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1. Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study

Author

Lambertini, M, Blondeaux, E, Agostinetto, E, Hamy, A, Kim, H, Di Meglio, A, Molho, R, Hilbers, F, Pogoda, K, Carrasco, E, Punie, K, Bajpai, J, Ignatiadis, M, Moore, H, Phillips, K, Toss, A, Rousset-Jablonski, C, Peccatori, F, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Ruddy, K, Dieci, M, Matikas, A, Rozenblit, M, Villarreal-Garza, C, De Marchis, L, Del Mastro, L, Puglisi, F, Estevez-Diz, M, Rodriguez-Wallberg, K, Mrinakova, B, Meister, S, Livraghi, L, Clatot, F, Yerushalmi, R, De Angelis, C, Sanchez-Bayona, R, Meattini, I, Cichowska-Cwalinska, N, Berliere, M, Salama, M, De Giorgi, U, Sonnenblick, A, Chiodi, C, Lee, Y, Maria, C, Azim, H, Boni, L, Partridge, A, Lambertini M., Blondeaux E., Agostinetto E., Hamy A. -S., Kim H. J., Di Meglio A., Molho R. B., Hilbers F., Pogoda K., Carrasco E., Punie K., Bajpai J., Ignatiadis M., Moore H. C. F., Phillips K. -A., Toss A., Rousset-Jablonski C., Peccatori F. A., Renaud T., Ferrari A., Paluch-Shimon S., Fruscio R., Cui W., Wong S. M., Vernieri C., Ruddy K. J., Dieci M. V., Matikas A., Rozenblit M., Villarreal-Garza C., De Marchis L., Del Mastro L., Puglisi F., Estevez-Diz M. D. P., Rodriguez-Wallberg K. A., Mrinakova B., Meister S., Livraghi L., Clatot F., Yerushalmi R., De Angelis C., Sanchez-Bayona R., Meattini I., Cichowska-Cwalinska N., Berliere M., Salama M., De Giorgi U., Sonnenblick A., Chiodi C., Lee Y. -J., Maria C., Azim H. A., Boni L., Partridge A. H., Lambertini, M, Blondeaux, E, Agostinetto, E, Hamy, A, Kim, H, Di Meglio, A, Molho, R, Hilbers, F, Pogoda, K, Carrasco, E, Punie, K, Bajpai, J, Ignatiadis, M, Moore, H, Phillips, K, Toss, A, Rousset-Jablonski, C, Peccatori, F, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Ruddy, K, Dieci, M, Matikas, A, Rozenblit, M, Villarreal-Garza, C, De Marchis, L, Del Mastro, L, Puglisi, F, Estevez-Diz, M, Rodriguez-Wallberg, K, Mrinakova, B, Meister, S, Livraghi, L, Clatot, F, Yerushalmi, R, De Angelis, C, Sanchez-Bayona, R, Meattini, I, Cichowska-Cwalinska, N, Berliere, M, Salama, M, De Giorgi, U, Sonnenblick, A, Chiodi, C, Lee, Y, Maria, C, Azim, H, Boni, L, Partridge, A, Lambertini M., Blondeaux E., Agostinetto E., Hamy A. -S., Kim H. J., Di Meglio A., Molho R. B., Hilbers F., Pogoda K., Carrasco E., Punie K., Bajpai J., Ignatiadis M., Moore H. C. F., Phillips K. -A., Toss A., Rousset-Jablonski C., Peccatori F. A., Renaud T., Ferrari A., Paluch-Shimon S., Fruscio R., Cui W., Wong S. M., Vernieri C., Ruddy K. J., Dieci M. V., Matikas A., Rozenblit M., Villarreal-Garza C., De Marchis L., Del Mastro L., Puglisi F., Estevez-Diz M. D. P., Rodriguez-Wallberg K. A., Mrinakova B., Meister S., Livraghi L., Clatot F., Yerushalmi R., De Angelis C., Sanchez-Bayona R., Meattini I., Cichowska-Cwalinska N., Berliere M., Salama M., De Giorgi U., Sonnenblick A., Chiodi C., Lee Y. -J., Maria C., Azim H. A., Boni L., and Partridge A. H.

Abstract

(Abstracted from JAMA 2024;331(1):49-59 Individuals who are diagnosed with breast cancer at a young age are often carriers of a pathogenic variant in the BRCA1 or BRCA2 genes, and many young women in this situation are interested in preserving future fertility, if possible. Reproductive counseling in this situation can be complex due to the risk of passing on the variant, as well as the implications on their own fertility, as the mutation can impact ovarian reserve, fertility potential, and other factors.

Published
2024

2. Characteristics and clinical outcomes of breast cancer in young BRCA carriers according to tumor histology

Author

Agostinetto, E, Bruzzone, M, Hamy, A, Kim, H, Chiodi, C, Bernstein-Molho, R, Linn, S, Pogoda, K, Carrasco, E, Derouane, F, Bajpai, J, Nader-Marta, G, Lopetegui-Lia, N, Partridge, A, Cortesi, L, Rousset-Jablonski, C, Giugliano, F, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Ruddy, K, Dieci, M, Matikas, A, Rozenblit, M, Aguilar Y Mendez, D, De Marchis, L, Borea, R, Puglisi, F, Pistelli, M, Kufel-Grabowska, J, Di Rocco, R, Mariamidze, E, Atzori, F, Kourie, H, Popovic, L, de Azambuja, E, Blondeaux, E, Lambertini, M, Hamy, A-S, Kim, H J, Partridge, A H, Wong, S M, Ruddy, K J, Dieci, M V, Kourie, H R, Agostinetto, E, Bruzzone, M, Hamy, A, Kim, H, Chiodi, C, Bernstein-Molho, R, Linn, S, Pogoda, K, Carrasco, E, Derouane, F, Bajpai, J, Nader-Marta, G, Lopetegui-Lia, N, Partridge, A, Cortesi, L, Rousset-Jablonski, C, Giugliano, F, Renaud, T, Ferrari, A, Paluch-Shimon, S, Fruscio, R, Cui, W, Wong, S, Vernieri, C, Ruddy, K, Dieci, M, Matikas, A, Rozenblit, M, Aguilar Y Mendez, D, De Marchis, L, Borea, R, Puglisi, F, Pistelli, M, Kufel-Grabowska, J, Di Rocco, R, Mariamidze, E, Atzori, F, Kourie, H, Popovic, L, de Azambuja, E, Blondeaux, E, Lambertini, M, Hamy, A-S, Kim, H J, Partridge, A H, Wong, S M, Ruddy, K J, Dieci, M V, and Kourie, H R

Abstract

Background: Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer. Methods: This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival. Results: Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index. Conclusions: In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis.

Published
2024

3. Patient perceptions of altering chemotherapy treatment due to peripheral neuropathy

Author

Hertz, D, Tofthagen, C, Rossi, E, Bernasconi, D, Lim, J, Carlson, M, Sheffield, K, Nekhlyudov, L, Grech, L, Von Ah, D, Mayo, S, Ruddy, K, Chan, A, Alberti, P, Lustberg, M, Tanay, M, Hertz, Daniel L, Tofthagen, Cindy, Rossi, Emanuela, Bernasconi, Davide Paolo, Lim, Jiyoon, Carlson, Martha, Sheffield, Katharine E, Nekhlyudov, Larissa, Grech, Lisa, Von Ah, Diane, Mayo, Samantha J, Ruddy, Kathryn J, Chan, Alexandre, Alberti, Paola, Lustberg, Maryam B, Tanay, Mary, Hertz, D, Tofthagen, C, Rossi, E, Bernasconi, D, Lim, J, Carlson, M, Sheffield, K, Nekhlyudov, L, Grech, L, Von Ah, D, Mayo, S, Ruddy, K, Chan, A, Alberti, P, Lustberg, M, Tanay, M, Hertz, Daniel L, Tofthagen, Cindy, Rossi, Emanuela, Bernasconi, Davide Paolo, Lim, Jiyoon, Carlson, Martha, Sheffield, Katharine E, Nekhlyudov, Larissa, Grech, Lisa, Von Ah, Diane, Mayo, Samantha J, Ruddy, Kathryn J, Chan, Alexandre, Alberti, Paola, Lustberg, Maryam B, and Tanay, Mary

Abstract

Purpose: Clinical practice guidelines recommend altering neurotoxic chemotherapy treatment in patients experiencing intolerable chemotherapy-induced peripheral neuropathy (CIPN). The primary objective of this survey was to understand patient’s perspectives on altering neurotoxic chemotherapy treatment, including their perceptions of the benefits of preventing irreversible CIPN and the risks of reducing treatment efficacy. Methods: A cross-sectional online survey was distributed via social networks to patients who were currently receiving or had previously received neurotoxic chemotherapy for cancer. Survey results were analyzed using descriptive statistics and qualitative analysis. Results: Following data cleaning, 447 participants were included in the analysis. The median age was 57 years, 93% were white, and most were from the UK (53%) or USA (38%). Most participants who were currently or recently treated expected some CIPN symptom resolution (86%), but 45% of those who had completed treatment more than a year ago reported experiencing no symptom resolution. Participants reported that they would discontinue chemotherapy treatment for less severe CIPN if they knew their symptoms would be permanent than if symptoms would disappear after treatment. Most patients stated that the decision to alter chemotherapy or not was usually made collaboratively between the patient and their treating clinician (61%). The most common reason participants were reluctant to talk with their clinician about CIPN was fear that treatment would be altered. Participants noted a need for improved understanding of CIPN symptoms and their permanence, better patient education relating to CIPN prior to and after treatment, and greater clinician understanding and empathy around CIPN. Conclusions: This survey highlights the importance of shared decision-making, including a consideration of both the long-term benefits and risks of altering neurotoxic chemotherapy treatment due to CIPN. Additional wo

Published
2024

5. Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer

Author

Partridge, AH, Niman, SM, Ruggeri, M, Peccatori, FA, Azim, HA, Colleoni, M, Saura, C, Shimizu, C, Saetersdal, AB, Kroep, JR, Mailliez, A, Warner, E, Borges, VF, Amant, F, Gombos, A, Kataoka, A, Rousset-Jablonski, C, Borstnar, S, Takei, J, Lee, JE, Walshe, JM, Ruiz-Borrego, M, Moore, HCF, Saunders, C, Bjelic-Radisic, V, Susnjar, S, Cardoso, F, Smith, KL, Ferreiro, T, Ribi, K, Ruddy, K, Kammler, R, El-Abed, S, Viale, G, Piccart, M, Korde, LA, Goldhirsch, A, Gelber, RD, Pagani, O, Partridge, AH, Niman, SM, Ruggeri, M, Peccatori, FA, Azim, HA, Colleoni, M, Saura, C, Shimizu, C, Saetersdal, AB, Kroep, JR, Mailliez, A, Warner, E, Borges, VF, Amant, F, Gombos, A, Kataoka, A, Rousset-Jablonski, C, Borstnar, S, Takei, J, Lee, JE, Walshe, JM, Ruiz-Borrego, M, Moore, HCF, Saunders, C, Bjelic-Radisic, V, Susnjar, S, Cardoso, F, Smith, KL, Ferreiro, T, Ribi, K, Ruddy, K, Kammler, R, El-Abed, S, Viale, G, Piccart, M, Korde, LA, Goldhirsch, A, Gelber, RD, and Pagani, O

Abstract

BACKGROUND: Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. METHODS: We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. RESULTS: Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. CONCLUSIONS: Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a grea

Published
2023

8. Fertility

Author

Ruddy, K. J., Partridge, A. H., Castiglione, Monica, editor, and Piccart, Martine J., editor

Published
2009
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9. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program

Author

Cardoso, F, Bartlett, J M S, Slaets, L, van Deurzen, C H M, van Leeuwen-Stok, E, Porter, P, Linderholm, B, Hedenfalk, I, Schröder, C, Martens, J, Bayani, J, van Asperen, C, Murray, M, Hudis, C, Middleton, L, Vermeij, J, Punie, K, Fraser, J, Nowaczyk, M, Rubio, I T, Aebi, S, Kelly, C, Ruddy, K J, Winer, E, Nilsson, C, Dal Lago, L, Korde, L, Benstead, K, Bogler, O, Goulioti, T, Peric, A, Litière, S, Aalders, K C, Poncet, C, Tryfonidis, K, and Giordano, S H

Published
2018
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10. White Matter Abnormalities in the Amputation Variant of Body Integrity Dysphoria

Author

Saetta, G, Ruddy, K, Zapparoli, L, Gandola, M, Salvato, G, Sberna, M, Bottini, G, Brugger, P, Lenggenhager, B, Saetta, Gianluca, Ruddy, Kathy, Zapparoli, Laura, Gandola, Martina, Salvato, Gerardo, Sberna, Maurizio, Bottini, Gabriella, Brugger, Peter, Lenggenhager, Bigna, Saetta, G, Ruddy, K, Zapparoli, L, Gandola, M, Salvato, G, Sberna, M, Bottini, G, Brugger, P, Lenggenhager, B, Saetta, Gianluca, Ruddy, Kathy, Zapparoli, Laura, Gandola, Martina, Salvato, Gerardo, Sberna, Maurizio, Bottini, Gabriella, Brugger, Peter, and Lenggenhager, Bigna

Abstract

“Body integrity dysphoria” (BID) is a severe condition affecting nonpsychotic individuals. In the amputation variant of BID, a limb may be experienced as not being part of the body, despite normal anatomical development and intact sensorimotor functions. We previously demonstrated altered brain structural (gray matter) and functional connectivity in 16 men with BID with a long-lasting and exclusive desire for left leg amputation. Here, we aimed to identify, in the same sample, altered patterns of white matter structural connectivity. Fractional anisotropy (FA), derived from diffusion tensor imaging data, was considered as a measure of structural connectivity. Results showed reduced structural connectivity of: (i) the right superior parietal lobule (rSPL) with the right cuneus, with the superior occipital and with the posterior cingulate gyri, (ii) the pars orbitalis of the right middle frontal gyrus (rMFGOrb) with the putamen, and (iii) the left middle temporal gyrus (lMTG) with the pars triangularis of the left inferior frontal gyrus. Increased connectivity was found between the right paracentral lobule (rPLC) and the right caudate nucleus. By using a complementary method of investigation, we confirmed and extended previous results from the same sample of individuals with BID, showing structural alterations between areas tuned to the processing of the sensorimotor representations of the affected leg (rPCL), and to higher-order components of bodily representation such as the body image (rSPL) and visual processing. Alongside this network for bodily awareness, other networks such as the limbic (rMFGOrb) and the mirror (lMTG) systems showed alterations in structural connectivity. These findings consolidate current understanding of the neural correlates of the amputation variant of BID, which might in turn guide diagnostics and rehabilitative treatments.

Published
2022

12. CYP3A7*1C allele:linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Author

Johnson, N. (Nichola), Maguire, S. (Sarah), Morra, A. (Anna), Kapoor, P. M. (Pooja Middha), Tomczyk, K. (Katarzyna), Jones, M. E. (Michael E.), Schoemaker, M. J. (Minouk J.), Gilham, C. (Clare), Bolla, M. K. (Manjeet K.), Wang, Q. (Qin), Dennis, J. (Joe), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Augustinsson, A. (Annelie), Baynes, C. (Caroline), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Boeckx, B. (Bram), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chanock, S. J. (Stephen J.), Chenevix-Trench, G. (Georgia), Clarke, C. L. (Christine L.), Conroy, D. M. (Don M.), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Doerk, T. (Thilo), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Floris, G. (Giuseppe), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Gaudet, M. M. (Mia M.), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P. A. (Patricia A.), Hart, S. N. (Steven N.), Hooning, M. J. (Maartje J.), Hopper, J. L. (John L.), Howell, A. (Anthony), Hunter, D. J. (David J.), Jager, A. (Agnes), Jakubowska, A. (Anna), John, E. M. (Esther M.), Kaaks, R. (Rudolf), Keeman, R. (Renske), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Linet, M. (Martha), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J. W. (John W. M.), Mavroudis, D. (Dimitrios), Mayes, R. (Rebecca), Meindl, A. (Alfons), Milne, R. L. (Roger L.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Obi, N. (Nadia), Olshan, A. F. (Andrew F.), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orban, E. (Ester), Park-Simon, T.-W. (Tjoung-Won), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Pylkäs, K. (Katri), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Ruddy, K. J. (Kathryn J.), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Scott, C. (Christopher), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Smichkoska, S. (Snezhana), Sohn, C. (Christof), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stone, J. (Jennifer), Tamimi, R. M. (Rulla M.), Taylor, J. A. (Jack A.), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Wang, S. S. (Sophia S.), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Wildiers, H. (Hans), Winqvist, R. (Robert), Wolk, A. (Alicja), Zheng, W. (Wei), Ziogas, A. (Argyrios), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Howie, A. F. (A. Forbes), Peto, J. (Julian), dos-Santos-Silva, I. (Isabel), Swerdlow, A. J. (Anthony J.), Chang-Claude, J. (Jenny), Schmidt, M. K. (Marjanka K.), Orr, N. (Nick), and Fletcher, O. (Olivia)

Abstract

Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10⁻¹⁸); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10⁻¹⁸). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.

Published
2021

22. Polygenic risk scores for prediction of breast cancer and breast cancer subtypes

Author

Mavaddat, N. (Nasim), Michailidou, K. (Kyriaki), Dennis, J. (Joe), Lush, M. (Michael), Fachal, L. (Laura), Lee, A. (Andrew), Tyrer, J. P. (Jonathan P.), Chen, T.-H. (Ting-Huei), Wang, Q. (Qin), Bolla, M. K. (Manjeet K.), Yang, X. (Xin), Adank, M. A. (Muriel A.), Ahearn, T. (Thomas), Aittomaki, K. (Kristiina), Allen, J. (Jamie), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Auvinen, P. (Paivi), Barrdahl, M. (Myrto), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Bremer, M. (Michael), Brenner, H. (Hermann), Brentnall, A. (Adam), Brock, I. W. (Ian W.), Brooks-Wilson, A. (Angela), Brucker, S. Y. (Sara Y.), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Campa, D. (Daniele), Carter, B. D. (Brian D.), Castelao, J. E. (Jose E.), Chanock, S. J. (Stephen J.), Chlebowski, R. (Rowan), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, J. M. (J. Margriet), Cordina-Duverger, E. (Emilie), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doerk, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Durcan, L. (Lorraine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foersti, A. (Asta), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Georgoulias, V. (Vassilios), Giles, G. G. (Graham G.), Gilyazova, I. R. (Irina R.), Glendon, G. (Gord), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Alnaes, G. I. (Grethe I. Grenaker), Grip, M. (Mervi), Gronwald, J. (Jacek), Grundy, A. (Anne), Guenel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hamann, U. (Ute), Hankinson, S. E. (Susan E.), Harkness, E. F. (Elaine F.), Hart, S. N. (Steven N.), He, W. (Wei), Hein, A. (Alexander), Heyworth, J. (Jane), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakimovska, M. (Milena), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jukkola-Vuorinen, A. (Arja), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kaczmarek, K. (Katarzyna), Kataja, V. (Vesa), Keeman, R. (Renske), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kiiski, J. I. (Johanna, I), Knight, J. A. (Julia A.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kruger, U. (Ute), Kuehl, T. (Tabea), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lilyquist, J. (Jenna), Lindblom, A. (Annika), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Long, J. (Jirong), Lubinski, J. (Jan), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Makalic, E. (Enes), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), McLean, C. (Catriona), Meindl, A. (Alfons), Menon, U. (Usha), Middha, P. (Pooja), Miller, N. (Nicola), Moreno, F. (Fernando), Mulligan, A. M. (Anna Marie), Mulot, C. (Claire), Munoz-Garzon, V. M. (Victor M.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Norman, A. (Aaron), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orr, N. (Nick), Pankratz, V. S. (V. Shane), Park-Simon, T.-W. (Tjoung-Won), Perez, J. I. (Jose I. A.), Perez-Barrios, C. (Clara), Peterlongo, P. (Paolo), Peto, J. (Julian), Pinchev, M. (Mila), Plaseska-Karanfilska, D. (Dijana), Polley, E. C. (Eric C.), Prentice, R. (Ross), Presneau, N. (Nadege), Prokofyeva, D. (Darya), Purrington, K. (Kristen), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rau-Murthy, R. (Rohini), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Robson, M. (Mark), Romero, A. (Atocha), Ruddy, K. J. (Kathryn J.), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, D. F. (Daniel F.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Schumacher, F. (Fredrick), Schuermann, P. (Peter), Schwentner, L. (Lukas), Scott, C. (Christopher), Scott, R. J. (Rodney J.), Seynaeve, C. (Caroline), Shah, M. (Mitul), Sherman, M. E. (Mark E.), Shrubsole, M. J. (Martha J.), Shu, X.-O. (Xiao-Ou), Slager, S. (Susan), Smeets, A. (Ann), Sohn, C. (Christof), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stegmaier, C. (Christa), Stone, J. (Jennifer), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Thoene, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Truong, T. (Therese), Tzardi, M. (Maria), Ulmer, H.-U. (Hans-Ulrich), Untch, M. (Michael), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Vijai, J. (Joseph), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. (Walter), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zhang, Y. (Yan), Zheng, W. (Wei), Ziogas, A. (Argyrios), Clarke, C. (Christine), Balleine, R. (Rosemary), Baxter, R. (Robert), Braye, S. (Stephen), Carpenter, J. (Jane), Dahlstrom, J. (Jane), Forbes, J. (John), Lee, C. S. (C. Soon), Marsh, D. (Deborah), Morey, A. (Adrienne), Pathmanathan, N. (Nirmala), Scott, R. (Rodney), Simpson, P. (Peter), Spigelman, A. (Allan), Wilcken, N. (Nicholas), Yip, D. (Desmond), Zeps, N. (Nikolajs), Sexton, A. (Adrienne), Dobrovic, A. (Alex), Christian, A. (Alice), Trainer, A. (Alison), Fellows, A. (Andrew), Shelling, A. (Andrew), De Fazio, A. (Anna), Blackburn, A. (Anneke), Crook, A. (Ashley), Meiser, B. (Bettina), Patterson, B. (Briony), Clarke, C. (Christobel), Saunders, C. (Christobel), Hunt, C. (Clare), Scott, C. (Clare), Amor, D. (David), Ortega, D. G. (David Gallego), Marsh, D. (Deb), Edkins, E. (Edward), Salisbury, E. (Elizabeth), Haan, E. (Eric), Macrea, F. (Finlay), Farshid, G. (Gelareh), Lindeman, G. (Geoff), Trench, G. (Georgia), Mann, G. (Graham), Giles, G. (Graham), Gill, G. (Grantley), Thorne, H. (Heather), Campbell, I. (Ian), Hickie, I. (Ian), Caldon, L. (Liz), Winship, I. (Ingrid), Cui, J. (James), Flanagan, J. (James), Kollias, J. (James), Visvader, J. (Jane), Taylor, J. (Jessica), Burke, J. (Jo), Saunus, J. (Jodi), Forbs, J. (John), Hopper, J. (John), Beesley, J. (Jonathan), Kirk, J. (Judy), French, J. (Juliet), Tucker, K. (Kathy), Wu, K. (Kathy), Phillips, K. (Kelly), Forrest, L. (Laura), Lipton, L. (Lara), Andrews, L. (Leslie), Lobb, L. (Lizz), Walker, L. (Logan), Kentwell, M. (Maira), Spurdle, M. (Mandy), Cummings, M. (Margaret), Gleeson, M. (Margaret), Harris, M. (Marion), Jenkins, M. (Mark), Young, M. A. (Mary Anne), Delatycki, M. (Martin), Wallis, M. (Mathew), Burgess, M. (Matthew), Brown, M. (Melissa), Southey, M. (Melissa), Bogwitz, M. (Michael), Field, M. (Michael), Friedlander, M. (Michael), Gattas, M. (Michael), Saleh, M. (Mona), Aghmesheh, M. (Morteza), Hayward, N. (Nick), Pachter, N. (Nick), Cohen, P. (Paul), Duijf, P. (Pascal), James, P. (Paul), Simpson, P. (Pete), Fong, P. (Peter), Butow, P. (Phyllis), Williams, R. (Rachael), Kefford, R. (Rick), Simard, J. (Jacques), Balleine, R.-M. (Rose-Mary), Dawson, S.-J. (Sarah-Jane), Lok, S. (Sheau), O'connell, S. (Shona), Greening, S. (Sian), Nightingale, S. (Sophie), Edwards, S. (Stacey), Fox, S. (Stephen), McLachlan, S.-A. (Sue-Anne), Lakhani, S. (Sunil), Dudding, T. (Tracy), Antill, Y. (Yoland), Sahlberg, K. K. (Kristine K.), Ottestad, L. (Lars), Karesen, R. (Rolf), Schlichting, E. (Ellen), Holmen, M. M. (Marit Muri), Sauer, T. (Toril), Haakensen, V. (Vilde), Engebraten, O. (Olav), Naume, B. (Bjorn), Fossa, A. (Alexander), Kiserud, C. E. (Cecile E.), Reinertsen, K. V. (Kristin, V), Helland, A. (Aslaug), Riis, M. (Margit), Geisler, J. (Juergen), Dunning, A. M. (Alison M.), Thompson, D. J. (Deborah J.), Chenevix-Trench, G. (Georgia), Chang-Claude, J. (Jenny), Schmidt, M. K. (Marjanka K.), Hall, P. (Per), Milne, R. L. (Roger L.), Pharoah, P. D. (Paul D. P.), Antoniou, A. C. (Antonis C.), Chatterjee, N. (Nilanjan), Kraft, P. (Peter), Garcia-Closas, M. (Montserrat), Easton, D. F. (Douglas F.), Mavaddat, N. (Nasim), Michailidou, K. (Kyriaki), Dennis, J. (Joe), Lush, M. (Michael), Fachal, L. (Laura), Lee, A. (Andrew), Tyrer, J. P. (Jonathan P.), Chen, T.-H. (Ting-Huei), Wang, Q. (Qin), Bolla, M. K. (Manjeet K.), Yang, X. (Xin), Adank, M. A. (Muriel A.), Ahearn, T. (Thomas), Aittomaki, K. (Kristiina), Allen, J. (Jamie), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Auvinen, P. (Paivi), Barrdahl, M. (Myrto), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Bremer, M. (Michael), Brenner, H. (Hermann), Brentnall, A. (Adam), Brock, I. W. (Ian W.), Brooks-Wilson, A. (Angela), Brucker, S. Y. (Sara Y.), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Campa, D. (Daniele), Carter, B. D. (Brian D.), Castelao, J. E. (Jose E.), Chanock, S. J. (Stephen J.), Chlebowski, R. (Rowan), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, J. M. (J. Margriet), Cordina-Duverger, E. (Emilie), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doerk, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Durcan, L. (Lorraine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foersti, A. (Asta), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Georgoulias, V. (Vassilios), Giles, G. G. (Graham G.), Gilyazova, I. R. (Irina R.), Glendon, G. (Gord), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Alnaes, G. I. (Grethe I. Grenaker), Grip, M. (Mervi), Gronwald, J. (Jacek), Grundy, A. (Anne), Guenel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hamann, U. (Ute), Hankinson, S. E. (Susan E.), Harkness, E. F. (Elaine F.), Hart, S. N. (Steven N.), He, W. (Wei), Hein, A. (Alexander), Heyworth, J. (Jane), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakimovska, M. (Milena), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jukkola-Vuorinen, A. (Arja), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kaczmarek, K. (Katarzyna), Kataja, V. (Vesa), Keeman, R. (Renske), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kiiski, J. I. (Johanna, I), Knight, J. A. (Julia A.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kruger, U. (Ute), Kuehl, T. (Tabea), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lilyquist, J. (Jenna), Lindblom, A. (Annika), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Long, J. (Jirong), Lubinski, J. (Jan), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Makalic, E. (Enes), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), McLean, C. (Catriona), Meindl, A. (Alfons), Menon, U. (Usha), Middha, P. (Pooja), Miller, N. (Nicola), Moreno, F. (Fernando), Mulligan, A. M. (Anna Marie), Mulot, C. (Claire), Munoz-Garzon, V. M. (Victor M.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Norman, A. (Aaron), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orr, N. (Nick), Pankratz, V. S. (V. Shane), Park-Simon, T.-W. (Tjoung-Won), Perez, J. I. (Jose I. A.), Perez-Barrios, C. (Clara), Peterlongo, P. (Paolo), Peto, J. (Julian), Pinchev, M. (Mila), Plaseska-Karanfilska, D. (Dijana), Polley, E. C. (Eric C.), Prentice, R. (Ross), Presneau, N. (Nadege), Prokofyeva, D. (Darya), Purrington, K. (Kristen), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rau-Murthy, R. (Rohini), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Robson, M. (Mark), Romero, A. (Atocha), Ruddy, K. J. (Kathryn J.), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, D. F. (Daniel F.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Schumacher, F. (Fredrick), Schuermann, P. (Peter), Schwentner, L. (Lukas), Scott, C. (Christopher), Scott, R. J. (Rodney J.), Seynaeve, C. (Caroline), Shah, M. (Mitul), Sherman, M. E. (Mark E.), Shrubsole, M. J. (Martha J.), Shu, X.-O. (Xiao-Ou), Slager, S. (Susan), Smeets, A. (Ann), Sohn, C. (Christof), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stegmaier, C. (Christa), Stone, J. (Jennifer), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Thoene, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Truong, T. (Therese), Tzardi, M. (Maria), Ulmer, H.-U. (Hans-Ulrich), Untch, M. (Michael), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Vijai, J. (Joseph), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. (Walter), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zhang, Y. (Yan), Zheng, W. (Wei), Ziogas, A. (Argyrios), Clarke, C. (Christine), Balleine, R. (Rosemary), Baxter, R. (Robert), Braye, S. (Stephen), Carpenter, J. (Jane), Dahlstrom, J. (Jane), Forbes, J. (John), Lee, C. S. (C. Soon), Marsh, D. (Deborah), Morey, A. (Adrienne), Pathmanathan, N. (Nirmala), Scott, R. (Rodney), Simpson, P. (Peter), Spigelman, A. (Allan), Wilcken, N. (Nicholas), Yip, D. (Desmond), Zeps, N. (Nikolajs), Sexton, A. (Adrienne), Dobrovic, A. (Alex), Christian, A. (Alice), Trainer, A. (Alison), Fellows, A. (Andrew), Shelling, A. (Andrew), De Fazio, A. (Anna), Blackburn, A. (Anneke), Crook, A. (Ashley), Meiser, B. (Bettina), Patterson, B. (Briony), Clarke, C. (Christobel), Saunders, C. (Christobel), Hunt, C. (Clare), Scott, C. (Clare), Amor, D. (David), Ortega, D. G. (David Gallego), Marsh, D. (Deb), Edkins, E. (Edward), Salisbury, E. (Elizabeth), Haan, E. (Eric), Macrea, F. (Finlay), Farshid, G. (Gelareh), Lindeman, G. (Geoff), Trench, G. (Georgia), Mann, G. (Graham), Giles, G. (Graham), Gill, G. (Grantley), Thorne, H. (Heather), Campbell, I. (Ian), Hickie, I. (Ian), Caldon, L. (Liz), Winship, I. (Ingrid), Cui, J. (James), Flanagan, J. (James), Kollias, J. (James), Visvader, J. (Jane), Taylor, J. (Jessica), Burke, J. (Jo), Saunus, J. (Jodi), Forbs, J. (John), Hopper, J. (John), Beesley, J. (Jonathan), Kirk, J. (Judy), French, J. (Juliet), Tucker, K. (Kathy), Wu, K. (Kathy), Phillips, K. (Kelly), Forrest, L. (Laura), Lipton, L. (Lara), Andrews, L. (Leslie), Lobb, L. (Lizz), Walker, L. (Logan), Kentwell, M. (Maira), Spurdle, M. (Mandy), Cummings, M. (Margaret), Gleeson, M. (Margaret), Harris, M. (Marion), Jenkins, M. (Mark), Young, M. A. (Mary Anne), Delatycki, M. (Martin), Wallis, M. (Mathew), Burgess, M. (Matthew), Brown, M. (Melissa), Southey, M. (Melissa), Bogwitz, M. (Michael), Field, M. (Michael), Friedlander, M. (Michael), Gattas, M. (Michael), Saleh, M. (Mona), Aghmesheh, M. (Morteza), Hayward, N. (Nick), Pachter, N. (Nick), Cohen, P. (Paul), Duijf, P. (Pascal), James, P. (Paul), Simpson, P. (Pete), Fong, P. (Peter), Butow, P. (Phyllis), Williams, R. (Rachael), Kefford, R. (Rick), Simard, J. (Jacques), Balleine, R.-M. (Rose-Mary), Dawson, S.-J. (Sarah-Jane), Lok, S. (Sheau), O'connell, S. (Shona), Greening, S. (Sian), Nightingale, S. (Sophie), Edwards, S. (Stacey), Fox, S. (Stephen), McLachlan, S.-A. (Sue-Anne), Lakhani, S. (Sunil), Dudding, T. (Tracy), Antill, Y. (Yoland), Sahlberg, K. K. (Kristine K.), Ottestad, L. (Lars), Karesen, R. (Rolf), Schlichting, E. (Ellen), Holmen, M. M. (Marit Muri), Sauer, T. (Toril), Haakensen, V. (Vilde), Engebraten, O. (Olav), Naume, B. (Bjorn), Fossa, A. (Alexander), Kiserud, C. E. (Cecile E.), Reinertsen, K. V. (Kristin, V), Helland, A. (Aslaug), Riis, M. (Margit), Geisler, J. (Juergen), Dunning, A. M. (Alison M.), Thompson, D. J. (Deborah J.), Chenevix-Trench, G. (Georgia), Chang-Claude, J. (Jenny), Schmidt, M. K. (Marjanka K.), Hall, P. (Per), Milne, R. L. (Roger L.), Pharoah, P. D. (Paul D. P.), Antoniou, A. C. (Antonis C.), Chatterjee, N. (Nilanjan), Kraft, P. (Peter), Garcia-Closas, M. (Montserrat), and Easton, D. F. (Douglas F.)

Abstract

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

Published
2019

23. Abstract GS6-01: Surgical treatment after neoadjuvant systemic therapy in young women with breast cancer: Results from a prospective cohort study

Author

Kim, HJ, primary, Dominici, L, additional, Rosenberg, S, additional, Pak, LM, additional, Poorvu, PD, additional, Ruddy, K, additional, Tamimi, R, additional, Schapira, L, additional, Come, S, additional, Peppercorn, J, additional, Borges, V, additional, Warner, E, additional, Vardeh, H, additional, Collins, L, additional, King, T, additional, and Partridge, A, additional

Published
2019
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24. Abstract PD7-12: Molecular subtyping of male breast cancer by the International male breast cancer program (IMBC): EORTC 10085/TBCRC 0-29/BIG 2-07/NABCG/BOOG 2009-04

Author

Martens, JWM, primary, Sieuwerts, A, additional, Ponchet, C, additional, Smid, M, additional, de Weerd, V, additional, Slaets, L, additional, Piper, T, additional, van Deurzen, CHM, additional, Schroder, CP, additional, Stangle, C, additional, Kloosterman, W, additional, van Leeuwen-Stok, E, additional, Nilsson, C, additional, Vermeij, J, additional, Peeters, S, additional, Goulioti, T, additional, Nowaczyk, M, additional, Aebi, S, additional, Rubio, IT, additional, Kelly, C, additional, Bayani, J, additional, Porter, P, additional, Murray, M, additional, Hudis, C, additional, Middleton, L, additional, Korde, L, additional, Ruddy, K, additional, Winer, E, additional, Bogler, O, additional, van den Weyngaert, D, additional, dal Lago, L, additional, Fraser, J, additional, Benstead, K, additional, van Asperen, C, additional, Linderholm, B, additional, Hedenfalk, I, additional, Tryfonidis, K, additional, Giordano, S, additional, Bartlett, J, additional, and Cardoso, F, additional

Published
2018
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26. Comparison of oxaliplatin and paclitaxel-induced neuropathy (Alliance A151505)

Author

Pachman, D, Qin, R, Seisler, D, Smith, E, Kaggal, S, Novotny, P, Ruddy, K, Lafky, J, Ta, L, Beutler, A, Wagner Johnston, N, Staff, N, Grothey, A, Dougherty, P, Cavaletti, G, Loprinzi, C, CAVALETTI, GUIDO ANGELO, Loprinzi, C., Pachman, D, Qin, R, Seisler, D, Smith, E, Kaggal, S, Novotny, P, Ruddy, K, Lafky, J, Ta, L, Beutler, A, Wagner Johnston, N, Staff, N, Grothey, A, Dougherty, P, Cavaletti, G, Loprinzi, C, CAVALETTI, GUIDO ANGELO, and Loprinzi, C.

Abstract

Purpose: Oxaliplatin and paclitaxel are commonly used chemotherapies associated with acute and chronic neuropathies. There is a need to better understand the similarities and differences of these clinical syndromes. Methods: Neuropathy data were pooled from patients receiving adjuvant oxaliplatin and weekly paclitaxel or every 3 weeks of paclitaxel. Patients completed daily questionnaires after each chemotherapy dose and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy before each chemotherapy cycle and for 12 months post-treatment. Results: Acute neuropathy symptoms from both drugs peaked around day 3. Acute symptoms experienced in cycle 1 predicted occurrence in subsequent cycles. Paclitaxel-induced acute symptoms were similar in intensity in each cycle and largely resolved between cycles. Oxaliplatin-induced acute symptoms were about half as severe in the first cycle as in later cycles and did not resolve completely between cycles. Both drugs caused a predominantly sensory chronic neuropathy (with numbness and tingling being more common than pain). Oxaliplatin-induced neuropathy worsened after the completion of treatment and began to improve 3 months post-treatment. In contrast, paclitaxel-induced neuropathy began improving immediately after chemotherapy cessation. During treatment, the incidence of paclitaxel sensory symptoms was similar in the hands and feet; with oxaliplatin, the hands were affected more than the feet. Both paclitaxel- and oxaliplatin-induced acute neurotoxicity appeared to predict the severity of chronic neuropathy, more prominently with oxaliplatin. Conclusions: Knowledge of the similarities and differences between neuropathy syndromes may provide insight into their underlying pathophysiology and inform future research to identify preventative treatment approaches.

Published
2016

33. Presentation of breast cancer in young women

Author

Ruddy, K. J., primary, Gelber, S., additional, Tamimi, R., additional, Schapira, L., additional, Come, S., additional, Kereakoglow, S., additional, Lin, N. U., additional, Winer, E. P., additional, and Partridge, A. H., additional

Published
2009
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36. Detecting and Filtering Immune-Related Adverse Events Signal Based on Text Mining and Observational Health Data Sciences and Informatics Common Data Model: Framework Development Study

Author

Yu, Yue, Ruddy, Kathryn, Mansfield, Aaron, Zong, Nansu, Wen, Andrew, Tsuji, Shintaro, Huang, Ming, Liu, Hongfang, Shah, Nilay, and Jiang, Guoqian

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundImmune checkpoint inhibitors are associated with unique immune-related adverse events (irAEs). As most of the immune checkpoint inhibitors are new to the market, it is important to conduct studies using real-world data sources to investigate their safety profiles. ObjectiveThe aim of the study was to develop a framework for signal detection and filtration of novel irAEs for 6 Food and Drug Administration–approved immune checkpoint inhibitors. MethodsIn our framework, we first used the Food and Drug Administration’s Adverse Event Reporting System (FAERS) standardized in an Observational Health Data Sciences and Informatics (OHDSI) common data model (CDM) to collect immune checkpoint inhibitor-related event data and conducted irAE signal detection. OHDSI CDM is a standard-driven data model that focuses on transforming different databases into a common format and standardizing medical terms to a common representation. We then filtered those already known irAEs from drug labels and literature by using a customized text-mining pipeline based on clinical text analysis and knowledge extraction system with Medical Dictionary for Regulatory Activities (MedDRA) as a dictionary. Finally, we classified the irAE detection results into three different categories to discover potentially new irAE signals. ResultsBy our text-mining pipeline, 490 irAE terms were identified from drug labels, and 918 terms were identified from the literature. In addition, of the 94 positive signals detected using CDM-based FAERS, 53 signals (56%) were labeled signals, 10 (11%) were unlabeled published signals, and 31 (33%) were potentially new signals. ConclusionsWe demonstrated that our approach is effective for irAE signal detection and filtration. Moreover, our CDM-based framework could facilitate adverse drug events detection and filtration toward the goal of next-generation pharmacovigilance that seamlessly integrates electronic health record data for improved signal detection.

Published
2020
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40. White Matter Abnormalities in the Amputation Variant of Body Integrity Dysphoria

Author

Saetta, Gianluca, ruddy, kathy, Zapparoli, Laura, Gandola, Martina, Salvato, Gerardo, Sberna, Maurizio, Bottini, Gabriella, Brugger, Peter, Lenggenhager, Bigna, Saetta, G, Ruddy, K, Zapparoli, L, Gandola, M, Salvato, G, Sberna, M, Bottini, G, Brugger, P, and Lenggenhager, B

Subjects
Male, Cognitive Neuroscience, Structural connectivity, ICD 11, Experimental and Cognitive Psychology, Limb ownership, Magnetic Resonance Imaging, White Matter, Body Integrity Dysphoria, ICD 11, Body Image, Limb Ownership, structural connectivity, Amputation, Surgical, Body integrity dysphoria, Diffusion Tensor Imaging, Neuropsychology and Physiological Psychology, Body image, ddc:150, Anisotropy, Humans
Abstract

“Body integrity dysphoria" (BID) is a severe condition affecting non-psychotic individuals. In the amputation variant of BID a limb may be experienced as not being part of the body, despite normal anatomical development and intact sensorimotor functions. We previously demonstrated altered brain structural (gray matter) and functional connectivity in 16 men with BID with a long-lasting and exclusive desire for left leg amputation. Here we aimed to identify, in the same sample, altered patterns of white matter structural connectivity. Fractional anisotropy (FA), derived from Diffusion Tensor Imaging data, was considered as a measure of structural connectivity. Results showed reduced structural connectivity of: i) the right superior parietal lobule (rSPL) with the right cuneus, with the superior occipital and with the posterior cingulate gyri ii) the pars orbitalis of the right middle frontal gyrus (rMFGOrb) with the putamen, and iii) the left middle temporal gyrus (lMTG) with the pars triangularis of the left inferior frontal gyrus. Increased connectivity was found between the right paracentral lobule (rPLC) and the right caudate nucleus. By using a complementary method of investigation, we confirmed and extended previous results from the same sample of individuals with BID, showing structural alterations between areas tuned to the processing of the sensorimotor representations of the affected leg (rPCL), and to higher-order components of bodily representation such as the body image (rSPL) and visual processing areas. Alongside this network for bodily awareness, other networks such as the limbic (rMFGOrb) and the mirror (lMTG) systems showed alterations in structural connectivity. These findings consolidate current understanding of the neural correlates of the amputation variant of BID, which might in turn guide diagnostics and rehabilitative treatments. published

Published
2022

41. Screening breast magnetic resonance imaging (MRI) in early-stage breast cancer survivors.

Author

Dowton, A. A., Meyer, M. E., Ruddy, K. J., Yeh, E. D., and Partridge, A. H.

Subjects
*BREAST cancer research, *CANCER patients, *MEDICAL screening, *IMAGING of cancer, *CANCER treatment
Abstract

Background: Limited evidence is available regarding the value of screening breast MRI in female early stage breast cancer survivors. We sought to evaluate outcomes of index screening breast MRI in breast cancer survivors in the modern era of breast cancer treatment and imaging. Methods: Using a large prospective institutional database, we identified all women who underwent breast MRI between 7/2006 and 6/2008, were ≥1 year and ≤ 3 years after diagnosis of stage I-IIIa breast cancer, had remaining breast tissue after treatment, and had consented to a record review protocol at our center (95% uptake rate). Sociodemographic, disease, staging and treatment information (see table 1), indications and outcomes for breast MRI, as well as disease status at 2 years after the index MRI were ascertained. Results: 643 patients were identified as having undergone at least 1 MRI of the breast(s); 248 (38.5%) were diagnostic MRIs (had identified clinical indication or imaging abnormality); 12 (2%) were missing clinical data; 383 (59.5%) were screening MRIs. 338/383 (88%) patients who had screening MRI had stage I-IIIa invasive breast cancer. 220/338 (65%) MRIs performed were index MRIs (index MRI defined as first MRI >1 year post diagnosis). For this preliminary analysis, we include only the 155 patients (70%) who were within 1-3 years of diagnosis at the time of index MRI (see table 1 for patient and disease characteristics). 24/155 (15.5%) screening MRIs were considered not normal. Five women (21%) underwent biopsy based on abnormal MRI finding; 1 resulted in the detection of a local recurrence (4.2%, 95% CI=0.1%-21.1%). 3/131 patients who had a normal index MRI were found to have local/regional recurrence or contralateral breast cancer diagnosed within 2 years of the MRI (2.3%, 95% CI=0.5%-6.6%). A statistically significant difference in the proportions was not observed based on Fisher's test (p = 0.50). 6/155 patients (3.9 %) had a systemic recurrence in the 2 years following index MRI. Conclusion: The vast majority of first screening breast MRIs obtained 1-3 years following treatment in early stage breast cancer survivors are normal, and very few detect cancer. Planned further analysis in this dataset will evaluate frequency of cancer detection in longer -term survivors. Additional research is necessary to determine the risks and benefits of screening breast MRIs being performed in this population. [ABSTRACT FROM AUTHOR]

Published
2012
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42. Comparison of oxaliplatin and paclitaxel-induced neuropathy (Alliance A151505)

Author

Nathan P. Staff, Kathryn J. Ruddy, Deirdre R. Pachman, Andreas S. Beutler, Guido Cavaletti, Suneetha Kaggal, Nina D. Wagner-Johnston, Paul J. Novotny, Charles L. Loprinzi, Patrick M. Dougherty, Axel Grothey, Lauren E. Ta, Jacqueline M. Lafky, Drew K. Seisler, Rui Qin, Ellen M. Lavoie Smith, Pachman, D, Qin, R, Seisler, D, Smith, E, Kaggal, S, Novotny, P, Ruddy, K, Lafky, J, Ta, L, Beutler, A, Wagner Johnston, N, Staff, N, Grothey, A, Dougherty, P, Cavaletti, G, and Loprinzi, C

Subjects
Oncology, Adult, Male, Paclitaxel neuropathy, medicine.medical_specialty, Organoplatinum Compounds, Paclitaxel, Oxaliplatin neuropathy, Pain medicine, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Aged, Chemotherapy-induced peripheral neuropathy, business.industry, Nursing research, Peripheral Nervous System Diseases, Middle Aged, Antineoplastic Agents, Phytogenic, Oxaliplatin, chemistry, 030220 oncology & carcinogenesis, Female, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Purpose: Oxaliplatin and paclitaxel are commonly used chemotherapies associated with acute and chronic neuropathies. There is a need to better understand the similarities and differences of these clinical syndromes. Methods: Neuropathy data were pooled from patients receiving adjuvant oxaliplatin and weekly paclitaxel or every 3weeks of paclitaxel. Patients completed daily questionnaires after each chemotherapy dose and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy before each chemotherapy cycle and for 12months post-treatment. Results: Acute neuropathy symptoms from both drugs peaked around day 3. Acute symptoms experienced in cycle 1 predicted occurrence in subsequent cycles. Paclitaxel-induced acute symptoms were similar in intensity in each cycle and largely resolved between cycles. Oxaliplatin-induced acute symptoms were about half as severe in the first cycle as in later cycles and did not resolve completely between cycles. Both drugs caused a predominantly sensory chronic neuropathy (with numbness and tingling being more common than pain). Oxaliplatin-induced neuropathy worsened after the completion of treatment and began to improve 3months post-treatment. In contrast, paclitaxel-induced neuropathy began improving immediately after chemotherapy cessation. During treatment, the incidence of paclitaxel sensory symptoms was similar in the hands and feet; with oxaliplatin, the hands were affected more than the feet. Both paclitaxel- and oxaliplatin-induced acute neurotoxicity appeared to predict the severity of chronic neuropathy, more prominently with oxaliplatin. Conclusions: Knowledge of the similarities and differences between neuropathy syndromes may provide insight into their underlying pathophysiology and inform future research to identify preventative treatment approaches.

Published
2016

43. Association of Gene Variant Type and Location with Breast Cancer Risk in the General Population.

Author

Akamandisa MP, Boddicker NJ, Yadav S, Hu C, Hart SN, Ambrosone C, Anton-Culver H, Auer PL, Bodelon C, Burnside ES, Chen F, Eliassen HA, Goldgar DE, Haiman C, Hodge JM, Huang H, John EM, Karam R, Lacey JV, Lindstroem S, Martinez E, Na J, Neuhausen SL, O'Brien KM, Olson JE, Pal T, Palmer JR, Patel AV, Pesaran T, Polley EC, Richardson ME, Ruddy K, Sandler DP, Teras LR, Trentham-Dietz A, Vachon CM, Weinberg C, Winham SJ, Yao S, Zirpoli G, Kraft P, Weitzel JN, Domchek SM, Couch FJ, and Nathanson KL

Abstract

Importance: Pathogenic variants (PVs) in ATM, BRCA1, BRCA2, CHEK2 , and PALB2 are associated with increased breast cancer risk. However, it is unknown whether breast cancer risk differs by PV type or location in carriers ascertained from the general population., Objective: To evaluate breast cancer risks associated with PV type and location in ATM, BRCA1, BRCA2, CHEK2 , and PALB2 ., Design: Age adjusted case-control association analysis for all participants, subsets of PV carriers, and women with no breast cancer family history in population-based and clinical testing cohorts., Setting: Twelve US population-based studies within the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium, and breast cancer cases from the UK-Biobank and an Ambry Genetics clinical testing cohort., Participants: 32,247 women with and 32,544 age-matched women without a breast cancer diagnosis from CARRIERS; 237 and 1351 women with BRCA2 PVs and breast cancer from the UKBB and Ambry Genetics, respectively., Exposures: PVs in ATM, BRCA1, BRCA2, CHEK2, and PALB2., Main Outcomes and Measures: PVs were grouped by type and location within genes and assessed for risks of breast cancer (odds ratios (OR), 95% confidence intervals (CI), and p-values) using logistic regression. Mean ages at diagnosis were compared using linear regression., Results: Compared to women carrying BRCA2 exon 11 protein truncating variants (PTVs) in the CARRIERS population-based study, women with BRCA2 ex13-27 PTVs (OR=2.7, 95%CI 1.1-7.9) and ex1-10 PTVs (OR=1.6, 95%CI 0.8-3.5) had higher breast cancer risks, lower rates of ER-negative breast cancer (ex13-27 OR=0.5, 95%CI 0.2-0.9; ex1-10 OR=0.5, 95%CI 0.1-1.0), and earlier age of breast cancer diagnosis (ex13-27 5.5 years, p<0.001; ex1-10 2.4 years, p=0.17). These associations with ER-negative breast cancer and age replicated in a high-risk clinical cohort and the population-based UK Biobank cohort. No differences in risk or age at diagnosis by gene region were observed for PTVs in other predisposition genes., Conclusions and Relevance: Population-based and clinical high-risk cohorts establish that PTVs in exon 11 of BRCA2 are associated with reduced risk of breast cancer, later age at diagnosis, and greater risk of ER-negative disease. These differential risks may improve individualized risk prediction and clinical management for women carrying BRCA2 PTVs., Key Points: Question: Does ATM , BRCA1 , BRCA2 , CHEK2 and PALB2 pathogenic variant type and location influence breast cancer risk in population-based studies? Findings: Breast cancer risk and estrogen receptor status differ based on the type and location of pathogenic variants in BRCA2 . Women carrying protein truncating variants in exon 11 have a lower breast cancer risk in the population-based cohorts, older age at diagnosis and higher rates of estrogen receptor negative breast cancer than women with exon 1-10 or exon 13-27 truncation variants in population-based and clinical testing cohorts. Meaning: Incorporating pathogenic variant type and location in cancer risk models may improve individualized risk prediction.

Published
2024
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44. Characteristics and clinical outcomes of breast cancer in young BRCA carriers according to tumor histology.

Author

Agostinetto E, Bruzzone M, Hamy AS, Kim HJ, Chiodi C, Bernstein-Molho R, Linn S, Pogoda K, Carrasco E, Derouane F, Bajpai J, Nader-Marta G, Lopetegui-Lia N, Partridge AH, Cortesi L, Rousset-Jablonski C, Giugliano F, Renaud T, Ferrari A, Paluch-Shimon S, Fruscio R, Cui W, Wong SM, Vernieri C, Ruddy KJ, Dieci MV, Matikas A, Rozenblit M, Aguilar Y Mendez D, De Marchis L, Borea R, Puglisi F, Pistelli M, Kufel-Grabowska J, Di Rocco R, Mariamidze E, Atzori F, Kourie HR, Popovic L, de Azambuja E, Blondeaux E, and Lambertini M

Subjects
Humans, Female, Retrospective Studies, Adult, BRCA1 Protein genetics, Young Adult, Prognosis, Breast Neoplasms genetics, Breast Neoplasms pathology, BRCA2 Protein genetics
Abstract

Background: Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer., Methods: This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival., Results: Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index., Conclusions: In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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45. Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy.

Author

Azim HA Jr, Niman SM, Partridge AH, Demeestere I, Ruggeri M, Colleoni M, Saura C, Shimizu C, Saetersdal AB, Kroep JR, Mailliez A, Warner E, Borges VF, Amant F, Gombos A, Kataoka A, Rousset-Jablonski C, Borstnar S, Takei J, Lee JE, Walshe JM, Ruíz-Borrego M, Moore HCF, Saunders C, Bjelic-Radisic V, Susnjar S, Cardoso F, Klar NJ, Spanic T, Ruddy K, Piccart M, Korde LA, Goldhirsch A, Gelber RD, Pagani O, and Peccatori FA

Subjects
Humans, Female, Adult, Pregnancy, Prospective Studies, Chemotherapy, Adjuvant adverse effects, Ovulation Induction methods, Ovulation Induction adverse effects, Antineoplastic Agents, Hormonal adverse effects, Antineoplastic Agents, Hormonal administration & dosage, Antineoplastic Agents, Hormonal therapeutic use, Middle Aged, Cryopreservation, Breast Neoplasms drug therapy, Fertility Preservation methods, Reproductive Techniques, Assisted
Abstract

Purpose: We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor-positive breast cancer (BC) desiring future pregnancy., Patients and Methods: POSITIVE is an international, single-arm, prospective trial, in which 518 women temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. We evaluated menstruation recovery and factors associated with time to pregnancy and investigated if ART use was associated with achieving pregnancy. The cumulative incidence of BC-free interval (BCFI) events was estimated according to the use of ovarian stimulation at diagnosis. The median follow-up was 41 months., Results: Two hundred seventy-three patients (53%) reported amenorrhea at enrollment, of whom 94% resumed menses within 12 months. Among 497 patients evaluable for pregnancy, 368 (74%) reported at least one pregnancy. Young age was the main factor associated with shorter time to pregnancy with cumulative incidences of pregnancy by 1 year of 63.5%, 54.3%, and 37.7% for patients age <35, 35-39, and 40-42 years, respectively. One hundred and seventy-nine patients (36%) had embryo/oocyte cryopreservation at diagnosis, of whom 68 reported embryo transfer after enrollment. Cryopreserved embryo transfer was the only ART associated with higher chance of pregnancy (odds ratio, 2.41 [95% CI, 1.75 to 4.95]). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis, 9.7% (95% CI, 6.0 to 15.4), compared with those who did not, 8.7% (95% CI, 6.0 to 12.5)., Conclusion: In POSITIVE, fertility preservation using ovarian stimulation was not associated with short-term detrimental impact on cancer prognosis. Pregnancy rates were highest among those who underwent embryo/oocyte cryopreservation followed by embryo transfer.

Published
2024
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46. Helping ourselves, helping others: the Young Women's Breast Cancer Study (YWS) - a multisite prospective cohort study to advance the understanding of breast cancer diagnosed in women aged 40 years and younger.

Author

Rosenberg SM, Zheng Y, Ruddy K, Poorvu PD, Snow C, Kirkner GJ, Meyer ME, Tamimi RM, Schapira L, Peppercorn J, Come S, Borges VF, Warner E, Gelber S, Collins L, Winer EP, and Partridge AH

Subjects
Humans, Female, Prospective Studies, Adult, Young Adult, Pregnancy, Fertility Preservation psychology, North America, Patient Reported Outcome Measures, Stress Disorders, Post-Traumatic epidemiology, Stress Disorders, Post-Traumatic psychology, Breast Neoplasms psychology, Breast Neoplasms diagnosis, Quality of Life
Abstract

Purpose: Compared with older women diagnosed with breast cancer, younger women are more likely to die of breast cancer and more likely to suffer psychosocially in both the short-term and long term. The Young Women's Breast Cancer Study (YWS) is a multisite prospective cohort study established to address gaps in our knowledge about this vulnerable and understudied population., Participants: The YWS enrolled 1302 women newly diagnosed with stages 0-IV breast cancer at age 40 years or younger at 13 academic and community sites in North America between 2006 and 2016. Longitudinal patient-reported outcome data are complemented by clinical data abstraction and biospecimen collection at multiple timepoints., Findings to Date: Key findings related to fertility include that nearly 40% of participants were interested in pregnancy following diagnosis; of those who reported interest, 10% pursued fertility preservation. Overall, approximately 10% of YWS participants became pregnant in the first 5 years after diagnosis; follow-up is ongoing for pregnancies after 5 years. Studies focused on psychosocial outcomes have characterised quality of life, post-traumatic stress and fear of recurrence, with findings detailing the factors associated with the substantial psychosocial burden many young women face during and following active treatment. Multiple studies have leveraged YWS biospecimens, including whole-exome sequencing of tumour analyses that revealed that select somatic alterations occur at different frequencies in young (age≤35) versus older women with luminal A breast cancer, and a study that explored clonal hematopoiesis of indeterminate potential found it to be rare in young survivors., Future Plans: With a median follow-up of approximately 10 years, the cohort is just maturing for many relevant long-term outcomes and provides outstanding opportunities to further study and build collaborations to address gaps in our knowledge, with the ultimate objective to improve care and outcomes for young women with breast cancer., Trial Registration Number: NCT01468246., Competing Interests: Competing interests: SMR reports grant funding from Conquer Cancer/Pfizer. VFB reports research funding (paid to institution) from SeaGen, AstraZeneca, Gilead and Olema; consultation for SeaGen, AstraZeneca, Lilly, Gilead and Olema; and stock/founder of PEARL Scientific. AHP reports royalties from Wolters Kluwer (paid to self) for authorship of UpToDate. All remaining authors have no disclosures to report., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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47. A robust brain network for sustained attention from adolescence to adulthood that predicts later substance use.

Author

Weng Y, Kruschwitz J, Rueda-Delgado LM, Ruddy K, Boyle R, Franzen L, Serin E, Nweze T, Hanson J, Smyth A, Farnan T, Banaschewski T, Bokde ALW, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Martinot JL, Martinot MP, Artiges E, McGrath J, Nees F, Orfanos DP, Paus T, Poustka L, Holz N, Fröhner JH, Smolka MN, Vaidya N, Schumann G, Walter H, and Whelan R

Abstract

Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance-use or a marker of the inclination to engage in such behaviour. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1,000 participants. Behaviours and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use., Competing Interests: Dr. Banaschewski served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Novartis, Shire. He received conference support or speaker’s fee by Lilly, Medice Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. Dr Walter received a speaker honorarium from Servier (2014). The other authors report no biomedical financial interests or potential conflicts of interest.

Published
2024
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48. Gastrointestinal and Neuropsychological Symptoms Are Associated With Distinct Vomiting Profiles in Patients Receiving Chemotherapy.

Author

Singh KP, Cooper BA, Paul SM, Ruddy K, Singh AB, Chen J, Pituch KA, Grys TE, Singh P, Batalini F, Hammer MJ, Levine JD, and Miaskowski C

Subjects
Humans, Male, Female, Middle Aged, Adult, Aged, Risk Factors, Gastrointestinal Diseases chemically induced, Diarrhea chemically induced, Diarrhea epidemiology, Aged, 80 and over, Vomiting chemically induced, Vomiting epidemiology, Antineoplastic Agents adverse effects, Neoplasms drug therapy, Neoplasms complications, Nausea chemically induced, Nausea epidemiology
Abstract

Objectives: To identify subgroups of patients with distinct chemotherapy-induced vomiting (CIV) profiles; determine how these subgroups differ on several demographic, clinical, and symptom characteristics; and evaluate factors associated with chemotherapy-induced nausea and CIV profiles., Sample & Setting: Adult patients (N = 1,338) receiving cancer chemotherapy., Methods & Variables: Data were collected on demographic, clinical, and symptom characteristics. Differences among subgroups of patients with distinct CIV profiles were evaluated using parametric and nonparametric tests., Results: Three CIV profiles (None, Decreasing, and Increasing) were identified. Compared with the None class, Decreasing and Increasing classes were more likely to have lower household income and a higher comorbidity burden, as well as to report higher rates of dry mouth, nausea, diarrhea, depression, anxiety, sleep disturbance, morning fatigue, and pain interference., Implications for Nursing: Clinicians need to assess common and distinct risk factors for CIV and chemotherapy-induced nausea.

Published
2024
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49. The Effect of Low-Dose Glucocorticoids Over Two Years on Weight and Blood Pressure in Rheumatoid Arthritis.

Author

Arkfeld D, Gonzales SAB, and Ruddy K

Subjects
Humans, Blood Pressure, Glucocorticoids therapeutic use, Vital Signs, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid drug therapy
Abstract

Competing Interests: Disclosures: Authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L24-0003.

Published
2024
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50. Integrating 4 methods to evaluate physical function in patients with cancer (In4M): protocol for a prospective cohort study.

Author

Thanarajasingam G, Kluetz P, Bhatnagar V, Brown A, Cathcart-Rake E, Diamond M, Faust L, Fiero MH, Huntington S, Jeffery MM, Jones L, Noble B, Paludo J, Powers B, Ross JS, Ritchie JD, Ruddy K, Schellhorn S, Tarver M, Dueck AC, and Gross C

Subjects
United States, Humans, Female, Prospective Studies, Medical Oncology, Ambulatory Care Facilities, Breast Neoplasms, Fabaceae, Lymphoma
Abstract

Introduction: Accurate, patient-centred evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterise the longitudinal measurement characteristics of physical function assessments, including clinician-reported outcome, patient-reported ported outcome (PRO), performance outcome tests and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice., Methods and Analysis: In this prospective study, we are enrolling 200 English-speaking and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centred health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multimodal physical function data collection in real-world patients with breast cancer or lymphoma will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform and PROs., Ethics and Dissemination: This study has received approval from IRBs at Mayo Clinic, Yale University and the US Food and Drug Administration. Results will be made available to participants, funders, the research community and the public., Trial Registration Number: NCT05214144; Pre-results., Competing Interests: Competing interests: GT has received research funding from the from the Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938) that directly supports this work. She also receives grant funding from the US National Cancer Institute (NCI) U01 Tolerability Consortium (U01CA 2330463), and the Mayo Clinic Center for Clinical and Translational Research (CTSA) (KL2TR 023794). CG has received research funding from the NCCN Foundation (Astra-Zeneca) and Genentech, as well as funding from Johnson and Johnson to help devise and implement new approaches to sharing clinical trial data. Over the past three years, MMJ reports grant funding from the US Food and Drug Administration, National Institutes on Drug Abuse, Centers for Disease Control and Prevention, Agency for Healthcare Research and Quality, American Cancer Society, and the National Center for Advancing Translational Sciences. JSR currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938), from the Medical Devices Innovation Consortium as part of the National Evaluation System for Health Technology (NEST), from the Agency for Healthcare Research and Quality (R01HS022882), from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644), and from Arnold Ventures for the Collaboration for Regulatory Rigor, Integrity, and Transparency (CRRIT); in addition, Ross is an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen. JDR currently receives research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing and from the US Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938). SH has received consulting fees outside of this work from Janssen, Genentech, AbbVie, Flatiron Health, BeiGene, AstraZeneca, ADC Therapeutics, Epizyme, Merck, Seattle Genetics, TG Therapeutics, Tyme, Pharmacyclics, SeaGen, and Arvinas. Over the past three years, KR reports grant funding from the US Food and Drug Administration, National Institutes of Health, United States Department of Defense, and American Cancer Society. SS has received consulting fees from Eisai, Celgene, SeaGen, and Cardinal Health. She has previously received research funding to her institution from Genetech and Pfizer. All other authors have no relevant conflicts of interest to disclose., (© Where applicable, author(s) (or their employer(s)) 2024. Re-use permitted under [CC BY]. Published by BMJ.)

Published
2024
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