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11 results on '"Hou, M.-F."'

1. Evidence that the 5p12 variant rs10941679 confers susceptibility to estrogen receptor positive breast cancer through FGF10 and MRPS30 regulation

Author

Ghoussaini, M, French, J.D., Michailidou, K., Nord, S., Beesley, J., Canisus, S., Hillman, K.M., Kaufmann, S., Sivakumaran, H., Marjaneh, M.M., Lee, J.S., Dennis, J., Bolla, M.K., Wang, Q., Dicks, E., Milne, R.L., Hopper, J.L., Southey, M.C., Schmidt, M.K., Broeks, A., Muir, K., Lophatananon, A, Fasching, P.A., Beckmann, M.W., Fletcher, O., Johnson, N., Sawyer, E.J., Tomlinson, I., Burwinkel, B., Marme, F., Guenel, P., Truong, T., Bojesen, S.E., Flyger, H., Benitez, J., González-Neira, A., Alonson, M.R., Pita, G., Neuhausen, S.L., Anton-Culver, H., Brenner, H., Arndt, V., Meindl, A., Schmutzler, R.K., Brauch, H., Hamann, U., Tessier, D.C., Vincent, D., Nevanlinna, H., Khan, S., Matsuo, K., Ito, H., Dörk, T., Bogdanova, N.V., Lindblom, A., Margolin, S., Mannermaa, A., Kosma, V-M., kConFab/AOCS Investigators, Wu, A.H., Van Den Berg, D., Lambrechts, D., Floris, G., Chang-Claude, J., Rudolph, A., Radice, P., Barile, M., Couch, F.J., Hallberg, E., Giles, G.G., Haiman, C.A., Le Marchand, L., Goldberg, M.S., Teo, S.H., Yip, C.H., Borresen-Dale, A-L., NBCS Collaborators, Zheng, W., Cai, Q., Winqvist, R., Pylkäs, K., Andrulis, I.L., Devilee, P., Tollenaar, R.A.E.M., García-Closas, M., Figueroa, J., Hall, P., Czene, K, Brand, J.S., Darabi, H, Eriksson, M., Hooning, M.J., Koppert, L.B., Jingmei, L., Shu, X-O., Zheng, Y., Cox, A, Cross, S.S., Shah, M., Rhenius, V., Choi, J-Y., Kang, D., Hartman, M., Chia, K.S., Kabisch, M., Torres, D., Luccarini, C., Conroy, D.M, Jakubowska, A., Libinski, J., Sangrajrang, S., Brennan, P., Olswold, C., Slager, S., Shen, C-Y., Hou, M-F., Swerdlow, A., Schoemaker, M.J., Simard, J., Pharoah, P.D.P, Kristensen, V., Chenevix-Trench, G., Easton, D.F., Dunning, A.M., and Edwards, S.L.

Abstract

Genome-wide association studies (GWAS) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine-mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). Using data for 3,365 genotyped and imputed single nucleotide polymorphisms (SNPs) across a 1Mb (positions 44394495-45364167; NCBI build 37) panel we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen receptor-positive (ER+) breast cancer (per-g allele OR ER+=1.15; 95% CI 1.13-1.18; P=8.35x10-30). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER-) breast cancer (lead SNP rs6864776: per-a allele OR ER-=1.10; 95% CI 1.05-1.14; P-conditional=1.44E-12); and a single signal 3 SNP (rs200229088: per-t allele OR ER+=1.12; 95% CI 1.09-1.15; P-conditional=1.12E-05). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is over-expressed in ~10% of human breast cancers, while MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis.

Published
2016

2. Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer

Author

Shi, J., Zhang, Y., Zheng, W., Michailidou, K., Ghoussaini, M., Bolla, M.K., Wang, Q., Dennis, J., Lush, M., Milne, R.L., Shu, X-O., Beesley, J., Kar, S., Andrulis, I.L., Anton-Culver, H., Arndt, V., Beckmann, M.W., Zhao, Z., Guo, X., Benitez, J., Beeghly-Fadiel, A., Blot, W., Bogdanova, N.V., Bojesen, S.E., Brauch, H., Brenner, H., Brinton, L., Broeks, A., Brüning, T., Burwinkel, B., Cai, H., Canisius, S., Chang-Claude, J., Choi, J-Y., Couch, F.J., Cox, A., Cross, S.S., Czene, K., Darabi, H., Devilee, P., Droit, A., Dork, T., Fasching, P.A., Fletcher, O., Flyger, H., Fostira, F., Gaborieau, V., García-Closas, M., Giles, G.G., Grip, M., Guenel, P., Haiman, C.A., Hamann, U., Hartman, M., Miao, H., Hollestelle, A., Hopper, J.L., Hsiung, C-N., Ito, H., Jakubowska, A., Johnson, N., Torres, D., Kabisch, M., Kang, D., Khan, S., Knight, J.A., Kosma, V-M., Lambrechts, D., Li, J., Lindblom, A., Lophatananon, A., Lubinski, J., Mannermaa, A., Manoukian, S., Le Marchand, L., Margolin, S., Marme, F., Matsuo, K., McLean, C., Meindl, A., Muir, K., Neuhausen, S.L., Nevanlinna, H., Nord, S., Børresen-Dale, A-L., Olson, J.E., Orr, N., van den Ouweland, A.M.W, Peterlongo, P., Putti, T.C., Rudolph, A., Sangrajrang, S., Sawyer, E.J., Schmidt, M.K., Schmutzler, R.K., Shen, C-Y., Hou, M-F., Shrubsole, M.J., Southey, M.C., Swerdlow, A., Teo, S.H., Thienpont, B., Toland, A.E., Tollenaar, R.A.E.M., Tomlinson, I., Truong, T., Tseng, C-C., Wen, W., Winqvist, R., Wu, A.H., Yip, C.H., Zamora, P.M., Zheng, Y., Floris, G., Cheng, C-Y., Hooning, M.J., Martens, J.W.M., Seynaeve, C., Kristensen, V.N., Hall, P., Pharoah, P.D.P., Simard, J., Chenevix-Trench, G., Dunning, A.M., Antoniou, A.C., Easton, D.F., Cai, Q., Long, J., Clinical Genetics, Medical Oncology, and Obstetrics & Gynecology

Subjects
SDG 3 - Good Health and Well-being
Abstract

Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. We conducted a fine-mapping study across 2.06 Mb (chr8:127,561,724 -129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium. We found three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional P = 5.8 × 10-6), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional P = 1.1 × 10-6), and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional P = 1.1 × 10-4). Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas, and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r2 = 0.77), were putatively functional variants for two of the five independent association signals. Our results highlight multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry

Published
2016

3. Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study

Author

Johnson, N., Dudbridge, F., Orr, N., Gibson, L., Jones, M.E., Schoemaker, M.J., Folkerd, E.J., Haynes, B.P., Hopper, J.L., Southey, M.C., Dite, G.S., Apicella, C., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Atsma, F., Muir, K., Lophatananon, A., Fasching, P.A., Beckmann, M.W., Ekici, A.B., Renner, S.P., Sawyer, E., Tomlinson, I., Kerin, M., Miller, N., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Guenel, P., Truong, T., Cordina, E., Menegaux, F., Bojesen, S.E., Nordestgaard, B.G., Flyger, H., Milne, R., Zamora, M.P., Arias Perez, J.I., Benitez, J., Bernstein, L., Anton-Culver, H., Ziogas, A., Dur, C.C., Brenner, H., Mueller, H., Arndt, V., Dieffenbach, A.K., Meindl, A., Heil, J., Bartram, C.R., Schmutzler, R.K., Brauch, H., Justenhoven, C., Ko, Y-D., Nevanlinna, H., Muranen, T.A., Aittomaeki, K., Blomqvist, C., Matsuo, K., Doerk, T., Bogdanova, NV., Antonenkova, N.N., Lindblom, A., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J.M., Chenevix-Trench, G., Beesley, J., Wu, A.H., Van den Berg, D., Tseng, C-C., Lambrechts, D., Smeets, D., Neven, P., Wildiers, H., Chang-Claude, J., Rudolph, A., Nickels, S., Flesch-Janys, D., Radice, P., Peterlongo, P., Bonanni, B., Pensotti, V., Couch, F.J., Olson, J.E., Wang, X., Fredericksen, Z., Pankratz, V.S., Giles, G.G., Severi, G., Baglietto, L., Haiman, C., Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Soucy, P., Teo, S., Yip, C.H., Phuah, S.Y., Cornes, B.K., Kristensen, V.N., Alnaes, G.G., Borresen-Dale, A-L., Zheng, W., Winqvist, R., Pylkaes, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L, Knight, J.A., Glendon, G., Mulligan, A.M., Devillee, P., Figueroa, J., Chanock, S.J., Lissowska, J., Sherman, M.E., Hall, P., Schoof, N., Hooning, M., Hollestelle, A., Oldenburg, R.A., Tilanus-Linthorst, M., Liu, J., Cox, A., Brock, I.W., Reed, M.W.R., Cross, S.S., Blot, W., Signorello, L.B., Pharoah, P.D.P., Dunning, A.M., Shah, M., Kang, D., Noh, D-Y., Park, S.K., Choi, J-Y., Hartman, M., Miao, H., Lim, W.Y., Tang, A., Hamann, U., Foersti, A., Ruediger, T., Ulmer, H.U., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Slager, S., Toland, A.E., Vachon, C., Yannoukakos, D., Shen, C-Y., Yu, J-C., Huang, C-S., Hou, M-F., Gonzalez-Neira, A., Tessier, D.C., Vincent, D., Bacot, F., Luccarini, C., Dennis, J., Michailidou, K., Bolla, M.K., Wang, J., Easton, D.F., Garcia-Closas, M., Dowsett, M., Ashworth, A., Swerdlow, A.J., Peto, J., Silva, I.D.S., Fletcher, O., Breast, G.E.I., Investigators, K., Grp, AOCS, Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Dennis, Joe [0000-0003-4591-1214], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository

Subjects
Adult, Menarche, Genotype, Age Factors, Breast Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, White People, Premenopause, Risk Factors, Cytochrome P-450 CYP3A, Humans, Female, Genetic Predisposition to Disease, Age of Onset, Reproductive History, Genetic Association Studies, Aged
Abstract

Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to\ud the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and\ud a modest reduction in risk of breast cancer in women age ≤50 years.\ud Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of\ud 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping\ud of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine\ud whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.\ud Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found\ud no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were\ud OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (Ptrend = 0.02). There was\ud no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche\ud in controls (Ptrend = 0.005) but not cases (Ptrend = 0.97). Consequently the association between rs10235235 and breast\ud cancer risk differed according to age at menarche (Phet = 0.02); the rare allele of rs10235235 was associated with a\ud reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94;\ud ORhom = 0.81, 95% CI 0.51, 1.30; Ptrend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06,\ud 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; Ptrend = 0.29).\ud Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both\ud breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche\ud and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

Published
2014

4. Comparison of 6q25 Breast Cancer Hits from Asian and\ud European Genome Wide Association Studies in the\ud Breast Cancer Association Consortium (BCAC)

Author

Hein, R., Maranian, M., Hopper, J.L., Kapuscinski, M.K., Southey, M.C., Park, D.J., Schmidt, M.K., Broeks, A., Hogervorst, F.B.L., Bueno-de-Mesquit, H.B., Muir, K.R., Lophatananon, A., Rattanamongkongul, S., Puttawibul, P., Fasching, P.A., Hein, A., Ekici, A.B., Beckmann, M.W., Fletcher, O., Johnson, N., Silva, I.D.S., Peto, J., Sawyer, E., Tomlinson, I., Kerin, M., Miller, N., Marmee, F., Schneeweiss, A., Sohn, C., Burwinkel, B., Guenel, P., Cordina-Duverger, E., Menegaux, F., Truong, T., Bojesen, S.E., Nordestgaard, B.G., Flyger, H., Milne, R.L., Arias Perez, J.I., Pilar Zamora, M., Benitez, J., Anton-Culver, H., Ziogas, A., Bernstein, L., Clarke, C.A., Brenner, H., Mueller, H., Arndt, V., Stegmaier, C., Rahman, N., Seal, S., Turnbull, C., Renwick, A., Meindl, A., Schott, S., Bartram, C.R., Schmutzler, R.K., Brauch, H., Hamann, U., Ko, Y-D., Wang-Gohrke, S., Doerk, T., Schuermann, P., Karstens, J.H., Hillemanns, P., Nevanlinna, H., Heikkinen, T., Aittomaki, K., Blomqvist, C., Bogdanova, N.V., Zalutsky, I.V., Antonenkova, N.N., Bermisheva, M., Prokovieva, D., Farahtdinova, A., Khusnutdinova, E., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J., Chen, X., Beesley, J., Lambrechts, D., Zhao, H., Neven, P., Wildiers, H., Nickels, S., Flesch-Janys, D., Radice, P., Peterlongo, P., Manoukian, S., Barile, M., Couch, F.J., Olson, J.E., Wang, X., Fredericksen, Z., Giles, G.G., Baglietto, L., McLean, C.A., Severi, G., Offit, K., Robson, M., Gaudet, M.M., Vijai, J., Alnaes, G.G., Kristensen, V., Borresen-Dale, A-L., John, E.M., Miron, A., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Figueroa, J.D., Garcia-Closas, M., Lissowska, J., Sherman, M.E., Hooning, M., Martens, J.W.M., Seynaeve, C., Collee, M., Hall, P., Humpreys, K., Czene, K., Liu, J., Cox, A., Brock, I.W., Cross, S.S., Reed, M.W.R., Ahmed, S., Ghoussaini, M., Pharoah, P.D.P., Kang, D., Yoo, K-Y., Noh, D-Y., Jakubowska, A., Jaworska, K., Durda, K., Zlowocka, E., Sangrajrang, S., Gaborieau, V., Brennan, P., McKay, J., Shen, C-Y., Yu, J-C., Hsu, H-M., Hou, M-F., Orr, N., Schoemaker, M., Ashworth, A., Swerdlow, A., Trentham-Dietz, A., Newcomb, P.A., Titus, L., Egan, K.M., Chenevix-Trench, G., Antoniou, A.C., Humphreys, M.K., Morrison, J., Chang-Claude, J., Easton, D.F., Dunning, A.M., Network, GENICA, Investigators, K, and Group, AOCS

Abstract

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single\ud nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports\ud about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP,\ud tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from fortyfour\ud studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European\ud descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were\ud used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER2) tumours. Models including both SNPs\ud were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer\ud risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26–\ud 1.48), p = 7.6610214 in Asians and 1.09 (95% CI 1.07–1.11), p = 6.8610218 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI\ud 1.19–1.41), p = 1.261029 in Asians and 1.12 (95% CI 1.08–1.17), p = 3.861029 in Europeans]. SNP rs2046210 is associated with a\ud significantly greater risk of ER2 than ER+ tumours in Europeans [OR (ER2) = 1.20 (95% CI 1.15–1.25), p = 1.8610217 versus OR\ud (ER+) = 1.07 (95% CI 1.04–1.1), p = 1.361027\ud , pheterogeneity = 5.161026\ud ]. In these Asian studies, by contrast, there is no clear\ud evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other\ud SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in\ud Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER2 tumours.

Published
2012

6. Association analysis identifies 65 new breast cancer risk loci

Author

Michailidou, K, Lindström, S, Dennis, J, Beesley, J, Hui, S, Kar, S, Lemaçon, A, Soucy, P, Glubb, D, Rostamianfar, A, Bolla, MK, Wang, Q, Tyrer, J, Dicks, E, Lee, A, Wang, Z, Allen, J, Keeman, R, Eilber, U, French, JD, Qing Chen, X, Fachal, L, McCue, K, McCart Reed, AE, Ghoussaini, M, Carroll, JS, Jiang, X, Finucane, H, Adams, M, Adank, MA, Ahsan, H, Aittomäki, K, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Arun, B, Auer, PL, Bacot, F, Barrdahl, M, Baynes, C, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bernstein, L, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bonanni, B, Børresen-Dale, A-L, Brand, JS, Brauch, H, Brennan, P, Brenner, H, Brinton, L, Broberg, P, Brock, IW, Broeks, A, Brooks-Wilson, A, Brucker, SY, Brüning, T, Burwinkel, B, Butterbach, K, Cai, Q, Cai, H, Caldés, T, Canzian, F, Carracedo, A, Carter, BD, Castelao, JE, Chan, TL, David Cheng, T-Y, Seng Chia, K, Choi, J-Y, Christiansen, H, Clarke, CL, NBCS Collaborators, Collée, M, Conroy, DM, Cordina-Duverger, E, Cornelissen, S, Cox, DG, Cox, A, Cross, SS, Cunningham, JM, Czene, K, Daly, MB, Devilee, P, Doheny, KF, Dörk, T, Dos-Santos-Silva, I, Dumont, M, Durcan, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Ellberg, C, Elvira, M, Engel, C, Eriksson, M, Fasching, PA, Figueroa, J, Flesch-Janys, D, Fletcher, O, Flyger, H, Fritschi, L, Gaborieau, V, Gabrielson, M, Gago-Dominguez, M, Gao, Y-T, Gapstur, SM, García-Sáenz, JA, Gaudet, MM, Georgoulias, V, Giles, GG, Glendon, G, Goldberg, MS, Goldgar, DE, González-Neira, A, Grenaker Alnæs, GI, Grip, M, Gronwald, J, Grundy, A, Guénel, P, Haeberle, L, Hahnen, E, Haiman, CA, Håkansson, N, Hamann, U, Hamel, N, Hankinson, S, Harrington, P, Hart, SN, Hartikainen, JM, Hartman, M, Hein, A, Heyworth, J, Hicks, B, Hillemanns, P, Ho, DN, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Hou, M-F, Hsiung, C-N, Huang, G, Humphreys, K, Ishiguro, J, Ito, H, Iwasaki, M, Iwata, H, Jakubowska, A, Janni, W, John, EM, Johnson, N, Jones, K, Jones, M, Jukkola-Vuorinen, A, Kaaks, R, Kabisch, M, Kaczmarek, K, Kang, D, Kasuga, Y, Kerin, MJ, Khan, S, Khusnutdinova, E, Kiiski, JI, Kim, S-W, Knight, JA, Kosma, V-M, Kristensen, VN, Krüger, U, Kwong, A, Lambrechts, D, Le Marchand, L, Lee, E, Lee, MH, Lee, JW, Neng Lee, C, Lejbkowicz, F, Li, J, Lilyquist, J, Lindblom, A, Lissowska, J, Lo, W-Y, Loibl, S, Long, J, Lophatananon, A, Lubinski, J, Luccarini, C, Lux, MP, Ma, ESK, MacInnis, RJ, Maishman, T, Makalic, E, Malone, KE, Kostovska, IM, Mannermaa, A, Manoukian, S, Manson, JE, Margolin, S, Mariapun, S, Martinez, ME, Matsuo, K, Mavroudis, D, McKay, J, McLean, C, Meijers-Heijboer, H, Meindl, A, Menéndez, P, Menon, U, Meyer, J, Miao, H, Miller, N, Taib, NAM, Muir, K, Mulligan, AM, Mulot, C, Neuhausen, SL, Nevanlinna, H, Neven, P, Nielsen, SF, Noh, D-Y, Nordestgaard, BG, Norman, A, Olopade, OI, Olson, JE, Olsson, H, Olswold, C, Orr, N, Pankratz, VS, Park, SK, Park-Simon, T-W, Lloyd, R, Perez, JIA, Peterlongo, P, Peto, J, Phillips, K-A, Pinchev, M, Plaseska-Karanfilska, D, Prentice, R, Presneau, N, Prokofyeva, D, Pugh, E, Pylkäs, K, Rack, B, Radice, P, Rahman, N, Rennert, G, Rennert, HS, Rhenius, V, Romero, A, Romm, J, Ruddy, KJ, Rüdiger, T, Rudolph, A, Ruebner, M, Rutgers, EJT, Saloustros, E, Sandler, DP, Sangrajrang, S, Sawyer, EJ, Schmidt, DF, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schumacher, F, Schürmann, P, Scott, RJ, Scott, C, Seal, S, Seynaeve, C, Shah, M, Sharma, P, Shen, C-Y, Sheng, G, Sherman, ME, Shrubsole, MJ, Shu, X-O, Smeets, A, Sohn, C, Southey, MC, Spinelli, JJ, Stegmaier, C, Stewart-Brown, S, Stone, J, Stram, DO, Surowy, H, Swerdlow, A, Tamimi, R, Taylor, JA, Tengström, M, Teo, SH, Beth Terry, M, Tessier, DC, Thanasitthichai, S, Thöne, K, Tollenaar, RAEM, Tomlinson, I, Tong, L, Torres, D, Truong, T, Tseng, C-C, Tsugane, S, Ulmer, H-U, Ursin, G, Untch, M, Vachon, C, Van Asperen, CJ, Van Den Berg, D, Van Den Ouweland, AMW, Van Der Kolk, L, Van Der Luijt, RB, Vincent, D, Vollenweider, J, Waisfisz, Q, Wang-Gohrke, S, Weinberg, CR, Wendt, C, Whittemore, AS, Wildiers, H, Willett, W, Winqvist, R, Wolk, A, Wu, AH, Xia, L, Yamaji, T, Yang, XR, Har Yip, C, Yoo, K-Y, Yu, J-C, Zheng, W, Zheng, Y, Zhu, B, Ziogas, A, Ziv, E, ABCTB Investigators, ConFab/AOCS Investigators, Lakhani, Antoniou, AC, Droit, A, Andrulis, IL, Amos, CI, Couch, FJ, Pharoah, PDP, Chang-Claude, J, Hall, P, Hunter, DJ, Milne, RL, García-Closas, M, Schmidt, MK, Chanock, SJ, Dunning, AM, Edwards, SL, Bader, GD, Chenevix-Trench, G, Simard, J, Kraft, P, and Easton, DF

Subjects
ConFab/AOCS Investigators, ABCTB Investigators, skin and connective tissue diseases, 3. Good health, NBCS Collaborators
Abstract

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

8. Symptom clusters analysis in bone metastases patients

Author

Chiu, L., Chow, E., Chiu, N., Zhang, L., Bedard, G., Fairchild, A., Vassiliou, V., El-Din, M. A. A., Jesus-Garcia, R., Forges, F., Tseng, L. -M, Hou, M. -F, Chie, W. -C, Satoh, T., Ma, B. B., Lam, H., and Bottomley, A.

11. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

Author

Cristina Saura, Suzette Delaloge, Sung Bae Kim, Mafalda Oliveira, Yen-Shen Lu, Bin Yao, John Crown, Ming-Shen Dai, Hong-Tai Chang, Thomas Yau, Takaaki Fujii, Nala Investigators, Daniele Fagnani, Maureen E. Trudeau, Ming-Feng Hou, William J. Gradishar, Johanna Mattson, Marketa Palacova, Barbara Haley, Masato Takahashi, Beverly Moy, Yu-Min Yeh, Richard Bryce, Kiana Keyvanjah, Miki Yamaguchi, Shang Wen Chen, Judith Bebchuk, Adam Brufsky, Norikazu Masuda, Michelino De Laurentiis, Yin-Hsun Feng, Johnson Lin, Toshimi Takano, Sara A. Hurvitz, Hans Wildiers, Yoon Sim Yap, Institut Català de la Salut, [Saura C, Oliveira M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. SOLTI Breast Cancer Cooperative Group, Barcelona, Spain. [Feng YH, Dai MS, Chen SW] Chi Mei Medical Centre, Liouying, Tainan, Taiwan and Tri-Service General Hospital, Taipei, Taiwan. [Hurvitz SA] University of California Los Angeles/Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA, Vall d'Hebron Barcelona Hospital Campus, Saura, C., Oliveira, M., Feng, Y. -H., Dai, M. -S., Chen, S. -W., Hurvitz, S. A., Kim, S. -B., Moy, B., Delaloge, S., Gradishar, W., Masuda, N., Palacova, M., Trudeau, M. E., Mattson, J., Yap, Y. S., Hou, M. -F., De Laurentiis, M., Yeh, Y. -M., Chang, H. -T., Yau, T., Wildiers, H., Haley, B., Fagnani, D., Lu, Y. -S., Crown, J., Lin, J., Takahashi, M., Takano, T., Yamaguchi, M., Fujii, T., Yao, B., Bebchuk, J., Keyvanjah, K., Bryce, R., and Brufsky, A.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Receptor, ErbB-2, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Quinoline, Medicaments antineoplàstics - Ús terapèutic, Kaplan-Meier Estimate, THERAPY, Tyrosine-kinase inhibitor, law.invention, chemistry.chemical_compound, ErbB-2, 0302 clinical medicine, Randomized controlled trial, Mama - Càncer, law, Antineoplastic Combined Chemotherapy Protocols, Other subheadings::/therapeutic use [Other subheadings], neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Brain Neoplasms, Nausea, ORIGINAL REPORTS, Middle Aged, OPEN-LABEL, Metastatic breast cancer, Progression-Free Survival, 3. Good health, Survival Rate, TRASTUZUMAB EMTANSINE, 030220 oncology & carcinogenesis, Neratinib, Retreatment, Quinolines, Female, Life Sciences & Biomedicine, Breast Neoplasm, medicine.drug, Human, Diarrhea, medicine.medical_specialty, medicine.drug_class, Clinical Sciences, Oncology and Carcinogenesis, Breast Neoplasms, Lapatinib, Breast Neoplasms, Male, Capecitabine, Brain Neoplasm, 03 medical and health sciences, Internal medicine, Breast Cancer, medicine, Humans, Oncology & Carcinogenesis, Progression-free survival, COMBINATION, terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Aged, Science & Technology, Antineoplastic Combined Chemotherapy Protocol, RECEPTOR, business.industry, Otros calificadores::/uso terapéutico [Otros calificadores], Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], medicine.disease, 030104 developmental biology, chemistry, Trastuzumab emtansine, Quality of Life, NALA Investigators, business
Abstract

PURPOSE NALA (ClinicalTrials.gov identifier: NCT01808573 ) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens. METHODS Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL). RESULTS A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .0004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups. CONCLUSION N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.

Published
2020

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