Triple-negative breast cancer: The importance of molecular and histologic subtyping, and recognition of low-grade variants

npj Breast Cancer

Volumn 2, Issue 1, 2016, Pages

  Pareja, Fresia ^a   Geyer, Felipe C ^a   Marchiò, Caterina ^b   Burke, Kathleen A ^a   Weigelt, Britta ^a   Reis Filho, Jorge S ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b UNIVERSITY OF TURIN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85044152834     PISSN: None     EISSN: 23744677     Source Type: Journal    
DOI: 10.1038/npjbcancer.2016.36     Document Type: Review

References (114)

1. Foulkes, W. D., Smith, I. E. & Reis-Filho, J. S. Triple-negative breast cancer. N. Engl. J. Med. 363, 1938–1948 (2010).
2. Carey, L. A. et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295, 2492–2502 (2006).
3. Dent, R. et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin. Cancer Res. 13, 4429–4434 (2007).
4. Turner, N. C. & Reis-Filho, J. S. Tackling the diversity of triple-negative breast cancer. Clin. Cancer Res. 19, 6380–6388 (2013).
5. Guerini-Rocco, E. et al. The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: an exploratory, hypothesis-generating study. J. Pathol. 237, 166–178 (2015).
6. Del Castillo, M. et al. Secretory breast carcinoma: a histopathologic and genomic spectrum characterized by a joint specific ETV6-NTRK3 gene fusion. Am. J. Surg. Pathol. 39, 1458–1467 (2015).
7. Fusco N. et al. Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer. Mod. Pathol. (2016); Epub ahead of print, doi: 10.1038/modpathol.2016.134.
8. Wen, Y. H., Weigelt, B. & Reis-Filho, J. S. Microglandular adenosis: a non-obligate precursor of triple-negative breast cancer? Histol. Histopathol. 28, 1099–1108 (2013).
9. Guerini-Rocco, E. et al. Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations. J Pathol. 238, 677–688 (2016).
10. Brenton, J. D., Carey, L. A., Ahmed, A. A. & Caldas, C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J. Clin. Oncol. 23, 7350–7360 (2005).
11. Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747–752 (2000).
12. Hammond, M. E. et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J. Clin. Oncol. 28, 2784–2795 (2010).
13. Wolff, A. C. et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J. Clin. Oncol. 31, 3997–4013 (2013).
14. Kandoth, C. et al. Mutational landscape and significance across 12 major cancer types. Nature 502, 333–339 (2013).
15. Ng, C. K., Schultheis, A. M., Bidard, F. C., Weigelt, B. & Reis-Filho, J. S. Breast cancer genomics from microarrays to massively parallel sequencing: paradigms and new insights. J. Natl Cancer Inst 107, djv015 (2015).
16. Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47–54 (2016).
17. Shah, S. P. et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486, 395–399 (2012).
18. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 490, 61–70 (2012).
19. Turner, N. et al. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene 29, 2013–2023 (2010).
20. Reis-Filho, J. S. et al. EGFR amplification and lack of activating mutations in metaplastic breast carcinomas. J. Pathol. 209, 445–453 (2006).
21. Shiu, K. K., Natrajan, R., Geyer, F. C., Ashworth, A. & Reis-Filho, J. S. DNA amplifications in breast cancer: genotypic-phenotypic correlations. Future Oncol. 6, 967–984 (2010).
22. Natrajan, R. et al. Loss of 16q in high grade breast cancer is associated with estrogen receptor status: Evidence for progression in tumors with a luminal phenotype? Genes Chromosomes Cancer 48, 351–365 (2009).
23. Curtis, C. et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486, 346–352 (2012).
24. Robinson, D. R. et al. Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer. Nat. Med. 17, 1646–1651 (2011).
25. Wang, K. et al. PEST domain mutations in notch receptors comprise an oncogenic driver segment in triple-negative breast cancer sensitive to a gamma-secretase inhibitor. Clin. Cancer Res. 21, 1487–1496 (2015).
26. Banerji, S. et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 486, 405–409 (2012).
27. Mosquera, J. M. et al. MAGI3-AKT3 fusion in breast cancer amended. Nature 520, E11–E12 (2015).
28. Cortazar, P. et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384, 164–172 (2014).
29. von Minckwitz, G. et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J. Clin. Oncol. 30, 1796–1804 (2012).
30. von Minckwitz, G. et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 15, 747–756 (2014).
31. Turner, N., Tutt, A. & Ashworth, A. Hallmarks of 'BRCAness' in sporadic cancers. Nat. Rev. Cancer. 4, 814–819 (2004).
32. Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).
33. Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917 (2005).
34. Sikov, W. M. et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J. Clin. Oncol. 33, 13–21 (2015).
35. Schouten, P. C. & Linn, S. C. Challenges in the Use of DNA Repair Deficiency As a Biomarker in Breast Cancer. J. Clin. Oncol. 33, 1867–1869 (2015).
36. Liedtke, C. et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J. Clin. Oncol. 26, 1275–1281 (2008).
37. Balko, J. M. et al. Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov. 4, 232–245 (2014).
38. Balko, J. M. et al. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Nat. Med. 18, 1052–1059 (2012).
39. Baglia, M. L. et al. Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome. Breast Cancer Res. Treat. 148, 211–220 (2014).
40. Bastien, R. R. et al. PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers. BMC Med. Genomics 5, 44 (2012).
41. Prat, A. et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 12, R68 (2010).
42. Lehmann, B. D. et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J. Clin. Invest. 121, 2750–2767 (2011).
43. Lehmann, B. D. & Pietenpol, J. A. Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes. J. Pathol. 232, 142–150 (2014).
44. Prat, A. & Perou, C. M. Deconstructing the molecular portraits of breast cancer. Mol. Oncol. 5, 5–23 (2011).
45. Masuda, H. et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin. Cancer Res. 19, 5533–5540 (2013).
46. Dawson, S. J., Rueda, O. M., Aparicio, S. & Caldas, C. A new genome-driven integrated classification of breast cancer and its implications. EMBO J. 32, 617–628 (2013).
47. Burstein, M. D. et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin. Cancer Res. 21, 1688–1698 (2015).
48. Weigelt, B. et al. Breast cancer molecular profiling with single sample predictors: a retrospective analysis. Lancet Oncol. 11, 339–349 (2010).
49. Reis-Filho, J. S. & Pusztai, L. Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet 378, 1812–1823 (2011).
50. Weigelt, B., Baehner, F. L. & Reis-Filho, J. S. The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: a retrospective of the last decade. J. Pathol. 220, 263–280 (2010).
51. Desmedt, C. et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin. Cancer Res. 14, 5158–5165 (2008).
52. 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).
53. Teschendorff, A. E. & Caldas, C. A robust classifier of high predictive value to identify good prognosis patients in ER-negative breast cancer. Breast Cancer Res. 10, R73 (2008).
54. Bianchini, G. et al. Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and-negative cancers. J. Clin. Oncol. 28, 4316–4323 (2010).
55. Denkert, C. et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J. Clin. Oncol. 28, 105–113 (2010).
56. Loi, S. et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J. Clin. Oncol. 31, 860–867 (2013).
57. Adams, S. et al. 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. 32, 2959–2966 (2014).
58. Salgado, R. et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann. Oncol. 26, 259–271 (2015).
59. Pruneri, G. et al. Clinical validity of tumor-infiltrating lymphocytes analysis in patients with triple-negative breast cancer. Ann. Oncol. 27, 249–256 (2016).
60. Denkert, C. et al. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group. Mod. Pathol. 29, 1155–1164 (2016).
61. Denkert, C. 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. 33, 983–991 (2015).
62. Dieci, M. V. et al. Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study. Ann. Oncol. 25, 611–618 (2014).
63. Montagna, E. et al. Heterogeneity of triple-negative breast cancer: histologic subtyping to inform the outcome. Clin. Breast Cancer 13, 31–39 (2013).
64. Farmer, P. et al. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24, 4660–4671 (2005).
65. Takeuchi, H., Tsuji, K., Ueo, H., Kano, T. & Maehara, Y. Clinicopathological feature and long-term prognosis of apocrine carcinoma of the breast in Japanese women. Breast Cancer Res. Treat. 88, 49–54 (2004).
66. Choi, J. E., Kang, S. H., Lee, S. J. & Bae, Y. K. Androgen receptor expression predicts decreased survival in early stage triple-negative breast cancer. Ann. Surg. Oncol. 22, 82–89 (2015).
67. Vera-Badillo, F. E. et al. Androgen receptor expression and outcomes in early breast cancer: a systematic review and meta-analysis. J. Natl Cancer Inst. 106, djt319 (2014).
68. Lakhani, S. R., Ellis, I. O., Schnitt, S. J., Tan, P. H. & van de Vijver, M. J. WHO Classification of Tumours of the Breast (IARC, 2012).
69. Huober, J. et al. Prognosis of medullary breast cancer: analysis of 13 International Breast Cancer Study Group (IBCSG) trials. Ann. Oncol. 23, 2843–2851 (2012).
70. Weigelt, B., Eberle, C., Cowell, C. F., Ng, C. K. & Reis-Filho, J. S. Metaplastic breast carcinoma: more than a special type. Nat. Rev. Cancer 14, 147–148 (2014).
71. Jung, S. Y. et al. Worse prognosis of metaplastic breast cancer patients than other patients with triple-negative breast cancer. Breast Cancer Res. Treat. 120, 627–637 (2010).
72. Geyer, F. C. et al. Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas. J. Pathol. 220, 562–573 (2010).
73. Weigelt, B., Ng, C. K., Shen, R., Popova, T., Schizas, M., Natrajan, R. et al. Metaplastic breast carcinomas display genomic and transcriptomic heterogeneity [corrected]. Mod Pathol. 28, 340–351 (2015).
74. Weigelt, B., Kreike, B., Reis-Filho, J. S. Metaplastic breast carcinomas are basal-like breast cancers: a genomic profiling analysis. Breast Cancer Res Treat. 117, 273–280 (2009).
75. Hennessy, B. T. et al. Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res. 69, 4116–4124 (2009).
76. Hayes, M. J., Thomas, D., Emmons, A., Giordano, T. J. & Kleer, C. G. Genetic changes of Wnt pathway genes are common events in metaplastic carcinomas of the breast. Clin. Cancer Res. 14, 4038–4044 (2008).
77. Persson, M. et al. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc. Natl Acad. Sci. USA 106, 18740–18744 (2009).
78. Tognon, C. et al. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell 2, 367–376 (2002).
79. Weinreb, I. et al. Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands. Nat. Genet. 46, 1166–1169 (2014).
80. O'Neill, I. D. t(11;19) translocation and CRTC1-MAML2 fusion oncogene in mucoepidermoid carcinoma. Oral Oncol. 45, 2–9 (2009).
81. Grunewald, I. et al. Targeted next generation sequencing of parotid gland cancer uncovers genetic heterogeneity. Oncotarget 6, 18224–18237 (2015).
82. Marchio, C., Weigelt, B. & Reis-Filho, J. S. Adenoid cystic carcinomas of the breast and salivary glands (or 'The strange case of Dr Jekyll and Mr Hyde' of exocrine gland carcinomas). J. Clin. Pathol. 63, 220–228 (2010).
83. Weigelt, B. et al. Refinement of breast cancer classification by molecular characterization of histological special types. J. Pathol. 216, 141–150 (2008).
84. Martelotto, L. G. et al. Genomic landscape of adenoid cystic carcinoma of the breast. J. Pathol. 237, 179–189 (2015).
85. Gonda, T. J. & Ramsay, R. G. Adenoid cystic carcinoma can be driven by MYB or MYBL1 rearrangements: new insights into MYB and tumor biology. Cancer Discov. 6, 125–127 (2016).
86. Ho, A. S. et al. The mutational landscape of adenoid cystic carcinoma. Nat. Genet. 45, 791–798 (2013).
87. Wetterskog, D. et al. Mutation profiling of adenoid cystic carcinomas from multiple anatomical sites identifies mutations in the RAS pathway, but no KIT mutations. Histopathology 62, 543–550 (2013).
88. Seethala, R. R., Cieply, K., Barnes, E. L. & Dacic, S. Progressive genetic alterations of adenoid cystic carcinoma with high-grade transformation. Arch. Pathol. Lab. Med. 135, 123–130 (2011).
89. Seethala, R. R., Hunt, J. L., Baloch, Z. W., Livolsi, V. A. & Leon Barnes, E. Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature. Am. J. Surg. Pathol. 31, 1683–1694 (2007).
90. D'Alfonso, T. M. et al. MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features. Hum. Pathol. 45, 2270–2280 (2014).
91. Liu, H. et al. High frequency of loss of PTEN expression in human solid salivary adenoid cystic carcinoma and its implication for targeted therapy. Oncotarget 6, 11477–11491 (2015).
92. Vranic, S., Frkovic-Grazio, S., Bilalovic, N. & Gatalica, Z. Angiogenesis in triple-negative adenoid cystic carcinomas of the breast. Virchows Arch. 459, 377–382 (2011).
93. Horowitz, D. P., Sharma, C. S., Connolly, E., Gidea-Addeo, D. & Deutsch, I. Secretory carcinoma of the breast: results from the survival, epidemiology and end results database. Breast 21, 350–353 (2012).
94. Letessier, A. et al. ETV6 gene rearrangements in invasive breast carcinoma. Genes Chromosomes Cancer 44, 103–108 (2005).
95. Taipale, M. et al. Chaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells. Nat. Biotechnol. 31, 630–637 (2013).
96. Skalova, A. et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am. J. Surg. Pathol. 34, 599–608 (2010).
97. Reis-Filho, J. S. et al. Is acinic cell carcinoma a variant of secretory carcinoma? A FISH study using ETV6 'split apart' probes. Histopathology 52, 840–846 (2008).
98. Skalova, A. et al. Mammary analogue secretory carcinoma of salivary glands. Molecular analysis of 25 ETV6 gene rearranged tumors with lack of detection of classical ETV6-NTRK3 fusion transcript by standard RT-PCR: report of 4 cases harboring ETV6-X gene fusion. Am. J. Surg. Pathol. 40, 3–13 (2016).
99. Diallo, R. et al. Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry. Hum. Pathol. 34, 1299–1305 (2003).
100. Lambros, M. B. et al. Genomic profile of a secretory breast cancer with an ETV6-NTRK3 duplication. J. Clin. Pathol. 62, 604–612 (2009).
101. Lopez-Garcia, M. A., Geyer, F. C., Lacroix-Triki, M., Marchio, C. & Reis-Filho, J. S. Breast cancer precursors revisited: molecular features and progression pathways. Histopathology 57, 171–192 (2010).
102. Khalifeh, I. M. et al. Clinical, histopathologic, and immunohistochemical features of microglandular adenosis and transition into in situ and invasive carcinoma. Am. J. Surg. Pathol. 32, 544–552 (2008).
103. Tavassoli, F. A. & Norris, H. J. Microglandular adenosis of the breast. A clinicopathologic study of 11 cases with ultrastructural observations. Am. J. Surg. Pathol. 7, 731–737 (1983).
104. Geyer, F. C. et al. Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma. Histopathology 55, 732–743 (2009).
105. Geyer, F. C. et al. Molecular evidence in support of the neoplastic and precursor nature of microglandular adenosis. Histopathology 60, E115–E130 (2012).
106. Geyer, F. C. et al. Genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family. Mod Pathol. (2016); doi: 10.1038/modpathol. 2016.161.
107. Pia-Foschini, M., Reis-Filho, J. S., Eusebi, V. & Lakhani, S. R. Salivary gland-like tumours of the breast: surgical and molecular pathology. J. Clin. Pathol. 56, 497–506 (2003).
108. Limite, G. et al. Acinic cell carcinoma of the breast: review of the literature. Int. J. Surg. 12 Suppl 1, S35–S39 (2014).
109. Piscuoglio, S. et al. Are acinic cell carcinomas of the breast and salivary glands distinct diseases?. Histopathology 67, 529–537 (2015).
110. Carey, L., Winer, E., Viale, G., Cameron, D. & Gianni, L. Triple-negative breast cancer: disease entity or title of convenience? Nat. Rev. Clin. Oncol. 7, 683–692 (2010).
111. Ripamonti, C. B. et al. First description of an acinic cell carcinoma of the breast in a BRCA1 mutation carrier: a case report. BMC Cancer 13, 46 (2013).
112. Liu, X. et al. Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1-mutated basal-like breast cancer. Proc. Natl Acad. Sci. USA 104, 12111–12116 (2007).
113. Futreal, P. A. et al. A census of human cancer genes. Nat. Rev. Cancer 4, 177–183 (2004).
114. Lawrence, M. S. et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505, 495–501 (2014).