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:

High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes.

Purpose To investigate the associations between BRCA mutation status and computed tomography (CT) phenotypes of high-grade serous ovarian cancer (HGSOC) and to evaluate CT indicators of cytoreductive outcome and survival in patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 108 patients (33 with BRCA mutant and 75 with BRCA wild-type HGSOC) who underwent CT before primary debulking. Two radiologists independently reviewed the CT findings for various qualitative CT features. Associations between CT features, BRCA mutation status, cytoreductive outcome, and progression-free survival (PFS) were evaluated by using logistic regression and Cox proportional hazards regression, respectively. Results Peritoneal disease (PD) pattern, presence of PD in gastrohepatic ligament, mesenteric involvement, and supradiaphragmatic lymphadenopathy at CT were associated with BRCA mutation status (multiple regression: P < .001 for each CT feature). While clinical and CT features were not associated with cytoreductive outcome for patients with BRCA-mutant HGSOC, presence of PD in lesser sac (odds ratio [OR] = 2.40) and left upper quadrant (OR = 1.19), mesenteric involvement (OR = 7.10), and lymphadenopathy in supradiaphragmatic (OR = 2.83) and suprarenal para-aortic (OR = 4.79) regions were associated with higher odds of incomplete cytoreduction in BRCA wild-type HGSOC (multiple regression: P < .001 each CT feature). Mesenteric involvement at CT was associated with significantly shorter PFS for both patients with BRCA-mutant HGSOC (multiple regression: hazard ratio [HR] = 26.7 P < .001) and those with BRCA wild-type HGSOC (univariate analysis: reader 1, HR = 2.42, P < .001; reader 2, HR = 2.61; P < .001). Conclusion Qualitative CT features differed between patients with BRCA-mutant HGSOC and patients with BRCA wild-type HGSOC. CT indicators of cytoreductive outcome varied according to BRCA mutation status. Mesenteric involvement at CT was an indicator of significantly shorter PFS for both patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. © RSNA, 2017 Online supplemental material is available for this article.
Authors
Nougaret, S; Lakhman, Y; Gönen, M; Goldman, DA; Miccò, M; D'Anastasi, M; Johnson, SA; Juluru, K; Arnold, AG; Sosa, RE; Soslow, RA; Vargas, HA; Hricak, H; Kauff, ND; Sala, E
MLA Citation
Nougaret, Stephanie, et al. “High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes..” Radiology, vol. 285, no. 2, Nov. 2017, pp. 472–81. Pubmed, doi:10.1148/radiol.2017161697.
URI
https://scholars.duke.edu/individual/pub1327340
PMID
28628421
Source
pubmed
Published In
Radiology
Volume
285
Published Date
Start Page
472
End Page
481
DOI
10.1148/radiol.2017161697

Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.

IMPORTANCE: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE: To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS: Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES: Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES: Breast and ovarian cancer risks. RESULTS: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.
Authors
Rebbeck, TR; Mitra, N; Wan, F; Sinilnikova, OM; Healey, S; McGuffog, L; Mazoyer, S; Chenevix-Trench, G; Easton, DF; Antoniou, AC; Nathanson, KL; CIMBA Consortium,; Laitman, Y; Kushnir, A; Paluch-Shimon, S; Berger, R; Zidan, J; Friedman, E; Ehrencrona, H; Stenmark-Askmalm, M; Einbeigi, Z; Loman, N; Harbst, K; Rantala, J; Melin, B; Huo, D; Olopade, OI; Seldon, J; Ganz, PA; Nussbaum, RL; Chan, SB; Odunsi, K; Gayther, SA; Domchek, SM; Arun, BK; Lu, KH; Mitchell, G; Karlan, BY; Walsh, C; Lester, J; Godwin, AK; Pathak, H; Ross, E; Daly, MB; Whittemore, AS; John, EM; Miron, A; Terry, MB; Chung, WK; Goldgar, DE; Buys, SS; Janavicius, R; Tihomirova, L; Tung, N; Dorfling, CM; van Rensburg, EJ; Steele, L; Neuhausen, SL; Ding, YC; Ejlertsen, B; Gerdes, A-M; Hansen, TVO; Ramón y Cajal, T; Osorio, A; Benitez, J; Godino, J; Tejada, M-I; Duran, M; Weitzel, JN; Bobolis, KA; Sand, SR; Fontaine, A; Savarese, A; Pasini, B; Peissel, B; Bonanni, B; Zaffaroni, D; Vignolo-Lutati, F; Scuvera, G; Giannini, G; Bernard, L; Genuardi, M; Radice, P; Dolcetti, R; Manoukian, S; Pensotti, V; Gismondi, V; Yannoukakos, D; Fostira, F; Garber, J; Torres, D; Rashid, MU; Hamann, U; Peock, S; Frost, D; Platte, R; Evans, DG; Eeles, R; Davidson, R; Eccles, D; Cole, T; Cook, J; Brewer, C; Hodgson, S; Morrison, PJ; Walker, L; Porteous, ME; Kennedy, MJ; Izatt, L; Adlard, J; Donaldson, A; Ellis, S; Sharma, P; Schmutzler, RK; Wappenschmidt, B; Becker, A; Rhiem, K; Hahnen, E; Engel, C; Meindl, A; Engert, S; Ditsch, N; Arnold, N; Plendl, HJ; Mundhenke, C; Niederacher, D; Fleisch, M; Sutter, C; Bartram, CR; Dikow, N; Wang-Gohrke, S; Gadzicki, D; Steinemann, D; Kast, K; Beer, M; Varon-Mateeva, R; Gehrig, A; Weber, BH; Stoppa-Lyonnet, D; Houdayer, C; Belotti, M; Gauthier-Villars, M; Damiola, F; Boutry-Kryza, N; Lasset, C; Sobol, H; Peyrat, J-P; Muller, D; Fricker, J-P; Collonge-Rame, M-A; Mortemousque, I; Nogues, C; Rouleau, E; Isaacs, C; De Paepe, A; Poppe, B; Claes, K; De Leeneer, K; Piedmonte, M; Rodriguez, G; Wakely, K; Boggess, J; Blank, SV; Basil, J; Azodi, M; Phillips, K-A; Caldes, T; de la Hoya, M; Romero, A; Nevanlinna, H; Aittomäki, K; van der Hout, AH; Hogervorst, FBL; Verhoef, S; Collée, JM; Seynaeve, C; Oosterwijk, JC; Gille, JJP; Wijnen, JT; Gómez Garcia, EB; Kets, CM; Ausems, MGEM; Aalfs, CM; Devilee, P; Mensenkamp, AR; Kwong, A; Olah, E; Papp, J; Diez, O; Lazaro, C; Darder, E; Blanco, I; Salinas, M; Jakubowska, A; Lubinski, J; Gronwald, J; Jaworska-Bieniek, K; Durda, K; Sukiennicki, G; Huzarski, T; Byrski, T; Cybulski, C; Toloczko-Grabarek, A; Złowocka-Perłowska, E; Menkiszak, J; Arason, A; Barkardottir, RB; Simard, J; Laframboise, R; Montagna, M; Agata, S; Alducci, E; Peixoto, A; Teixeira, MR; Spurdle, AB; Lee, MH; Park, SK; Kim, S-W; Friebel, TM; Couch, FJ; Lindor, NM; Pankratz, VS; Guidugli, L; Wang, X; Tischkowitz, M; Foretova, L; Vijai, J; Offit, K; Robson, M; Rau-Murthy, R; Kauff, N; Fink-Retter, A; Singer, CF; Rappaport, C; Gschwantler-Kaulich, D; Pfeiler, G; Tea, M-K; Berger, A; Greene, MH; Mai, PL; Imyanitov, EN; Toland, AE; Senter, L; Bojesen, A; Pedersen, IS; Skytte, A-B; Sunde, L; Thomassen, M; Moeller, ST; Kruse, TA; Jensen, UB; Caligo, MA; Aretini, P; Teo, S-H; Selkirk, CG; Hulick, PJ; Andrulis, I
MLA Citation
Rebbeck, Timothy R., et al. “Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer..” Jama, vol. 313, no. 13, Apr. 2015, pp. 1347–61. Pubmed, doi:10.1001/jama.2014.5985.
URI
https://scholars.duke.edu/individual/pub1327350
PMID
25849179
Source
pubmed
Published In
Jama
Volume
313
Published Date
Start Page
1347
End Page
1361
DOI
10.1001/jama.2014.5985

Rare de novo germline copy-number variation in testicular cancer.

Although heritable factors are an important determinant of risk of early-onset cancer, the majority of these malignancies appear to occur sporadically without identifiable risk factors. Germline de novo copy-number variations (CNVs) have been observed in sporadic neurocognitive and cardiovascular disorders. We explored this mechanism in 382 genomes of 116 early-onset cancer case-parent trios and unaffected siblings. Unique de novo germline CNVs were not observed in 107 breast or colon cancer trios or controls but were indeed found in 7% of 43 testicular germ cell tumor trios; this percentage exceeds background CNV rates and suggests a rare de novo genetic paradigm for susceptibility to some human malignancies.
Authors
Stadler, ZK; Esposito, D; Shah, S; Vijai, J; Yamrom, B; Levy, D; Lee, Y-H; Kendall, J; Leotta, A; Ronemus, M; Hansen, N; Sarrel, K; Rau-Murthy, R; Schrader, K; Kauff, N; Klein, RJ; Lipkin, SM; Murali, R; Robson, M; Sheinfeld, J; Feldman, D; Bosl, G; Norton, L; Wigler, M; Offit, K
MLA Citation
Stadler, Zsofia K., et al. “Rare de novo germline copy-number variation in testicular cancer..” Am J Hum Genet, vol. 91, no. 2, Aug. 2012, pp. 379–83. Pubmed, doi:10.1016/j.ajhg.2012.06.019.
URI
https://scholars.duke.edu/individual/pub1327362
PMID
22863192
Source
pubmed
Published In
Am J Hum Genet
Volume
91
Published Date
Start Page
379
End Page
383
DOI
10.1016/j.ajhg.2012.06.019

Genome-wide association studies of cancer predisposition.

Genome-wide association studies (GWAS) have now been performed in nearly all common malignancies and have identified more than 100 common genetic risk variants that confer a modest increased risk of cancer. For most discovered germline risk variants, the per allele effect size is small (<1.5) and the biologic mechanism of the detected association remains unexplained. Exceptions are the risk variants identified in JAK2 in myeloproliferative neoplasm and in the KITLG gene in testicular cancer, which are each associated with nearly a 3-fold increased risk of disease. GWAS have provided an efficient approach to identifying common, low-penetrance risk variants, and have implicated several novel cancer susceptibility loci. However, the identified low-penetrance risk variants explain only a small fraction of the heritability of cancer and the clinical usefulness of using these variants for cancer-risk prediction is to date limited. Studies involving more heterogeneous populations, determination of the causal variants, and functional studies are now necessary to further elucidate the potential biologic and clinical significance of the observed associations.
Authors
Stadler, ZK; Vijai, J; Thom, P; Kirchhoff, T; Hansen, NAL; Kauff, ND; Robson, M; Offit, K
MLA Citation
Stadler, Zsofia K., et al. “Genome-wide association studies of cancer predisposition..” Hematol Oncol Clin North Am, vol. 24, no. 5, Oct. 2010, pp. 973–96. Pubmed, doi:10.1016/j.hoc.2010.06.009.
URI
https://scholars.duke.edu/individual/pub1327409
PMID
20816582
Source
pubmed
Published In
Hematol Oncol Clin North Am
Volume
24
Published Date
Start Page
973
End Page
996
DOI
10.1016/j.hoc.2010.06.009

Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions.

Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2, associated with Hereditary Breast/Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast cancer and up to a 46% lifetime risk ovarian cancer. Similarly, women with mutations in the DNA mismatch repair genes, MLH1, MSH2 or MSH6, associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40-60% lifetime risk of both endometrial and colorectal cancer as well as a 9-12% lifetime risk of ovarian cancer. Genetic risk assessment enables physicians to provide individualized evaluation of the likelihood of having one of these gynecologic cancer predisposition syndromes, as well the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes. Hereditary cancer risk assessment is a process that includes assessment of risk, education and counseling conducted by a provider with expertise in cancer genetics, and may include genetic testing after appropriate consent is obtained. This commentary provides guidance on identification of patients who may benefit from hereditary cancer risk assessment for Hereditary Breast/Ovarian Cancer and the Lynch/Hereditary Non-Polyposis Colorectal Cancer syndrome.
Authors
Lancaster, JM; Powell, CB; Kauff, ND; Cass, I; Chen, L-M; Lu, KH; Mutch, DG; Berchuck, A; Karlan, BY; Herzog, TJ; Society of Gynecologic Oncologists Education Committee,
MLA Citation
Lancaster, Johnathan M., et al. “Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions.Gynecol Oncol, vol. 107, no. 2, Nov. 2007, pp. 159–62. Pubmed, doi:10.1016/j.ygyno.2007.09.031.
URI
https://scholars.duke.edu/individual/pub760528
PMID
17950381
Source
pubmed
Published In
Gynecol Oncol
Volume
107
Published Date
Start Page
159
End Page
162
DOI
10.1016/j.ygyno.2007.09.031