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Irene Andrulis
PhD
Andrulis's laboratory conducts multi-disciplinary studies to identify genetic alterations that play a role in breast cancer and sarcoma and to determine their clinical importance. Our goals are to explore the biology of these genetic alterations, to aid in diagnosis and treatment, and to discover novel targets for therapeutics.
Research Synopsis
Axillary lymph node status in breast cancer is the most important factor in predicting a patient’s risk of recurrence of disease. Patients whose disease has not spread to the lymph nodes (axillary node-negative, ANN) generally have a good prognosis; however, 20-30% of ANN patients will experience disease recurrence. This limit in prognostic ability of lymph node status has led me and my colleagues to a search for markers with prognostic power to aid in determining which ANN patients may benefit from chemotherapy and hormonal therapy. Our studies have led to the identification of novel genes involved in breast cancer. My goal as a molecular geneticist with an interest in molecular medicine is to assist in the translation of our basic research results into clinical practice.
Breast cancer is a heterogeneous disease that has been subdivided by gene expression profiling into different molecular subtypes (basal-like, HER2 enriched, luminal A and B, and normal breast-like). Even within the established subtypes, the clinical course of the disease can be diverse. For example, basal-like tumours have been shown to be associated with a poor prognosis; however, emerging evidence from our group and others suggests that this effect is time-dependent and that there exists a group of women with basal-like cancers who, in the long term, have a more favourable outcome.
Our group has taken a multi-disciplinary approach to identify novel genes and pathways with predictive and/or prognostic power in breast cancer. We have prospectively recruited two large cohorts of women, one with axillary lymph node-negative breast cancer and the other with familial breast cancer. In our node-negative cohort, we found that lymphovascular invasion is an independent predictor of recurrence. We have used expression arrays and tissue microarrays to determine patterns of gene expression that distinguish tumours with and without lymphovascular invasion, as well as patterns that distinguish women who had a recurrence versus those who remained disease free. Our studies on the differentially expressed genes and associations with breast cancer subtypes and clinical outcome will be discussed. We found that expression of some genes such as jagged1 and c-Met are correlated with the basal subtype and poor prognosis; whereas podocalyxin levels are associated with basal features but a good prognosis. Of interest, we discovered that previously unrecognized genes involved in immune system cytokine and chemokine signaling pathways exhibited differences in expression among breast tumours with different phenotypes. There is growing evidence that the tumour microenvironment plays an important role in breast cancer progression. Our preliminary evidence leads us to question whether these cytokine and chemokine signaling pathways used by the immune system are involved in breast tumour progression and may have clinical prognostic value. Our goals are to explore the clinical importance of these genetic alterations and to identify novel targets for new cancer therapeutics.
I am PI of the Ontario Familial Breast Cancer Registry, part of the international Breast Cancer Family Registry. This registry has been used in numerous research projects. Current work includes studies of breast cancer risk, recurrence, survival, and studies of gene-environment interactions. These projects require large numbers of subjects and multi-disciplinary expertise; therefore, we are participating in several international consortia. We have identified novel cancer susceptibility genes and expect to detect additional genes involved in breast cancer susceptibility and outcome.
One of our major goals has been to establish a youth cohort from the breast cancer families participating in our research studies. One of the strongest risk factors is a family history of breast cancer. Most studies have focused on genetic and lifestyle factors in adult women. However, there is growing evidence that young girls may be particularly sensitive to exposures that initiate or protect against breast cancer. We were recently funded by the US National Institutes of Health to establish a LEGACY cohort of girls who are the offspring of women enrolled in the Breast Cancer Family Registry and a comparison group of girls from families without breast cancer. We are conducting studies in young girls that will inform our understanding of when breast cancer susceptibility begins and how it impacts psychosocial adjustment and behaviors.
Recent Publications
Bull,S.B., Ozcelik, H., Pinnaduwage, D., Blackstein, M.E., Sutherland, D., Pritchard K.I., Tzontcheva A., Sidlofsky, S., Hanna, W., Qizilbash, M.D., Tweeddale, M., Fine, S., McCready, D., Andrulis, I.L. (2004) The Combination of p53 Mutation and neu/erbB-2 Amplification is Associated with Increased Risk of Recurrence in Node-Negative Breast Cancer. J. Clin. Oncol. 22: 86-96.
John, E.M., Hopper, J.L., Beck, J.C., Knight, J.A., Neuhausen, S.L., Senie, R.T., Ziogas, A., Andrulis, I.L., Anton-Culver, H., Boyd, N., Buys, S., Daly, M.B., Santella, R.M., Southey, M.C., Venne, V., Venter, D.J., West, D., Whittemore, A.S., and Seminara, D. and the Breast Cancer Family Registry. (2004) The Breast Cancer Family Registry (Breast CFR): An Infrastructure for Co-operative Multinational, Interdisciplinary and Translational Studies of the Genetic Epidemiology of Breast Cancer. Breast Cancer Res. 6: R375-R389.
Wunder, J.S., Gokgoz, N., Parkes, R., Bull, S.B., Eskandarian, S., Davis, A.M., Beauchamp, C.P., Conrad, E.U., Grimer, R.J., Healey, J.H., Malkin, D., Mangham, D.C., Rock, M.J., Bell, R.S., and Andrulis, I.L. (2005) TP53 Mutations and Outcome in Osteosarcoma: A Prospective, Multicenter Study. J Clin. Oncol. 23:1483-1490.
Pritchard K.I., Shepherd L.E., O’Malley F.P., Andrulis I.L., Tu D., and Levine M.N. for the National Cancer Institute of Canada Clinical Trials Group. (2006) Neu/ErbB2 and responsiveness of breast cancer to adjuvant chemotherapy. New England Journal of Medicine 354:2103-2111.
Bane, A.L., Beck, J.C., Bleiweiss, I., .. Andrulis, I.L., O’Malley, F.P. for the BCFR (2007) BRCA2 Mutation-Associated Breast Cancers Exhibit a Distinguishing Phenotype Based on Morphology and Molecular Profiles from Tissue Microarrays. Am J Surg Pathol. 31:121-128.
Reedijk, M., Pinnaduwage, D., Dickson, B.C., Mulligan, A.M., Zhang, H., Bull, S.B., O’Malley, F.P., Egan, S. E., and Andrulis, I.L. (2008) Elevated JAG1 mRNA expression, associated with the basal phenotype, is a poor-prognosis indicator in lymph node-negative breast cancer. Breast Cancer Res Treat. 111:439-448.
Mulligan, A.M., Pinnaduwage, D., Bull, S.B., O’Malley, F.P., and Andrulis, I.L. (2008) The prognostic impact of basal-like breast cancers is time dependent: evidence from Tissue Microarray studies on a lymph node negative cohort. Clin. Cancer Res. 14: 4168-4174
O’Malley, F.P., Chia, S., Tu, D., Shepherd, L.E., Levine, M.N., Bramwell, V.H., Andrulis, I.L., and Pritchard, K.I. (2009) Topoisomerase II alpha and Responsiveness of Breast Cancer to Adjuvant Chemotherapy. J Natl. Cancer Inst 101:644-650.
Viloria-Petit, A.M., Erdemir, T., Bane, A., Pinnaduwage, D., Roncari, R., Bose, L., Narimatsu, M., Wong, J., Kerbel, R.S., O’Malley, F.P., Andrulis, I.L., and Wrana, J. (2009) The TGFβ-Par6 Polarity Pathway Controls Breast Cancer Invasion and Metastasis. Proc Natl Acad Sci USA. 106:14028-14033.
Ponzo, M.G., Lesurf, R., Petkiewicz, S., O’Malley, F.P., Pinnaduwage, D., Andrulis, I.L., Bull, S.B., Chughtai, N., Germain, D., Omeroglu, A., Cardiff, R.D., Hallett, M., and Park, M. (2009) Met induces mammary tumors with multiple pathologies and is associated with both poor outcome and basal-type breast cancers. Proc Natl Acad Sci USA 106:12903-12908.
Mulligan, A.M., Pinnaduwage, D., Bane, A.L., Bull, S.B., O’Malley, F.P., and Andrulis, I.L. (2011) CK8/18 expression, the basal phenotype and family history in identifying BRCA1-associated breast cancer in the Ontario site of the Breast Cancer Family Registry. Cancer 117: 1350-1359.
Asimit, J.L., Andrulis, I.L. and Bull, S.B. (2011) A scan statistic for identifying chromosomal regions of association between gene expression and copy number. Statistics in Medicine. 30:1157-1178.
Bane, A. L., Pinnaduwage, D., Weerasooriya, N, O'Malley, F.P. and Andrulis, I.L. (2011) EMSY & CCND1 Amplification in Familial Breast Cancer: From the Ontario Site of the Breast Cancer Family Registry. Breast Cancer Research and Treatment 127:831-839.
O’Malley, F.P., Chia, S.,Tu, D., Shepherd, L.E. Levine, M.N., Huntsman, D., Bramwell, V.H., Andrulis, I.L., and Pritchard, K.I. (2011) Topoisomerase II alpha protein and responsiveness of breast cancer to adjuvant chemotherapy with CEF compared to CMF in the NCIC CTG randomized MA.5 adjuvant trial. Breast Cancer Research and Treatment. 128:401-409.
Kurian, A.W., Gong, G.D., John, E.M., Johnston, D.A., Felberg, A., West, D.W., Miron, A., Andrulis, I.l., Hopper, J.L., Knight, J. A., Ozcelik, H., Dite, G.S., Apicella, C., Southey, M.C., and Whittemore, A.S. (2011) Breast Cancer Risk for Non-Carriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings from the Breast Cancer Family Registry. J Clin Oncol. 29:4505-4509.
Zhang, R.L, Chiarelli, A.M., Glendon, G., Mirea, L., Knight, J.A., Andrulis, I.L., Ritvo P. (2011) Influence of perceived breast cancer risk on screening behaviors of female relatives from the Ontario Site of the Breast Cancer Family Registry. European Journal of Cancer Prevention 20:255-262.
Mulligan, A.M., Couch, F.J., Barrowdale, D., Domchek, S.M., Eccles, D., Nevanlinna, H., Ramus, S.J., Robson, M., Sherman, M. Spurdle, A.B., Wappenschmidt, B., Lee, A., McGuffog, L., Healey, S., Sinilnikova, O.M., Janavicius, R., Hansen, T.v.O., Nielsen, F.C., Ejlertsen, B., Osorio, A., Muñoz-Repeto, I., Durán, M., Godino, J., Pertesi, M., Benítez, J., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Bonanni, B., Viel, A., Pasini, B., Papi, L., Ottini, L., Savarese, A., Bernard, L., Radice, P., Hamann, U., Verheus, M., Meijers-Heijboer, H.E.J., Wijnen, J., Gómez García, E.B., Nelen, M. R., Kets, M., Seynaeve, C., Tilanus-Linthorst, M.M.A., van der Luijt, R.B., van Os, T., Rookus, M., HEBON, Frost, D., Jones, J.L., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Cook, J., Donaldson, A., Dorkins, H., Gregory, H., Eason, J., Houghton, C., Barwell, J., Side, L.E., McCann, E., Murray, A., Peock, S., EMBRACE, Godwin, A., Schmutzler, R.K., Rhiem, K., Engel, C., Meindl, A., Ruehl, I., Arnold, N., Niederacher, D., Sutter, C., Deissler, H., Gadzicki, D., Kast, K., Preisler-Adams, S., Varon-Mateeva, R., Schoenbuchner, I., Fiebig, B., Heinritz, W., Schäfer, D., Gevensleben, H., Caux-Moncoutier, V., Fassy-Colcombet, M., Cornelis, F., Mazoyer, S., Léoné, M., Boutry-Kryza, N., Hardouin, A., Berthet, P., Muller, D., Fricker, J-P., Mortemousque, I., Pujol, P., Coupier, I., Lebrun, M., Kientz, C., Longy, M., Sevenet, N., Stoppa-Lyonnet, D., GEMO, Isaacs, C., Caldes, T., de la Hoya, M., Heikkinen, T., Aittomäki, K., Blanco, I., Lazaro, C., Barkardottir, R.B., Soucy, P., Dumont, M., Simard, J., Montagna, M., Tognazzo, S., D’Andrea, E., Fox, S., Yan, M., kConFab, Rebbeck, T., Olopade, O.I., Weitzel, J.N., Lynch, H.T., Ganz, P.A., Tomlinson, G.E., Wang, X., Fredericksen, Z., Pankratz, V.S., Lindor, N.M., Szabo, C., Offit, K., Sakr, R., Gaudet, M., Bhatia, J., Kauff, N., Singer, C.F., Tea, M-K., Geschwantler-Kaulich, D., Fink-Retter, A., Mai, P.L., Greene, M.H., Imyanitov, E., O'Malley, F.P., Ozcelik, H., Glendon, G., OCGN, Toland, A.E., Gerdes, A-M., Thomassen, M., Kruse, T.A., Jensen, U.B., Skytte, A-B., Caligo, M.A., Soller, M., Henriksson, K., von Wachenfeldt, A., Arver, B., Stenmark-Askmalm, M., Karlsson, P., SWE-BRCA, Chun Ding, Y., Neuhausen, S.L., Beattie, M., Pharoah, P.D.P., Moysich, K.P., Nathanson, K.L., Karlan, B.Y., Gross, J., John, E.M., Daly, M.J., Buys, S.M., Southey, M.C., Hopper, J.L., Terry, M.B., Chung, W., Miron, A.F., Goldgar, D., BCFR, Chenevix-Trench, G., Easton, D.F., Andrulis, I.L., and Antoniou, A.C. (2011) Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2. Breast Cancer Res.13(6):R110.
Greenwood, C.M.T., Paterson, A.D., Linton, L., Andrulis, I.L., Apicella, C., Dimitromanolakis, A., Kriukov, V., Martin, L.J., Salleh, A., Samiltchuk, E., Satariano, E., Southey, M.C., John, E.M., Hopper, J.L., Boyd, N.F., and Rommens, J.M. A genome-wide linkage study of mammographic density, a risk factor for breast cancer, using B-CFR and collected families. (2011) Breast Cancer Res. 13(6):R132.
Ghoussaini, M., Fletcher, O., Michailidou, K., Turnbull, C., Schmidt, M.K., Dicks, E., Dennis, J., Wang, Q., Humphreys, M.K., Luccarini, C., Baynes, C., Conroy, D., Maranian, M., Ahmed, S., Driver, K., Johnson, N., Orr, N., dos Santos Silva, I., Waisfisz, Q., Meijers-Heijboer, H., Uitterlinden, A,G., Rivadeneira, F., HEBON, Hall, P., Czene, K., Irwanto, A., Liu, J., Nevanlinna, H., Aittomäki, K., Blomqvist, C., Meindl, A., Schmutzler, R.K., Müller-Myhsok, B., Chang-Claude, J., Hein, R., Nickels, S., Flesch-Janys, D., Tsimiklis, H., Makalic, E., Schmidt, D., Bui, M., Hopper, J.L., Apicella, C., Park, D.J., Southey, M., Hunter, D.J., Chanock, S.J., Broeks, A., Verhoef, S., Hogervorst, F.B.l., Fasching, P.A., Sawyer, E., Tomlinson, I., Kerin, M., Marme, F., Schneeweiss, A., Sohn, C., Burwinkel, B., Guénel, P., Truong, T., Cordina-Duverger, E., Menegaux, F., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Milne, R.L., Alonso, R., González-Neira, A., Benítez, J., Anton-Culver, H., Ziogas, A., Bernstein, L., Clarke Dur, C., Brenner, H., Müller, H., Arndt, V., Stegmaier, C., FBCS, Justenhoven, C., Brauch, H., Pesch, B., GENICA, Wang-Gohrke, S., Eilber, U., Dörk, T., Schürmann, P., Bremer, M., Hillemanns, P., Bogdanova, N.V., Antonenkova, N.N., Rogov, Y.I., Karstens, J.H., Bermisheva, M., Prokofieva, D., Khusnutdinova, E., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J.M., Lambrechts, D., Yesilyurt, B.T., Floris, G., Leunen, K., Manoukian, S., Bonanni, B., Fortuzzi, S., Peterlongo, P., Couch, F.J., Wang, X., Stevens, K., Lee, A., Giles, G.G., Baglietto, L., Severi, G., McLean, C., Alnæs, G.G., Kristensen, V., Børrensen-Dale, A-L., John, E.M., Miron, A., Winqvist, R., Pylkäs, K., Jukkola-Vuorinen, A., Kauppila, S., Andrulis, I.L., Glendon, G., Mulligan, A.M., Devilee, P., van Asperen, C.J., Tollenaar, R.A.E.M., Seynaeve, C., Figueroa, J.D., Garcia-Closas, M., Brinton, L., Lissowska, J., Hooning, M.J., Hollestelle, A., Oldenburg, R.A., van den Ouweland, A.M.W., Cox, A., Reed, M.W.R., Shah, M., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Jones, M., Schoemaker, M., Ashworth, A., Swerdlow, A., Beesley, J., Chen, X., kConFab, AOCSG, Muir, K.R., Lophatananon, A., Rattanamongkongul, S., Chaiwerawattana, A., Kang, D., Yoo, K-Y., Noh, D-Y., Shen, C-Y., Yu, Y-C., Wu, P-E., Hsiung, C.N., Perkins, A., Swann, R., Velentzis, L., Eccles, D.M., Tapper, W.J., Gerty, S.M., Graham, N.J., Ponder, B.A.J., Chenevix-Trench, G., Pharoah, P.D.P., Lathrop, M., Dunning, A.M., Rahman, N., Peto, J., and Easton, D.F. (2012) Genome-wide association analyses identifies three new breast cancer susceptibility loci. Nature Genetics. 44:312-318.
Bolton, K.L., Chenevix-Trench, G., Goh, C., Sadetzki, S., Ramus, S.J., Lambrechts, D., Despierre, E., Barrowdale, D., McGuffog, L., Healey, S., Easton, D.F., Sinilnikova, O., Benitez, J., García, M.J., Neuhausen, S., Gail, M.H., Hartge, P., EMBRACE, Peock, S., Frost, D., Evans, D.G., Eeles, R., Godwin, A., Daly, M., Kwong, A., Ma, E.S.K., Lázaro, C., Blanco, I., Montagna, M., D'Andrea, E., Nicoletto, O., kConFab, Johnatty, S., Krüger Kjær, S., Jensen, A., Høgdall, E., Goode, E.L., Fridley, B.L., Loud, J.T., Greene, M.h., Mai, P.L., Chetrit, A., Lubin, F., Hirsh-Yechezkel, G., Glendon, G., Andrulis, I.L., Toland, A.E., Senter, L., Gore, M.E., Gourley, C., Michie, C.O., Song, H., Tyrer, J., Whittemore, A.S., McGuire, V., Sieh, W., Kristoffersson, U., Olsson, H., Borg, A., Levine, D.A., Cancer Genome Atlas Research Network, Steele, L., Beattie, M.S., Chan, S., Nussbaum, R., Moysich, K.B., Gross, J., Cass, I., Walsh, C., Li, A., Leuchter, R., Gordon, O., Karlan, B.Y., Garcia-Closas, M., Gayther, S.A., Chanock, S.J., Antoniou, A.C., and Pharoah, P.D.P. (2012) A multi-center study to evaluate the impact of germline BRCA1 and BRCA2 mutations on Ovarian Cancer Survival. JAMA 307:382-390.
Park, D.J., Lesueur, F., Nguyen-Dumont, T., Pertesi, M., Odefrey, F., Hammet, F., Neuhausen, S.L., John, E.M., Andrulis, I.L., Terry, M.B., Daly, M., Buys, S., Le Calvez-Kelm, F., Lonie, A., Pope, B.J., Tsimiklis, H., Voegele, C., Hilbers, F.M., Hoogerbrugge, N., Barroso, A., Osorio, A., BCFR, kConFab, Giles, G.G., Devilee, P., Benitez, J., Hopper, J.L., Tavtigian, S.V., Goldgar, D.E., and Southey, M.C. (2012) Rare mutations in XRCC2 confer increased risk of breast cancer. Amer J Hum Genet 90:1-6.
Goodwin, P.J., Phillips, K-A., West, D.W., Ennis, M., Hopper, J.L., John, E.M., O'Malley, F.P., Milne, R.L., Andrulis, I.L., Friedlander, M.L., Southey, M.C., Giles, G.G., Apicella, C. and Longacre, T.A. (2012) Breast cancer prognosis of BRCA1 and BRCA2 mutation carriers: an international prospective population-based cohort study. J Clin Oncol. 30:19-26.
Vachon, C.M., Scott, C.G., Fasching, P.A., Hall, P., Tamimi, R.M., Li, J., Stone, J., Apicella, C., Odefrey, F., Gierach, G.L., Jud, S.M., Heusinger, K., Beckmann, M.W., Pollan. M., Fernandez-Navarro, P., Gonzalez-Neira, A., Benítez, J., van Gils, C.H., Lokate, M.A., Onland-Moret, N.C., Peeters, P.H., Brown, J., Leyland, J., Varghese, J.S., Easton, D.F., Thompson, D.J., Luben, R.N., Warren, R.M., Wareham, N.J., Loos, R.J., Khaw, K.T., Ursin, G., Lee, E., Gayther, S.A., Ramus, S.J., Eeles, R.A., Leach, M.O., Kwan-Lim, G. For The Uk Study Of Mri Screening, Couch, F.J., Giles, G.G., Baglietto, L., Krishnan, K., Southey, M.C., Le Marchand, L., Kolonel, L.N., Woolcott, C., Maskarinec, G., Haiman, C.A., Walker, K., Johnson, N., McCormack, V.A., Biong, M., Grenaker, A.G., Torhild, G.I., Kristensen, V.N., Borresen-Dale, A.L., Lindström, S., Hankinson, S.E., Hunter, D.J., Andrulis, I.L., Knight, J.A., Boyd, N.F., Figueroa, J.D., Lissowska, J., Wesolowska, E., Peplonska, B., Bukowska, A., Reszka, E., Liu, J., Eriksson, L., Czene, K., Audley, T., Wu, A.H., Pankratz, V.S., Hopper, J.L., Dos. Santos, S.I. (2012) Common Breast Cancer Susceptibility Variants in LSP1 and RAD51L1 Are Associated with Mammographic Density Measures that Predict Breast Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2012 Mar 27. [Epub ahead of print]
Weischer, M., Nordestgaard, B.G., Pharoah, P., Humphreys, M.K., Nevanlinna, H., van 't Veer, L.J., Garcia-Closas, M., Hopper, J.L., Hall, P., Andrulis, I.L., Devilee, P., Fasching, P.A., Anton-Culver, H.A., Lambrechts, D., Hooning, M., Cox, A., Giles, G.G., Burwinkel, B., Lindblom, A., Couch, F., Mannermaa, A., Alnæs, G.G., John, E.M., Dörk, T., Flyger, H., Dunning, A.M., Wang, Q., Muranen, T.A., van Hien, R., Figueroa, J., Southey, M.C., Czene, K., Knight, J.A., Tollenaar, R.A.E.M., Beckmann, M.W., Ziogas, A., Christiaens, M-R., Collée, J.M., Reed, M.W.R., Severi, G., Marme, F., Margolin, S., Olson, J.E., Kosma, V-M., Kristensen, V.N., Miron, A., Bogdanova, N., Shah, M., Blomqvist, C., Broeks, A., Sherman, M., Phillips, K., Li, J., Liu, J.J., Glendon, G., Seynaeve, C., Ekici, A.B., Leunen, K., Krieger, M., Cross, S.S., Baglietto, L., Sohn, C., Wang, X., Kataja, V., Børresen-Dale, A-L., Meyer, A., Easton, D.F., Schmidt, M.K., and Bojesen, S.E. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer specific death, and increased risk of a second breast cancer. J Clin Oncol (in press).
Work, M.E., Andrulis, I.L., John, E.M., Hopper, J.L., Liao, Y., Zhang, F.F., Knight, J.A., West, D.W., Milne, R.L., Giles, G.G., Longacre, T.A., O’Malley, F., Mulligan, A.M., Southey, M.C., Hibshoosh, H., Terry, M.B. (2012) Risk Factors for Uncommon Histologic Subtypes of Breast Cancer in the Breast Cancer Family Registry, Using Centralized Pathology Review. Breast Cancer Research and Treatment April 25 (Epub ahead of print).