Noah Kauff

Positions:

Instructor, Temporary in the Obstetrics and Gynecology

Obstetrics and Gynecology, Gynecologic Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1993

University of Pennsylvania

Grants:

Publications:

The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome

© 2019, The Author(s). Purpose: There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients. Methods: Stakeholders from Europe and North America worked together over a two-day workshop to achieve consensus on best practice. Results: Guidance was developed in four key areas: (1) whether women with gynecological cancer should be screened for Lynch syndrome and (2) how this should be done, (3) whether there was a role for gynecological surveillance in women at risk of Lynch syndrome, and (4) what preventive measures should be recommended for women with Lynch syndrome to reduce their risk of gynecological cancer. Conclusion: This document provides comprehensive clinical guidance that can be referenced by both patients and clinicians so that women with Lynch syndrome can expect and receive appropriate standards of care.
Authors
Crosbie, EJ; Ryan, NAJ; Arends, MJ; Bosse, T; Burn, J; Cornes, JM; Crawford, R; Eccles, D; Frayling, IM; Ghaem-Maghami, S; Hampel, H; Kauff, ND; Kitchener, HC; Kitson, SJ; Manchanda, R; McMahon, RFT; Monahan, KJ; Menon, U; Møller, P; Möslein, G; Rosenthal, A; Sasieni, P; Seif, MW; Singh, N; Skarrott, P; Snowsill, TM; Steele, R; Tischkowitz, M; Evans, DG
MLA Citation
Crosbie, E. J., et al. “The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome.” Genetics in Medicine, Jan. 2019. Scopus, doi:10.1038/s41436-019-0489-y.
URI
https://scholars.duke.edu/individual/pub1379698
Source
scopus
Published In
Genetics in Medicine : Official Journal of the American College of Medical Genetics
Published Date
DOI
10.1038/s41436-019-0489-y

IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer.

IL-15 has pivotal roles in the control of CD8(+) memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-γ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-γ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-γ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-γ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy.
Authors
Heon, EK; Wulan, H; Macdonald, LP; Malek, AO; Braunstein, GH; Eaves, CG; Schattner, MD; Allen, PM; Alexander, MO; Hawkins, CA; McGovern, DW; Freeman, RL; Amir, EP; Huse, JD; Zaltzman, JS; Kauff, NP; Meyers, PG; Gleason, MH; Overholtzer, MG; Wiseman, SS; Streutker, CD; Asa, SW; McAlindon, TP; Newcomb, PO; Sorensen, PM; Press, OA
MLA Citation
Heon, Elise K., et al. “IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer..” Biochem Biophys Res Commun, vol. 464, no. 1, Aug. 2015, pp. 360–66. Pubmed, doi:10.1016/j.bbrc.2015.06.162.
URI
https://scholars.duke.edu/individual/pub1370244
PMID
26141233
Source
pubmed
Published In
Biochemical and Biophysical Research Communications
Volume
464
Published Date
Start Page
360
End Page
366
DOI
10.1016/j.bbrc.2015.06.162

Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk.

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
Authors
Couch, FJ; Wang, X; McGuffog, L; Lee, A; Olswold, C; Kuchenbaecker, KB; Soucy, P; Fredericksen, Z; Barrowdale, D; Dennis, J; Gaudet, MM; Dicks, E; Kosel, M; Healey, S; Sinilnikova, OM; Lee, A; Bacot, F; Vincent, D; Hogervorst, FBL; Peock, S; Stoppa-Lyonnet, D; Jakubowska, A; kConFab Investigators,; Radice, P; Schmutzler, RK; SWE-BRCA,; Domchek, SM; Piedmonte, M; Singer, CF; Friedman, E; Thomassen, M; Ontario Cancer Genetics Network,; Hansen, TVO; Neuhausen, SL; Szabo, CI; Blanco, I; Greene, MH; Karlan, BY; Garber, J; Phelan, CM; Weitzel, JN; Montagna, M; Olah, E; Andrulis, IL; Godwin, AK; Yannoukakos, D; Goldgar, DE; Caldes, T; Nevanlinna, H; Osorio, A; Terry, MB; Daly, MB; van Rensburg, EJ; Hamann, U; Ramus, SJ; Toland, AE; Caligo, MA; Olopade, OI; Tung, N; Claes, K; Beattie, MS; Southey, MC; Imyanitov, EN; Tischkowitz, M; Janavicius, R; John, EM; Kwong, A; Diez, O; Balmaña, J; Barkardottir, RB; Arun, BK; Rennert, G; Teo, S-H; Ganz, PA; Campbell, I; van der Hout, AH; van Deurzen, CHM; Seynaeve, C; Gómez Garcia, EB; van Leeuwen, FE; Meijers-Heijboer, HEJ; Gille, JJP; Ausems, MGEM; Blok, MJ; Ligtenberg, MJL; Rookus, MA; Devilee, P; Verhoef, S; van Os, TAM; Wijnen, JT; HEBON,; EMBRACE,; Frost, D; Ellis, S; Fineberg, E; Platte, R; Evans, DG; Izatt, L; Eeles, RA; Adlard, J; Eccles, DM; Cook, J; Brewer, C; Douglas, F; Hodgson, S; Morrison, PJ; Side, LE; Donaldson, A; Houghton, C; Rogers, MT; Dorkins, H; Eason, J; Gregory, H; McCann, E; Murray, A; Calender, A; Hardouin, A; Berthet, P; Delnatte, C; Nogues, C; Lasset, C; Houdayer, C; Leroux, D; Rouleau, E; Prieur, F; Damiola, F; Sobol, H; Coupier, I; Venat-Bouvet, L; Castera, L; Gauthier-Villars, M; Léoné, M; Pujol, P; Mazoyer, S; Bignon, Y-J; GEMO Study Collaborators,; Złowocka-Perłowska, E; Gronwald, J; Lubinski, J; Durda, K; Jaworska, K; Huzarski, T; Spurdle, AB; Viel, A; Peissel, B; Bonanni, B; Melloni, G; Ottini, L; Papi, L; Varesco, L; Tibiletti, MG; Peterlongo, P; Volorio, S; Manoukian, S; Pensotti, V; Arnold, N; Engel, C; Deissler, H; Gadzicki, D; Gehrig, A; Kast, K; Rhiem, K; Meindl, A; Niederacher, D; Ditsch, N; Plendl, H; Preisler-Adams, S; Engert, S; Sutter, C; Varon-Mateeva, R; Wappenschmidt, B; Weber, BHF; Arver, B; Stenmark-Askmalm, M; Loman, N; Rosenquist, R; Einbeigi, Z; Nathanson, KL; Rebbeck, TR; Blank, SV; Cohn, DE; Rodriguez, GC; Small, L; Friedlander, M; Bae-Jump, VL; Fink-Retter, A; Rappaport, C; Gschwantler-Kaulich, D; Pfeiler, G; Tea, M-K; Lindor, NM; Kaufman, B; Shimon Paluch, S; Laitman, Y; Skytte, A-B; Gerdes, A-M; Pedersen, IS; Moeller, ST; Kruse, TA; Jensen, UB; Vijai, J; Sarrel, K; Robson, M; Kauff, N; Mulligan, AM; Glendon, G; Ozcelik, H; Ejlertsen, B; Nielsen, FC; Jønson, L; Andersen, MK; Ding, YC; Steele, L; Foretova, L; Teulé, A; Lazaro, C; Brunet, J; Pujana, MA; Mai, PL; Loud, JT; Walsh, C; Lester, J; Orsulic, S; Narod, SA; Herzog, J; Sand, SR; Tognazzo, S; Agata, S; Vaszko, T; Weaver, J; Stavropoulou, AV; Buys, SS; Romero, A; de la Hoya, M; Aittomäki, K; Muranen, TA; Duran, M; Chung, WK; Lasa, A; Dorfling, CM; Miron, A; BCFR,; Benitez, J; Senter, L; Huo, D; Chan, SB; Sokolenko, AP; Chiquette, J; Tihomirova, L; Friebel, TM; Agnarsson, BA; Lu, KH; Lejbkowicz, F; James, PA; Hall, P; Dunning, AM; Tessier, D; Cunningham, J; Slager, SL; Wang, C; Hart, S; Stevens, K; Simard, J; Pastinen, T; Pankratz, VS; Offit, K; Easton, DF; Chenevix-Trench, G; Antoniou, AC; CIMBA,
MLA Citation
Couch, Fergus J., et al. “Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk..” Plos Genet, vol. 9, no. 3, 2013. Pubmed, doi:10.1371/journal.pgen.1003212.
URI
https://scholars.duke.edu/individual/pub1327358
PMID
23544013
Source
pubmed
Published In
Plos Genet
Volume
9
Published Date
Start Page
e1003212
DOI
10.1371/journal.pgen.1003212

Genetic counseling's critical role in managing hereditary cancers

Authors
MLA Citation
Kauff, N. D. “Genetic counseling's critical role in managing hereditary cancers.” Contemporary Ob/Gyn, vol. 56, no. 4, Apr. 2011.
URI
https://scholars.duke.edu/individual/pub1327414
Source
scopus
Published In
Contemporary Ob/Gyn
Volume
56
Published Date
Start Page
34

Risk-reducing salpingo-oophorectomy for the prevention of inherited breast and ovarian cancer

© 2008 by Informa Healthcare USA, Inc. Heritable mutations in one of the BRCA genes cause approximately 8% to 13% of epithelial ovarian cancers (1-3). Women with mutations in BRCA1 have a 35% to 60% chance of developing a BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer by age 70, corresponding to a relative risk of 30 to 45 times that of women in the general population (4-6). Similarly, women with mutations in BRCA2 have a 10% to 27% chance of developing a BRCA-associated gynecologic cancer by age 70, corresponding to a relative risk of 6 to 20. Women with mutations in either of these genes are also at tremendously increased risk of breast cancer, with 56% to 84% of mutation carriers developing breast cancer by age 70 (4-7). Over the past decade, a great deal has been learned about the efficacy of risk-reducing strategies in women with an inherited predisposition secondary to a mutation in one of these genes. Unfortunately, currently available ovarian cancer screening modalities have not proven to be effective for women with an inherited risk of ovarian cancer. While chemoprevention with oral contraceptives may reduce the risk of ovarian cancer, both the incomplete prevention conferred against ovarian cancer as well as possible deleterious impact on breast cancer risk limit their use as a risk reduction strategy in isolation. Given these issues, risk-reducing salpingo-oophorectomy (RRSO) has become one of the cornerstones of risk reduction for women with an inherited risk of ovarian cancer and should be considered in all women who harbor a deleterious germline mutation in BRCA1 or BRCA2. In this chapter, the sentinel studies supporting RRSO will be reviewed as well as the salient issues surrounding both pre-and postoperative counseling.
Authors
Lewin, SN; Kauff, ND
MLA Citation
Lewin, S. N., and N. D. Kauff. “Risk-reducing salpingo-oophorectomy for the prevention of inherited breast and ovarian cancer.” Hereditary Gynecologic Cancer: Risk, Prevention and Management, 2008, pp. 79–91.
URI
https://scholars.duke.edu/individual/pub1361299
Source
scopus
Published Date
Start Page
79
End Page
91