Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype

Sunil R Lakhani, Jorge S Reis-Filho, Laura Fulford, Frederique Penault-Llorca, Marc van der Vijver, Suzanne Parry, Timothy Bishop, Javier Benitez, Carmen Rivas, Yves-Jean Bignon, Jenny Chang-Claude, Ute Hamann, Cees J Cornelisse, Peter Devilee, Matthias W Beckmann, Carolin Nestle-Krämling, Peter A Daly, Neva Haites, Jenny Varley, Fiona Lalloo & 17 others Gareth Evans, Christine Maugard, Hanne Meijers-Heijboer, Jan G M Klijn, Edith Olah, Barry A Gusterson, Silvana Pilotti, Paolo Radice, Siegfried Scherneck, Hagay Sobol, Jocelyne Jacquemier, Teresa Wagner, Julian Peto, Michael R Stratton, Lesley McGuffog, Douglas F Easton, Breast Cancer Linkage Consortium

Research output: Contribution to journalArticle

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Abstract

Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.

Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.

Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls.

Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.

Original languageEnglish
Pages (from-to)5175-5180
Number of pages6
JournalClinical Cancer Research
Volume11
Issue number14
DOIs
Publication statusPublished - Jul 2005

Keywords

  • invasive ductal carcinomas
  • gene-expression profiles
  • central acellular zones
  • myoepithelial cells
  • prognostic markers
  • mutations
  • differentiation
  • pathology
  • disease
  • benign

Cite this

Lakhani, S. R., Reis-Filho, J. S., Fulford, L., Penault-Llorca, F., van der Vijver, M., Parry, S., ... Breast Cancer Linkage Consortium (2005). Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clinical Cancer Research, 11(14), 5175-5180. https://doi.org/10.1158/1078-0432.CCR-04-2424

Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. / Lakhani, Sunil R; Reis-Filho, Jorge S; Fulford, Laura; Penault-Llorca, Frederique; van der Vijver, Marc; Parry, Suzanne; Bishop, Timothy; Benitez, Javier; Rivas, Carmen; Bignon, Yves-Jean; Chang-Claude, Jenny; Hamann, Ute; Cornelisse, Cees J; Devilee, Peter; Beckmann, Matthias W; Nestle-Krämling, Carolin; Daly, Peter A; Haites, Neva; Varley, Jenny; Lalloo, Fiona; Evans, Gareth; Maugard, Christine; Meijers-Heijboer, Hanne; Klijn, Jan G M; Olah, Edith; Gusterson, Barry A; Pilotti, Silvana; Radice, Paolo; Scherneck, Siegfried; Sobol, Hagay; Jacquemier, Jocelyne; Wagner, Teresa; Peto, Julian; Stratton, Michael R; McGuffog, Lesley; Easton, Douglas F; Breast Cancer Linkage Consortium.

In: Clinical Cancer Research, Vol. 11, No. 14, 07.2005, p. 5175-5180.

Research output: Contribution to journalArticle

Lakhani, SR, Reis-Filho, JS, Fulford, L, Penault-Llorca, F, van der Vijver, M, Parry, S, Bishop, T, Benitez, J, Rivas, C, Bignon, Y-J, Chang-Claude, J, Hamann, U, Cornelisse, CJ, Devilee, P, Beckmann, MW, Nestle-Krämling, C, Daly, PA, Haites, N, Varley, J, Lalloo, F, Evans, G, Maugard, C, Meijers-Heijboer, H, Klijn, JGM, Olah, E, Gusterson, BA, Pilotti, S, Radice, P, Scherneck, S, Sobol, H, Jacquemier, J, Wagner, T, Peto, J, Stratton, MR, McGuffog, L, Easton, DF & Breast Cancer Linkage Consortium 2005, 'Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype', Clinical Cancer Research, vol. 11, no. 14, pp. 5175-5180. https://doi.org/10.1158/1078-0432.CCR-04-2424
Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S et al. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clinical Cancer Research. 2005 Jul;11(14):5175-5180. https://doi.org/10.1158/1078-0432.CCR-04-2424
Lakhani, Sunil R ; Reis-Filho, Jorge S ; Fulford, Laura ; Penault-Llorca, Frederique ; van der Vijver, Marc ; Parry, Suzanne ; Bishop, Timothy ; Benitez, Javier ; Rivas, Carmen ; Bignon, Yves-Jean ; Chang-Claude, Jenny ; Hamann, Ute ; Cornelisse, Cees J ; Devilee, Peter ; Beckmann, Matthias W ; Nestle-Krämling, Carolin ; Daly, Peter A ; Haites, Neva ; Varley, Jenny ; Lalloo, Fiona ; Evans, Gareth ; Maugard, Christine ; Meijers-Heijboer, Hanne ; Klijn, Jan G M ; Olah, Edith ; Gusterson, Barry A ; Pilotti, Silvana ; Radice, Paolo ; Scherneck, Siegfried ; Sobol, Hagay ; Jacquemier, Jocelyne ; Wagner, Teresa ; Peto, Julian ; Stratton, Michael R ; McGuffog, Lesley ; Easton, Douglas F ; Breast Cancer Linkage Consortium. / Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 14. pp. 5175-5180.
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abstract = "Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61{\%} versus 12{\%}; CK5/6: 58{\%} versus 7{\%}; CK17: 53{\%} versus 10{\%}; osteonectin: 43{\%} versus 19{\%}; EGFR: 67{\%} versus 21{\%}; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls.Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.",
keywords = "invasive ductal carcinomas, gene-expression profiles, central acellular zones, myoepithelial cells, prognostic markers, mutations, differentiation, pathology, disease, benign",
author = "Lakhani, {Sunil R} and Reis-Filho, {Jorge S} and Laura Fulford and Frederique Penault-Llorca and {van der Vijver}, Marc and Suzanne Parry and Timothy Bishop and Javier Benitez and Carmen Rivas and Yves-Jean Bignon and Jenny Chang-Claude and Ute Hamann and Cornelisse, {Cees J} and Peter Devilee and Beckmann, {Matthias W} and Carolin Nestle-Kr{\"a}mling and Daly, {Peter A} and Neva Haites and Jenny Varley and Fiona Lalloo and Gareth Evans and Christine Maugard and Hanne Meijers-Heijboer and Klijn, {Jan G M} and Edith Olah and Gusterson, {Barry A} and Silvana Pilotti and Paolo Radice and Siegfried Scherneck and Hagay Sobol and Jocelyne Jacquemier and Teresa Wagner and Julian Peto and Stratton, {Michael R} and Lesley McGuffog and Easton, {Douglas F} and {Breast Cancer Linkage Consortium}",
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T1 - Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype

AU - Lakhani, Sunil R

AU - Reis-Filho, Jorge S

AU - Fulford, Laura

AU - Penault-Llorca, Frederique

AU - van der Vijver, Marc

AU - Parry, Suzanne

AU - Bishop, Timothy

AU - Benitez, Javier

AU - Rivas, Carmen

AU - Bignon, Yves-Jean

AU - Chang-Claude, Jenny

AU - Hamann, Ute

AU - Cornelisse, Cees J

AU - Devilee, Peter

AU - Beckmann, Matthias W

AU - Nestle-Krämling, Carolin

AU - Daly, Peter A

AU - Haites, Neva

AU - Varley, Jenny

AU - Lalloo, Fiona

AU - Evans, Gareth

AU - Maugard, Christine

AU - Meijers-Heijboer, Hanne

AU - Klijn, Jan G M

AU - Olah, Edith

AU - Gusterson, Barry A

AU - Pilotti, Silvana

AU - Radice, Paolo

AU - Scherneck, Siegfried

AU - Sobol, Hagay

AU - Jacquemier, Jocelyne

AU - Wagner, Teresa

AU - Peto, Julian

AU - Stratton, Michael R

AU - McGuffog, Lesley

AU - Easton, Douglas F

AU - Breast Cancer Linkage Consortium

PY - 2005/7

Y1 - 2005/7

N2 - Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls.Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.

AB - Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls.Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.

KW - invasive ductal carcinomas

KW - gene-expression profiles

KW - central acellular zones

KW - myoepithelial cells

KW - prognostic markers

KW - mutations

KW - differentiation

KW - pathology

KW - disease

KW - benign

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DO - 10.1158/1078-0432.CCR-04-2424

M3 - Article

VL - 11

SP - 5175

EP - 5180

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

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