Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Maroun Bou Zerdan
 + 2188 word(s) 2188 2022-03-08 10:15:09 |
2 update layout and reference
Rita Xu
Meta information modification 2188 2022-03-09 04:34:00 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Bou Zerdan, M. Triple-Negative Breast Cancer Molecular Subtyping. Encyclopedia. Available online: https://encyclopedia.pub/entry/20340 (accessed on 06 July 2024).
Bou Zerdan M. Triple-Negative Breast Cancer Molecular Subtyping. Encyclopedia. Available at: https://encyclopedia.pub/entry/20340. Accessed July 06, 2024.
Bou Zerdan, Maroun. "Triple-Negative Breast Cancer Molecular Subtyping" Encyclopedia, https://encyclopedia.pub/entry/20340 (accessed July 06, 2024).
Bou Zerdan, M. (2022, March 08). Triple-Negative Breast Cancer Molecular Subtyping. In Encyclopedia. https://encyclopedia.pub/entry/20340
Bou Zerdan, Maroun. "Triple-Negative Breast Cancer Molecular Subtyping." Encyclopedia. Web. 08 March, 2022.
Triple-Negative Breast Cancer Molecular Subtyping
Edit
This entry is adapted from the peer-reviewed paper 10.3390/cancers14051253

Breast cancer (BC) is the most common malignancy affecting women. It is a highly heterogeneous disease broadly defined by the differential expression of cell surface receptors. In the United States, triple negative breast cancer (TNBC) represents 15 to 20% of all BC. When compared with other subtypes of BC, TNBC tends to present in younger women, and has a higher mortality rate of 40% in advanced stages within the first 5 years after diagnosis. TNBC has historically had limited treatment options when compared to other types of BC.

triple negative breast neoplasms Poly (ADP-ribose) polymerase inhibitors immune checkpoint inhibitors

1. Introduction

Breast cancer (BC) is the most common malignancy affecting women. It is a highly heterogeneous disease, encompassing several BC molecular subtypes, broadly defined by the differential expression of cell surface receptors. Triple negative breast cancer (TNBC) refers to breast neoplasms that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) on their cell surface. In the United States, TNBC represents 15 to 20% of all BC [1]. BC common intrinsic molecular subtypes include Luminal A, Luminal B, and Her2 overexpressing, and basal cell tumors, further stratified into special subtypes [2]. Gene expression profiling analysis classifies TNBC as a subtype of basal-like BC, with a 56% overlap in gene expression profiles [3]. When compared with other subtypes of BC, TNBC tends to present in younger women, and has a higher mortality rate of 40% in advanced stages within the first 5 years after diagnosis [4][5]. Around 45% of patients diagnosed with advanced stage TNBC will develop distant metastasis to the brain and/or visceral organs, with a median survival time of 13.3 months [6]. Some reports also suggested a higher recurrence rate in TNBC, reaching as high as 25%. Specifically, residual micro-metastatic disease following neoadjuvant chemotherapy in TNBC is associated with an increased risk of tumor recurrence, with limited options for conventional postoperative adjuvant chemotherapy. As a result, there has been a significant and constant increase in the number of clinical trials targeting TNBC [7].

2. Triple-Negative Breast Cancer Molecular Subtyping

In 2011, Lehmann et al. categorized TNBC into six subtypes [8]: basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M), mesenchymal stem-like (MSL), immunomodulatory (IM), and luminal androgen receptor (LAR), by performing gene expression profiling of tumor samples from 587 TNBC patients [9]. In 2015 Burstein et al. studied samples from 198 patients and suggested dividing TNBC into two major groups based on quantitative DNA expression, further categorized into four subtypes based on identified potential targets [10] including the LAR group, which expresses androgen receptors (AR) and cell-surface mucin receptors (MUC1)—this subtype alone forms group 1; the mesenchymal subtype (MES) which expresses growth factor receptors such as platelet-derived growth factor receptor-α [PDGFRα] and c-Kit receptor; the basal-like immunosuppressed (BLIS) subtype, which expresses the immunosuppressive molecule V-Set Domain Containing T-cell activation inhibitor 1 (VTCN1); and the basal-like immune-activated (BLIA) subtype, which exhibits activation of the signal transducer and activator of transcription (STAT). The three subtypes MES, BLIS, and BLIA formed group 2, as they had similar gene expression profiles.
In view of the emerging important role of long noncoding RNAs (lncRNAs) in cellular processes, a new classification incorporating both messenger RNA (mRNA) and lncRNA transcriptome profiles was suggested to help provide a better understanding of the heterogeneity of TNBC (Figure 1). In 2016, Liu et al. performed a categorization analysis of 165 TNBC samples that combined mRNA expression analysis and co-expression network analysis, aiming to identify interactions between mRNAs and lncRNAs [11]. They also investigated IM subtype genes, previously linked to the stimulation of T-cells and to innate and regular immune responses (Table 1) [6]. A strong association was identified between immune cell processes and TNBC tumorigenesis. IM subtype genes were identified to engage in regulating immune cells through their modulation of cytokine signaling, antigen processing, and immune cell signaling pathways involving T-cells, B-cells, chemokines and the nuclear factor-κB (NF-κB) [11]. Receptor-interacting protein 2 (RIP2) has been linked to chemoresistance of TNBC against paclitaxel. Jaafar et al. demonstrated that high expression of RIP2 correlated with a worse prognosis and a higher risk of recurrence since RIP2 lead to NF-κB activation, which contributed to higher expression of pro-survival proteins and cell survival [12]. Other genes, known to impact immune response—such as C-C motif chemokine teceptor-2 (CCR2), chemokine ligand 5 (CCL5), cluster of differentiation 1 (CD1C), C-X-C motif chemokine ligand 10 (CXCL10), C-X-C motif chemokine ligand 11 (CXCL11), and C-X-C motif chemokine ligand 13 (CXCL13)—were also expressed in the TNBC IM subtype, further confirming the role of immunity in TNBC IM tumorigenesis.
Cancers 14 01253 g001
Figure 1. TNBC classification over the years.
Table 1. TNBC subtypes based on the FUSCC (Fudan University Shanghai Cancer Center) classification criteria [6].
FUSCC Classification Pathways
IM (immunomodulatory) ↑
  • Cytokine–cytokine receptor interaction
  • T cell receptor signaling pathway
  • B cell receptor signaling pathway
  • Chemokine signaling pathway
  • NF-kappa-B signaling pathway
LAR (luminal androgen receptor) ↑
  • Steroid hormone biosynthesis
  • Porphyrin and chlorophyll metabolism
  • PPAR signaling pathway
  • Androgen and estrogen metabolism
MES (mesenchymal-like) ↑
  • ECM-receptor interaction
  • Focal adhesion
  • TGF-beta signaling pathway
  • ABC transporter
  • Adipocytokine signaling pathway
BLIS (basal-like and immune suppressed) ↑
  • Mitotic cell cycle
  • Mitotic prometaphase
  • M phase of mitotic cell cycle
  • DNA replication
  • DNA repair
↓
  • Immune response
  • Innate immune response
  • T cell receptor signaling
Conversely, tumorigenesis in the LAR subtype is closely related to hormonal regulation and activity, particularly the metabolism of androgen, chlorophyll, estrogen, and porphyrin, as well as the biosynthesis of hormones. LAR cells also show an increased expression of the peroxisome proliferator-activated receptor-γ (PPAR-γ). PPAR-γ is implicated in tumor cell proliferation, growth invasion, and phenotypic changes in differentiation status, but also correlates with quantitative androgen receptor expression, a defining feature of LAR [13]. Interestingly, despite lack of ER expression on its cell surface, LAR is clinically responsive to both anti-estrogen and anti-androgen therapy. This can be explained by the positive molecular activity of the estrogen receptor signaling pathway implicated in LAR tumorigenesis, despite LAR cells being ER-negative [10].
On the other hand, the MES subtype harbors a unique gene ontology, characterized by the interaction between extracellular matrix receptors, gap junction transmembrane channels, the transforming Growth Factor-β (TGF-β) signaling pathway, and growth factor-associated pathways, notably the adipokine pathway and ATP-binding cassette (ABC) transporters pathway [14].
Furthermore, the BLIS subtype is distinguished by a pathogenesis that strongly implicates cell cycle and resultant cell division processes in addition to DNA repair, replication, and regulation mechanisms. BLIS cells show increased quantitative expression of genes involved in cell proliferation such as the mitotic checkpoint serine/threonine-protein kinase budding uninhibited by benzimidazoles 1 (BUB1), and the protein coding genes centromere protein F (CENPF) and protein regulator of cytokinesis 1 (PRC1). This translates into a highly proliferative clinical nature of BLIS tumors [11], further allowed by the downregulation of immunologic processes specifically involving T-cell signaling, B-cell activation and dendritic cells chemotaxis. These molecular processes translate into shorter relapse-free survival (RFS) and increased recurrence rate on the clinical level, supporting previous findings by Burstein et al. [11].
Although progress in next generation sequencing has facilitated unraveling potentially actionable targets, not many findings have not been translated into daily clinical practice due to limited benefit from targeted therapy observed in clinical trials for unselected TNBC patients. The molecular subtyping enables the identification of molecularly homogenous groups with enrichment of certain genomic alterations. This paves the way for effective methods for drug development using subtype-specific clinical investigations. A precision medicine paradigm in the context of transcriptomic subtyping should be developed and fine-tuned for patients with TNBC.

3. Chemotherapy for Triple Negative Breast Cancer

TNBC has historically had limited treatment options when compared to other types of BC. The mainstay of treatment for TNBC remains cytotoxic chemotherapy, despite the emergence of new biologic and targeted agents. The therapeutic benefits of cytotoxic chemotherapy in TNBC are well established, with comprehensive data on the efficacy of chemotherapy in the neoadjuvant, adjuvant, and metastatic settings. Compared with hormone receptor-positive (HR+) BC, the use of chemotherapy regimens in the neoadjuvant treatment of TNBC has a significantly higher pathological response rate and can considerably ameliorate the prognosis of TNBC patients [15]. Nevertheless, TNBC carries an overall inferior prognosis despite its chemo-sensitivity [16]. The use of neoadjuvant systemic treatment (NST) in the early stages is becoming the standard of care in TNBCs and is associated with higher pathological complete response (pCR) rates (30–40%) as compared to other BC subtypes [17]. Patients who achieve pCR with primary therapy have improved survival outcomes [18]. As such, pCR is predictive of improved long-term outcomes for TNBC and is a reliable endpoint in clinical trials evaluating the efficacy of neoadjuvant chemotherapy.
Adriamycin, cyclophosphamide, and paclitaxel combinations are considered to be standard neoadjuvant chemotherapy regimen against TNBC and result in pCR rates of 35–45% [19]. The addition of platinum-based chemotherapy has been proposed. Despite improved short term pCR rates, long term outcomes remain unknown [20]. The systemic chemotherapy regimens options for TNBC recommended by National Comprehensive Cancer Network (NCCN) guidelines include the following: Docetaxel and Cyclophosphamide (TC), Taxel/Docetaxel, Adriamycin, and Cyclophosphamide (TAC), Adriamycin and Cyclophosphamide (AC), Cyclophosphamide, Methotrexate, and Fluorouracil (CMF), Cyclophosphamide, Adriamycin, and Fluorouracil (CAF), and Cyclophosphamide, Epirubicin, Fluorouracil and Paclitaxel/Docetaxel (CEF-T). These DNA damaging agents show increased activity in cancers with a germline BRCA mutation, as BRCA 1/2 proteins play an essential role in repairing DNA damage [21].
TNBC is also highly sensitive to platinum salts because a high proportion of these tumors exhibit BRCA-like status [20][22][23]. Two large, randomized trials—CALGB 40603/Alliance trial and GeparSixto—compared conventional chemotherapy regimens with or without added Carboplatin and showed higher pCR rates with inclusion of the platinum-based agent. The CALGB 40603/Alliance trial assessed the value of adding Bevacizumab +/− Carboplatin to neoadjuvant chemotherapy in stage II and III TNBC in 443 patients [24]. The proportion of patients who attained pCR increased remarkably from 41% to 54% with the use of Carboplatin (OR = 1.71; p = 0.0029). The long-term OS was not powered in the trial, and the addition of Carboplatin to conventional chemotherapy did not increase long-term OS [25]. The GeparSixto trial involved 595 patients diagnosed with stages II or III TNBC, who were randomized to receive either Carboplatin or no Carboplatin with a backbone regimen of Paclitaxel, liposomal Doxorubicin, and Bevacizumab [26]. The pCR rates were considerably higher in the carboplatin group: 53.2% vs. 36.9 (p = 0.005) (Table 2). The result of a meta-analysis looking at 9 randomized controlled trials (RCTs) (n = 2109) revealed that adding platinum to neoadjuvant chemotherapy considerably improved pCR rate from 37.0% to 52.1% (OR 1.96, 95% confidential interval (CI) 1.46–2.62, p < 0.001) [27]. Loibl et al. presented their updates from the BrighTNess trial, a randomized phase III clinical trial, with three treatment arms and a total of 634 patients with TNBC: the established neoadjuvant regimen consisting of Paclitaxel alone (P) (n = 158), Paclitaxel and Carboplatin alone (PCb) (n = 160), and Paclitaxel, Carboplatin and the PPAR inhibitor Veliparib (PCbV) (n = 316). Event-free survival, OS, and safety outcomes were assessed with a ≥4 years of follow-up period [28]. pCR was significantly improved when Carboplatin was added, with or without the addition of Veliparib, to Paclitaxel-based neoadjuvant chemotherapy. Also, adding Carboplatin to Paclitaxel improved pCR and EFS without increasing myelodysplastic syndrome or acute myeloid leukemia [28]. When compared to P alone, HR for EFS with PCbV was 0.63 (95% CI: 0.43–0.92, p = 0.016), and HR for EFS with PCb was 0.57 (95% CI 0.36–0.91, p = 0.018) [28]. Based on the latest American Society of Oncology (ASCO) recommendations, carboplatin may be offered to patients with TNBC to increase pathologic complete response [29].
Table 2. Frequencies of pCR from clinical trials involving carboplatin.
Trials
(References)		 Regimen 1 (R1) Nb. of Patients Regimen 2 (R2) Nb of Patients pCR Rate (R1 vs. R2) p-Value
GeparOcto GBG84 [30] P + NPLD + Cb;
q1w for 18 weeks		 203 E then P then C;
q2w/3 cycles over 18 weeks		 200 51.7% vs. 48.5% 0.518
GALGB40603 Alliance [24] (P q1w for 12 weeks then ddAC q2w/4 cycles) + (Cb q3w/4 cycles ± Bev. q2w/9cycles) 221 P q1w for 12 weeks then ddAC q2w/4 cycle 212 54% vs. 41% 0.0029
GeparSixto GBG66 [26] (P q1w for 18 weeks + NPLD q1w for 18 weeks + Bev. q3w/6 cycles) + Cb q1w for 18 weeks 158 P q1w for 18 weeks + NPLD q1w for 18 weeks + Bev. q3w/6 cycles 157 53.2% vs. 36.9% 0.005
Zhang et al. [31] P + Cb q3w/4–6 cycles 47 P + E q3w/4–6 cycles 44 38.6% vs. 14.0% 0.014
Ando et al. [32] (P q2w/2 cycles then CEF q2w/4 cycles) + Cb q3w/4 cycles 37 P q2w/2 cycles then CEF q2w/4 cycles 38 61.2% vs. 6.3% 0.003

P = Paclitaxel; NPLD = Nonpegylated Liposomal Doxorubicin; Cb = Carboplatin; E = Epirubicin; C = Cyclophosphamide; ddAC = Doxorubicin plus Cyclophosphamide; Bev. = Bevacizumab; CEF = Cyclophosphamide plus Epirubicin plus 5-fluorouracil.

4. Detecting PDL-1 Expression in TNBC

As the importance of immunotherapies targeting PD-1/ PD-L1 is evolving, concerns are arising regarding diagnostic tests that detect the level of these molecules and thus predict outcomes in cancer patients. Routinely, immunohistochemistry is used to measure PD-L1 expression. Currently, many of the commercially available tests are designed by antibody clones that detect the presence of the PD-L1 protein. Moreover, multiple expression scores and cutoffs exist [33]. Of the relevant PD-L1 scores are the tumor cell score, tumor proportion score, the immune cell score, and the combined positive score [34][35].
There are four PD-L1 immunohistochemical (IHC) assays registered with the FDA, using four different PD-L1 antibodies (22C3, 28–8, SP263, SP142), on two different IHC platforms (Dako and Ventana), each with their own scoring systems [36]. Attempts at harmonization of PD-L1 IHC antibodies and staining platforms are underway [37]. While PD-L1 IHC can be used to predict likelihood of response to anti-PD-1 or anti-PD-L1 therapy, a proportion of patients that are negative can have response and identification of alternative biomarkers is critical to further refine selection of patients most likely to respond to these therapies [36][38][39][40].

References

  1. Bilani, N.; Zabor, E.C.; Elson, L.; Elimimian, E.B.; Nahleh, Z. Breast cancer in the United States: A cross-sectional overview. J. Cancer Epidemiol. 2020, 2020, 6387378.
  2. Goldhirsch, A.; Winer, E.P.; Coates, A.; Gelber, R.; Piccart-Gebhart, M.; Thürlimann, B.; Senn, H.-J.; Albain, K.S.; André, F.; Bergh, J. Personalizing the treatment of women with early breast cancer: Highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann. Oncol. 2013, 24, 2206–2223.
  3. Perou, C.M.; Sørlie, T.; Eisen, M.B.; Van De Rijn, M.; Jeffrey, S.S.; Rees, C.A.; Pollack, J.R.; Ross, D.T.; Johnsen, H.; Akslen, L.A. Molecular portraits of human breast tumours. Nature 2000, 406, 747–752.
  4. Morris, G.J.; Naidu, S.; Topham, A.K.; Guiles, F.; Xu, Y.; McCue, P.; Schwartz, G.F.; Park, P.K.; Rosenberg, A.L.; Brill, K. Differences in breast carcinoma characteristics in newly diagnosed African–American and Caucasian patients: A single-institution compilation compared with the National Cancer Institute’s Surveillance, Epidemiology, and end results database. Cancer Interdiscip. Int. J. Am. Cancer Soc. 2007, 110, 876–884.
  5. Dent, R.; Trudeau, M.; Pritchard, K.I.; Hanna, W.M.; Kahn, H.K.; Sawka, C.A.; Lickley, L.A.; Rawlinson, E.; Sun, P.; Narod, S.A. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin. Cancer Res. 2007, 13, 4429–4434.
  6. Lin, N.U.; Claus, E.; Sohl, J.; Razzak, A.R.; Arnaout, A.; Winer, E.P. Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: High incidence of central nervous system metastases. Cancer 2008, 113, 2638–2645.
  7. Chaudhary, L.N.; Wilkinson, K.H.; Kong, A. Triple-negative breast cancer: Who should receive neoadjuvant chemotherapy? Surg. Oncol. Clin. 2018, 27, 141–153.
  8. Lehmann, B.D.; Bauer, J.A.; Chen, X.; Sanders, M.E.; Chakravarthy, A.B.; Shyr, Y.; Pietenpol, J.A. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J. Clin. Investig. 2011, 121, 2750–2767.
  9. Lehmann, B.D.; Pietenpol, J.A. Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes. J. Pathol. 2014, 232, 142–150.
  10. Burstein, M.D.; Tsimelzon, A.; Poage, G.M.; Covington, K.R.; Contreras, A.; Fuqua, S.A.; Savage, M.I.; Osborne, C.K.; Hilsenbeck, S.G.; Chang, J.C. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin. Cancer Res. 2015, 21, 1688–1698.
  11. Liu, Y.-R.; Jiang, Y.-Z.; Xu, X.-E.; Yu, K.-D.; Jin, X.; Hu, X.; Zuo, W.-J.; Hao, S.; Wu, J.; Liu, G.-Y. Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer. Breast Cancer Res. 2016, 18, 33.
  12. Jaafar, R.; Mnich, K.; Dolan, S.; Hillis, J.; Almanza, A.; Logue, S.E.; Samali, A.; Gorman, A.M. RIP2 enhances cell survival by activation of NF-ĸB in triple negative breast cancer cells. Biochem. Biophys. Res. Commun. 2018, 497, 115–121.
  13. Abduljabbar, R.; Al-Kaabi, M.M.; Negm, O.H.; Jerjees, D.; Muftah, A.A.; Mukherjee, A.; Lai, C.F.; Buluwela, L.; Ali, S.; Tighe, P.J. Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer. Breast Cancer Res. Treat. 2015, 150, 511–522.
  14. Yin, L.; Duan, J.-J.; Bian, X.-W.; Yu, S.-c. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020, 22, 61.
  15. Wahba, H.A.; El-Hadaad, H.A. Current approaches in treatment of triple-negative breast cancer. Cancer Biol. Med. 2015, 12, 106.
  16. Ismail-Khan, R.; Bui, M.M. A review of triple-negative breast cancer. Cancer Control. 2010, 17, 173–176.
  17. Dieci, M.V.; Del Mastro, L.; Cinquini, M.; Montemurro, F.; Biganzoli, L.; Cortesi, L.; Zambelli, A.; Criscitiello, C.; Levaggi, A.; Conte, B. Inclusion of platinum agents in neoadjuvant chemotherapy regimens for triple-negative breast cancer patients: Development of grade (Grades of Recommendation, Assessment, Development and Evaluation) recommendation by the Italian Association of Medical Oncology (AIOM). Cancers 2019, 11, 1137.
  18. Birgisdottir, V.; Stefansson, O.A.; Bodvarsdottir, S.K.; Hilmarsdottir, H.; Jonasson, J.G.; Eyfjord, J.E. Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006, 8, R38.
  19. Biswas, T.; Efird, J.T.; Prasad, S.; Jindal, C.; Walker, P.R. The survival benefit of neoadjuvant chemotherapy and pCR among patients with advanced stage triple negative breast cancer. Oncotarget 2017, 8, 112712.
  20. Isakoff, S.J.; Mayer, E.L.; He, L.; Traina, T.A.; Carey, L.A.; Krag, K.J.; Rugo, H.S.; Liu, M.C.; Stearns, V.; Come, S.E. TBCRC009: A multicenter phase II clinical trial of platinum monotherapy with biomarker assessment in metastatic triple-negative breast cancer. J. Clin. Oncol. 2015, 33, 1902.
  21. Byrski, T.; Gronwald, J.; Huzarski, T.; Grzybowska, E.; Budryk, M.; Stawicka, M.; Mierzwa, T.; Szwiec, M.; Wiśniowski, R.; Siolek, M. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J. Clin. Oncol. 2010, 28, 375–379.
  22. Silver, D.P.; Richardson, A.L.; Eklund, A.C.; Wang, Z.C.; Szallasi, Z.; Li, Q.; Juul, N.; Leong, C.-O.; Calogrias, D.; Buraimoh, A. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J. Clin. Oncol. 2010, 28, 1145.
  23. Byrski, T.; Dent, R.; Blecharz, P.; Foszczynska-Kloda, M.; Gronwald, J.; Huzarski, T.; Cybulski, C.; Marczyk, E.; Chrzan, R.; Eisen, A. Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer. Breast Cancer Res. 2012, 14, R110.
  24. Sikov, W.M.; Berry, D.A.; Perou, C.M.; Singh, B.; Cirrincione, C.T.; Tolaney, S.M.; Kuzma, C.S.; Pluard, T.J.; Somlo, G.; Port, E.R. 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. 2015, 33, 13.
  25. Sikov, W.M.; Polley, M.-Y.; Twohy, E.; Perou, C.M.; Singh, B.; Berry, D.A.; Tolaney, S.M.; Somlo, G.; Port, E.R.; Ma, C.X. CALGB (Alliance) 40603: Long-term outcomes (LTOs) after neoadjuvant chemotherapy (NACT)+/-carboplatin (Cb) and bevacizumab (Bev) in triple-negative breast cancer (TNBC). Am. Soc. Clin.Oncol. 2019, 37, 591.
  26. Von Minckwitz, G.; Schneeweiss, A.; Loibl, S.; Salat, C.; Denkert, C.; Rezai, M.; Blohmer, J.U.; Jackisch, C.; Paepke, S.; Gerber, B. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): A randomised phase 2 trial. Lancet Oncol. 2014, 15, 747–756.
  27. Poggio, F.; Bruzzone, M.; Ceppi, M.; Pondé, N.; La Valle, G.; Del Mastro, L.; De Azambuja, E.; Lambertini, M. Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: A systematic review and meta-analysis. Ann. Oncol. 2018, 29, 1497–1508.
  28. Loibl, S.; Sikov, W.; Huober, J.; Rugo, H.S.; Wolmark, N.; O’Shaughnessy, J.; Maag, D.; Untch, M.; Golshan, M.; Lorenzo, J.P.; et al. Event-Free Survival (EFS), Overall Survival (OS), and Safety of Adding Veliparib (V) Plus Carboplatin (Cb) or Carboplatin Alone to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer (TNBC) after ≥4 Years of Follow-Up: BrighTNess, a Randomized Phase III Trial. Available online: https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/event-free-survival-efs-overall-survival-os-and-safety-of-adding-veliparib-v-plus-carboplatin-cb-or-carboplatin-alone-to-neoadjuvant-chem (accessed on 12 October 2021).
  29. Chen, H.; Marsiglia, W.M.; Cho, M.-K.; Huang, Z.; Deng, J.; Blais, S.P.; Gai, W.; Bhattacharya, S.; Neubert, T.A.; Traaseth, N.J. Elucidation of a four-site allosteric network in fibroblast growth factor receptor tyrosine kinases. eLife 2017, 6, e21137.
  30. Schneeweiss, A.; Moebus, V.; Tesch, H.; Hanusch, C.; Denkert, C.; Luebbe, K.; Huober, J.; Klare, P.; Kuemmel, S.; Untch, M. Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto—GBG 84): A randomised phase III trial. Eur. J. Cancer 2019, 106, 181–192.
  31. Zhang, P.; Yin, Y.; Mo, H.; Zhang, B.; Wang, X.; Li, Q.; Yuan, P.; Wang, J.; Zheng, S.; Cai, R. Better pathologic complete response and relapse-free survival after carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for locally advanced triple-negative breast cancer: A randomized phase 2 trial. Oncotarget 2016, 7, 60647.
  32. Ando, M.; Yamauchi, H.; Aogi, K.; Shimizu, S.; Iwata, H.; Masuda, N.; Yamamoto, N.; Inoue, K.; Ohono, S.; Kuroi, K. Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer without HER2 overexpression. Breast Cancer Res. Treat. 2014, 145, 401–409.
  33. Erber, R.; Hartmann, A. Understanding PD-L1 testing in breast cancer: A practical approach. Breast Care 2020, 15, 481–490.
  34. Eckstein, M.; Cimadamore, A.; Hartmann, A.; Lopez-Beltran, A.; Cheng, L.; Scarpelli, M.; Montironi, R.; Gevaert, T. PD-L1 assessment in urothelial carcinoma: A practical approach. Ann. Transl. Med. 2019, 7, 690.
  35. Herbst, R.S.; Baas, P.; Kim, D.-W.; Felip, E.; Pérez-Gracia, J.L.; Han, J.-Y.; Molina, J.; Kim, J.-H.; Arvis, C.D.; Ahn, M.-J. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 2016, 387, 1540–1550.
  36. Ancevski Hunter, K.; Socinski, M.A.; Villaruz, L.C. PD-L1 Testing in Guiding Patient Selection for PD-1/PD-L1 Inhibitor Therapy in Lung Cancer. Mol Diagn 2018, 22, 1–10.
  37. U.S Food & Drug Administration. List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools). Available online: https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools (accessed on 12 October 2021).
  38. Garon, E.B.; Rizvi, N.A.; Hui, R.; Leighl, N.; Balmanoukian, A.S.; Eder, J.P.; Patnaik, A.; Aggarwal, C.; Gubens, M.; Horn, L. Pembrolizumab for the treatment of non–small-cell lung cancer. N. Engl. J. Med. 2015, 372, 2018–2028.
  39. Roach, C.; Zhang, N.; Corigliano, E.; Jansson, M.; Toland, G.; Ponto, G.; Dolled-Filhart, M.; Emancipator, K.; Stanforth, D.; Kulangara, K. Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non–small-cell lung cancer. Appl. Immunohistochem. Mol. Morphol. 2016, 24, 392.
  40. Scheel, A.H.; Dietel, M.; Heukamp, L.C.; Jöhrens, K.; Kirchner, T.; Reu, S.; Rüschoff, J.; Schildhaus, H.-U.; Schirmacher, P.; Tiemann, M. Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod. Pathol. 2016, 29, 1165–1172.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Oncology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Maroun Bou Zerdan
View Times: 563
Revisions: 2 times (View History)
Update Date: 09 Mar 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback