, Sander

AU - Ahearn, Thomas U

AU - Andrulis, Irene L

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Auer, Paul L

AU - Augustinsson, Annelie

AU - Beane Freeman, Laura E

AU - Becher, Heiko

AU - Beckmann, Matthias W

AU - Behrens, Sabine

AU - Bojesen, Stig E

AU - Bolla, Manjeet K

AU - Brenner, Hermann

AU - Brüning, Thomas

AU - Buys, Saundra S

AU - Caan, Bette

AU - Campa, Daniele

AU - Canzian, Federico

AU - Castelao, Jose E

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J

AU - Cheng, Ting-Yuan David

AU - Clarke, Christine L

AU - Colonna, Sarah V

AU - Couch, Fergus J

AU - Cox, Angela

AU - Cross, Simon S

AU - Czene, Kamila

AU - Daly, Mary B

AU - Dennis, Joe

AU - Dörk, Thilo

AU - Dossus, Laure

AU - Dunning, Alison M

AU - Dwek, Miriam

AU - Eccles, Diana M

AU - Ekici, Arif B

AU - Eliassen, A Heather

AU - Eriksson, Mikael

AU - Evans, D Gareth

AU - Fasching, Peter A

AU - Flyger, Henrik

AU - Fritschi, Lin

AU - Gago-Dominguez, Manuela

AU - García-Sáenz, José A

AU - Giles, Graham G

AU - Grip, Mervi

AU - Guénel, Pascal

AU - Gündert, Melanie

AU - Hahnen, Eric

AU - Haiman, Christopher A

AU - Håkansson, Niclas

AU - Hall, Per

AU - Hamann, Ute

AU - Hart, Steven N

AU - Hartikainen, Jaana M

AU - Hartmann, Arndt

AU - He, Wei

AU - Hooning, Maartje J

AU - Hoppe, Reiner

AU - Hopper, John L

AU - Howell, Anthony

AU - Hunter, David J

AU - Jager, Agnes

AU - Jakubowska, Anna

AU - Janni, Wolfgang

AU - John, Esther M

AU - Jung, Audrey Y

AU - Kaaks, Rudolf

AU - Keupers, Machteld

AU - Kitahara, Cari M

AU - Koutros, Stella

AU - Kraft, Peter

AU - Kristensen, Vessela N

AU - Kurian, Allison W

AU - Lacey, James V

AU - Lambrechts, Diether

AU - Le Marchand, Loic

AU - Lindblom, Annika

AU - Linet, Martha

AU - Luben, Robert N

AU - Lubiński, Jan

AU - Lush, Michael

AU - Mannermaa, Arto

AU - Manoochehri, Mehdi

AU - Margolin, Sara

AU - Martens, John W M

AU - Martinez, Maria Elena

AU - Mavroudis, Dimitrios

AU - Michailidou, Kyriaki

AU - Milne, Roger L

AU - Mulligan, Anna Marie

AU - Muranen, Taru A

AU - Nevanlinna, Heli

AU - Newman, William G

AU - Nielsen, Sune F

AU - Nordestgaard, Børge G

AU - Olshan, Andrew F

AU - Olsson, Håkan

AU - Orr, Nick

AU - Park-Simon, Tjoung-Won

AU - Patel, Alpa V

AU - Peissel, Bernard

AU - Peterlongo, Paolo

AU - Plaseska-Karanfilska, Dijana

AU - Prajzendanc, Karolina

AU - Prentice, Ross

AU - Presneau, Nadege

AU - Rack, Brigitte

AU - Rennert, Gad

AU - Rennert, Hedy S

AU - Rhenius, Valerie

AU - Romero, Atocha

AU - Roylance, Rebecca

AU - Ruebner, Matthias

AU - Saloustros, Emmanouil

AU - Sawyer, Elinor J

AU - Schmutzler, Rita K

AU - Schneeweiss, Andreas

AU - Scott, Christopher

AU - Shah, Mitul

AU - Smichkoska, Snezhana

AU - Southey, Melissa C

AU - Stone, Jennifer

AU - Surowy, Harald

AU - Swerdlow, Anthony J

AU - Tamimi, Rulla M

AU - Tapper, William J

AU - Teras, Lauren R

AU - Terry, Mary Beth

AU - Tollenaar, Rob A E M

AU - Tomlinson, Ian

AU - Troester, Melissa A

AU - Truong, Thérèse

AU - Vachon, Celine M

AU - Wang, Qin

AU - Hurson, Amber N

AU - Winqvist, Robert

AU - Wolk, Alicja

AU - Ziogas, Argyrios

AU - Brauch, Hiltrud

AU - García-Closas, Montserrat

AU - Pharoah, Paul D P

AU - Easton, Douglas F

AU - Chenevix-Trench, Georgia

AU - Schmidt, Marjanka K

AU - NBCS Collaborators

N1 - © 2021. The Author(s).

PY - 2021/8/18

Y1 - 2021/8/18

N2 - BACKGROUND: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.METHODS: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15).RESULTS: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy.CONCLUSIONS: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.

AB - BACKGROUND: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.METHODS: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15).RESULTS: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy.CONCLUSIONS: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.

U2 - 10.1186/s13058-021-01450-7

DO - 10.1186/s13058-021-01450-7

M3 - SCORING: Journal article

C2 - 34407845

VL - 23

SP - 86

JO - BREAST CANCER RES

JF - BREAST CANCER RES

SN - 1465-5411

IS - 1

ER -