Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine
Abstract
:1. Background on Breast Cancer
Biomarkers and Precision Medicine
2. Personalization Based on Histopathological and Clinical Parameters
2.1. Personalization in Endocrine-Positive Breast Cancer
2.1.1. Endocrine Resistance
2.1.2. Overcoming the Resistance to Endocrine Therapy
- a.
- Elacestrant.
- b.
- Camizestrant.
- c.
- Imlumestrant.
- d.
- Lasofoxifene.
- e.
- Rintodestrant.
- f.
- SERDS and other novel agents in ESR1 mutant breast cancers.
Agent | Class | Clinical Trials | Patient Population | Endpoints | Salient Results | Status |
---|---|---|---|---|---|---|
Elacestrant [43,44] | Oral SERM/ SERD | EMERALD (NCT03778931) Randomized P-III | Patients with ESR1 mut. and ESTwt | PFS | ESR1 mut. = mPFS 3.8 vs. 1.9 months [HR = 0.55, 95% CI: 0.39–0.77] ESR1wt HR 0.86 (95% CI: 0.63–1.19) | Yes, only in patients with ESR1 mutation |
Elacestrant + Abemaciclib [46] | Oral SERM/ SERD + CDK 4/6i | NCT04791384 (P-Ib and II) | Breast cancer with brain metastasis | Safety and tolerability ORR CBR | Ongoing | |
Elacestrant + Samuraciclib [47] | Oral SERM/ SERD + CDK7 | NCT05963997 (P-Ib/2) | Locally advanced or metastatic patients HR-positive, HER2-unamplified | Safety and Tolerability, PFS, ORR, CBR, DOR | Ongoing | |
Elacestrant + everolimus, alpelisib, palbociclib and ribociclib [48] | Oral SERM/ SERD + CDK 4/6i or mTOR inhibitor or PIK3CAi | NCT05563220 (P-Ib/2) | Locally advanced or metastatic patients HR-positive, HER2-unamplified | Safety and tolerability, PFS, ORR, CBR, DOR, OS | Ongoing | |
Elacestrant [49] | Oral SERM/SERD | NCT05596409 (early P-II) | Locally advanced or metastatic patients HR-positive, HER2-unamplified (CDK 4/6i naïve) | PFS, OS, CBR, DOR | Ongoing | |
Camizestrant | SERD | SERENA-1 (NCT03616586) P-1 | Heavily pre-treated patients with ESR-1 mut. | ORR, CBR, PFS | ORR 10% CBR 35.3% across all dose levels. CBR 53.3% a dmPFS for 11.1 months at 75 mg dose | Ongoing |
Camizestrant + Palbociclib [51] | SERD + CDK 4/6i | SERENA-1 (NCT03616586) Dose expansion cohort | Heavily pre-treated patients with ESR-1 mut. | ORR CBR | ORR 6.3% CBR 50% | Ongoing |
Camizestrant vs. Fulvestrant [52] | SERD | SERENA-2 (NCT04214288) P-II | Heavily pre-treated patients | PFS, ORR, DOR, CBR | Ongoing | |
Camizestrant + Palbociclib vs. AI + Palbociclib [53] | SERD + CDK 4/6 i | SERENA-4 (NCT04711252) P-III | Denovo stage IV or locally advanced early-stage breast cancer | PFS, OS, CBR, secondary PFS | Ongoing | |
AI + CDK 4/6i vs. AI + CDK 4/6i + Camizestrant [54] | SERD + CDK 4/6 i | SERENA-6 (NCT04964934) | Metastatic or locally advanced Ca breast with ESR1 mut. emergence before radiographic progression | PFS1, PFS2, OS, ORR, CBR, QOL | Ongoing | |
Imlunestrant + alpelisib, abemaciclib, everolimus, trastuzumab +/− abemaciclib [56] | SERD + CDK 4/6i, anti-HER2 mAb, mTORi | EMBER-I P-I/II (NCT04647487) | Metastatic breast and endometrial cancer | Safety and tolerability, ESR-1 clearance, mPFS | 73% clearance or ctDNA with ESR-1 mutation, mPFS 6.5 vs. 4.3 months. | Ongoing |
Imlunestrant vs. Imlunestrant + abemaciclib [57] | SERD + CDK 4/6i, | EMBER-3 3 (NCT04975308), P-III | Previously treated endocrine-positive tumors | PFS, OS, ORR, CBR | Ongoing | |
Lasofoxifene vs. Fulvestrant [59] | SERM | ELAINE-I trial (NCT03781063), P-II | Previously treated endocrine-positive tumors with ESR-1 mut. | PFS; safety and tolerability | mPFS 5.6 vs. 3.7 months, p = 0.138, CBR 36.5% vs. 21.6%; p = 0.117, ORR 13.2% vs. 2.9%; p = 0.124 | Ongoing |
Lasofoxifene + Abemaciclib [58] | SERM + CDK 4/6i | ELAINE-II (NCT04432454), P-II | Previously treated endocrine-positive tumors with ESR-1 mut. | Safety and tolerability, PFS, CBR, ORR, DOR | Ongoing | |
Rintodestrant + Palbociclib [60,61] | SERD + CDK 4/6i | P-1/P-II | Previously treated endocrine-positive tumors with ESR-1 mut. (without prior CDK 4/6 exposure) | Safety and tolerability, ORR, CBR | ORR 5%, CBR 60% | Ongoing |
Borestrant (monotherapy) Or Borestrant + Palbociclib [62] | SERD/SERD + CDK4/6i | P-I and P-II (NCT04669587) | Metastatic or locally advanced Ca Breast | Recommended dose, response as monotherapy, response in combination, ORR, CBR | Ongoing | |
D-0502 (monotherapy) Or D-0502 + Palbociclib [63] | SERD/SERD + CDK4/6i | P-I (NCT03471663) | Metastatic or locally advanced breast cancer | MTD, DLT, ORR, PFS | Combination was better | Ongoing |
ZN-c5 Or ZN-c5 + Palbociclib [64,65] | SERD/SERD + CDK 4/6i | P-I/II (NCT03560531) | Pre- and postmenopausal women with advanced ER-positive breast cancer | MTD, RP2D; safety and tolerability. ORR, CBR | Monotherapy showed ORR of 5% and CBR of 38% | P-II is still ongoing |
H3B-6545 | SERCA | P-I/II | Pre- and postmenopausal women with advanced ER-positive breast cancer (patient received at least 3 previous lines of therapy), including CDK 4/6i | MTD, ORR, CBR, PFS | ORR = 16.6% CBR 39.7% mPFS = 3.8 months | |
H3B-6545 + Palbociclib [67,68] | SERCA + CDK 4/6i | P-I (NCT04288089) | Pre- and postmenopausal women with advanced ER-positive breast cancer (patient received at least 3 previous lines of therapy) | MTD, ORR, CBR, DOR | Ongoing | |
OP-1250 [70] | CERAN | P-I and P-II (NCT04505826) | Pre- and postmenopausal women with advanced ER-positive breast cancer with ESR-1 mut | DLT, MTD, ORR, CBR | P-I “ORR = 18%, CBR 38%” P-II ORR = 18%, CBR 38% |
3. Personalization in Human Epidermal Growth Factor Receptos-2 (HER2)-Amplified Breast Cancer
3.1. Level of HER2 and HER3 Expression
3.2. DNA and Gene-Based Biomarkers in HER2-Positive Tumors
3.3. Biomarkers for Predicting Pathological Response to HER2-Directed Therapy
4. Triple-Negative Breast Cancer
4.1. Molecular Basis of TNBC Heterogenicity
4.2. Programmed Death-Ligand 1 (PD-L1) Protein Expression as a Biomarker
4.3. Microsatellite Instability and Tumor Mutation Burden
4.4. Tumor Infiltrating Lymphocytes
4.5. Immune Gene Expression in TNBC
5. Circulating Tumor DNA as a Predictive and Prognostic Biomarker
5.1. Role of ctDNA in Locally Advanced Early-Stage Breast Cancer
5.2. Role of ctDNA in Metastatic Breast Cancer
Gene Mutation | Clinical Utility |
---|---|
ESR1 Hotspots: Y537C, Y537N, Y537C, S463P, D538G | Resistance to the endocrine therapy. Therapeutic agents: elacestrant, camizestrant, imlunestrant, lasofoxifene, rintodestrant [47,48,49,50,51,52,53,54,55,56,57,58,59,60,61], |
AKT Hotspots: E17K | Therapeutic agent: capivasertib, ipatasertib (AKT kinase) [227,231]. |
HER2 Hotspots: V777L, L755S | Increased sensitivity to HER2 targeted therapies. Therapeutic targets: neratinib, lapatinib (bind to kinase domains) [232,233,234] |
PTEN Hotspots: R130Q, R130G, R130*, R130P, R130Qfs*4 | Confers resistance to PI3Ki (loss of PTEN) and confers sensitivity to AKT inhibitors. Therapeutic targets: capivasertib, ipatasertib (AKT kinase) [227] |
PIK3CA Hotspots: H1047R, H1047L, N345K, E545K, E524K, E726K | Truncal mutation confers resistance to endocrine therapy. Therapeutic agents: alpelisib, taselisib, buparlisib, copanlisib, capivasertib [227,228,229] |
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Breast Cancer Statistics: How Common Is Breast Cancer? Breast Cancer Statistics|How Common Is Breast Cancer?|American Cancer Society. Available online: https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html#:~:text=The%20American%20Cancer%20Society%27s%20estimates,will%20die%20from%20breast%20cancer (accessed on 30 May 2024).
- Sørlie, T.; Perou, C.M.; Tibshirani, R.; Aas, T.; Geisler, S.; Johnsen, H.; Hastie, T.; Eisen, M.B.; van de Rijn, M.; Jeffrey, S.S.; et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl. Acad. Sci. USA 2001, 98, 10869–10874. [Google Scholar] [CrossRef] [PubMed]
- Loi, S. The ESMO clinical practise guidelines for early breast cancer: Diagnosis, treatment and follow-up: On the winding road to personalized medicine. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2019, 30, 1183–1184. [Google Scholar] [CrossRef] [PubMed]
- Turner, K.M.; Yeo, S.K.; Holm, T.M.; Shaughnessy, E.; Guan, J.L. Heterogeneity within molecular subtypes of breast cancer. Am. J. Physiol. Cell Physiol. 2021, 321, C343–C354. [Google Scholar] [CrossRef] [PubMed]
- Ahmad, A. Breast cancer statistics: Recent trends. In Breast Cancer Metastasis and Drug Resistance: Challenges and Progress; Springer: Cham, Switzerland, 2019; pp. 1–7. [Google Scholar]
- Bou Zerdan, M.; Ghorayeb, T.; Saliba, F.; Allam, S.; Bou Zerdan, M.; Yaghi, M.; Bilani, N.; Jaafar, R.; Nahleh, Z. Triple negative breast cancer: Updates on classification and treatment in 2021. Cancers 2022, 14, 1253. [Google Scholar] [CrossRef] [PubMed]
- Rodrigues-Ferreira, S.; Nahmias, C. Predictive biomarkers for personalized medicine in breast cancer. Cancer Lett. 2022, 545, 215828. [Google Scholar] [CrossRef] [PubMed]
- Collins, F.S.; Varmus, H. A new initiative on precision medicine. N. Engl. J. Med. 2015, 372, 793–795. [Google Scholar] [CrossRef] [PubMed]
- Low, S.K.; Zembutsu, H.; Nakamura, Y. Breast cancer: The translation of big genomic data to cancer precision medicine. Cancer Sci. 2018, 109, 497–506. [Google Scholar] [CrossRef] [PubMed]
- Califf, R.M. Biomarker definitions and their applications. Exp. Biol. Med. 2018, 243, 213–221. [Google Scholar] [CrossRef]
- Duffy, M.J.; Crown, J. Circulating tumor DNA as a biomarker for monitoring patients with solid cancers: Comparison with standard protein biomarkers. Clin. Chem. 2022, 68, 1381–1390. [Google Scholar] [CrossRef] [PubMed]
- Sarker, D.; Workman, P. Pharmacodynamic biomarkers for molecular cancer therapeutics. Adv. Cancer Res. 2006, 96, 213–268. [Google Scholar]
- FDA-NIH Biomarker Working Group. Safety Biomarker. BEST (Biomarkers, EndpointS, and other Tools). 2016. Available online: https://www.ncbi.nlm.nih.gov/books/NBK326791/ (accessed on 12 April 2024).
- Antman, E.M.; Loscalzo, J. Precision medicine in cardiology. Nat. Rev. Cardiol. 2016, 13, 591–602. [Google Scholar] [CrossRef] [PubMed]
- Xin, L.; Liu, Y.H.; Martin, T.A.; Jiang, W.G. The era of multigene panels comes? The clinical utility of oncotype DX and MammaPrint. World J. Oncol. 2017, 8, 34. [Google Scholar] [CrossRef]
- Beelen, K.; Zwart, W.; Linn, S.C. Can predictive biomarkers in breast cancer guide adjuvant endocrine therapy? Nat. Rev. Clin. Oncol. 2012, 9, 529–541. [Google Scholar] [CrossRef]
- Adashek, J.J.; Subbiah, V.; Kurzrock, R. From tissue-agnostic to N-of-one therapies:(R) evolution of the precision paradigm. Trends Cancer 2021, 7, 15–28. [Google Scholar] [CrossRef] [PubMed]
- Ma, Y.; Gamagedara, S. Biomarker analysis for oncology. Biomark. Med. 2015, 9, 845–850. [Google Scholar] [CrossRef]
- Yersal, O.; Barutca, S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J. Clin. Oncol. 2014, 5, 412. [Google Scholar] [CrossRef] [PubMed]
- Korde, L.A.; Somerfield, M.R.; Carey, L.A.; Crews, J.R.; Denduluri, N.; Hwang, E.S.; Khan, S.A.; Loibl, S.; Morris, E.A.; Perez, A.; et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J. Clin. Oncol. 2021, 39, 1485. [Google Scholar] [CrossRef] [PubMed]
- Krop, I.; Ismaila, N.; Andre, F.; Bast, R.C.; Barlow, W.; Collyar, D.E.; Hammond, M.E.; Kuderer, N.M.; Liu, M.C.; Mennel, R.G.; et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2017, 35, 2838. [Google Scholar] [CrossRef] [PubMed]
- Miranda, F.; Prazeres, H.; Mendes, F.; Martins, D.; Schmitt, F. Resistance to endocrine therapy in HR+ and/or HER2+ breast cancer: The most promising predictive biomarkers. Mol. Biol. Rep. 2022, 49, 717–733. [Google Scholar] [CrossRef]
- Cardoso, F.; Senkus, E.; Costa, A.; Papadopoulos, E.; Aapro, M.; André, F.; Harbeck, N.; Lopez, B.A.; Barrios, C.; Bergh, J.; et al. 4th ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 4). Ann. Oncol. 2018, 29, 1634–1657. [Google Scholar] [CrossRef]
- Chavez-MacGregor, M.; Valero, V. Clinically Used Breast Cancer Markers Such As Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Are Unstable Throughout Tumor Progression. Breast Dis. A Year Book Q. 2013, 2, 143–144. [Google Scholar] [CrossRef]
- Murphy, C.G.; Dickler, M.N. Endocrine resistance in hormone-responsive breast cancer: Mechanisms and therapeutic strategies. Endocr. Relat. Cancer 2016, 23, R337–R352. [Google Scholar] [CrossRef]
- Osborne, C.K.; Schiff, R. Mechanisms of endocrine resistance in breast cancer. Annu. Rev. Med. 2011, 62, 233–247. [Google Scholar] [CrossRef] [PubMed]
- Toy, W.; Weir, H.; Razavi, P.; Lawson, M.; Goeppert, A.U.; Mazzola, A.M.; Smith, A.; Wilson, J.; Morrow, C.; Wong, W.L.; et al. Activating ESR1 mutations differentially affect the efficacy of ER antagonists. Cancer Discov. 2017, 7, 277–287. [Google Scholar] [CrossRef] [PubMed]
- Schiavon, G.; Hrebien, S.; Garcia-Murillas, I.; Cutts, R.J.; Pearson, A.; Tarazona, N.; Fenwick, K.; Kozarewa, I.; Lopez-Knowles, E.; Ribas, R.; et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci. Transl. Med. 2015, 7, 313ra182. [Google Scholar] [CrossRef] [PubMed]
- Fribbens, C.; O’Leary, B.; Kilburn, L.; Hrebien, S.; Garcia-Murillas, I.; Beaney, M.; Cristofanilli, M.; Andre, F.; Loi, S.; Loibl, S.; et al. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J. Clin. Oncol. 2016, 34, 2961–2968. [Google Scholar] [CrossRef] [PubMed]
- Jeselsohn, R.; Yelensky, R.; Buchwalter, G.; Frampton, G.; Meric-Bernstam, F.; Gonzalez-Angulo, A.M.; Ferrer-Lozano, J.; Perez-Fidalgo, J.A.; Cristofanilli, M.; Gomez, H.; et al. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor–positive breast cancer. Clin. Cancer Res. 2014, 20, 1757–1767. [Google Scholar] [CrossRef] [PubMed]
- Robinson, D.R.; Wu, Y.M.; Vats, P.; Su, F.; Lonigro, R.J.; Cao, X.; Kalyana-Sundaram, S.; Wang, R.; Ning, Y.; Hodges, L.; et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat. Genet. 2013, 45, 1446–1451. [Google Scholar] [CrossRef] [PubMed]
- Toy, W.; Shen, Y.; Won, H.; Green, B.; Sakr, R.A.; Will, M.; Li, Z.; Gala, K.; Fanning, S.; King, T.A.; et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat. Genet. 2013, 45, 1439–1445. [Google Scholar] [CrossRef]
- Fox, E.M.; Miller, T.W.; Balko, J.M.; Kuba, M.G.; Sánchez, V.; Smith, R.A.; Liu, S.; González-Angulo, A.M.; Mills, G.B.; Ye, F.; et al. A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer. Cancer Res. 2011, 71, 6773–6784. [Google Scholar] [CrossRef]
- Frogne, T.; Benjaminsen, R.V.; Sonne-Hansen, K.; Sorensen, B.S.; Nexo, E.; Laenkholm, A.V.; Rasmussen, L.M.; Riese, D.J.; de Cremoux, P.; Stenvang, J.; et al. Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant. Breast Cancer Res. Treat. 2009, 114, 263–275. [Google Scholar] [CrossRef] [PubMed]
- Ellis, M.J.; Tao, Y.; Young, O.; White, S.; Proia, A.D.; Murray, J.; Renshaw, L.; Faratian, D.; Thomas, J.; Dowsett, M.; et al. Estrogen-independent proliferation is present in estrogen-receptor HER2-positive primary breast cancer after neoadjuvant letrozole. J. Clin. Oncol. 2006, 24, 3019–3025. [Google Scholar] [CrossRef] [PubMed]
- Campbell, R.A.; Bhat-Nakshatri, P.; Patel, N.M.; Constantinidou, D.; Ali, S.; Nakshatri, H. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor α: A new model for anti-estrogen resistance. J. Biol. Chem. 2011, 276, 9817–9824. [Google Scholar] [CrossRef]
- Engelman, J.A.; Luo, J.; Cantley, L.C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet. 2006, 7, 606–619. [Google Scholar] [CrossRef] [PubMed]
- Lauring, J.; Park, B.H.; Wolff, A.C. The phosphoinositide-3-kinase-Akt-mTOR pathway as a therapeutic target in breast cancer. J. Natl. Compr. Cancer Netw. 2013, 11, 670–678. [Google Scholar] [CrossRef]
- Knudsen, E.S.; Pruitt, S.C.; Hershberger, P.A.; Witkiewicz, A.K.; Goodrich, D.W. Cell cycle and beyond: Exploiting new RB1 controlled mechanisms for cancer therapy. Trends Cancer 2019, 5, 308–324. [Google Scholar] [CrossRef] [PubMed]
- Stendahl, M.; Kronblad, Å.; Rydén, L.; Emdin, S.; Bengtsson, N.O.; Landberg, G. Cyclin D1 overexpression is a negative predictive factor for tamoxifen response in postmenopausal breast cancer patients. Br. J. Cancer 2004, 90, 1942–1948. [Google Scholar] [CrossRef]
- Bidard, F.C.; Hardy-Bessard, A.C.; Dalenc, F.; Bachelot, T.; Pierga, J.Y.; de la Motte Rouge, T.; Sabatier, R.; Dubot, C.; Frenel, J.S.; Ferrero, J.M.; et al. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2022, 23, 1367–1377. [Google Scholar] [CrossRef]
- Patel, R.; Klein, P.; Tiersten, A.; Sparano, J.A. An emerging generation of endocrine therapies in breast cancer: A clinical perspective. Npj Breast Cancer 2023, 9, 20. [Google Scholar] [CrossRef]
- US Food and Drug Administration. FDA Approves Elacestrant for ER-Positive, HER2-Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer. FDA. 2023. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-elacestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast-cancer (accessed on 30 May 2024).
- Bardia, A.; Aftimos, P.; Bihani, T.; Anderson-Villaluz, A.T.; Jung, J.; Conlan, M.G.; Kaklamani, V.G. EMERALD: Phase III trial of elacestrant (RAD1901) vs endocrine therapy for previously treated ER+ advanced breast cancer. Future Oncol. 2019, 15, 3209–3218. [Google Scholar] [CrossRef]
- NCT04797728 Elacestrant in Preoperative Setting, a Window of Opportunity Study (ELIPSE). Available online: https://clinicaltrials.gov/ct2/show/NCT04797728?term=elacestrant&cond=Breast+Cancer&draw=2&rank=5 (accessed on 4 December 2023).
- NCT04791384 Phase Ib/II Trial of Abemaciclib and Elacestrant in Patients with Brain Metastasis Due to HR+/Her2-Breast Cancer. Available online: https://clinicaltrials.gov/ct2/show/NCT04791384?term=elacestrant&cond=Breast+Cancer&draw=2&rank=1 (accessed on 5 December 2023).
- A Study of Samuraciclib and Elacestrant in Participants with Metastatic or Locally Advanced HR+/HER2-Negative Breast Cancer (SUMIT-ELA). Available online: https://clinicaltrials.gov/study/NCT05963997?cond=elacestrant&term=Breast%20Cancer&aggFilters=status:rec&rank=3, (accessed on 5 December 2023).
- Open-Label Umbrella Study to Evaluate Safety and Efficacy of Elacestrant in Various Combination in Patients with Metastatic Breast Cancer (ELEVATE). Available online: https://clinicaltrials.gov/study/NCT05563220?cond=elacestrant&term=Breast%20Cancer&aggFilters=status:rec&rank=4; (accessed on 5 December 2023).
- ELACESTRANT in Women and Men With CDK4/6 Inhibitor-Naive Estrogen Receptor Positive, HER-2 Negative Metastatic Breast Cancer Study (ELCIN). Available online: https://clinicaltrials.gov/study/NCT05596409?cond=elacestrant&term=Breast%20Cancer&aggFilters=status:rec&rank=5; (accessed on 5 December 2023).
- Hamilton, E.P.; Oliveira, M.; Banerji, U.; Hernando, C.; Garcia-Corbacho, J.; Armstrong, A.; Ciruelos, E.; Patel, M.R.; Incorvati, J.; Twelves, C. A phase I dose escalation and expansion study of the next generation oral SERD AZD9833 in women with ER-positive, HER2-negative advanced breast cancer. J. Clin. Oncol. 2020, 38, 1024. [Google Scholar] [CrossRef]
- Oliveira, M.; Hamilton, E.P.; Incorvati, J.; Bermejo de la Heras, B.; Calvo, E.; García-Corbacho, J.; Ruiz-Borrego, M.; Vaklavas, C.; Turner, N.C.; Ciruelos, E.M.; et al. Serena-1: Updated analyses from a phase 1 study (parts C/D) of the next-generation oral SERD camizestrant (AZD9833) in combination with palbociclib, in women with ER-positive, HER2-negative advanced breast cancer. J. Clin. Oncol. 2022, 40, 1032. [Google Scholar] [CrossRef]
- Oliveira, M.; Bennett, M.; Khalil, A.; Mather, R.; Maudsley, R.; McGuinness, S.; Morrow, C.J.; Sykes, A.; Zhang, L.; Klinowska, T.; et al. Abstract OT-09-02: A randomized, open-label, parallel-group, multicenter phase 2 study comparing the efficacy and safety of oral AZD9833 versus fulvestrant in women with advanced ER-positive HER2-negative breast cancer (SERENA-2). Cancer Res. 2021, 81, OT-09-02. [Google Scholar] [CrossRef]
- Andre, F.; Im, S.A.; Neven, P.; Baird, R.D.; Ettl, J.; Goetz, M.P.; Hamilton, E.; Iwata, H.; Jiang, Z.; Joy, A.A.; et al. SERENA-4: A Phase III comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive/HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease. Cancer Res. 2022, 82. [Google Scholar] [CrossRef]
- Bidard, F.C.; Kalinsky, K.; Cristofanilli, M.; Bianchini, G.; Chia, S.K.; Janni, W.; Ma, C.X.; Mayer, E.L.; Park, Y.H.; Fox, S.; et al. Abstract OT2-11-05: SERENA-6: A Phase III study to assess the efficacy and safety of AZD9833 (camizestrant) compared with aromatase inhibitors when given in combination with palbociclib or abemaciclib in patients with HR+/HER2-metastatic breast cancer with detectable ESR1 m who have not experienced disease progression on first-line therapy. Cancer Res. 2022, 82, OT2-11. [Google Scholar]
- Robertson, J.F.; Moppett, I.; Rocha, J.E.B.; Dzagnidze, G.; Harding, J.; Klinowska, T.; Mather, R.; Mathewson, A.; Maudsley, R.; Morrow, C.J.; et al. Abstract OT-09-05: A randomized, pre-surgical study to investigate the biological effects of AZD9833 doses in women with ER-positive HER2-negative primary breast cancer (SERENA-3). Cancer Res. 2021, 81, OT-09-05. [Google Scholar] [CrossRef]
- Jhaveri, K.L.; Jeselsohn, R.; Lim, E.; Hamilton, E.P.; Yonemori, K.; Beck, J.T.; Kaufman, P.A.; Sammons, S.; Bhave, M.A.; Saura, C.; et al. A phase 1a/b trial of imlunestrant (LY3484356), an oral selective estrogen receptor degrader (SERD) in ER-positive (ER+) advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): Monotherapy results from EMBER. J. Clin. Oncol. 2022, 40, P1021. [Google Scholar] [CrossRef]
- Jhaveri, K.; Harbeck, N.; Aftimos, P.; Kim, S.B.; Pivot, X.; Saura, C.; Curigliano, G.; Casalnuovo, M.; Wang, X.A.; Young, S.R.; et al. EMBER-3: A randomized phase 3 study of LY3484356, a novel, oral selective estrogen receptor degrader vs investigator’s choice of endocrine therapy of either fulvestrant or exemestane, in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer previously treated with endocrine-based therapy. Cancer Res. 2022, 82, OT2-11-01. [Google Scholar]
- Wander, S.A. The ELAINE trials and the future of personalized therapy for hormone-receptor positive metastatic breast cancer. Ann. Oncol. 2023, 34, 1071–1073. [Google Scholar] [CrossRef] [PubMed]
- Goetz, M.P.; Bagegni, N.A.; Batist, G.; Brufsky, A.; Cristofanilli, M.A.; Damodaran, S.; Daniel, B.R.; Fleming, G.F.; Gradishar, W.J.; Graff, S.L.; et al. Lasofoxifene versus fulvestrant for ER+/HER2− metastatic breast cancer with an ESR1 mutation: Results from the randomized, phase II ELAINE 1 trial. Ann. Oncol. 2023, 34, 1141–1151. Available online: https://clinicaltrials.gov/ct2/show/NCT04647487(2023) (accessed on 30 May 2024). [CrossRef]
- Dees, E.C.; Aftimos, P.G.; van Oordt, H.; De Vries, E.G.E.; Neven, P.; Pegram, M.D.; Iqbal, R.; Boers, J.; Xiao, J.; Sipes, C.; et al. Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2-locally advanced or metastatic breast cancer (ABC). Ann. Oncol. 2019, 30, v121–v122. [Google Scholar] [CrossRef]
- Maglakelidze, M.; Bulat, I.; Ryspayeva, D.; Krastev, B.M.; Gogiladze, M.; Crijanovschi, A.; Aftimos, P.G.; Neven, P.; Pegram, M.D.; Menke, C.W. Rintodestrant (G1T48), an oral selective estrogen receptor degrader, in combination with palbociclib for ER+/HER2–advanced breast cancer: Phase 1 results. J. Clin. Oncol. 2021, 39, 1063. [Google Scholar] [CrossRef]
- Guo, S.; Zhang, C.; Bratton, M.; Mottamal, M.; Liu, J.; Ma, P.; Zheng, S.; Zhong, Q.; Yang, L.; Wiese, T.E.; et al. ZB716, a steroidal selective estrogen receptor degrader (SERD), is orally efficacious in blocking tumor growth in mouse xenograft models. Oncotarget 2018, 9, 6924. [Google Scholar] [CrossRef] [PubMed]
- Osborne, C.; Richards, D.A.; Wilks, S.T.; Diab, S.; Juric, D.; Lathrop, K.; Silber, A.; Edenfield, W.; Aulakh, A.; Cho, B.; et al. A phase 1 study of D-0502, an orally bioavailable SERD, for advanced or metastatic HR-positive and HER2-negative breast cancer. Cancer Res. 2021, 81, PS11-26. [Google Scholar] [CrossRef]
- Kalinksy, K.; Abramson, V.; Chalasani, P.; Linden, H.M.; Alidzanovic, J.; Layman, R.M.; Vranješ, Ž.; Nangia, J.R.; Crew, K.D.; Andric, Z.; et al. Abstract P1-17-02: ZN-c5, an oral selective estrogen receptor degrader (SERD), in women with advanced estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Cancer Res. 2022, 82, P1-17-02. [Google Scholar] [CrossRef]
- Keogh, G.P.; Papish, S.; Piskorski, W.; Ulanska, M.; Jackson, B.; Suster, M.; Ptaszynski, M.; Mina, L. 564TiP A phase Ib dose-escalation study of ZN-c5, an oral selective estrogen receptor degrader (SERD), in combination with abemaciclib in patients with advanced estrogen receptor (ER)+/HER2-breast cancer. Ann. Oncol. 2021, 32, S618–S619. [Google Scholar] [CrossRef]
- Puyang, X.; Furman, C.; Zheng, G.Z.; Wu, Z.J.; Banka, D.; Aithal, K.; Agoulnik, S.; Bolduc, D.M.; Buonamici, S.; Caleb, B.; et al. Discovery of selective estrogen receptor covalent antagonists for the treatment of ERαWT and ERαMUT breast cancer. Cancer Discov. 2018, 8, 1176–1193. [Google Scholar] [CrossRef]
- Hamilton, E.P.; Wang, J.S.; Pluard, T.J.; Johnston, S.R.; Morikawa, A.; Dees, E.C.; Jones, R.H.; Haley, B.B.; Armstrong, A.C.; Cohen, A.L.; et al. Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. J. Clin. Oncol. 2021, 39, 1018. [Google Scholar] [CrossRef]
- Johnston, S.R.; Pluard, T.J.; Wang, J.S.; Hamilton, E.P.; Juric, D.; Scholz, C.R.; Hnitecki, E.; Gao, L.; Cantagallo, L.; Korpal, M.; et al. Phase 1b study of H3B-6545 in combination with palbociclib in women with metastatic estrogen receptor–positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative breast cancer. J. Clin. Oncol. 2021, 39, e13025. [Google Scholar] [CrossRef]
- Hodges-Gallagher, L.; Sun, R.; Myles, D.C.; Harmon, C.L.; Kushner, P.J. Abstract P5-05-02: Preclinical development of OP-1250, an oral complete estrogen receptor antagonist (CERAN) that shrinks ER-positive breast tumors in xenograft models. Cancer Res. 2022, 80, P5-05-02. [Google Scholar] [CrossRef]
- Hodges-Gallagher, L.; Parisian, A.D.; Sun, R.; Myles, D.C.; Klein, P.M.; Harmon, C.L.; Kushner, P.J. Abstract LB122: The complete estrogen receptor antagonist (CERAN) OP-1250 shrinks ER+ brain metastases in an intracranial xenograft tumor model expressing mutant ESR1. Cancer Res. 2021, 81, LB122. [Google Scholar] [CrossRef]
- Patel, M.; Alemany, C.; Mitri, Z.; Makower, D.; Borges, V.; Sparano, J.; Le, T.; Klein, P.; Lawrence, J.; Kushner, P.; et al. Abstract P1-17-12: Preliminary data from a phase I/II, multicenter, dose escalation study of OP-1250, an oral CERAN/SERD, in subjects with advanced and/or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer. Cancer Res. 2022, 82, P1-17-12. [Google Scholar] [CrossRef]
- Guarneri, V.; Barbieri, E.; Dieci, M.V.; Piacentini, F.; Conte, P. Anti-HER2 neoadjuvant and adjuvant therapies in HER2 positive breast cancer. Cancer Treat. Rev. 2012, 36, S62–S66. [Google Scholar] [CrossRef] [PubMed]
- Deluche, E.; Antoine, A.; Bachelot, T.; Lardy-Cleaud, A.; Dieras, V.; Brain, E.; Debled, M.; Jacot, W.; Mouret-Reynier, M.A.; Goncalves, A.; et al. Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008–2016. Eur. J. Cancer 2020, 129, 60–70. [Google Scholar] [CrossRef] [PubMed]
- Dieci, M.V.; Miglietta, F.; Griguolo, G.; Guarneri, V. Biomarkers for HER2-positive metastatic breast cancer: Beyond hormone receptors. Cancer Treat. Rev. 2020, 88, 102064. [Google Scholar] [CrossRef] [PubMed]
- Griguolo, G.; Brasò-Maristany, F.; Pascual, T.; Chic, N.; Vidal, M.; Adamo, B.; Giarratano, T.; Dieci, M.V.; Guarneri, V.; Prat, A. ERBB2 mRNA as predictor of response to anti-HER2 antibody-drug conjugates (ADC) in breast cancer (BC). Ann. Oncol. 2019, 30, iii7. [Google Scholar] [CrossRef]
- Perez, E.A.; De Haas, S.L.; Eiermann, W.; Barrios, C.H.; Toi, M.; Im, Y.H.; Conte, P.F.; Martin, M.; Pienkowski, T.; Pivot, X.B.; et al. Relationship between tumor biomarkers and efficacy in MARIANNE, a phase III study of trastuzumab emtansine±pertuzumab versus trastuzumab plus taxane in HER2-positive advanced breast cancer. BMC Cancer 2019, 19, 517. [Google Scholar]
- Kim, S.B.; Wildiers, H.; Krop, I.E.; Smitt, M.; Yu, R.; Lysbet de Haas, S.; Gonzalez-Martin, A. Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastu- zumab emtansine (T-DM1) vs. treatment of physician’s choice in previously treated HER2-positive advanced breast cancer. Int. J. Cancer 2016, 139, 2336–2342. [Google Scholar] [CrossRef] [PubMed]
- Modi, S.; Saura, C.; Yamashita, T.; Park, Y.H.; Kim, S.B.; Tamura, K.; Andre, F.; Iwata, H.; Ito, Y.; Tsurutani, J.; et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N. Engl. J. Med. 2020, 382, 610–621. [Google Scholar] [CrossRef]
- Hurvitz, S.A.; Martin, M.; Jung, K.H.; Huang, C.S.; Harbeck, N.; Valero, V.; Stroyakovskiy, D.; Wildiers, H.; Campone, M.; Boileau, J.F.; et al. Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2–positive breast cancer: Three-year outcomes from the phase III KRISTINE study. J. Clin. Oncol. 2019, 37, 2206. [Google Scholar] [CrossRef]
- Stanek, L.; Gurlich, R.; Whitley, A.; Tesarova, P.; Musil, Z.; Novakova, L. HER-3 molecular classification, expression of PD-L1 and clinical importance in breast cancer. Bratisl. Med. J./Bratisl. Lek. Listy 2020, 123. [Google Scholar] [CrossRef] [PubMed]
- Romaniello, D.; Marrocco, I.; Belugali Nataraj, N.; Ferrer, I.; Drago-Garcia, D.; Vaknin, I.; Oren, R.; Lindzen, M.; Ghosh, S.; Kreitman, M.; et al. Targeting HER3, a catalytically defective receptor tyrosine kinase, prevents resistance of lung cancer to a third-generation EGFR kinase inhibitor. Cancers 2020, 12, 2394. [Google Scholar] [CrossRef]
- Narayan, M.; Wilken, J.A.; Harris, L.N.; Baron, A.T.; Kimbler, K.D.; Maihle, N.J. Trastuzumab-induced HER reprogramming in “resistant” breast carcinoma cells. Cancer Res. 2009, 69, 2191–2194. [Google Scholar] [CrossRef]
- Pistilli, B.; Wildiers, H.; Hamilton, E.P.; Ferreira, A.A.; Dalenc, F.; Vidal, M.; Gavila, J.; Goncalves, A.; Murias, C.; Mouret-Reynier, M.A.; et al. Clinical activity of MCLA-128 (zenocutuzumab) in combination with endocrine therapy (ET) in ER+/HER2-low, non-amplified metastatic breast cancer (MBC) patients (pts) with ET-resistant disease who had progressed on a CDK4/6 inhibitor (CDK4/6i). J. Clin. Oncol. 2020, 38, 1037. [Google Scholar] [CrossRef]
- Saeki, T.; Mukai, H.; Aogi, K.; Shigekawa, T.; Ueda, S.; Naito, Y.; Matsubara, N.; Takashima, S.; Hara, F.; Yamashita, T.; et al. Phase I study of HER3 targeted antibody patritumab in combination with trastuzumab and paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC). J. Clin. Oncol. 2015, 33, 584. [Google Scholar] [CrossRef]
- Krop, I.E.; Masuda, N.; Mukohara, T.; Takahashi, S.; Nakayama, T.; Inoue, K.; Iwata, H.; Toyama, T.; Yamamoto, Y.; Hansra, D.M.; et al. Results from the phase 1/2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC). J. Clin. Oncol. 2020, 38, 1002. [Google Scholar] [CrossRef]
- Higgins, M.J.; Doyle, C.; Paepke, S.; Azaro, A.; Martin, M.; Semiglazov, V.; Smirnova, I.; Krasnozhon, D.; Manikhas, A.; Harb, W.A.; et al. A randomized, double-blind phase II trial of exemestane plus MM-121 (a monoclonal antibody targeting ErbB3) or placebo in postmenopausal women with locally advanced or metastatic ER+/PR+, HER2-negative breast cancer. J. Clin. Oncol. 2014, 32, 587. [Google Scholar] [CrossRef]
- Schneeweiss, A.; Park-Simon, T.W.; Albanell, J.; Lassen, U.; Cortés, J.; Dieras, V.; May, M.; Schindler, C.; Marmé, F.; Cejalvo, J.M.; et al. Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer. Investig. New Drugs 2018, 36, 848–859. [Google Scholar] [CrossRef] [PubMed]
- Cejalvo, J.M.; Pascual, T.; Fernández-Martínez, A.; Adamo, B.; Chic, N.; Vidal, M.; Rodelo, L.; Munoz, M.; Prat, A. Distribution of the PAM50 breast cancer subtypes within each pathology-based group: A combined analysis of 15,339 patients across 29 studies. Ann. Oncol. 2017, 28, v603. [Google Scholar] [CrossRef]
- Dieci, M.V.; Prat, A.; Tagliafico, E.; Paré, L.; Ficarra, G.; Bisagni, G.; Piacentini, F.; Generali, D.G.; Conte, P.; Guarneri, V. Integrated evaluation of PAM50 subtypes and immune modulation of pCR in HER2-positive breast cancer patients treated with chemotherapy and HER2-targeted agents in the CherLOB trial. Ann. Oncol. 2016, 27, 1867–1873. [Google Scholar] [CrossRef]
- Tolaney, S.M.; Wardley, A.M.; Zambelli, S.; Hilton, J.; Troso-Sandoval, T.; Ricci, F.; Im, S.A.; Kim, S.B.; Johnston, S.R.D.; Chan, A.; et al. MonarcHER: A randomized phase II study of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with HR+, HER2+ advanced breast cancer (ABC). Ann. Oncol. 2019, 30, v861–v862. [Google Scholar] [CrossRef]
- Bose, R.; Kavuri, S.M.; Searleman, A.C.; Shen, W.; Shen, D.; Koboldt, D.C.; Monsey, J.; Goel, N.; Aronson, A.B.; Li, S.; et al. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov. 2013, 3, 224–237. [Google Scholar] [CrossRef] [PubMed]
- Mavaddat, N.; Barrowdale, D.; Andrulis, I.L.; Domchek, S.M.; Eccles, D.; Nevanlinna, H.; Ramus, S.J.; Spurdle, A.; Robson, M.; Sherman, M.; et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol. Biomark. Prev. 2022, 21, 134–147. [Google Scholar] [CrossRef]
- Eccles, D.M.; Mitchell, G.; Monteiro, A.N.A.; Schmutzler, R.; Couch, F.J.; Spurdle, A.B.; Gómez-García, E.B.; Driessen, R.; Lindor, N.M.; Blok, M.J.; et al. BRCA1 and BRCA2 genetic testing—Pitfalls and recommendations for managing variants of uncertain clinical significance. Ann. Oncol. 2015, 26, 2057–2065. [Google Scholar] [CrossRef]
- Toomey, S.; Eustace, A.J.; Fay, J.; Sheehan, K.M.; Carr, A.; Milewska, M.; Madden, S.F.; Teiserskiene, A.; Kay, E.W.; O’Donovan, N.; et al. Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies. Breast Cancer Res. 2017, 19, 87. [Google Scholar] [CrossRef] [PubMed]
- Martínez-Sáez, O.; Chic, N.; Pascual, T.; Adamo, B.; Vidal, M.; González-Farré, B.; Sanfeliu, E.; Schettini, F.; Conte, B.; Brasó-Maristany, F.; et al. Frequency and spectrum of PIK3CA somatic mutations in breast cancer. Breast Cancer Res. 2020, 22, 45. [Google Scholar] [CrossRef]
- Reinhardt, K.; Stückrath, K.; Hartung, C.; Kaufhold, S.; Uleer, C.; Hanf, V.; Lantzsch, T.; Peschel, S.; John, J.; Pöhler, M.; et al. PIK3CA-mutations in breast cancer. Breast Cancer Res. Treat. 2022, 196, 483–493. [Google Scholar] [CrossRef]
- Dieci, M.V.; Guarneri, V. PIK3CA: A Target or a Marker in Breast Cancers. Curr. Breast Cancer Rep. 2015, 7, 161–169. [Google Scholar] [CrossRef]
- Hurvitz, S.A.; Andre, F.; Jiang, Z.; Shao, Z.; Mano, M.S.; Neciosup, S.P.; Tseng, L.M.; Zhang, Q.; Shen, K.; Liu, D.; et al. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): A phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015, 16, 816–829. [Google Scholar] [CrossRef]
- André, F.; O’Regan, R.; Ozguroglu, M.; Toi, M.; Xu, B.; Jerusalem, G.; Masuda, N.; Wilks, S.; Arena, F.; Isaacs, C.; et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014, 15, 580–591. [Google Scholar] [CrossRef]
- Pistilli, B.; Pluard, T.; Urruticoechea, A.; Farci, D.; Kong, A.; Bachelot, T.; Chan, S.; Han, H.S.; Jerusalem, G.; Urban, P.; et al. Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy. Breast Cancer Res. Treat. 2018, 168, 357–364. [Google Scholar] [CrossRef]
- Guerin, M.; Rezai, K.; Isambert, N.; Campone, M.; Autret, A.; Pakradouni, J.; Provansal, M.; Camerlo, J.; Sabatier, R.; Bertucci, F.; et al. PIKHER2: A phase IB study evaluating buparlisib in combination with lapatinib in trastuzumab-resistant HER2-positive advanced breast cancer. Eur. J. Cancer 2017, 86, 28–36. [Google Scholar] [CrossRef]
- Tolaney, S.; Burris, H.; Gartner, E.; Mayer, I.A.; Saura, C.; Maurer, M.; Ciruelos, E.; Garcia, A.A.; Campana, F.; Wu, B.; et al. Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer. Breast Cancer Res. Treat. 2015, 149, 151–161. [Google Scholar] [CrossRef] [PubMed]
- Metzger Filho, O.; Goel, S.; Barry, W.T.; Hamilton, E.P.; Tolaney, S.M.; Yardley, D.A.; Rees, R.; Demeo, M.; Mills, C.; Hafner, M.; et al. A mouse-human phase I co-clinical trial of taselisib in combination with TDM1 in advanced HER2-positive breast cancer (MBC). J. Clin. Oncol. 2017, 35, 1030. [Google Scholar] [CrossRef]
- Jain, S.; Shah, A.N.; Santa-Maria, C.A.; Siziopikou, K.; Rademaker, A.; Helenowski, I.; Cristofanilli, M.; Gradishar, W.J. Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy. Breast Cancer Res. Treat. 2018, 171, 371–381. [Google Scholar] [CrossRef] [PubMed]
- Shah, P.D.; Chandarlapaty, S.; Dickler, M.N.; Ulaner, G.; Zamora, S.J.; Sterlin, V.; Iasonos, A.; Coughlin, C.M.; Morozov, A.; Ero, J.; et al. Phase I study of LJM716, BYL719, and trastuzumab in patients (pts) with HER2-amplified (HER2+) metastatic breast cancer (MBC). J. Clin. Oncol. 2015, 33, 590. [Google Scholar] [CrossRef]
- Ipatasertib + Pertuzumab +Trastuzumab in Advanced HER2+ PI3KCA-Mutant Breast Cancer Patients (IPATHER). Available online: https://clinicaltrials.gov/study/NCT04253561?cond=HER2-positive%20Breast%20Cancer&term=PI3K%20Gene%20Mutation&intr=Breast%20cancer&aggFilters=status:rec&rank=5 (accessed on 7 December 2023).
- Wolff, A.C.; Somerfield, M.R.; Dowsett, M.; Hammond, M.E.H.; Hayes, D.F.; McShane, L.M.; Saphner, T.J.; Spears, P.A.; Allison, K.H. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO–College of American Pathologists Guideline Update. J. Clin. Oncol. 2023, 41, 3867–3872. [Google Scholar] [CrossRef] [PubMed]
- Dent, S.; Oyan, B.; Honig, A.; Mano, M.; Howell, S. HER2-targeted therapy in breast cancer: A systematic review of neoadjuvant trials. Cancer Treat. Rev. 2013, 39, 622–631. [Google Scholar] [CrossRef]
- Dukić, N.; Gojković, Z.; Lalović, N.; Vladičić, M.J.; Jokanović, D.; Mašić, S.; Popović, S.; Čančar, O. Neoadjuvant therapy for HER2-positive breast cancer. Biomed. Istraživanja 2019, 10, 83–90. [Google Scholar]
- Dey, N.; Aske, J.; De, P. Targeted neoadjuvant therapies in HR+/HER2− breast cancers: Challenges for improving pCR. Cancers 2021, 13, 458. [Google Scholar] [CrossRef]
- Falato, C.; Schettini, F.; Pascual, T.; Brasó-Maristany, F.; Prat, A. Clinical implications of the intrinsic molecular subtypes in hormone receptor-positive and HER2-negative metastatic breast cancer. Cancer Treat. Rev. 2023, 112, 102496. [Google Scholar] [CrossRef]
- Prat, A.; Perou, C.M. Deconstructing the molecular portraits of breast cancer. Mol. Oncol. 2011, 5, 5–23. [Google Scholar] [CrossRef]
- Berns, K.; Horlings, H.M.; Halfwerk, J.B.G.; Hennessy, B.T.; Linn, S.C.; Hauptmann, M.; Mills, G.B.; van de Vijver, M.J.; Bernards, R. A functional genetic approach identifies the PI3K pathway as a major determinant of Trastuzumab resistance in breast cancer. EJC Suppl. 2009, 2, 17. [Google Scholar] [CrossRef]
- Franke, T.F.; Kaplan, D.R.; Cantley, L.C.; Toker, A. Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3, 4-bisphosphate. Science 1997, 275, 665–668. [Google Scholar] [CrossRef]
- Bianchini, G.; Gianni, L. The immune system and response to HER2-targeted treatment in breast cancer. Lancet Oncol. 2014, 15, e58–e68. [Google Scholar] [CrossRef]
- Garaud, S.; Buisseret, L.; Solinas, C.; Gu-Trantien, C.; de Wind, A.; Van den Eynden, G.; Naveaux, C.; Lodewyckx, J.N.; Boisson, A.; Duvillier, H.; et al. Tumor-infiltrating B cells signal functional humoral immune responses in breast cancer. JCI Insight 2019, 4, e129641. [Google Scholar] [CrossRef]
- Hortobagyi, G.N.; Chen, D.; Piccart, M.; Rugo, H.S.; Burris III, H.A.; Pritchard, K.I.; Campone, M.; Noguchi, S.; Perez, A.T.; Deleu, I.; et al. Correlative analysis of genetic alterations and everolimus benefit in hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: Results from BOLERO-2. J. Clin. Oncol. 2016, 34, 419. [Google Scholar] [CrossRef] [PubMed]
- Von Minckwitz, G.; Schneeweiss, A.; Loibl, S.; Salat, C.; Denkert, C.; Rezai, M.; Blohmer, J.U.; Jackisch, C.; Paepke, S.; Gerber, B.; 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. 2014, 15, 747–756. [Google Scholar] [CrossRef] [PubMed]
- Di Cosimo, S.; Campbell, C.; Azim, H.A., Jr.; Galli, G.; Bregni, G.; Curigliano, G.; Criscitiello, C.; Izquierdo, M.; de la Pena, L.; Fumagalli, D.; et al. The use of breast imaging for predicting response to neoadjuvant lapatinib, trastuzumab and their combination in HER2-positive breast cancer: Results from Neo-ALTTO. Eur. J. Cancer 2018, 89, 42–48. [Google Scholar] [CrossRef] [PubMed]
- Brown, J.R.; DiGiovanna, M.P.; Killelea, B.; Lannin, D.R.; Rimm, D.L. Quantitative assessment Ki-67 score for prediction of response to neoadjuvant chemotherapy in breast cancer. Lab. Investig. 2014, 94, 98–106. [Google Scholar] [CrossRef] [PubMed]
- Vici, P.; Pizzuti, L.; Natoli, C.; Gamucci, T.; Di Lauro, L.; Barba, M.; Sergi, D.; Botti, C.; Michelotti, A.; Moscetti, L.; et al. Triple positive breast cancer: A distinct subtype? Cancer Treat. Rev. 2015, 41, 69–76. [Google Scholar] [CrossRef] [PubMed]
- Rimawi, M.F.; Cecchini, R.S.; Rastogi, P.; Geyer, C.E., Jr.; Fehrenbacher, L.; Stella, P.J.; Dayao, Z.; Rabinovitch, R.; Dyar, S.H.; Flynn, P.J.; et al. Abstract S3-06: A phase III trial evaluating pCR in patients with HR+, HER2-positive breast cancer treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP)+/-estrogen deprivation: NRG Oncology/NSABP B-52. Cancer Res. 2017, 77, S3–S06. [Google Scholar] [CrossRef]
- Bianchini, G.; De Angelis, C.; Licata, L.; Gianni, L. Treatment landscape of triple-negative breast cancer—Expanded options, evolving needs. Nat. Rev. Clin. Oncol. 2022, 19, 91–113. [Google Scholar] [CrossRef] [PubMed]
- Brandão, M.; Caparica, R.; Malorni, L.; Prat, A.; Carey, L.A.; Piccart, M. What is the real impact of estrogen receptor status on the prognosis and treatment of HER2-positive early breast cancer? Clin. Cancer Res. 2020, 26, 2783–2788. [Google Scholar] [CrossRef] [PubMed]
- Lodi, M.; Voilquin, L.; Alpy, F.; Molière, S.; Reix, N.; Mathelin, C.; Chenard, M.P.; Tomasetto, C.L. STARD3: A New Biomarker in HER2-Positive Breast Cancer. Cancers 2023, 15, 362. [Google Scholar] [CrossRef]
- Glynn, R.W.; Miller, N.; Kerin, M.J. 17q12-21–The pursuit of targeted therapy in breast cancer. Cancer Treat. Rev. 2010, 36, 224–229. [Google Scholar] [CrossRef]
- Vassilev, B.; Sihto, H.; Li, S.; Hölttä-Vuori, M.; Ilola, J.; Lundin, J.; Isola, J.; Kellokumpu-Lehtinen, P.L.; Joensuu, H.; Ikonen, E. Elevated levels of StAR-related lipid transfer protein 3 alter cholesterol balance and adhesiveness of breast cancer cells: Potential mechanisms contributing to progression of HER2-positive breast cancers. Am. J. Pathol. 2015, 185, 987–1000. [Google Scholar] [CrossRef]
- Wilhelm, L.P.; Wendling, C.; Védie, B.; Kobayashi, T.; Chenard, M.P.; Tomasetto, C.; Drin, G.; Alpy, F. STARD 3 mediates endoplasmic reticulum-to-endosome cholesterol transport at membrane contact sites. EMBO J. 2017, 36, 1412–1433. [Google Scholar] [CrossRef]
- Schmid, P.; Adams, S.; Rugo, H.S.; Schneeweiss, A.; Barrios, C.H.; Iwata, H.; Diéras, V.; Hegg, R.; Im, S.A.; Shaw Wright, G.; et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 2018, 379, 2108–2121. [Google Scholar] [CrossRef]
- Chehade, R.; Awan, A.A.; Fernandes, R. A narrative review of biomarkers in advanced triple negative breast cancer. Precis. Cancer Med. 2021, 4, 24. [Google Scholar]
- Voorwerk, L.; Kok, M. IMpassionate conflicts’ in immunotherapy trials for metastatic triple-negative breast cancer. Ann. Oncol. 2021, 32, 947–949. [Google Scholar] [CrossRef] [PubMed]
- Narayan, P.; Wahby, S.; Gao, J.J.; Amiri-Kordestani, L.; Ibrahim, A.; Bloomquist, E.; Tang, S.; Xu, Y.; Liu, J.; Fu, W.; et al. FDA approval summary: Atezolizumab plus paclitaxel protein-bound for the treatment of patients with advanced or metastatic TNBC whose tumors express PD-L1. Clin. Cancer Res. 2020, 26, 2284–2289. [Google Scholar] [CrossRef] [PubMed]
- Shah, M.; Osgood, C.L.; Amatya, A.K.; Fiero, M.H.; Pierce, W.F.; Nair, A.; Herz, J.; Robertson, K.J.; Mixter, B.D.; Tang, S.; et al. FDA approval summary: Pembrolizumab for neoadjuvant and adjuvant treatment of patients with high-risk early-stage triple-negative breast cancer. Clin. Cancer Res. 2022, 28, 5249–5253. [Google Scholar] [CrossRef] [PubMed]
- US Food and Drug Administration. FDA Approves Pembrolizumab for High-Risk Early-Stage Triple-Negative Breast Cancer. 2021. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-high-risk-early-stage-triple-negative-breast-cancer (accessed on 16 December 2023).
- Schmid, P.; Cortés, J.; Dent, R.; Pusztai, L.; McArthur, H.L.; Kuemmel, S.; Bergh, J.; Denkert, C.; Park, Y.H.; Hui, R.; et al. KEYNOTE-522: Phase III study of pembrolizumab (pembro)+ chemotherapy (chemo) vs placebo (pbo)+ chemo as neoadjuvant treatment, followed by pembro vs pbo as adjuvant treatment for early triple-negative breast cancer (TNBC). Ann. Oncol. 2019, 30, v853–v854. [Google Scholar] [CrossRef]
- 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.; et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin. Cancer Res. 2015, 21, 1688–1698. [Google Scholar] [CrossRef]
- Jiang, Y.Z.; Ma, D.; Suo, C.; Shi, J.; Xue, M.; Hu, X.; Xiao, Y.; Yu, K.D.; Liu, Y.R.; Yu, Y.; et al. Genomic and transcriptomic landscape of triple-negative breast cancers: Subtypes and treatment strategies. Cancer Cell 2019, 35, 428–440. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Lehmann, B.D.; Jovanović, B.; Chen, X.I.; Estrada, M.V.; Johnson, K.N.; Shyr, Y.; Moses, H.L.; Sanders, M.E.; Pietenpol, J.A. Refinement of triple-negative breast cancer molecular subtypes: Implications for neoadjuvant chemotherapy selection. PLoS ONE 2016, 11, e0157368. [Google Scholar] [CrossRef]
- Cortes, J.; Rugo, H.S.; Cescon, D.W.; Im, S.A.; Yusof, M.M.; Gallardo, C.; Lipatov, O.; Barrios, C.H.; Perezx-Garcia, J.; Iwata, H.; et al. Pembrolizumab plus Chemotherapy in Advanced Tri-ple-Negative Breast Cancer. N. Engl. J. Med. 2022, 387, 217–226. [Google Scholar] [CrossRef]
- Emens, L.A.; Cruz, C.; Eder, J.P.; Braiteh, F.; Chung, C.; Tolaney, S.M.; Kuter, I.; Nanda, R.; Cassier, P.A.; Delord, J.P.; et al. Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer: A phase 1 study. JAMA Oncol. 2019, 5, 74–82. [Google Scholar] [CrossRef]
- Bareche, Y.; Buisseret, L.; Gruosso, T.; Girard, E.; Venet, D.; Dupont, F.; Desmedt, C.; Larsimont, D.; Park, M.; Rothé, F.; et al. Unraveling triple-negative breast cancer tumor microenvironment heterogeneity: Towards an optimized treatment approach. JNCI J. Natl. Cancer Inst. 2020, 112, 708–719. [Google Scholar] [CrossRef]
- Lemery, S.; Keegan, P.; Pazdur, R. First FDA approval agnostic of cancer site-when a biomarker defines the indication. N. Engl. J. Med. 2017, 377, 1409–1412. [Google Scholar] [CrossRef]
- Prasad, V.; Addeo, A. The FDA approval of pembrolizumab for patients with TMB> 10 mut/Mb: Was it a wise decision? No. Ann. Oncol. 2020, 31, 1112–1114. [Google Scholar] [CrossRef]
- Winer, E.P.; Lipatov, O.; Im, S.A.; Goncalves, A.; Muñoz-Couselo, E.; Lee, K.S.; Schmid, P.; Testa, L.; Witzel, I.; Ohtani, S.; et al. Association of tumor mutational burden (TMB) and clinical outcomes with pembrolizumab (pembro) versus chemotherapy (chemo) in patients with metastatic triple-negative breast cancer (mTNBC) from KEYNOTE-119. J. Clin. Oncol. 2020, 38, 1013. [Google Scholar] [CrossRef]
- Barroso-Sousa, R.; Jain, E.; Cohen, O.; Kim, D.; Buendia-Buendia, J.; Winer, E.; Lin, N.; Tolaney, S.M.; Wagle, N. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Ann. Oncol. 2020, 31, 387–394. [Google Scholar] [CrossRef]
- Bareche, Y.; Venet, D.; Ignatiadis, M.; Aftimos, P.; Piccart, M.; Rothe, F.; Sotiriou, C. Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis. Ann. Oncol. 2018, 29, 895–902. [Google Scholar] [CrossRef]
- Paula, B.D.; Crocamo, S.; de Sousa, C.A.M.; Valverde, P.; Rezende, F.; Abdelhay, E. Triple-Negative Breast Cancer Subclassified by Immunohistochemistry: Correlation with Clinical and Pathological Outcomes in Patients Receiving Neoadjuvant Chemotherapy. Int. J. Mol. Sci. 2024, 25, 5825. [Google Scholar] [CrossRef] [PubMed]
- Loi, S.; Adams, S.; Schmid, P.; Cortés, J.; Cescon, D.W.; Winer, E.P.; Toppmeyer, D.L.; Rugo, H.S.; De Laurentiis, M.; Nanda, R.; et al. Relationship between tumor infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mTNBC): Results from KEYNOTE-086. Ann. Oncol. 2017, 28, v608. [Google Scholar] [CrossRef]
- Loi, S.; Winer, E.; Lipatov, O.; Goncalves, A. Abstract PD5-03: Relationship between tumor-infiltrating lymphocytes (TILs) and outcomes in the KEYNOTE-119 study of pembrolizumab vs chemotherapy for previously treated metastatic triple-negative breast cancer (mTNBC). Cancer Res. 2020, 80, 1158–1159. [Google Scholar] [CrossRef]
- Bianchini, G.; Huang, C.S.; Egle, D.; Bermejo, B.; Zamagni, C.; Thill, M.; Anton, A.; Zambelli, S.; Russo, S.; Ciruelos, E.M.; et al. LBA13 Tumour infiltrating lymphocytes (TILs), PD-L1 expression and their dynamics in the NeoTRIPaPDL1 trial. Ann. Oncol. 2020, 31, S1145–S1146. [Google Scholar] [CrossRef]
- Bachelot, T.; Filleron, T.; Bieche, I.; Arnedos, M.; Campone, M.; Dalenc, F.; Coussy, F.; Sablin, M.P.; Debled, M.; Lefeuvre-Plesse, C.; et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat. Med. 2021, 27, 250–255. [Google Scholar] [CrossRef]
- Masuda, H.; Harano, K.; Miura, S.; Wang, Y.; Hirota, Y.; Harada, O.; Jolly, M.K.; Matsunaga, Y.; Lim, B.; Wood, A.L.; et al. Changes in triple-negative breast cancer molecular subtypes in patients without pathologic complete response after neoadjuvant systemic chemotherapy. JCO Precis. Oncol. 2022, 6, e2000368. [Google Scholar] [CrossRef]
- Buisseret, L.; Garaud, S.; de Wind, A.; Van den Eynden, G.; Boisson, A.; Solinas, C.; Gu-Trantien, C.; Naveaux, C.; Lodewyckx, J.N.; Duvillier, H.; et al. Tumor-infiltrating lymphocyte composition, organization and PD-1/PD-L1 expression are linked in breast cancer. Oncoimmunology 2017, 6, e1257452. [Google Scholar] [CrossRef]
- Ni, Y.; Tsang, J.Y.; Shao, Y.; Poon, I.K.; Tam, F.; Shea, K.H.; Tse, G.M. Combining analysis of tumor-infiltrating lymphocytes (TIL) and PD-L1 refined the prognostication of breast cancer subtypes. Oncologist 2022, 27, e313–e327. [Google Scholar] [CrossRef] [PubMed]
- Gruosso, T.; Gigoux, M.; Manem, V.S.K.; Bertos, N.; Zuo, D.; Perlitch, I.; Saleh, S.M.I.; Zhao, H.; Souleimanova, M.; Johnson, R.M.; et al. Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers. J. Clin. Investig. 2019, 129, 1785–1800. [Google Scholar] [CrossRef]
- Sood, R.; Kumar, S.; Laroiya, I.; Khare, S.; Das, A.; Singh, G.; Bal, A. Assessment of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) across molecular subtypes of triple-negative breast cancer. Breast J. 2020, 26, 2424–2427. [Google Scholar] [CrossRef] [PubMed]
- Alves, A.M.; Paredes, J.; Schmitt, F. Expression of PD-L1 in primary breast carcinoma and lymph node metastases. Surg. Exp. Pathol. 2019, 2, 7. [Google Scholar] [CrossRef]
- Emens, L.A.; Molinero, L.; Loi, S.; Rugo, H.S.; Schneeweiss, A.; Diéras, V.; Iwata, H.; Barrios, C.H.; Nechaeva, M.; Nguyen-Duc, A.; et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer: Biomarker evaluation of the IMpassion130 study. JNCI J. Natl. Cancer Inst. 2021, 113, 1005–1016. [Google Scholar] [CrossRef]
- Doroshow, D.B.; Bhalla, S.; Beasley, M.B.; Sholl, L.M.; Kerr, K.M.; Gnjatic, S.; Wistuba, I.I.; Rimm, D.L.; Tsao, M.S.; Hirsch, F.R. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat. Rev. Clin. Oncol. 2021, 18, 345–362. [Google Scholar] [CrossRef] [PubMed]
- Schmid, P.; Cortes, J.; Pusztai, L.; McArthur, H.; Kümmel, S.; Bergh, J.; Denkert, C.; Park, Y.H.; Hui, R.; Harbeck, N.; et al. Pembrolizumab for early triple-negative breast cancer. N. Engl. J. Med. 2020, 382, 810–821. [Google Scholar] [CrossRef] [PubMed]
- Mittendorf, E.A.; Zhang, H.; Barrios, C.H.; Saji, S.; Jung, K.H.; Hegg, R.; Koehler, A.; Sohn, J.; Iwata, H.; Telli, M.L.; et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): A randomised, double-blind, phase 3 trial. Lancet 2020, 396, 1090–1100. [Google Scholar] [CrossRef]
- Sinn, B.V.; Loibl, S.; Hanusch, C.A.; Zahm, D.M.; Sinn, H.P.; Untch, M.; Weber, K.; Karn, T.; Becker, C.; Marmé, F.; et al. Immune-related gene expression predicts response to neoadjuvant chemotherapy but not additional benefit from PD-L1 inhibition in women with early triple-negative breast cancer. Clin. Cancer Res. 2021, 27, 2584–2591. [Google Scholar] [CrossRef] [PubMed]
- Cimino-Mathews, A.; Ye, X.; Meeker, A.; Argani, P.; Emens, L.A. Metastatic triple-negative breast cancers at first relapse have fewer tumor-infiltrating lymphocytes than their matched primary breast tumors: A pilot study. Hum. Pathol. 2013, 44, 2055–2063. [Google Scholar] [CrossRef] [PubMed]
- Szekely, B.; Bossuyt, V.; Li, X.; Wali, V.B.; Patwardhan, G.A.; Frederick, C.; Silber, A.; Park, T.; Harigopal, M.; Pelekanou, V.; et al. Immunological differences between primary and metastatic breast cancer. Ann. Oncol. 2018, 29, 2232–2239. [Google Scholar] [CrossRef]
- Emens, L.A.; Molinero, L.; Adams, S.; Rugo, H.S.; Schneeweiss, A.; Diéras, V.; Iwata, H.; Barrios, C.H.; Nechaeva, M.; Winer, E.P.; et al. 296P Tumour mutational burden and clinical outcomes with first-line atezolizumab and nab-paclitaxel in triple-negative breast cancer: Exploratory analysis of the phase III IMpassion130 trial. Ann. Oncol. 2020, 31, S360–S361. [Google Scholar] [CrossRef]
- Turajlic, S.; Litchfield, K.; Xu, H.; Rosenthal, R.; McGranahan, N.; Reading, J.L.; Wong, Y.N.S.; Rowan, A.; Kanu, N.; Al Bakir, M.; et al. Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: A pan-cancer analysis. Lancet Oncol. 2017, 18, 1009–1021. [Google Scholar] [CrossRef]
- Lehmann, B.D.; Colaprico, A.; Silva, T.C.; Chen, J.; An, H.; Ban, Y.; Huang, H.; Wang, L.; James, J.L.; Balko, J.M.; et al. Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes. Nat. Commun. 2020, 12, 6276. [Google Scholar] [CrossRef] [PubMed]
- Hainsworth, J.; Friedman, C.F.; Kurzrock, R.; Spigel, D.R.; Burris, H.; Sweeney, C.J.; Meric-Bernstam, F.; Wang, Y.; Levy, J.; Shames, D.; et al. Efficacy of atezolizumab in the treatment of solid tumors with high tumor mutational burden (TMB): A MyPathway study cohort. Cancer Res. 2021, 81, LB012. [Google Scholar] [CrossRef]
- Karn, T.; Denkert, C.; Weber, K.E.; Holtrich, U.; Hanusch, C.; Sinn, B.V.; Higgs, B.W.; Jank, P.; Sinn, H.P.; Huober, J.; et al. Tumor mutational burden and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early TNBC in GeparNuevo. Ann. Oncol. 2020, 31, 1216–1222. [Google Scholar] [CrossRef]
- Le, D.T.; Durham, J.N.; Smith, K.N.; Wang, H.; Bartlett, B.R.; Aulakh, L.K.; Lu, S.; Kemberling, H.; Wilt, C.; Luber, B.S.; et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017, 357, 409–413. [Google Scholar] [CrossRef]
- Gilson, P.; Levy, J.; Rouyer, M.; Demange, J.; Husson, M.; Bonnet, C.; Salleron, J.; Leroux, A.; Merlin, J.L.; Harlé, A. Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers. Sci. Rep. 2020, 10, 16386. [Google Scholar] [CrossRef] [PubMed]
- Ren, X.Y.; Song, Y.; Wang, J.; Chen, L.Y.; Pang, J.Y.; Zhou, L.R.; Shen, S.J.; Cao, X.; Wang, Y.X.; Shao, M.M.; et al. Mismatch repair deficiency and microsatellite instability in triple-negative breast cancer: A retrospective study of 440 patients. Front. Oncol. 2021, 11, 570623. [Google Scholar] [CrossRef] [PubMed]
- Savas, P.; Salgado, R.; Denkert, C.; Sotiriou, C.; Darcy, P.K.; Smyth, M.J.; Loi, S. Clinical relevance of host immunity in breast cancer: From TILs to the clinic. Nat. Rev. Clin. Oncol. 2016, 13, 228–241. [Google Scholar] [CrossRef] [PubMed]
- Stanton, S.E.; Adams, S.; Disis, M.L. Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: A systematic review. JAMA Oncol. 2016, 2, 1354–1360. [Google Scholar] [CrossRef] [PubMed]
- Kos, Z.; Roblin, E.; Kim, R.S.; Michiels, S.; Gallas, B.D.; Chen, W.; van de Vijver, K.K.; Goel, S.; Adams, S.; Demaria, S.; et al. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. NPJ Breast Cancer 2020, 6, 17. [Google Scholar] [CrossRef]
- Denkert, C.; Wienert, S.; Poterie, A.; Loibl, S.; Budczies, J.; Badve, S.; Bago-Horvath, Z.; Bane, A.; Bedri, S.; Brock, J.; 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. 2016, 29, 1155–1164. [Google Scholar] [CrossRef]
- Loi, S.; Salgado, R.; Adams, S.; Pruneri, G.; Francis, P.A.; Lacroix-Triki, M.; Joensuu, H.; Dieci, M.V.; Badve, S.; Demaria, S.; et al. Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer. NPJ Breast Cancer 2022, 8, 3. [Google Scholar] [CrossRef]
- Yuan, Y.; Lee, J.S.; Yost, S.E.; Li, S.M.; Frankel, P.H.; Ruel, C.; Schmolze, D.; Robinson, K.; Tang, A.; Martinez, N.; et al. Phase II Trial of Neoadjuvant Carboplatin and Nab-Paclitaxel in Patients with Triple-Negative Breast Cancer. Oncologist 2021, 26, e382–e393. [Google Scholar] [CrossRef]
- Loi, S.; Schmid, P.; Aktan, G.; Karantza, V.; Salgado, R. Relationship between tumor infiltrating lymphocytes (TILs) and response to pembrolizumab (pembro)+ chemotherapy (CT) as neoadjuvant treatment (NAT) for triple-negative breast cancer (TNBC): Phase Ib KEYNOTE-173 trial. Ann. Oncol. 2019, 30, iii2. [Google Scholar] [CrossRef]
- Nederlof, I.; Isaeva, O.I.; Bakker, N.; de Graaf, M.; Salgado, R.F.; Klioueva, N.; Van De Vijver, K.; van Duijnhoven, F.; Kalashnikova, E.; Willingham, S.; et al. LBA13 Nivolumab and ipilimumab in early-stage triple negative breast cancer (TNBC) with tumor-infiltrating lymphocytes (TILs): First results from the BELLINI trial. Ann. Oncol. 2022, 33, S1382. [Google Scholar] [CrossRef]
- Galluzzi, L.; Humeau, J.; Buqué, A.; Zitvogel, L.; Kroemer, G. Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat. Rev. Clin. Oncol. 2020, 17, 725–741. [Google Scholar] [CrossRef] [PubMed]
- Campbell, M.J.; Yau, C.; Bolen, J.; Vandenberg, S.; Hoyt, C.; Brown-Swigart, L.; Hirst, G.; Nanda, R.; Liu, M.; Asare, S.; et al. Abstract CT003: Analysis of immune cell infiltrates as predictors of response to the checkpoint inhibitor pembrolizumab in the neoadjuvant I-SPY 2 TRIAL. Cancer Res. 2019, 79, CT003. [Google Scholar] [CrossRef]
- Loi, S.; Schmid, P.; Cortes, J.; Cescon, D.W.; Winer, E.P.; Toppmeyer, D.L.; Rugo, H.S.; De Laurentiis, M.; Nanda, R.; Iwata, H.; et al. Abstract PD14-07: Association between biomarkers and response to pembrolizumab in patients with metastatic triple-negative breast cancer (mTNBC): Exploratory analysis from KEYNOTE-086. Cancer Res. 2021, 81, PD14-07. [Google Scholar] [CrossRef]
- Hammerl, D.; Martens, J.W.; Timmermans, M.; Smid, M.; Trapman-Jansen, A.M.; Foekens, R.; Isaeva, O.I.; Voorwerk, L.; Balcioglu, H.E.; Wijers, R.; et al. Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T cell evasion in triple negative breast cancer. Nat. Commun. 2021, 12, 5668. [Google Scholar] [CrossRef] [PubMed]
- Newman, A.M.; Liu, C.L.; Green, M.R.; Gentles, A.J.; Feng, W.; Xu, Y.; Hoang, C.D.; Diehn, M.; Alizadeh, A.A. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 2015, 12, 453–457. [Google Scholar] [CrossRef] [PubMed]
- Loi, S.; Schmid, P.; Cortés, J.; Cescon, D.W.; Winer, E.P.; Toppmeyer, D.; Rugo, H.S.; Laurentiis, M.D.; Nanda, R.; Iwata, H.; et al. Abstract LB-225: RNA molecular signatures as predictive biomarkers of response to monotherapy pembrolizumab in patients with metastatic triple-negative breast cancer: KEYNOTE-086. Cancer Res. 2019, 79, LB-225. [Google Scholar] [CrossRef]
- He, Y.; Jiang, Z.; Chen, C.; Wang, X. Classification of triple-negative breast cancers based on Immunogenomic profiling. J. Exp. Clin. Cancer Res. 2018, 37, 327. [Google Scholar] [CrossRef]
- Xiao, Y.; Ma, D.; Zhao, S.; Suo, C.; Shi, J.; Xue, M.Z.; Ruan, M.; Wang, H.; Zhao, J.; Li, Q.; et al. Multi-omics profiling reveals distinct microenvironment characterization and suggests immune escape mechanisms of triple-negative breast cancer. Clin. Cancer Res. 2019, 25, 5002–5014. [Google Scholar] [CrossRef]
- Fridman, W.H.; Zitvogel, L.; Sautès–Fridman, C.; Kroemer, G. The immune contexture in cancer prognosis and treatment. Nat. Rev. Clin. Oncol. 2017, 14, 717–734. [Google Scholar] [CrossRef]
- Lee, Y.J.; Kim, J.Y.; Jeon, S.H.; Nam, H.; Jung, J.H.; Jeon, M.; Kim, E.S.; Bae, S.J.; Ahn, J.; Yoo, T.K.; et al. CD39+ tissue-resident memory CD8+ T cells with a clonal overlap across compartments mediate antitumor immunity in breast cancer. Sci. Immunol. 2020, 7, eabn8390. [Google Scholar] [CrossRef]
- Dugo, M.; Huang, C.S.; Egle, D.; Bermejo, B.; Zamagni, C.; Seitz, R.S.; Nielsen, T.J.; Thill, M.; Anton, A.; Russo, S.; et al. Abstract PD10-06: Predictive value of RT-qPCR 27-gene IO score and comparison with RNA-Seq IO score in the NeoTRIPaPDL1 trial. Cancer Res. 2022, 82, PD10-06. [Google Scholar] [CrossRef]
- Wang, X.; Collet, L.; Rediti, M.; Debien, V.; De Caluwé, A.; Venet, D.; Romano, E.; Rothé, F.; Sotiriou, C.; Buisseret, L. Predictive Biomarkers for Response to Immunotherapy in Triple Negative Breast Cancer: Promises and Challenges. J. Clin. Med. 2023, 12, 953. [Google Scholar] [CrossRef] [PubMed]
- Chin, R.I.; Chen, K.; Usmani, A.; Chua, C.; Harris, P.K.; Binkley, M.S.; Azad, T.D.; Dudley, J.C.; Chaudhuri, A.A. Detection of solid tumor molecular residual disease (MRD) using circulating tumor DNA (ctDNA). Mol. Diagn. Ther. 2019, 23, 311–331. [Google Scholar] [CrossRef] [PubMed]
- Stroun, M.; Anker, P.; Maurice, P.; Lyautey, J.; Lederrey, C.; Beljanski, M. Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology 1989, 46, 318–322. [Google Scholar] [CrossRef]
- Liquid Biopsy The National Cancer Institute. Available online: https://www.cancer.gov/publications/dictionaries/cancer-terms/search/liquid%20biopsy/?searchMode=Begins (accessed on 9 February 2024).
- Thierry, A.R.; Mouliere, F.; El Messaoudi, S.; Mollevi, C.; Lopez-Crapez, E.; Rolet, F.; Gillet, B.; Gongora, C.; Dechelotte, P.; Robert, B.; et al. Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nat. Med. 2014, 20, 430–435. [Google Scholar] [CrossRef]
- Siravegna, G.; Marsoni, S.; Siena, S.; Bardelli, A. Integrating liquid biopsies into the management of cancer. Nat. Rev. Clin. Oncol. 2017, 14, 531–548. [Google Scholar] [CrossRef] [PubMed]
- Alix-Panabières, C.; Pantel, K. Liquid biopsy: From discovery to clinical application. Cancer Discov. 2021, 11, 858–873. [Google Scholar] [CrossRef] [PubMed]
- Kasi, P.M.; Chakrabarti, S.; Sawyer, S.; Krainock, M.; Poklepovic, A.; Ansstas, G.; Maninder, M.; Malhotra, M.; Ensor, J.; Gao, L.; et al. BESPOKE IO protocol: A multicentre, prospective observational study evaluating the utility of ctDNA in guiding immunotherapy in patients with advanced solid tumours. BMJ Open 2022, 12, e060342. [Google Scholar] [CrossRef]
- Vlataki, K.; Antonouli, S.; Kalyvioti, C.; Lampri, E.; Kamina, S.; Mauri, D.; Harissis, H.V.; Magklara, A. Circulating Tumor DNA in the Management of Early-Stage Breast Cancer. Cells 2023, 12, 1573. [Google Scholar] [CrossRef]
- Newman, A.M.; Bratman, S.V.; To, J.; Wynne, J.F.; Eclov, N.C.; Modlin, L.A.; Liu, C.L.; Neal, J.W.; Wakelee, H.A.; Merritt, R.E.; et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat. Med. 2014, 20, 548–554. [Google Scholar] [CrossRef]
- Vogelstein, B.; Kinzler, K.W. Digital pcr. Proc. Natl. Acad. Sci. USA 1999, 96, 9236–9241. [Google Scholar] [CrossRef]
- Diehl, F.; Li, M.; He, Y.; Kinzler, K.W.; Vogelstein, B.; Dressman, D. BEAMing: Single-molecule PCR on microparticles in water-in-oil emulsions. Nat. Methods 2006, 3, 551–559. [Google Scholar] [CrossRef] [PubMed]
- Kasi, P.M.; Sawyer, S.; Guilford, J.; Munro, M.; Ellers, S.; Wulff, J.; Hook, N.; Krinshpun, S.; Malashevich, A.K.; Malhotra, M.; et al. BESPOKE study protocol: A multicentre, prospective observational study to evaluate the impact of circulating tumour DNA guided therapy on patients with colorectal cancer. BMJ Open 2021, 11, e047831. [Google Scholar] [CrossRef] [PubMed]
- ROSS, A.A. Minimal residual disease in solid tumor malignancies: A review. J. Hematotherapy 1998, 7, 9–18. [Google Scholar] [CrossRef] [PubMed]
- Cohen, S.A.; Liu, M.C.; Aleshin, A. Practical recommendations for using ctDNA in clinical decision making. Nature 2023, 619, 259–268. [Google Scholar] [CrossRef] [PubMed]
- Sant, M.; Bernat-Peguera, A.; Felip, E.; Margelí, M. Role of ctDNA in breast cancer. Cancers 2022, 14, 310. [Google Scholar] [CrossRef] [PubMed]
- Neri, A.; Marrelli, D.; Rossi, S.; De Stefano, A.; Mariani, F.; De Marco, G.; Caruso, S.; Corso, G.; Cioppa, T.; Pinto, E.; et al. Breast cancer local recurrence: Risk factors and prognostic relevance of early time to recurrence. World J. Surg. 2007, 31, 36–45. [Google Scholar] [CrossRef]
- Cohen, J.D.; Li, L.; Wang, Y.; Thoburn, C.; Afsari, B.; Danilova, L.; Douville, C.; Javed, A.A.; Wong, F.; Mattox, A.; et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 2018, 359, 926–930. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Murillas, I.; Schiavon, G.; Weigelt, B.; Ng, C.; Hrebien, S.; Cutts, R.J.; Cheang, M.; Osin, P.; Nerurkar, A.; Kozarewa, I.; et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci. Transl. Med. 2015, 7, 302ra133. [Google Scholar] [CrossRef] [PubMed]
- Olsson, E.; Winter, C.; George, A.; Chen, Y.; Howlin, J.; Tang, M.H.E.; Dahlgren, M.; Schulz, R.; Grabau, D.; van Westen, D.; et al. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol. Med. 2015, 7, 1034–1047. [Google Scholar] [CrossRef] [PubMed]
- Coombes, R.C.; Page, K.; Salari, R.; Hastings, R.K.; Armstrong, A.; Ahmed, S.; Ali, S.; Cleator, S.; Kenny, L.; Stebbing, J.; et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin. Cancer Res. 2019, 25, 4255–4263. [Google Scholar] [CrossRef] [PubMed]
- Lipsyc-Sharf, M.; de Bruin, E.C.; Santos, K.; McEwen, R.; Stetson, D.; Patel, A.; Kirkner, G.J.; Hughes, M.E.; Tolaney, S.M.; Partridge, A.H.; et al. Circulating tumor DNA and late recurrence in high-risk hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer. J. Clin. Oncol. 2022, 40, 2408–2419. [Google Scholar] [CrossRef]
- Magbanua, M.J.M.; Swigart, L.B.; Wu, H.T.; Hirst, G.L.; Yau, C.; Wolf, D.M.; Tin, A.; Salari, R.; Shchegrova, S.; Pawar, H.; et al. Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann. Oncol. 2021, 32, 229–239. [Google Scholar] [CrossRef]
- Magbanua, M.J.M.; Swigart, L.B.; Ahmed, Z.; Sayaman, R.W.; Renner, D.; Kalashnikova, E.; Hirst, G.L.; Yau, C.; Wolf, D.M.; Li, W.; et al. Clinical significance and biology of circulating tumor DNA in high-risk early-stage HER2-negative breast cancer receiving neoadjuvant chemotherapy. Cancer Cell 2023, 41, 1091–1102. [Google Scholar] [CrossRef] [PubMed]
- Turner, N.C.; Swift, C.; Jenkins, B.; Kilburn, L.; Coakley, M.; Beaney, M.; Fox, L.; Goddard, K.; Garcia-Murillas, I.; Proszek, P.; et al. Results of the c-TRAK TN trial: A clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate-and high-risk early-stage triple-negative breast cancer. Ann. Oncol. 2023, 34, 200–211. [Google Scholar] [CrossRef]
- Tie, J.; Cohen, J.D.; Lahouel, K.; Lo, S.N.; Wang, Y.; Kosmider, S.; Wong, R.; Shapiro, J.; Lee, M.; Harris, S.; et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N. Engl. J. Med. 2022, 386, 2261–2272. [Google Scholar] [CrossRef] [PubMed]
- Raei, N.; Safaralizadeh, R.; Latifi-Navid, S. Clinical application of circulating tumor DNA in metastatic cancers. Expert Rev. Mol. Diagn. 2023, 23, 1209–1220. [Google Scholar] [CrossRef] [PubMed]
- Heidary, M.; Auer, M.; Ulz, P.; Heitzer, E.; Petru, E.; Gasch, C.; Riethdorf, S.; Mauermann, O.; Lafer, I.; Pristauz, G.; et al. The dynamic range of circulating tumor DNA in metastatic breast cancer. Breast Cancer Res. 2014, 16, 421. [Google Scholar] [CrossRef]
- Zhou, Y.; Xu, Y.; Gong, Y.; Zhang, Y.; Lu, Y.; Wang, C.; Yao, R.; Li, P.; Guan, Y.; Wang, J.; et al. Clinical factors associated with circulating tumor DNA (ct DNA) in primary breast cancer. Mol. Oncol. 2019, 13, 1033–1046. [Google Scholar] [CrossRef]
- Wang, R.; Li, X.; Zhang, H.; Wang, K.; He, J. Cell-free circulating tumor DNA analysis for breast cancer and its clinical utilization as a biomarker. Oncotarget 2017, 8, 75742. [Google Scholar] [CrossRef]
- Rossi, G.; Mu, Z.; Rademaker, A.W.; Austin, L.K.; Strickland, K.S.; Costa, R.L.B.; Nagy, R.J.; Zagonel, V.; Taxter, T.J.; Behdad, A.; et al. Cell-free DNA and circulating tumor cells: Comprehensive liquid biopsy analysis in advanced breast cancer. Clin. Cancer Res. 2018, 24, 560–568. [Google Scholar] [CrossRef]
- Dawson, S.J.; Tsui, D.W.; Murtaza, M.; Biggs, H.; Rueda, O.M.; Chin, S.F.; Dunning, M.J.; Gale, D.; Forshew, T.; Mahler-Araujo, B.; et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N. Engl. J. Med. 2013, 368, 1199–1209. [Google Scholar] [CrossRef] [PubMed]
- Fiste, O.; Liontos, M.; Koutsoukos, K.; Terpos, E.; Dimopoulos, M.A.; Zagouri, F. Circulating tumor DNA-based predictive biomarkers in breast cancer clinical trials: A narrative review. Ann. Transl. Med. 2020, 8, 1603. [Google Scholar] [CrossRef] [PubMed]
- Appierto, V.; Di Cosimo, S.; Reduzzi, C.; Pala, V.; Cappelletti, V.; Daidone, M.G. How to study and overcome tumor heterogeneity with circulating biomarkers: The breast cancer case. Semin. Cancer Biol. 2017, 44, 106–116. [Google Scholar] [CrossRef]
- Turner, N.C.; Kingston, B.; Kilburn, L.S.; Kernaghan, S.; Wardley, A.M.; Macpherson, I.R.; Baird, R.D.; Roylance, R.; Stephens, P.; Oikonomidou, O.; et al. Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): A multicentre, multicohort, phase 2a, platform trial. Lancet Oncol. 2020, 21, 1296–1308. [Google Scholar] [CrossRef] [PubMed]
- Krawczyk, N.; Fehm, T.; Banys-Paluchowski, M.; Janni, W.; Schramm, A. Liquid biopsy in metastasized breast cancer as basis for treatment decisions. Oncol. Res. Treat. 2016, 39, 112–116. [Google Scholar] [CrossRef] [PubMed]
- Kingston, B.; Cutts, R.J.; Bye, H.; Beaney, M.; Walsh-Crestani, G.; Hrebien, S.; Swift, C.; Kilburn, L.S.; Kernaghan, S.; Moretti, L.; et al. Genomic profile of advanced breast cancer in circulating tumour DNA. Nat. Commun. 2021, 12, 2423. [Google Scholar] [CrossRef]
- Turner, N.; Huang-Bartlett, C.; Kalinsky, K.; Cristofanilli, M.; Bianchini, G.; Chia, S.; Iwata, H.; Janni, W.; Ma, C.X.; Mayer, E.L.; et al. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol. 2023, 19, 559–573. [Google Scholar] [CrossRef]
- Hua, H.; Zhang, H.; Chen, J.; Wang, J.; Liu, J.; Jiang, Y. Targeting Akt in cancer for precision therapy. J. Hematol. Oncol. 2021, 14, 128. [Google Scholar] [CrossRef] [PubMed]
- Ma, C.X.; Bose, R.; Gao, F.; Freedman, R.A.; Telli, M.L.; Kimmick, G.; Winer, E.; Naughton, M.; Goetz, M.P.; Russell, C.; et al. Neratinib efficacy and circulating tumor DNA detection of HER2 mutations in HER2 nonamplified metastatic breast cancer. Clin. Cancer Res. 2017, 23, 5687–5695. [Google Scholar] [CrossRef]
- 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, 3. [Google Scholar] [CrossRef] [PubMed]
- Guan, X.; Liu, B.; Niu, Y.; Dong, X.; Zhu, X.; Li, C.; Li, L.; Yi, Z.; Sun, X.; Chen, H.; et al. Longitudinal HER2 amplification tracked in circulating tumor DNA for therapeutic effect monitoring and prognostic evaluation in patients with breast cancer. Breast 2020, 49, 261–266. [Google Scholar] [CrossRef] [PubMed]
- Modi, S.; Jacot, W.; Yamashita, T.; Sohn, J.; Vidal, M.; Tokunaga, E.; Tsurutani, J.; Ueno, N.T.; Prat, A.; Chae, Y.S.; et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N. Engl. J. Med. 2022, 387, 9–20. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.; Park, Y.H. Trastuzumab deruxtecan for HER2+ advanced breast cancer. Future Oncol. 2021, 18, 7–19. [Google Scholar] [CrossRef]
- Seligson, J.M.; Patron, A.M.; Berger, M.J.; Harvey, R.D.; Seligson, N.D. Sacituzumab govitecan-hziy: An antibody-drug conjugate for the treatment of refractory, metastatic, triple-negative breast cancer. Ann. Pharmacother. 2021, 55, 921–931. [Google Scholar] [CrossRef]
- Rugo, H.S.; Bardia, A.; Tolaney, S.M.; Arteaga, C.; Cortes, J.; Sohn, J.; Marmé, F.; Hong, Q.; Delaney, R.J.; Hafeez, A.; et al. TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2-metastatic breast cancer. Future Oncol. 2020, 16, 705–715. [Google Scholar] [CrossRef]
- Marcus, L.; Fashoyin-Aje, L.A.; Donoghue, M.; Yuan, M.; Rodriguez, L.; Gallagher, P.S.; Philip, R.; Ghosh, S.; Theoret, M.R.; Beaver, J.A.; et al. FDA approval summary: Pembrolizumab for the treatment of tumor mutational burden–high solid tumors. Clin. Cancer Res. 2021, 27, 4685–4689. [Google Scholar] [CrossRef] [PubMed]
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Afzal, M.Z.; Vahdat, L.T. Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine. J. Pers. Med. 2024, 14, 719. https://doi.org/10.3390/jpm14070719
Afzal MZ, Vahdat LT. Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine. Journal of Personalized Medicine. 2024; 14(7):719. https://doi.org/10.3390/jpm14070719
Chicago/Turabian StyleAfzal, Muhammad Zubair, and Linda T. Vahdat. 2024. "Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine" Journal of Personalized Medicine 14, no. 7: 719. https://doi.org/10.3390/jpm14070719