Skip to main content
Top
Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Review

Precision medicine in breast cancer: reality or utopia?

Authors: Ali Bettaieb, Catherine Paul, Stéphanie Plenchette, Jingxuan Shan, Lotfi Chouchane, François Ghiringhelli

Published in: Journal of Translational Medicine | Issue 1/2017

Login to get access

Abstract

Many cancers, including breast cancer, have demonstrated prognosis and support advantages thanks to the discovery of targeted therapies. The advent of these new approaches marked the rise of precision medicine, which leads to improve the diagnosis, prognosis and treatment of cancer. Precision medicine takes into account the molecular and biological specificities of the patient and their tumors that will influence the treatment determined by physicians. This new era of medicine is accessible through molecular genetics platforms, the development of high-speed sequencers and means of analysis of these data. Despite the spectacular results in the treatment of cancers including breast cancer, described in this review, not all patients however can benefit from this new strategy. This seems to be related to the many genetic mutations, which may be different from one patient to another or within the same patient. It comes to give new impetus to the research—both from a technological and biological point of view—to make the hope of precision medicine accessible to all.
Literature
1.
go back to reference Yang XR, Chang-Claude J, Goode EL, Couch FJ, Nevanlinna H, et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst. 2011;103(3):250–63.PubMedCrossRef Yang XR, Chang-Claude J, Goode EL, Couch FJ, Nevanlinna H, et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst. 2011;103(3):250–63.PubMedCrossRef
2.
go back to reference Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet. 2001;358(9291):1389–99.CrossRef Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet. 2001;358(9291):1389–99.CrossRef
3.
go back to reference Peto J, Mack TM. High constant incidence in twins and other relatives of women with breast cancer. Nat Genet. 2000;26(4):411–4.PubMedCrossRef Peto J, Mack TM. High constant incidence in twins and other relatives of women with breast cancer. Nat Genet. 2000;26(4):411–4.PubMedCrossRef
4.
go back to reference Workman P, de Bono J. Targeted therapeutics for cancer treatment: major progress towards personalised molecular medicine. Curr Opin Pharmacol. 2008;8(4):359–62.PubMedCrossRef Workman P, de Bono J. Targeted therapeutics for cancer treatment: major progress towards personalised molecular medicine. Curr Opin Pharmacol. 2008;8(4):359–62.PubMedCrossRef
5.
go back to reference Allison KH, Sledge GW. Heterogeneity and cancer. Oncology (Williston Park). 2014;28(9):772–8.PubMed Allison KH, Sledge GW. Heterogeneity and cancer. Oncology (Williston Park). 2014;28(9):772–8.PubMed
6.
go back to reference Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta. 2010;1805(1):105–17.PubMed Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta. 2010;1805(1):105–17.PubMed
7.
go back to reference Zardavas D, Baselga J, Piccart M. Emerging targeted agents in metastatic breast cancer. Nat Rev Clin Oncol. 2013;10(4):191–210.PubMedCrossRef Zardavas D, Baselga J, Piccart M. Emerging targeted agents in metastatic breast cancer. Nat Rev Clin Oncol. 2013;10(4):191–210.PubMedCrossRef
8.
go back to reference Koren S, Bentires-Alj M. Breast tumor heterogeneity: source of fitness, Hurdle for therapy. Mol Cell. 2015;60(4):537–46.PubMedCrossRef Koren S, Bentires-Alj M. Breast tumor heterogeneity: source of fitness, Hurdle for therapy. Mol Cell. 2015;60(4):537–46.PubMedCrossRef
9.
go back to reference Rakha EA, El-Sayed ME, Lee AH, Elston CW, Grainge MJ, Hodi Z, Blamey RW, Ellis IO. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol. 2008;26(19):3153–8.PubMedCrossRef Rakha EA, El-Sayed ME, Lee AH, Elston CW, Grainge MJ, Hodi Z, Blamey RW, Ellis IO. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol. 2008;26(19):3153–8.PubMedCrossRef
10.
go back to reference Tan PH, Schnitt SJ, van de Vijver MJ, Ellis IO, Lakhani SR. Papillary and neuroendocrine breast lesions: the WHO stance. Histopathology. 2015;66(6):761–70.PubMedCrossRef Tan PH, Schnitt SJ, van de Vijver MJ, Ellis IO, Lakhani SR. Papillary and neuroendocrine breast lesions: the WHO stance. Histopathology. 2015;66(6):761–70.PubMedCrossRef
11.
go back to reference Shah SP, Morin RD, Khattra J, Prentice L, et al. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature. 2009;461(7265):809–13.PubMedCrossRef Shah SP, Morin RD, Khattra J, Prentice L, et al. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature. 2009;461(7265):809–13.PubMedCrossRef
12.
go back to reference Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, Oldfield M, Dranitsaris G, Tomlinson G, Laupacis A, Tannock IF, Clemons M. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012;30(6):587–92.PubMedCrossRef Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, Oldfield M, Dranitsaris G, Tomlinson G, Laupacis A, Tannock IF, Clemons M. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012;30(6):587–92.PubMedCrossRef
13.
go back to reference Gonzalez-Angulo AM, Ferrer-Lozano J, Stemke-Hale K, Sahin A, Liu S, Barrera JA, Burgues O, Lluch AM, Chen H, Hortobagyi GN, Mills GB, Meric-Bernstam F. PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer. Mol Cancer Ther. 2011;10(6):1093–101.PubMedPubMedCentralCrossRef Gonzalez-Angulo AM, Ferrer-Lozano J, Stemke-Hale K, Sahin A, Liu S, Barrera JA, Burgues O, Lluch AM, Chen H, Hortobagyi GN, Mills GB, Meric-Bernstam F. PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer. Mol Cancer Ther. 2011;10(6):1093–101.PubMedPubMedCentralCrossRef
14.
go back to reference Sonnenblick A, Fumagalli D, Sotiriou C, Piccart M. Is the differentiation into molecular subtypes of breast cancer important for staging, local and systemic therapy, and follow up? Cancer Treat Rev. 2014;40(9):1089–95.PubMedCrossRef Sonnenblick A, Fumagalli D, Sotiriou C, Piccart M. Is the differentiation into molecular subtypes of breast cancer important for staging, local and systemic therapy, and follow up? Cancer Treat Rev. 2014;40(9):1089–95.PubMedCrossRef
15.
go back to reference Inic Z, Zegarac M, Inic M, Markovic I, Kozomara Z, Djurisic I, Inic I, Pupic G, Jancic S. Difference between luminal A and luminal B subtypes according to Ki-67, tumor size, and progesterone receptor negativity providing prognostic information. Clin Med Insights Oncol. 2014;8:107–11.PubMedPubMedCentralCrossRef Inic Z, Zegarac M, Inic M, Markovic I, Kozomara Z, Djurisic I, Inic I, Pupic G, Jancic S. Difference between luminal A and luminal B subtypes according to Ki-67, tumor size, and progesterone receptor negativity providing prognostic information. Clin Med Insights Oncol. 2014;8:107–11.PubMedPubMedCentralCrossRef
16.
go back to reference Toft DJ, Cryns VL. Minireview: basal-like breast cancer: from molecular profiles to targeted therapies. Mol Endocrinol. 2011;25(2):199–211.PubMedCrossRef Toft DJ, Cryns VL. Minireview: basal-like breast cancer: from molecular profiles to targeted therapies. Mol Endocrinol. 2011;25(2):199–211.PubMedCrossRef
17.
go back to reference Logan GJ, Dabbs DJ, Lucas PC, Jankowitz RC, Brown DD, Clark BZ, Oesterreich S, McAuliffe PF. Molecular drivers of lobular carcinoma in situ. Breast Cancer Res. 2015;17:76–85.PubMedPubMedCentralCrossRef Logan GJ, Dabbs DJ, Lucas PC, Jankowitz RC, Brown DD, Clark BZ, Oesterreich S, McAuliffe PF. Molecular drivers of lobular carcinoma in situ. Breast Cancer Res. 2015;17:76–85.PubMedPubMedCentralCrossRef
18.
go back to reference Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12(5):R68.PubMedPubMedCentralCrossRef Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12(5):R68.PubMedPubMedCentralCrossRef
19.
go back to reference Mazouni C, Rimareix F, Mathieu MC, Uzan C, Bourgier C, André F, Delaloge S, Garbay JR. Outcome in breast molecular subtypes according to nodal status and surgical procedures. Am J Surg. 2013;205(6):662–7.PubMedCrossRef Mazouni C, Rimareix F, Mathieu MC, Uzan C, Bourgier C, André F, Delaloge S, Garbay JR. Outcome in breast molecular subtypes according to nodal status and surgical procedures. Am J Surg. 2013;205(6):662–7.PubMedCrossRef
20.
go back to reference Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol. 2008;26(14):2373–8.PubMedCrossRef Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol. 2008;26(14):2373–8.PubMedCrossRef
21.
go back to reference Caudle AS, Yu TK, Tucker SL, Bedrosian I, Litton JK, Gonzalez-Angulo AM, Hoffman K, Meric-Bernstam F, Hunt KK, Buchholz TA, Mittendorf EA. Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy. Breast Cancer Res. 2012;14(3):R83.PubMedPubMedCentralCrossRef Caudle AS, Yu TK, Tucker SL, Bedrosian I, Litton JK, Gonzalez-Angulo AM, Hoffman K, Meric-Bernstam F, Hunt KK, Buchholz TA, Mittendorf EA. Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy. Breast Cancer Res. 2012;14(3):R83.PubMedPubMedCentralCrossRef
22.
go back to reference Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, et al. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat. 2012;132(3):1049–62.PubMedCrossRef Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, et al. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat. 2012;132(3):1049–62.PubMedCrossRef
23.
go back to reference Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN, Gonzalez-Angulo AM. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24(7):1037–44.PubMedCrossRef Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN, Gonzalez-Angulo AM. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24(7):1037–44.PubMedCrossRef
24.
go back to reference Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ, Panel Members. Tailoring therapies–improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;8:1533–46.CrossRef Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ, Panel Members. Tailoring therapies–improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;8:1533–46.CrossRef
25.
go back to reference Pritchard KI, Burris HA 3rd, Ito Y, Rugo HS, Dakhil S, et al. Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2. Clin Breast Cancer. 2013;13(6):421–32.PubMedCrossRef Pritchard KI, Burris HA 3rd, Ito Y, Rugo HS, Dakhil S, et al. Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2. Clin Breast Cancer. 2013;13(6):421–32.PubMedCrossRef
26.
go back to reference Smith IE. Letrozole versus tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy. J Steroid Biochem Mol Biol. 2003;86(3–5):289–93.PubMedCrossRef Smith IE. Letrozole versus tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy. J Steroid Biochem Mol Biol. 2003;86(3–5):289–93.PubMedCrossRef
27.
go back to reference Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.CrossRef Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.CrossRef
28.
go back to reference Strasser-Weippl K, Goss PE. Advances in adjuvant hormonal therapy for postmenopausal women. J Clin Oncol. 2005;23(8):1751–9.PubMedCrossRef Strasser-Weippl K, Goss PE. Advances in adjuvant hormonal therapy for postmenopausal women. J Clin Oncol. 2005;23(8):1751–9.PubMedCrossRef
29.
go back to reference Peng J, Sengupta S, Jordan VC. Potential of selective estrogen receptor modulators as treatments and preventives of breast cancer. Anticancer Agents Med Chem. 2009;9(5):481–99.PubMedPubMedCentralCrossRef Peng J, Sengupta S, Jordan VC. Potential of selective estrogen receptor modulators as treatments and preventives of breast cancer. Anticancer Agents Med Chem. 2009;9(5):481–99.PubMedPubMedCentralCrossRef
30.
go back to reference Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, et al. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014;20(7):1757–67.PubMedPubMedCentralCrossRef Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, et al. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014;20(7):1757–67.PubMedPubMedCentralCrossRef
31.
go back to reference Toy W, Shen Y, Won H, Green B, Sakr RA, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45(12):1439–45.PubMedPubMedCentralCrossRef Toy W, Shen Y, Won H, Green B, Sakr RA, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45(12):1439–45.PubMedPubMedCentralCrossRef
32.
go back to reference Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013;45(12):1446–51.PubMedPubMedCentralCrossRef Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013;45(12):1446–51.PubMedPubMedCentralCrossRef
33.
go back to reference Reinert T, Saad ED, Barrios CH, Bines J. Clinical implications of ESR1 mutations in hormone receptor-positive advanced breast cancer. Front Oncol. 2017;7:26.PubMedPubMedCentralCrossRef Reinert T, Saad ED, Barrios CH, Bines J. Clinical implications of ESR1 mutations in hormone receptor-positive advanced breast cancer. Front Oncol. 2017;7:26.PubMedPubMedCentralCrossRef
34.
go back to reference Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013;30(10):870–84.PubMedPubMedCentralCrossRef Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013;30(10):870–84.PubMedPubMedCentralCrossRef
35.
go back to reference Johnston SR. Enhancing endocrine therapy for hormone receptor-positive advanced breast cancer: cotargeting signaling pathways. J Natl Cancer Inst. 2015;107(10):212.CrossRef Johnston SR. Enhancing endocrine therapy for hormone receptor-positive advanced breast cancer: cotargeting signaling pathways. J Natl Cancer Inst. 2015;107(10):212.CrossRef
36.
go back to reference No authors listed. PI3K inhibitor improves PFS in BELLE-2 trial. Cancer Discov. 2016;6(2):115–6. No authors listed. PI3K inhibitor improves PFS in BELLE-2 trial. Cancer Discov. 2016;6(2):115–6.
37.
go back to reference Chandarlapaty S, Chen D, He W, Sung P, Samoila A, You D, Bhatt T, Patel P, Voi M, Gnant M, Hortobagyi G, Baselga J, Moynahan ME. Prevalence of ESR1 mutations in cell-free dna and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol. 2016;2(10):1310–5.PubMedCrossRef Chandarlapaty S, Chen D, He W, Sung P, Samoila A, You D, Bhatt T, Patel P, Voi M, Gnant M, Hortobagyi G, Baselga J, Moynahan ME. Prevalence of ESR1 mutations in cell-free dna and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol. 2016;2(10):1310–5.PubMedCrossRef
38.
go back to reference Schiavon G, Hrebien S, Garcia-Murillas I, Cutts RJ, Pearson A, Tarazona N, Fenwick K, Kozarewa I, Lopez-Knowles E, Ribas R, Nerurkar A, Osin P, Chandarlapaty S, Martin LA, Dowsett M, Smith IE, Turner NC. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 2015;7(313):313ra182.PubMedPubMedCentralCrossRef Schiavon G, Hrebien S, Garcia-Murillas I, Cutts RJ, Pearson A, Tarazona N, Fenwick K, Kozarewa I, Lopez-Knowles E, Ribas R, Nerurkar A, Osin P, Chandarlapaty S, Martin LA, Dowsett M, Smith IE, Turner NC. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med. 2015;7(313):313ra182.PubMedPubMedCentralCrossRef
39.
go back to reference Wang P, Bahreini A, Gyanchandani R, Lucas PC, Hartmaier RJ, et al. Sensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions, and cell-free DNA of breast cancer patients. Clin Cancer Res. 2016;22(5):1130–7.PubMedCrossRef Wang P, Bahreini A, Gyanchandani R, Lucas PC, Hartmaier RJ, et al. Sensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions, and cell-free DNA of breast cancer patients. Clin Cancer Res. 2016;22(5):1130–7.PubMedCrossRef
40.
go back to reference Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16(1):25–35.PubMedCrossRef Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16(1):25–35.PubMedCrossRef
41.
go back to reference Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925–36.PubMedCrossRef Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925–36.PubMedCrossRef
42.
go back to reference Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M, PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(3):209–19.PubMedCrossRef Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M, PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(3):209–19.PubMedCrossRef
43.
go back to reference Fribbens C, O’Leary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, Cristofanilli M, Andre F, Loi S, Loibl S, Jiang J, Bartlett CH, Koehler M, Dowsett M, Bliss JM, Johnston SR, Turner NC. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2016;34(25):2961–8.PubMedCrossRef Fribbens C, O’Leary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, Cristofanilli M, Andre F, Loi S, Loibl S, Jiang J, Bartlett CH, Koehler M, Dowsett M, Bliss JM, Johnston SR, Turner NC. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2016;34(25):2961–8.PubMedCrossRef
44.
go back to reference Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–48.PubMedCrossRef Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–48.PubMedCrossRef
45.
go back to reference Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.PubMedCrossRef Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.PubMedCrossRef
46.
go back to reference Jordan NV, Bardia A, Wittner BS, Benes C, Ligorio M, Zheng Y, Yu M, Sundaresan TK, Licausi JA, Desai R, O’Keefe RM, Ebright RY, Boukhali M, Sil S, Onozato ML, Iafrate AJ, Kapur R, Sgroi D, Ting DT, Toner M, Ramaswamy S, Haas W, Maheswaran S, Haber DA. HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature. 2016;537(7618):102–6.PubMedPubMedCentralCrossRef Jordan NV, Bardia A, Wittner BS, Benes C, Ligorio M, Zheng Y, Yu M, Sundaresan TK, Licausi JA, Desai R, O’Keefe RM, Ebright RY, Boukhali M, Sil S, Onozato ML, Iafrate AJ, Kapur R, Sgroi D, Ting DT, Toner M, Ramaswamy S, Haas W, Maheswaran S, Haber DA. HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature. 2016;537(7618):102–6.PubMedPubMedCentralCrossRef
47.
go back to reference Hayes DF, Smerage J. Is there a role for circulating tumor cells in the management of breast cancer? Clin Cancer Res. 2008;14(12):3646–50.PubMedCrossRef Hayes DF, Smerage J. Is there a role for circulating tumor cells in the management of breast cancer? Clin Cancer Res. 2008;14(12):3646–50.PubMedCrossRef
48.
go back to reference Stathopoulou A, Vlachonikolis I, Mavroudis D, Perraki M, Kouroussis Ch, Apostolaki S, Malamos N, Kakolyris S, Kotsakis A, Xenidis N, Reppa D, Georgoulias V. Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significance. J Clin Oncol. 2002;20(16):3404–12.PubMedCrossRef Stathopoulou A, Vlachonikolis I, Mavroudis D, Perraki M, Kouroussis Ch, Apostolaki S, Malamos N, Kakolyris S, Kotsakis A, Xenidis N, Reppa D, Georgoulias V. Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significance. J Clin Oncol. 2002;20(16):3404–12.PubMedCrossRef
49.
go back to reference Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91.PubMedCrossRef Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91.PubMedCrossRef
50.
go back to reference Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC, Matera J, Allard WJ, Doyle GV, Terstappen LW. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res. 2006;12(14 Pt 1):4218–24.PubMedCrossRef Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC, Matera J, Allard WJ, Doyle GV, Terstappen LW. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res. 2006;12(14 Pt 1):4218–24.PubMedCrossRef
51.
go back to reference Wülfing P, Borchard J, Buerger H, Heidl S, Zänker KS, Kiesel L, Brandt B. HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res. 2006;12(6):1715–20.PubMedCrossRef Wülfing P, Borchard J, Buerger H, Heidl S, Zänker KS, Kiesel L, Brandt B. HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res. 2006;12(6):1715–20.PubMedCrossRef
52.
go back to reference Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112(3):533–43.PubMedCrossRef Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112(3):533–43.PubMedCrossRef
53.
go back to reference Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Gonzalez-Angulo AM, Krop I, Levinson J, Lin NU, Modi S, Patt DA, Perez EA, Perlmutter J, Ramakrishna N, Winer EP. American Society of Clinical Oncology systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32(19):2078–99.PubMedCrossRef Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Gonzalez-Angulo AM, Krop I, Levinson J, Lin NU, Modi S, Patt DA, Perez EA, Perlmutter J, Ramakrishna N, Winer EP. American Society of Clinical Oncology systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32(19):2078–99.PubMedCrossRef
54.
go back to reference Nahta R, Yuan LX, Zhang B, Kobayashi R, Esteva FJ. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 hetero-dimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005;65(23):11118–28.PubMedCrossRef Nahta R, Yuan LX, Zhang B, Kobayashi R, Esteva FJ. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 hetero-dimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005;65(23):11118–28.PubMedCrossRef
55.
go back to reference Maroun CR, Rowlands T. The Met receptor tyrosine kinase: a key player in oncogenesis and drug resistance. Pharmacol Ther. 2014;142(3):316–38.PubMedCrossRef Maroun CR, Rowlands T. The Met receptor tyrosine kinase: a key player in oncogenesis and drug resistance. Pharmacol Ther. 2014;142(3):316–38.PubMedCrossRef
56.
go back to reference de Melo Gagliato D, Jardim DL, Marchesi MS, Hortobagyi GN. Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. Oncotarget. 2016;7(39):64431–46. de Melo Gagliato D, Jardim DL, Marchesi MS, Hortobagyi GN. Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. Oncotarget. 2016;7(39):64431–46.
57.
go back to reference Dey N, Williams C, Leyland-Jones B, De P. A critical role for HER3 in HER2-amplified and non-amplified breast cancers: function of a kinase-dead RTK. Am J Transl Res. 2015;7(4):733–50.PubMedPubMedCentral Dey N, Williams C, Leyland-Jones B, De P. A critical role for HER3 in HER2-amplified and non-amplified breast cancers: function of a kinase-dead RTK. Am J Transl Res. 2015;7(4):733–50.PubMedPubMedCentral
58.
go back to reference Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM, CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–19.PubMedCrossRef Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM, CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–19.PubMedCrossRef
59.
go back to reference Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov. 2013;3(2):224–37.PubMedCrossRef Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov. 2013;3(2):224–37.PubMedCrossRef
60.
go back to reference Hirotsu Y, Nakagomi H, Amemiya K, Oyama T, Inoue M, Mochizuki H, Omata M. Intrinsic HER2 V777L mutation mediates resistance to trastuzumab in a breast cancer patient. Med Oncol. 2017;34(1):3.PubMedCrossRef Hirotsu Y, Nakagomi H, Amemiya K, Oyama T, Inoue M, Mochizuki H, Omata M. Intrinsic HER2 V777L mutation mediates resistance to trastuzumab in a breast cancer patient. Med Oncol. 2017;34(1):3.PubMedCrossRef
61.
go back to reference Hanker AB, Red Brewer M, Sheehan JH, Koch JP, Sliwoski GR, Nagy R, Lanman R, Berger MF, Hyman DM, Solit DB, He J, Miller V, Cutler RE, Lalani AS, Cross D, Lovly CM, Meiler J, Arteaga CL. An acquired HER2 T798I gatekeeper mutation induces resistance to neratinib in a patient with HER2 mutant-driven breast cancer. Cancer Discov. 2017;7(6):575–85.PubMedCrossRef Hanker AB, Red Brewer M, Sheehan JH, Koch JP, Sliwoski GR, Nagy R, Lanman R, Berger MF, Hyman DM, Solit DB, He J, Miller V, Cutler RE, Lalani AS, Cross D, Lovly CM, Meiler J, Arteaga CL. An acquired HER2 T798I gatekeeper mutation induces resistance to neratinib in a patient with HER2 mutant-driven breast cancer. Cancer Discov. 2017;7(6):575–85.PubMedCrossRef
62.
go back to reference Giuliano M, Hu H, Wang YC, Fu X, Nardone A, Herrera S, Mao S, Contreras A, Gutierrez C, Wang T, Hilsenbeck SG, De Angelis C, Wang NJ, Heiser LM, Gray JW, Lopez-Tarruella S, Pavlick AC, Trivedi MV, Chamness GC, Chang JC, Osborne CK, Rimawi MF, Schiff R. Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy. Clin Cancer Res. 2015;21(17):3995–4003.PubMedPubMedCentralCrossRef Giuliano M, Hu H, Wang YC, Fu X, Nardone A, Herrera S, Mao S, Contreras A, Gutierrez C, Wang T, Hilsenbeck SG, De Angelis C, Wang NJ, Heiser LM, Gray JW, Lopez-Tarruella S, Pavlick AC, Trivedi MV, Chamness GC, Chang JC, Osborne CK, Rimawi MF, Schiff R. Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy. Clin Cancer Res. 2015;21(17):3995–4003.PubMedPubMedCentralCrossRef
63.
go back to reference Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergen RL, Mills GB, van de Vijver MJ, Bernards R. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12(4):395–402.PubMedCrossRef Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergen RL, Mills GB, van de Vijver MJ, Bernards R. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12(4):395–402.PubMedCrossRef
64.
go back to reference Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K, EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.PubMedPubMedCentralCrossRef Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K, EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.PubMedPubMedCentralCrossRef
65.
go back to reference Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, von Minckwitz G, Ejlertsen B, Chia SK, Mansi J, Barrios CH, Gnant M, Buyse M, Gore I, Smith J, Harker G, Masuda N, Petrakova K, Zotano AG, Iannotti N, Rodriguez G, Tassone P, Wong A, Bryce R, Ye Y, Yao B, Martin M, ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(3):367–77.PubMedCrossRef Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, von Minckwitz G, Ejlertsen B, Chia SK, Mansi J, Barrios CH, Gnant M, Buyse M, Gore I, Smith J, Harker G, Masuda N, Petrakova K, Zotano AG, Iannotti N, Rodriguez G, Tassone P, Wong A, Bryce R, Ye Y, Yao B, Martin M, ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(3):367–77.PubMedCrossRef
66.
go back to reference Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, Jung KH, Shen K, Ro J, Jassem J, Zhang Q, Im YH, Wojtukiewicz M, Sun Q, Chen SC, Goeldner RG, Uttenreuther-Fischer M, Xu B, Piccart-Gebhart M, LUX-Breast 1 study group. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016;17(3):357–66.PubMedCrossRef Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, Jung KH, Shen K, Ro J, Jassem J, Zhang Q, Im YH, Wojtukiewicz M, Sun Q, Chen SC, Goeldner RG, Uttenreuther-Fischer M, Xu B, Piccart-Gebhart M, LUX-Breast 1 study group. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016;17(3):357–66.PubMedCrossRef
67.
go back to reference Konecny GE, Meng YG, Untch M, Wang HJ, Bauerfeind I, Epstein M, Stieber P, Vernes JM, Gutierrez J, Hong K, Beryt M, Hepp H, Slamon DJ, Pegram MD. Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res. 2004;10(5):1706–16.PubMedCrossRef Konecny GE, Meng YG, Untch M, Wang HJ, Bauerfeind I, Epstein M, Stieber P, Vernes JM, Gutierrez J, Hong K, Beryt M, Hepp H, Slamon DJ, Pegram MD. Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res. 2004;10(5):1706–16.PubMedCrossRef
68.
go back to reference Pierga JY, Petit T, Delozier T, Ferrero JM, Campone M, Gligorov J, Lerebours F, Roché H, Bachelot T, Charafe-Jauffret E, Pavlyuk M, Kraemer S, Bidard FC, Viens P. Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study. Lancet Oncol. 2012;13(4):375–84.PubMedCrossRef Pierga JY, Petit T, Delozier T, Ferrero JM, Campone M, Gligorov J, Lerebours F, Roché H, Bachelot T, Charafe-Jauffret E, Pavlyuk M, Kraemer S, Bidard FC, Viens P. Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study. Lancet Oncol. 2012;13(4):375–84.PubMedCrossRef
69.
go back to reference Mittendorf EA, Clifton GT, Holmes JP, Schneble E, van Echo D, Ponniah S, Peoples GE. Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Ann Oncol. 2014;25(9):1735–42.PubMedPubMedCentralCrossRef Mittendorf EA, Clifton GT, Holmes JP, Schneble E, van Echo D, Ponniah S, Peoples GE. Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Ann Oncol. 2014;25(9):1735–42.PubMedPubMedCentralCrossRef
70.
go back to reference Mittendorf EA, Ardavanis A, Symanowski J, Murray JL, Shumway NM, Litton JK, Hale DF, Perez SA, Anastasopoulou EA, Pistamaltzian NF, Ponniah S, Baxevanis CN, von Hofe E, Papamichail M, Peoples GE. Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence. Ann Oncol. 2016;27(7):1241–8.PubMedCrossRef Mittendorf EA, Ardavanis A, Symanowski J, Murray JL, Shumway NM, Litton JK, Hale DF, Perez SA, Anastasopoulou EA, Pistamaltzian NF, Ponniah S, Baxevanis CN, von Hofe E, Papamichail M, Peoples GE. Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence. Ann Oncol. 2016;27(7):1241–8.PubMedCrossRef
71.
go back to reference Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109(9):1721–8.PubMedCrossRef Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109(9):1721–8.PubMedCrossRef
72.
go back to reference Le Du F, Eckhardt BL, Lim B, Litton JK, Moulder S, Meric-Bernstam F, Gonzalez-Angulo AM, Ueno NT. Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype? Oncotarget. 2015;6(15):12890–908.PubMedPubMedCentralCrossRef Le Du F, Eckhardt BL, Lim B, Litton JK, Moulder S, Meric-Bernstam F, Gonzalez-Angulo AM, Ueno NT. Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype? Oncotarget. 2015;6(15):12890–908.PubMedPubMedCentralCrossRef
73.
go back to reference Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67.PubMedPubMedCentralCrossRef Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67.PubMedPubMedCentralCrossRef
74.
go back to reference Colleoni M, Cole BF, Viale G, Regan MM, Price KN, Maiorano E, Mastropasqua MG, Crivellari D, Gelber RD, Goldhirsch A, Coates AS, Gusterson BA. Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Clin Oncol. 2010;28(18):2966–73.PubMedPubMedCentralCrossRef Colleoni M, Cole BF, Viale G, Regan MM, Price KN, Maiorano E, Mastropasqua MG, Crivellari D, Gelber RD, Goldhirsch A, Coates AS, Gusterson BA. Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Clin Oncol. 2010;28(18):2966–73.PubMedPubMedCentralCrossRef
75.
go back to reference Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX, Liu MC, Storniolo AM, Rimawi MF, Forero-Torres A, Wolff AC, Hobday TJ, Ivanova A, Chiu WK, Ferraro M, Burrows E, Bernard PS, Hoadley KA, Perou CM, Winer EP. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol. 2012;30(21):2615–23.PubMedPubMedCentralCrossRef Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX, Liu MC, Storniolo AM, Rimawi MF, Forero-Torres A, Wolff AC, Hobday TJ, Ivanova A, Chiu WK, Ferraro M, Burrows E, Bernard PS, Hoadley KA, Perou CM, Winer EP. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol. 2012;30(21):2615–23.PubMedPubMedCentralCrossRef
76.
go back to reference Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376(9737):235–44.PubMedCrossRef Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376(9737):235–44.PubMedCrossRef
77.
go back to reference O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, Specht JM, Yardley DA, Carlson RW, Finn RS, Charpentier E, Garcia-Ribas I, Winer EP. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014;32(34):3840–7.PubMedCrossRef O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, Specht JM, Yardley DA, Carlson RW, Finn RS, Charpentier E, Garcia-Ribas I, Winer EP. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014;32(34):3840–7.PubMedCrossRef
78.
go back to reference Telli ML, Jensen KC, Vinayak S, Kurian AW, Lipson JA, Flaherty PJ, Timms K, Abkevich V, Schackmann EA, Wapnir IL, Carlson RW, Chang PJ, Sparano JA, Head B, Goldstein LJ, Haley B, Dakhil SR, Reid JE, Hartman AR, Manola J, Ford JM. Phase II study of gemcitabine, carboplatin, and iniparib as neoadjuvant therapy for triple-negative and BRCA1/2 mutation-associated breast cancer with assessment of a tumor-based measure of genomic instability: PrECOG 0105. J Clin Oncol. 2015;33(17):1895–901.PubMedPubMedCentralCrossRef Telli ML, Jensen KC, Vinayak S, Kurian AW, Lipson JA, Flaherty PJ, Timms K, Abkevich V, Schackmann EA, Wapnir IL, Carlson RW, Chang PJ, Sparano JA, Head B, Goldstein LJ, Haley B, Dakhil SR, Reid JE, Hartman AR, Manola J, Ford JM. Phase II study of gemcitabine, carboplatin, and iniparib as neoadjuvant therapy for triple-negative and BRCA1/2 mutation-associated breast cancer with assessment of a tumor-based measure of genomic instability: PrECOG 0105. J Clin Oncol. 2015;33(17):1895–901.PubMedPubMedCentralCrossRef
79.
go back to reference Rugo HS, Olopade OI, DeMichele A, Yau C, van’t Veer LJ, et al. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016;375(1):23–34.PubMedPubMedCentralCrossRef Rugo HS, Olopade OI, DeMichele A, Yau C, van’t Veer LJ, et al. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016;375(1):23–34.PubMedPubMedCentralCrossRef
80.
go back to reference Masuda H, Baggerly KA, Wang Y, Zhang Y, Gonzalez-Angulo AM, Meric-Bernstam F, Valero V, Lehmann BD, Pietenpol JA, Hortobagyi GN, Symmans WF, Ueno NT. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res. 2013;19(19):5533–40.PubMedCrossRef Masuda H, Baggerly KA, Wang Y, Zhang Y, Gonzalez-Angulo AM, Meric-Bernstam F, Valero V, Lehmann BD, Pietenpol JA, Hortobagyi GN, Symmans WF, Ueno NT. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res. 2013;19(19):5533–40.PubMedCrossRef
81.
go back to reference Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ, Panel Members. Tailoring therapies–improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;26(8):1533–46.PubMedPubMedCentralCrossRef Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ, Panel Members. Tailoring therapies–improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;26(8):1533–46.PubMedPubMedCentralCrossRef
82.
go back to reference Loibl S, Müller BM, von Minckwitz G, Schwabe M, Roller M, Darb-Esfahani S, Ataseven B, du Bois A, Fissler-Eckhoff A, Gerber B, Kulmer U, Alles JU, Mehta K, Denkert C. Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2011;130(2):477–87.PubMedCrossRef Loibl S, Müller BM, von Minckwitz G, Schwabe M, Roller M, Darb-Esfahani S, Ataseven B, du Bois A, Fissler-Eckhoff A, Gerber B, Kulmer U, Alles JU, Mehta K, Denkert C. Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat. 2011;130(2):477–87.PubMedCrossRef
83.
go back to reference Yu KD, Zhu R, Zhan M, Rodriguez AA, Yang W, Wong S, Makris A, Lehmann BD, Chen X, Mayer I, Pietenpol JA, Shao ZM, Symmans WF, Chang JC. Identification of prognosis-relevant subgroups in patients with chemoresistant triple-negative breast cancer. Clin Cancer Res. 2013;19(10):2723–33.PubMedPubMedCentralCrossRef Yu KD, Zhu R, Zhan M, Rodriguez AA, Yang W, Wong S, Makris A, Lehmann BD, Chen X, Mayer I, Pietenpol JA, Shao ZM, Symmans WF, Chang JC. Identification of prognosis-relevant subgroups in patients with chemoresistant triple-negative breast cancer. Clin Cancer Res. 2013;19(10):2723–33.PubMedPubMedCentralCrossRef
84.
go back to reference Shah SP, Roth A, Goya R, Oloumi A, Ha G, et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. 2012;486(7403):395–9.PubMed Shah SP, Roth A, Goya R, Oloumi A, Ha G, et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. 2012;486(7403):395–9.PubMed
87.
go back to reference Hayes MJ, Thomas D, Emmons A, Giordano TJ, Kleer CG. Genetic changes of Wnt pathway genes are common events in metaplastic carcinomas of the breast. Clin Cancer Res. 2008;14(13):4038–44.PubMedPubMedCentralCrossRef Hayes MJ, Thomas D, Emmons A, Giordano TJ, Kleer CG. Genetic changes of Wnt pathway genes are common events in metaplastic carcinomas of the breast. Clin Cancer Res. 2008;14(13):4038–44.PubMedPubMedCentralCrossRef
88.
go back to reference Pires BR, Amorim ÍS DE, Souza LD, Rodrigues JA, Mencalha AL. Targeting cellular signaling pathways in breast cancer stem cells and its implication for cancer treatment. Anticancer Res. 2016;36(11):5681–91.PubMedCrossRef Pires BR, Amorim ÍS DE, Souza LD, Rodrigues JA, Mencalha AL. Targeting cellular signaling pathways in breast cancer stem cells and its implication for cancer treatment. Anticancer Res. 2016;36(11):5681–91.PubMedCrossRef
89.
go back to reference Samanta D, Gilkes DM, Chaturvedi P, Xiang L, Semenza GL. Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells. Proc Natl Acad Sci USA. 2014;111(50):E5429–38.PubMedPubMedCentralCrossRef Samanta D, Gilkes DM, Chaturvedi P, Xiang L, Semenza GL. Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells. Proc Natl Acad Sci USA. 2014;111(50):E5429–38.PubMedPubMedCentralCrossRef
90.
go back to reference Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM, Chang JC. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA. 2009;106(33):13820–5.PubMedPubMedCentralCrossRef Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM, Chang JC. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA. 2009;106(33):13820–5.PubMedPubMedCentralCrossRef
91.
go back to reference Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J, Chang JC. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100(9):672–9.PubMedCrossRef Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J, Chang JC. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100(9):672–9.PubMedCrossRef
92.
go back to reference Kim do Y, Park EY, Chang E, Kang HG, Koo Y, Lee EJ, Ko JY, Kong HK, Chun KH, Park JH. A novel miR-34a target, protein kinase D1, stimulates cancer stemness and drug resistance through GSK3/β-catenin signaling in breast cancer. Oncotarget. 2016;7(12):14791–802.PubMed Kim do Y, Park EY, Chang E, Kang HG, Koo Y, Lee EJ, Ko JY, Kong HK, Chun KH, Park JH. A novel miR-34a target, protein kinase D1, stimulates cancer stemness and drug resistance through GSK3/β-catenin signaling in breast cancer. Oncotarget. 2016;7(12):14791–802.PubMed
93.
go back to reference Liu J, Pan S, Hsieh MH, Ng N, Sun F, et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci USA. 2013;110(50):20224–9.PubMedPubMedCentralCrossRef Liu J, Pan S, Hsieh MH, Ng N, Sun F, et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci USA. 2013;110(50):20224–9.PubMedPubMedCentralCrossRef
95.
go back to reference Galon J, Angell HK, Bedognetti D, Marincola FM. The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity. 2013;39:11–26.PubMedCrossRef Galon J, Angell HK, Bedognetti D, Marincola FM. The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity. 2013;39:11–26.PubMedCrossRef
96.
go back to reference Luen SJ, Savas P, Fox SB, Salgado R, Loi S. Tumour-infiltrating lymphocytes and the emerging role of immunotherapy in breast cancer. Pathology. 2017;49(2):141–55.PubMedCrossRef Luen SJ, Savas P, Fox SB, Salgado R, Loi S. Tumour-infiltrating lymphocytes and the emerging role of immunotherapy in breast cancer. Pathology. 2017;49(2):141–55.PubMedCrossRef
97.
go back to reference Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoué F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pagès F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–4.PubMedCrossRef Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoué F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pagès F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–4.PubMedCrossRef
98.
go back to reference Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ, Loi S. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol. 2016;13(4):228–41.PubMedCrossRef Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ, Loi S. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol. 2016;13(4):228–41.PubMedCrossRef
99.
go back to reference Dushyanthen S, Beavis PA, Savas P, Teo ZL, Zhou C, Mansour M, Darcy PK, Loi S. Relevance of tumor-infiltrating lymphocytes in breast cancer. BMC Med. 2015;13:202.PubMedPubMedCentralCrossRef Dushyanthen S, Beavis PA, Savas P, Teo ZL, Zhou C, Mansour M, Darcy PK, Loi S. Relevance of tumor-infiltrating lymphocytes in breast cancer. BMC Med. 2015;13:202.PubMedPubMedCentralCrossRef
101.
go back to reference Stanton SE, Adams S, Disis ML. Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: a systematic review. JAMA Oncol. 2016;2(10):1354–60.PubMedCrossRef Stanton SE, Adams S, Disis ML. Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: a systematic review. JAMA Oncol. 2016;2(10):1354–60.PubMedCrossRef
102.
go back to reference Denkert C, Loibl S, Noske A, Roller M, Müller BM, Komor M, Budczies J, Darb-Esfahani S, Kronenwett R, Hanusch C, von Törne C, Weichert W, Engels K, Solbach C, Schrader I, Dietel M, von Minckwitz G. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010;28(1):105–13.PubMedCrossRef Denkert C, Loibl S, Noske A, Roller M, Müller BM, Komor M, Budczies J, Darb-Esfahani S, Kronenwett R, Hanusch C, von Törne C, Weichert W, Engels K, Solbach C, Schrader I, Dietel M, von Minckwitz G. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010;28(1):105–13.PubMedCrossRef
103.
go back to reference Ibrahim EM, Al-Foheidi ME, Al-Mansour MM, Kazkaz GA. The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis. Breast Cancer Res Treat. 2014;148(3):467–76.PubMedCrossRef Ibrahim EM, Al-Foheidi ME, Al-Mansour MM, Kazkaz GA. The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis. Breast Cancer Res Treat. 2014;148(3):467–76.PubMedCrossRef
104.
go back to reference Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, Kellokumpu-Lehtinen PL, Bono P, Kataja V, Desmedt C, Piccart MJ, Loibl S, Denkert C, Smyth MJ, Joensuu H, Sotiriou C. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014;25(8):1544–50.PubMedCrossRef Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, Kellokumpu-Lehtinen PL, Bono P, Kataja V, Desmedt C, Piccart MJ, Loibl S, Denkert C, Smyth MJ, Joensuu H, Sotiriou C. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014;25(8):1544–50.PubMedCrossRef
105.
go back to reference Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, Martino S, Wang M, Jones VE, Saphner TJ, Wolff AC, Wood WC, Davidson NE, Sledge GW, Sparano JA, Badve SS. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959–66.PubMedPubMedCentralCrossRef Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, Martino S, Wang M, Jones VE, Saphner TJ, Wolff AC, Wood WC, Davidson NE, Sledge GW, Sparano JA, Badve SS. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959–66.PubMedPubMedCentralCrossRef
106.
go back to reference Dieci MV, Mathieu MC, Guarneri V, Conte P, Delaloge S, Andre F, Goubar A. Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. Ann Oncol. 2015;26(8):1698–704.PubMedPubMedCentralCrossRef Dieci MV, Mathieu MC, Guarneri V, Conte P, Delaloge S, Andre F, Goubar A. Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. Ann Oncol. 2015;26(8):1698–704.PubMedPubMedCentralCrossRef
107.
go back to reference Pruneri G, Gray KP, Vingiani A, Viale G, Curigliano G, Criscitiello C, Láng I, Ruhstaller T, Gianni L, Goldhirsch A, Kammler R, Price KN, Cancello G, Munzone E, Gelber RD, Regan MM, Colleoni M. Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00. Breast Cancer Res Treat. 2016;158(2):323–31.PubMedCrossRef Pruneri G, Gray KP, Vingiani A, Viale G, Curigliano G, Criscitiello C, Láng I, Ruhstaller T, Gianni L, Goldhirsch A, Kammler R, Price KN, Cancello G, Munzone E, Gelber RD, Regan MM, Colleoni M. Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00. Breast Cancer Res Treat. 2016;158(2):323–31.PubMedCrossRef
108.
go back to reference Perez EA, Ballman KV, Tenner KS, Thompson EA, Badve SS, Bailey H, Baehner FL. Association of stromal tumor-infiltrating lymphocytes with recurrence-free survival in the N9831 adjuvant trial in patients with early-stage HER2-positive breast cancer. JAMA Oncol. 2016;2(1):56–64.PubMedPubMedCentralCrossRef Perez EA, Ballman KV, Tenner KS, Thompson EA, Badve SS, Bailey H, Baehner FL. Association of stromal tumor-infiltrating lymphocytes with recurrence-free survival in the N9831 adjuvant trial in patients with early-stage HER2-positive breast cancer. JAMA Oncol. 2016;2(1):56–64.PubMedPubMedCentralCrossRef
109.
go back to reference de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014;15(10):1137–46.PubMedCrossRef de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014;15(10):1137–46.PubMedCrossRef
110.
go back to reference Salgado R, Denkert C, Campbell C, Savas P, Nuciforo P, Aura C, de Azambuja E, Eidtmann H, Ellis CE, Baselga J, Piccart-Gebhart MJ, Michiels S, Bradbury I, Sotiriou C, Loi S. Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO trial. JAMA Oncol. 2015;1(4):448–54.PubMedCrossRef Salgado R, Denkert C, Campbell C, Savas P, Nuciforo P, Aura C, de Azambuja E, Eidtmann H, Ellis CE, Baselga J, Piccart-Gebhart MJ, Michiels S, Bradbury I, Sotiriou C, Loi S. Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO trial. JAMA Oncol. 2015;1(4):448–54.PubMedCrossRef
111.
go back to reference Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015;33(9):983–91.PubMedCrossRef Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015;33(9):983–91.PubMedCrossRef
112.
go back to reference Hendrickx W, Simeone I, Anjum S, Mokrab Y, Bertucci F, Finetti P, Curigliano G, Seliger B, Cerulo L, Tomei S, Delogu LG, Maccalli C, Wang E, Miller LD, Marincola FM, Ceccarelli M, Bedognetti D. Identification of genetic determinants of breast cancer immune phenotypes by integrative genome-scale analysis. Oncoimmunology. 2017;6(2):e1253654.PubMedPubMedCentralCrossRef Hendrickx W, Simeone I, Anjum S, Mokrab Y, Bertucci F, Finetti P, Curigliano G, Seliger B, Cerulo L, Tomei S, Delogu LG, Maccalli C, Wang E, Miller LD, Marincola FM, Ceccarelli M, Bedognetti D. Identification of genetic determinants of breast cancer immune phenotypes by integrative genome-scale analysis. Oncoimmunology. 2017;6(2):e1253654.PubMedPubMedCentralCrossRef
113.
go back to reference Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.PubMedPubMedCentralCrossRef Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.PubMedPubMedCentralCrossRef
114.
go back to reference Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, KEYNOTE-006 investigators. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.PubMedCrossRef Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, KEYNOTE-006 investigators. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.PubMedCrossRef
115.
go back to reference Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.PubMedCrossRef Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.PubMedCrossRef
116.
go back to reference Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.PubMedPubMedCentralCrossRef Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.PubMedPubMedCentralCrossRef
117.
go back to reference Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR, Vaishampayan UN, Drabkin HA, George S, Logan TF, Margolin KA, Plimack ER, Lambert AM, Waxman IM, Hammers HJ. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol. 2015;33(13):1430–7.PubMedCrossRef Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR, Vaishampayan UN, Drabkin HA, George S, Logan TF, Margolin KA, Plimack ER, Lambert AM, Waxman IM, Hammers HJ. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol. 2015;33(13):1430–7.PubMedCrossRef
118.
go back to reference Verret B, Loirat D. Immunotherapy and breast cancer. Oncologie. 2016;18:551–8.CrossRef Verret B, Loirat D. Immunotherapy and breast cancer. Oncologie. 2016;18:551–8.CrossRef
119.
go back to reference Sun S, Fei X, Mao Y, Wang X, Garfield DH, Huang O, Wang J, Yuan F, Sun L, Yu Q, Jin X, Wang J, Shen K. PD-1(+) immune cell infiltration inversely correlates with survival of operable breast cancer patients. Cancer Immunol Immunother. 2014;63(4):395–406.PubMedCrossRef Sun S, Fei X, Mao Y, Wang X, Garfield DH, Huang O, Wang J, Yuan F, Sun L, Yu Q, Jin X, Wang J, Shen K. PD-1(+) immune cell infiltration inversely correlates with survival of operable breast cancer patients. Cancer Immunol Immunother. 2014;63(4):395–406.PubMedCrossRef
120.
go back to reference Vonderheide RH, LoRusso PM, Khalil M, Gartner EM, Khaira D, Soulieres D, Dorazio P, Trosko JA, Rüter J, Mariani GL, Usari T, Domchek SM. Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin Cancer Res. 2010;16(13):3485–94.PubMedCrossRef Vonderheide RH, LoRusso PM, Khalil M, Gartner EM, Khaira D, Soulieres D, Dorazio P, Trosko JA, Rüter J, Mariani GL, Usari T, Domchek SM. Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin Cancer Res. 2010;16(13):3485–94.PubMedCrossRef
121.
go back to reference Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016;34(21):2460–7.PubMedCrossRef Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016;34(21):2460–7.PubMedCrossRef
122.
Metadata
Title
Precision medicine in breast cancer: reality or utopia?
Authors
Ali Bettaieb
Catherine Paul
Stéphanie Plenchette
Jingxuan Shan
Lotfi Chouchane
François Ghiringhelli
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1239-z

Other articles of this Issue 1/2017

Journal of Translational Medicine 1/2017 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.