Luminal breast cancer: From biology to treatment

Nature Reviews Clinical Oncology

Volumn 10, Issue 9, 2013, Pages 494-506

  Ignatiadis, Michail ^a   Sotiriou, Christos ^a  

^a JULES BORDET INSTITUTE   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANASTROZOLE; AROMATASE INHIBITOR; BISPHOSPHONIC ACID DERIVATIVE; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; CYCLOPHOSPHAMIDE; DOVITINIB; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; EVEROLIMUS; EXEMESTANE; FIBROBLAST GROWTH FACTOR RECEPTOR 1; FLUOROURACIL; FULVESTRANT; HISTONE DEACETYLASE; LAPATINIB; LETROZOLE; MAMMALIAN TARGET OF RAPAMYCIN; METHOTREXATE; PALBOCICLIB; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN MDM2; PROTEIN P53; TAMOXIFEN; TEMSIROLIMUS; TRASTUZUMAB; UNINDEXED DRUG; ZOLEDRONIC ACID;

CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER HORMONE THERAPY; CANCER MORTALITY; CANCER PROGNOSIS; CANCER RECURRENCE; CANCER RESISTANCE; CANCER SURVIVAL; CELL HETEROGENEITY; DISEASE FREE SURVIVAL; DRUG DOSE COMPARISON; EPISTASIS; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; GENE EXPRESSION PROFILING; GENE INTERACTION; GENE MUTATION; GENOME ANALYSIS; HUMAN; LOADING DRUG DOSE; META ANALYSIS (TOPIC); MINIMAL RESIDUAL DISEASE; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; NONHUMAN; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SEQUENCE ANALYSIS; TREATMENT DURATION; TUMOR CELLS AND CELL LINES; TUMOR INITIATING CELL; TUMOR MICROENVIRONMENT;

ANTINEOPLASTIC AGENTS, HORMONAL; BREAST NEOPLASMS; FEMALE; HUMANS; RECEPTORS, ESTROGEN;

EID: 84883453218     PISSN: 17594774     EISSN: 17594782     Source Type: Journal    
DOI: 10.1038/nrclinonc.2013.124     Document Type: Review

References (186)

1. Malvezzi, M., Bertuccio, P., Levi, F., La Vecchia, C. & Negri, E. European cancer mortality predictions for the year 2013. Ann. Oncol. 24, 792-800 2013
2. Goldhirsch, A. et al. Strategies for subtypes-dealing with the diversity of breast cancer: Highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann. Oncol. 22, 1736-1747 2011
3. Colleoni, M. et al. Outcome of special types of luminal breast cancer. Ann. Oncol. 23, 1428-1436 2012
4. Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747-752 2000
5. Sørlie, T. et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl Acad. Sci. USA 98, 10869-10874 2001
6. Sotiriou, C. et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc. Natl Acad. Sci. USA 100, 10393-10398 2003
7. Creighton, C. J. The molecular profile of luminal B breast cancer. Biologics 6, 289-297 2012
8. Sotiriou, C. & Pusztai, L. Gene-expression signatures in breast cancer. N. Engl. J. Med. 360, 790-800 2009
9. Ignatiadis, M. et al. Gene modules and response to neoadjuvant chemotherapy in breast cancer subtypes: A pooled analysis. J. Clin. Oncol. 30, 1996-2004 2012
10. Rouzier, R. et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin. Cancer Res. 11, 5678-5685 2005
11. Sorlie, T. et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc. Natl Acad. Sci. USA 100, 8418-8423 2003
12. Hu, Z. et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7, 96 2006
13. Parker, J. S. et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J. Clin. Oncol. 27, 1160-1167 2009
14. Desmedt, C. et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin. Cancer Res. 14, 5158-5165 2008
15. Wirapati, P. et al. Meta-analysis of gene expression profiles in breast cancer: Toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res. 10, R65 2008
16. Haibe-Kains, B. et al. A three-gene model to robustly identify breast cancer molecular subtypes. J. Natl Cancer Inst. 104, 311-325 2012
17. Weigelt, B. et al. Breast cancer molecular profiling with single sample predictors: A retrospective analysis. Lancet Oncol. 11, 339-349 2010
18. Paik, S. et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N. Engl. J. Med. 351, 2817-2826 2004
19. Vant Veer, L. J. et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415, 530-536 2002
20. Fan, C. et al. Concordance among gene-expression-based predictors for breast cancer. N. Engl. J. Med. 355, 560-569 2006
21. Teutsch, S. M. et al. The Evaluation of Genomic Applications in Practice and Prevention EGAPP initiative: Methods of the EGAPP Working Group. Genet. Med. 11, 3-14 2009
22. Simon, R. M., Paik, S. & Hayes, D. F. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J. Natl Cancer Inst. 101, 1446-1452 2009
23. Azim, H. A. Jr et al. Utility of prognostic genomic tests in breast cancer practice: The IMPAKT 2012 Working Group Consensus Statement. Ann. Oncol. 24, 647-654 2013
24. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT00310180 2013
25. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01272037 2013
26. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT00433589 2013
27. Dowsett, M. et al. Assessment of Ki67 in breast cancer: Recommendations from the International Ki67 in Breast Cancer working group. J. Natl Cancer Inst. 103, 1656-1664 2011
28. Nielsen, T. O. et al. An international Ki67 reproducibility study [abstract]. Cancer Res. 72 Suppl. 3, S4-S6 2012
29. Curtis, C. et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486, 346-352 2012
30. Stephens, P. J. et al. The landscape of cancer genes and mutational processes in breast cancer. Nature 486, 400-404 2012
31. Nik-Zainal, S. et al. Mutational processes molding the genomes of 21 breast cancers. Cell 149, 979-993 2012
32. Nik-Zainal, S. et al. The life history of 21 breast cancers. Cell 149, 994-1007 2012
33. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 490, 61-70 2012
34. Banerji, S. et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 486, 405-409 2012
35. Ellis, M. J. et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 486, 353-360 2012
36. Ellis, M. J. & Perou, C. M. The genomic landscape of breast cancer as a therapeutic roadmap. Cancer Discov. 3, 27-34 2013
37. Peto, R. et al. Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379, 432-444 2012
38. Sotiriou, C. et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J. Natl Cancer Inst. 98, 262-272 2006
39. Gnant, M. et al. Clinical validation of the PAM50 risk of recurrence ROR score for predicting residual risk of distant-recurrence DR after endocrine therapy in postmenopausal women with ER+ early breast cancer EBC: An ABCSG study [abstract]. Cancer Res. 72 Suppl. 3, P2-10-02 2012
40. Ma, X. J. et al. A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer. Clin. Cancer Res. 14, 2601-2608 2008
41. Filipits, M. et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res. 17, 6012-6020 2011
42. Dubsky, P. et al. EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer. Ann. Oncol. 24, 640-647 2013
43. Dowsett, M. et al. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: A TransATAC study. J. Clin. Oncol. 28, 1829-1834 2010
44. Rutgers, E. et al. The EORTC 10041/BIG 03-04 MINDACT trial is feasible: Results of the pilot phase. Eur. J. Cancer 47, 2742-2749 2011
45. Ravdin, P. M. et al. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J. Clin. Oncol. 19, 980-991 2001
46. Paik, S. et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J. Clin. Oncol. 24, 3726-3734 2006
47. Albain, K. S. et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: A retrospective analysis of a randomised trial. Lancet Oncol. 11, 55-65 2010
48. Small, G. W., Shi, Y. Y., Higgins, L. S. & Orlowski, R. Z. Mitogen-activated protein kinase phosphatase-1 is a mediator of breast cancer chemoresistance. Cancer Res. 67, 4459-4466 2007
49. Davies, C. et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials. Lancet 378, 771-784 2011
50. Dowsett, M. et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J. Clin. Oncol. 28, 509-518 2010
51. Goss, P. E. et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N. Engl. J. Med. 349, 1793-1802 2003
52. Jakesz, R. et al. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: Results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J. Natl Cancer Inst. 99, 1845-1853 2007
53. Mamounas, E. P. et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: Intention-to-treat analysis of the National Surgical Adjuvant Breast and Bowel Project B-33 trial. J. Clin. Oncol. 26, 1965-1971 2008
54. Goss, P. E. et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J. Natl Cancer Inst. 97, 1262-1271 2005
55. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01064635 2010
56. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT00382070 2012
57. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT00295620 2012
58. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT00301457 2013
59. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT00754845 2012
60. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT00553410 2012
61. Goss, P. E. & Chambers, A. F. Does tumour dormancy offer a therapeutic target? Nat. Rev. Cancer 10, 871-877 2010
62. Davies, C. et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381, 805-816 2013
63. Fisher, B., Dignam, J., Bryant, J. & Wolmark, N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J. Natl Cancer Inst. 93, 684-690 2001
64. Stewart, H. J. et al. Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. The Scottish Cancer Trials Breast Group. Br. J. Cancer 74, 297-299 1996
65. Tormey, D. C., Gray, R. & Falkson, H. C. Postchemotherapy adjuvant tamoxifen therapy beyond five years in patients with lymph node-positive breast cancer. Eastern Cooperative Oncology Group. J. Natl Cancer Inst. 88, 1828-1833 1996
66. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT00003678 2007
67. Kennecke, H. F. et al. Late risk of relapse and mortality among postmenopausal women with estrogen responsive early breast cancer after 5 years of tamoxifen. Ann. Oncol. 18, 45-51 2007
68. Goss, P. E. et al. Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole. Ann. Oncol. 24, 355-361 2013
69. Goss, P. E. et al. Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17. J. Clin. Oncol. 25, 2006-2011 2007
70. Sgroi, D. C. et al. Comparative performance of Breast Cancer Index BCI vs. Oncotype DX and IHC4 in the prediction of late recurrence in hormonal receptor-positive lymph node-negative breast cancer patients: A TransATAC Study [abstract]. Cancer Res. 72 Suppl. 3, S1-S9 2012
71. Dubsky, P. et al. The EndoPredict score identifies late distant metastases in ER+/HER2-breast cancer patients [abstract]. Cancer Res. 72 Suppl. 3, S4-S3 2012
72. Gnant, M. et al. Predicting risk for late metastasis: The PAM50 risk of recurrence ROR score after 5 years of endocrine therapy in postmenopausal women with HR+ early breast cancer: A study on 1,478 patients from the ABCSG-8 trial [abstract]. Ann. Oncol. 24 Suppl. 3, 53O-PR 2013
73. Sestak, I. et al. Comparison of five different scores for the prediction of late recurrence for oestrogen receptor positive breast cancer [abstract]. Ann. Oncol. 24 Suppl. 3, 54O-PR 2013
74. Aguirre-Ghiso, J. A. Models, mechanisms and clinical evidence for cancer dormancy. Nat. Rev. Cancer 7, 834-846 2007
75. Bragado, P., Sosa, M. S., Keely, P., Condeelis, J. & Aguirre-Ghiso, J. A. Microenvironments dictating tumor cell dormancy. Recent Results Cancer Res. 195, 25-39 2012
76. Uhr, J. W. & Pantel, K. Controversies in clinical cancer dormancy. Proc. Natl Acad. Sci. USA 108, 12396-12400 2011
77. Roodman, G. D. Mechanisms of bone metastasis. N. Engl. J. Med. 350, 1655-1664 2004
78. Akhtari, M., Mansuri, J., Newman, K. A., Guise, T. M. & Seth, P. Biology of breast cancer bone metastasis. Cancer Biol. Ther. 7, 3-9 2008
79. Coleman, R., Gnant, M., Morgan, G. & Clezardin, P. Effects of bone-targeted agents on cancer progression and mortality. J. Natl Cancer Inst. 104, 1059-1067 2012
80. Aft, R. et al. Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: An open label, randomised, phase 2 trial. Lancet Oncol. 11, 421-428 2010
81. Solomayer, E. F. et al. Influence of zoledronic acid on disseminated tumor cells in primary breast cancer patients. Ann. Oncol. 23, 2271-2277 2012
82. Coleman, R. E. et al. Breast-cancer adjuvant therapy with zoledronic acid. N. Engl. J. Med. 365, 1396-1405 2011
83. Gnant, M. et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N. Engl. J. Med. 360, 679-691 2009
84. Gnant, M. et al. Long-term follow-up in ABCSG-12: Significantly improved overall survival with adjuvant zoledronic acid in premenopausal patients with endocrine-receptor-positive early breast cancer [abstract]. Cancer Res. 24 Suppl. 3, S1-S2 2011
85. Coleman, R. et al. Zoledronic acid zoledronate for postmenopausal women with early breast cancer receiving adjuvant letrozole ZO-FAST study: Final 60-month results. Ann. Oncol. 24, 398-405 2013
86. Paterson, A. H. et al. Oral clodronate for adjuvant treatment of operable breast cancer National Surgical Adjuvant Breast and Bowel Project protocol B-34: A multicentre, placebo-controlled, randomised trial. Lancet Oncol. 13, 734-742 2012
87. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT00512993 2013
88. Dubsky, P. & Bartsch, R. Bisphosphonates in early breast cancer. Lancet Oncol. 13, 660-661 2012
89. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01077154 2013
90. Pantel, K., Brakenhoff, R. H. & Brandt, B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat. Rev. Cancer 8, 329-340 2008
91. Ignatiadis, M. & Piccart, M. Liquid biopsy to test new treatment strategies in breast cancer: Are we there yet? Ann. Oncol. 23, 1653-1655 2012
92. Lianidou, E. S. Circulating tumor cells-new challenges ahead. Clin. Chem. 58, 805-8072012
93. Bidard, F. C. et al. Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. Ann. Oncol. 21, 729-733 2010
94. Lucci, A. et al. Circulating tumour cells in non-metastatic breast cancer: A prospective study. Lancet Oncol. 13, 688-695 2012
95. Rack, B., Andergassen, U., Janni, W. & Neugebauer, J. CTCs in primary breast cancer I. Recent Results Cancer Res. 195, 179-185 2012
96. Paik, S., Kim, C. & Wolmark, N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N. Engl. J. Med. 358, 1409-1411 2008
97. Bozionellou, V. et al. Trastuzumab administration can effectively target chemotherapy-resistant cytokeratin-19 messenger RNA-positive tumor cells in the peripheral blood and bone marrow of patients with breast cancer. Clin. Cancer Res. 10, 8185-8194 2004
98. Georgoulias, V. et al. Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapy-resistant CK19 mRNA-positive circulating tumor cells: Results of a randomized phase II study. Ann. Oncol. 23, 1744-1750 2012
99. Ithimakin, S. et al. HER2 drives luminal breast cancer stem cells in the absence of HER2 amplification: Implications for efficacy of adjuvant trastuzumab. Cancer Res. 73, 1635-1646 2013
100. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01548677 2013
101. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01275677 2013
102. Di Leo, A. et al. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with oestrogen receptor-positive advanced breast cancer. J. Clin. Oncol. 28, 4594-4600 2010
103. Mehta, R. S. et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N. Engl. J. Med. 367, 435-444 2012
104. Bergh, J. et al. FACT: An open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J. Clin. Oncol. 30, 1919-1925 2012
105. Johnston, S. et al. Fulvestrant alone or with concomitant anastrozole vs exemestane following progression on non-steroidal aromatase inhibitor-first results of the SoFEa trial CRUKE/03/021 & CRUK/09/007 ISRCTN44195747 [abstract]. Eur. J. Cancer 48 Suppl. 3, 2LBA 2012
106. Baum, M. et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: First results of the ATAC randomised trial. Lancet 359, 2131-2139 2002
107. Schiff, R. et al. Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance. Clin. Cancer Res. 10 1 Pt 2, 331S-336S 2004
108. Johnston, S. et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J. Clin. Oncol. 27, 5538-5546 2009
109. Kaufman, B. et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: Results from the randomized phase III TAnDEM study. J. Clin. Oncol. 27, 5529-5537 2009
110. Zoncu, R., Efeyan, A. & Sabatini, D. M. mTOR: From growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell. Biol. 12, 21-35 2011
111. Sabine, V. S. et al. PIK3CA mutations are linked to PgR expression: A Tamoxifen Exemestane Adjuvant Multinational TEAM pathology study [abstract]. Cancer Res. 72 Suppl. 3, S1-S5 2012
112. Crowder, R. J. et al. PIK3CA and PIK3CB inhibition produce synthetic lethality when combined with estrogen deprivation in estrogen receptor-positive breast cancer. Cancer Res. 69, 3955-3962 2009
113. Stemke-Hale, K. et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 68, 6084-6091 2008
114. Loi, S. et al. PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor-positive breast cancer. Proc. Natl Acad. Sci. USA 107, 10208-10213 2010
115. Rodon, J., Dienstmann, R., Serra, V. & Tabernero, J. Development of PI3K inhibitors lessons learned from early clinical trials. Nat. Rev. Clin. Oncol. 10, 143-153 2013
116. Zardavas, D., Baselga, J. & Piccart, M. Emerging targeted agents in metastatic breast cancer. Nat. Rev. Clin. Oncol. 10, 191-210 2013
117. Baselga, J. et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N. Engl. J. Med. 366, 520-529 2012
118. Bachelot, T. et al. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: A GINECO study. J. Clin. Oncol. 30, 2718-2724 2012
119. Wolff, A. C. et al. Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J. Clin. Oncol. 31, 195-202 2013
120. Baselga, J. et al. Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J. Clin. Oncol. 27, 2630-2637 2009
121. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01674140 2013
122. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01805271 2013
123. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01610284 2013
124. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01633060 2013
125. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01437566 2013
126. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01082068 2013
127. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01248494 2012
128. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01219699 2013
129. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01791478 2013
130. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01296555 2013
131. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01344031 2013
132. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01597388 2013
133. Janku, F. et al. PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors. Mol. Cancer Ther. 10, 558-565 2011
134. Oliveira, M. et al. PI3K pathway PI3Kp dysregulation and response to pan-PI3K/AKT/mTOR/dual PI3K-mTOR inhibitors PI3Kpi in metastatic breast cancer MBC patients pts [abstract]. J. Clin. Oncol. 30 Suppl., a509 2012
135. Iyer, G. et al. Genome sequencing identifies a basis for everolimus sensitivity. Science 338, 221 2012
136. Klümpen, H. J. et al. mTOR inhibitor treatment of pancreatic cancer in a patient with Peutz-Jeghers syndrome. J. Clin. Oncol. 29, e150-e153 2011
137. Loi, S. et al. PIK3CA genotype and a PIK3CA mutation-related gene signature and response to everolimus and letrozole in estrogen receptor positive breast cancer. PLoS ONE 8, e53292 2013
138. Bachelot, T. et al. Translational studies within the TAMRAD randomized Gineco trial: Evidence for TORC1 activation marker as a predictive factor for everolimus efficacy in metastatic breast cancer [abstract]. Ann. Oncol. 23 Suppl. 2, 13O-PR 2012
139. Tabernero, J. et al. Dose-and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: A phase I tumor pharmacodynamic study in patients with advanced solid tumors. J. Clin. Oncol. 26, 1603-1610 2008
140. Carracedo, A. et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J. Clin. Invest. 118, 3065-3074 2008
141. Di Cosimo, S. et al. A phase I study of the oral mTOR inhibitor ridaforolimus RIDA in combination with the IGF-1R antibody dalotozumab DALO in patients pts with advanced solid tumors [abstract]. J. Clin. Oncol. 28 Suppl. 15, a3008 2010
142. Vilar, E., Perez-Garcia, J. & Tabernero, J. Pushing the envelope in the mTOR pathway: The second generation of inhibitors. Mol. Cancer Ther. 10, 395-403 2011
143. Piccart, M. et al. Assessment of genetic alterations in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer from the BOLERO-2 trial by next-generation sequencing [abstract]. Ann. Oncol. 24 Suppl. 3, 420-PR 2013
144. Rodon, J. et al. Towards defining the genetic framework for clinical response to treatment with BYL719, a PI3Kalpha-specific inhibitor [abstract]. Cancer Res. 72 Suppl. 1, LB-65 2013
145. Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell 81, 323-330 1995
146. Harbour, J. W., Luo, R. X., Dei, S. A., Postigo, A. A. & Dean, D. C. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 98, 859-869 1999
147. Finn, R. S. et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 11, R77 2009
148. Finn, R. S. et al. Results of a randomized phase 2 study of PD 0332991, a cyclin-dependent kinase CDK 4/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+/HER2-advanced breast cancer BC [abstract]. Cancer Res. 72 Suppl. 3, S1-S6 2012
149. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/show/NCT01740427 2013
150. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01394016 2013
151. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/ct2/show/NCT01237236 2013
152. Turner, N. & Grose, R. Fibroblast growth factor signalling: From development to cancer. Nat. Rev. Cancer 10, 116-129 2010
153. Dieci, M. V., Arnedos, M., Andre, F. & Soria, J. C. Fibroblast growth factor receptor inhibitors as a cancer treatment: From a biologic rationale to medical perspectives. Cancer Discov. 3, 264-279 2013
154. Elbauomy Elshaikh, S. et al. FGFR1 amplification in breast carcinomas: A chromogenic in situ hybridisation analysis. Breast Cancer Res. 9, R23 2007
155. Turner, N. et al. FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer Res. 70, 2085-2094 2010
156. Andre, F. et al. A multicenter, open-label phase II trial of dovitinib, a fibroblast growth factor receptor 1 FGFR1 inhibitor, in FGFR1-amplified and nonamplified metastatic breast cancer BC [abstract]. J. Clin. Oncol. 29 Suppl. 27, a289 2011
157. US National Library of Medicine. ClinicalTrials.gov [online], http://www.clinicaltrials.gov/show/NCT01528345 2013
158. Dienstmann, R. et al. Significant antitumor activity of E-3810, a novel FGFR and VEGFR inhibitor, in patients with FGFR1 amplified breast cancer [abstract]. Ann. Oncol. 23 Suppl. 9, a2115 2012
159. Yardley, D. A. et al. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J. Clin. Oncol. 31, 2128-2135 2013.
160. Piccart-Gebhart, M. J. et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 353, 1659-1672 2005
161. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031-1037 2001
162. Ashworth, A., Lord, C. J. & Reis-Filho, J. S. Genetic interactions in cancer progression and treatment. Cell 145, 30-38 2011
163. Yates, L. R. & Campbell, P. J. Evolution of the cancer genome. Nat. Rev. Genet. 13, 795-806 2012
164. Fong, P. C. et al. Inhibition of polyADP-ribose polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 361, 123-134 2009
165. Berns, K. et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12, 395-402 2007
166. Baselga, J. et al. Biomarker analyses in CLEOPATRA: A phase III, placebo-controlled study of pertuzumab in HER2-positive, first-line metastatic breast cancer MBC [abstract]. Cancer Res. 72 Suppl. 3, S5-S1 2012
167. Joensuu, H. et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N. Engl. J. Med. 354, 809-820 2006
168. Loi, S. et al. Somatic mutation profiling and associations with prognosis and trastuzumab benefit in early breast cancer. J. Natl Cancer Inst. 105, 960-967 2013
169. Courjal, F. et al. Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: Definition of phenotypic groups. Cancer Res. 57, 4360-4367 1997
170. Karlseder, J. et al. Patterns of DNA amplification at band q13 of chromosome 11 in human breast cancer. Genes Chromosomes Cancer 9, 42-48 1994
171. Ginestier, C. et al. Prognosis and gene expression profiling of 20q13-amplified breast cancers. Clin. Cancer Res. 12, 4533-4544 2006
172. Navin, N. E. Investigating breast cancer with single-cell sequencing [abstract]. Cancer Res. 72 Suppl. 3, ES5-ES3 2012
173. Gong, Y., Booser, D. J. & Sneige, N. Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma. Cancer 103, 1763-1769 2005
174. Lindström, L. S. et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J. Clin. Oncol. 30, 2601-2608 2012
175. Hoefnagel, L. D. et al. Receptor conversion in distant breast cancer metastases. Breast Cancer Res. 12, R75 2010
176. Cardoso, F. et al. Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 22 Suppl. 6, v25-v30 2011
177. Gerlinger, M. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366, 883-892 2012
178. Garraway, L A. & Baselga, J. Whole-genome sequencing and cancer therapy: Is too much ever enough? Cancer Discov. 2, 766-768 2012
179. Ignatiadis, M. & Reinholz, M. M. Minimal residual disease and circulating tumor cells in breast cancer. Breast Cancer Res. 13, 222 2011
180. Dawson, S. J. et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N. Engl. J. Med. 368, 1199-1209 2013
181. Murtaza, M. et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497, 108-112 2013
182. de Vries, E. G., Oude Munnink, T. H., van Vugt, M. A. & Nagengast, W. B. Toward molecular imaging-driven drug development in oncology. Cancer Discov. 1, 25-28 2011
183. Beltran, H. et al. Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur. Urol. 63, 920-926 2012
184. Roychowdhury, S. et al. Personalized oncology through integrative high-throughput sequencing: A pilot study. Sci. Transl. Med. 3, 111ra121 2011
185. Rodón, J. et al. Molecular prescreening to select patient population in early clinical trials. Nat. Rev. Clin. Oncol. 9, 359-366 2012
186. Tentler, J. J. et al. Patient-derived tumour xenografts as models for oncology drug development. Nat. Rev. Clin. Oncol. 9, 338-350 2012