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Book: The future of ErbB1 and ErbB2 pathway inhibition in breast cancer

Slamon, Dennis J.

targeting multiple receptors

(The oncologist ; 9, Suppl. 3)

2004

Author's details	guest ed. Dennis J. Slamon
Series title	The oncologist ; 9, Suppl. 3
Collection
Language	English
Size	28 S. : graph. Darst.
Publisher	AlphaMed Press
Publishing place	Miamisburg, Ohio
Publishing country	United States
Document type	Book
HBZ-ID	HT014223730
Database	Catalogue ZB MED Medicine, Health

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Shelf mark	Loan status	Location
Zs A 4845 -9,Suppl.3-	not available for loan	Zeitschriften-Lesesaal

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Article ; Online: Ribociclib plus Fulvestrant in Advanced Breast Cancer. Reply.

Slamon, Dennis J / Jerusalem, Guy

The New England journal of medicine

2020 Volume 382, Issue 23, Page(s) e85

MeSH term(s)	Aminopyridines ; Breast Neoplasms ; Fulvestrant ; Humans ; Purines
Chemical Substances	Aminopyridines ; Purines ; Fulvestrant (22X328QOC4) ; ribociclib (TK8ERE8P56)
Language	English
Publishing date	2020-06-03
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2004229
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Article ; Online: Frontiers in HER2-positive breast cancer in 2020.

Peddi, Parvin F / Slamon, Dennis J

Current opinion in obstetrics & gynecology

2020 Volume 33, Issue 1, Page(s) 48–52

Abstract: Purpose of review: The field of HER2-positive breast cancer has seen tremendous advances in the last 2 years with largest number of new drugs in decades. The present review aims to summarize the cutting-edge research of the past 2 years and future ... ...

Abstract	Purpose of review: The field of HER2-positive breast cancer has seen tremendous advances in the last 2 years with largest number of new drugs in decades. The present review aims to summarize the cutting-edge research of the past 2 years and future directions. Recent findings: This review will go over four new drugs, three of which have gained FDA approval within the past 18 months, in the treatment of HER2-positive breast cancer. We will go over early and mature clinical data on these therapeutics and ongoing clinical trials further exploring their role in the treatment of patients with advanced HER2-positive breast cancer and HER2 low breast cancer. Will also discuss ongoing trials using immunotherapy and CDK4/6 inhibitors in the advanced HER2-positive setting. Summary: : The therapies described in this review have quickly become standard of care for patients with HER2-positive breast cancer. Furthermore, they have the potential to change the landscape of breast cancer therapy further to include even patients with HER2 low breast cancer.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy ; Female ; Humans ; Receptor, ErbB-2/drug effects ; Receptor, ErbB-2/metabolism ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2020-12-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1049382-7
ISSN	1473-656X ; 1040-872X
ISSN (online)	1473-656X
ISSN	1040-872X
DOI	10.1097/GCO.0000000000000677
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Zs.A 3048: Show issues

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Article ; Online: Integrative transcriptomics and cell systems analyses reveal protective pathways controlled by Igfbp-3 in anthracycline-induced cardiotoxicity.

Chen, Junjie / Chapski, Douglas J / Jong, Jeremy / Awada, Jerome / Wang, Yijie / Slamon, Dennis J / Vondriska, Thomas M / Packard, René R Sevag

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2023 Volume 37, Issue 6, Page(s) e22977

Abstract: Anthracyclines such as doxorubicin (Dox) are effective chemotherapeutic agents; however, their use is hampered by subsequent cardiotoxicity risk. Our understanding of cardiomyocyte protective pathways activated following anthracycline-induced ... ...

Abstract	Anthracyclines such as doxorubicin (Dox) are effective chemotherapeutic agents; however, their use is hampered by subsequent cardiotoxicity risk. Our understanding of cardiomyocyte protective pathways activated following anthracycline-induced cardiotoxicity (AIC) remains incomplete. Insulin-like growth factor binding protein (IGFBP) 3 (Igfbp-3), the most abundant IGFBP family member in the circulation, is associated with effects on the metabolism, proliferation, and survival of various cells. Whereas Igfbp-3 is induced by Dox in the heart, its role in AIC is ill-defined. We investigated molecular mechanisms as well as systems-level transcriptomic consequences of manipulating Igfbp-3 in AIC using neonatal rat ventricular myocytes and human-induced pluripotent stem cell-derived cardiomyocytes. Our findings reveal that Dox induces the nuclear enrichment of Igfbp-3 in cardiomyocytes. Furthermore, Igfbp-3 reduces DNA damage, impedes topoisomerase IIβ expression (Top2β) which forms Top2β-Dox-DNA cleavage complex leading to DNA double-strand breaks (DSB), alleviates detyrosinated microtubule accumulation-a hallmark of increased cardiomyocyte stiffness and heart failure-and favorably affects contractility following Dox treatment. These results indicate that Igfbp-3 is induced by cardiomyocytes in an effort to mitigate AIC.
MeSH term(s)	Humans ; Animals ; Rats ; Anthracyclines ; Transcriptome ; Cardiotoxicity ; Antibiotics, Antineoplastic ; Myocytes, Cardiac
Chemical Substances	Anthracyclines ; doxorubicin-DNA ; Antibiotics, Antineoplastic
Language	English
Publishing date	2023-05-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202201885RR
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 296: Show issues

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Article ; Online: Targeting CDK4 and 6 in Cancer Therapy: Emerging Preclinical Insights Related to Abemaciclib.

Wander, Seth A / O'Brien, Neil / Litchfield, Lacey M / O'Dea, Declan / Morato Guimaraes, Claudia / Slamon, Dennis J / Goel, Shom

The oncologist

2022 Volume 27, Issue 10, Page(s) 811–821

Abstract: Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4 and 6) are approved for the treatment of subsets of patients with hormone receptor positive (HR+) breast cancer (BC). In metastatic disease, strategies involving endocrine therapy ... ...

Abstract	Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4 and 6) are approved for the treatment of subsets of patients with hormone receptor positive (HR+) breast cancer (BC). In metastatic disease, strategies involving endocrine therapy combined with CDK4 and 6 inhibitors (CDK4 and 6i) improve clinical outcomes in HR+ BCs. CDK4 and 6i prevent retinoblastoma tumor suppressor protein phosphorylation, thereby blocking the transcription of E2F target genes, which in turn inhibits both mitogen and estrogen-mediated cell proliferation. In this review, we summarize preclinical data pertaining to the use of CDK4 and 6i in BC, with a particular focus on several of the unique chemical, pharmacologic, and mechanistic properties of abemaciclib. As research efforts elucidate the novel mechanisms underlying abemaciclib activity, potential new applications are being identified. For example, preclinical studies have demonstrated abemaciclib can exert antitumor activity against multiple tumor types and can cross the blood-brain barrier. Abemaciclib has also demonstrated distinct activity as a monotherapeutic in the treatment of BC. Accordingly, we also discuss how a greater understanding of mechanisms related to CDK4 and 6 blockade highlight abemaciclib's unique in-class properties, and could pave new avenues for enhancing its therapeutic efficacy.
MeSH term(s)	Aminopyridines/pharmacology ; Aminopyridines/therapeutic use ; Benzimidazoles ; Breast Neoplasms/pathology ; Cyclin-Dependent Kinase 4 ; Cyclin-Dependent Kinase 6 ; Estrogens ; Female ; Humans ; Mitogens/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Tumor Suppressor Proteins
Chemical Substances	Aminopyridines ; Benzimidazoles ; Estrogens ; Mitogens ; Protein Kinase Inhibitors ; Tumor Suppressor Proteins ; abemaciclib (60UAB198HK) ; CDK4 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22) ; Cyclin-Dependent Kinase 6 (EC 2.7.11.22)
Language	English
Publishing date	2022-07-01
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyac138
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 494: Show issues

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Article ; Online: Overall Survival With Palbociclib Plus Letrozole in Advanced Breast Cancer.

Slamon, Dennis J / Diéras, Véronique / Rugo, Hope S / Harbeck, Nadia / Im, Seock-Ah / Gelmon, Karen A / Lipatov, Oleg N / Walshe, Janice M / Martin, Miguel / Chavez-MacGregor, Mariana / Bananis, Eustratios / Gauthier, Eric / Lu, Dongrui R / Kim, Sindy / Finn, Richard S

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2024 Volume 42, Issue 9, Page(s) 994–1000

Abstract: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial ... ...

Abstract	Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in
MeSH term(s)	Humans ; Female ; Letrozole ; Breast Neoplasms ; Receptor, ErbB-2/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Piperazines ; Pyridines
Chemical Substances	Letrozole (7LKK855W8I) ; palbociclib (G9ZF61LE7G) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Piperazines ; Pyridines
Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.23.00137
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 650: Show issues

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Article ; Online: Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease.

Cobleigh, Melody A / Vogel, Charles L / Tripathy, Debu / Robert, Nicholas J / Scholl, Susy / Fehrenbacher, Louis / Wolter, Janet M / Paton, Virginia / Shak, Steven / Lieberman, Gracie / Slamon, Dennis J

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2023 Volume 41, Issue 8, Page(s) 1501–1510

Abstract: Purpose: Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was ... ...

Abstract	Purpose: Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease. Patients and methods: Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals. Results: Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events. Conclusion: Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.
Language	English
Publishing date	2023-03-07
Publishing country	United States
Document type	Journal Article ; Corrected and Republished Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.22.02510
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 650: Show issues

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Article ; Online: Correction: PP2A inhibition overcomes acquired resistance to HER2 targeted therapy.

McDermott, Martina S J / Browne, Brigid C / Conlon, Neil T / O'Brien, Neil A / Slamon, Dennis J / Henry, Michael / Meleady, Paula / Clynes, Martin / Dowling, Paul / Crown, John / O'Donovan, Norma

Molecular cancer

2023 Volume 22, Issue 1, Page(s) 175

Language	English
Publishing date	2023-10-30
Publishing country	England
Document type	Published Erratum
ZDB-ID	2091373-4
ISSN	1476-4598 ; 1476-4598
ISSN (online)	1476-4598
ISSN	1476-4598
DOI	10.1186/s12943-023-01890-z
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Article ; Online: Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of

Vogel, Charles L / Cobleigh, Melody A / Tripathy, Debu / Gutheil, John C / Harris, Lyndsay N / Fehrenbacher, Louis / Slamon, Dennis J / Murphy, Maureen / Novotny, William F / Burchmore, Michael / Shak, Steven / Stewart, Stanford J / Press, Michael

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2023 Volume 41, Issue 9, Page(s) 1638–1645

Abstract: Purpose: To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with : Patients and methods: One hundred fourteen women with : Results: The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%) ...

Abstract	Purpose: To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with Patients and methods: One hundred fourteen women with Results: The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ Conclusion: Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with
Language	English
Publishing date	2023-02-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Corrected and Republished Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.22.02516
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE).

de Haas, Sanne L / Slamon, Dennis J / Martin, Miguel / Press, Michael F / Lewis, Gail D / Lambertini, Chiara / Prat, Aleix / Lopez-Valverde, Vanesa / Boulet, Thomas / Hurvitz, Sara A

Breast cancer research : BCR

2023 Volume 25, Issue 1, Page(s) 2

Abstract: Background: KRISTINE is an open-label, phase III study of trastuzumab emtansine + pertuzumab (T-DM1 + P) versus docetaxel + carboplatin + trastuzumab + pertuzumab (TCH + P) in patients with HER2-positive, stage II-III breast cancer. We investigated the ... ...

Abstract	Background: KRISTINE is an open-label, phase III study of trastuzumab emtansine + pertuzumab (T-DM1 + P) versus docetaxel + carboplatin + trastuzumab + pertuzumab (TCH + P) in patients with HER2-positive, stage II-III breast cancer. We investigated the association of biomarkers with clinical outcomes in KRISTINE. Methods: Patients were randomized to receive neoadjuvant T-DM1 + P or TCH + P and assessed for pathologic complete response (pCR; ypT0/is, ypN0). HER2 status (per central assessment), hormone receptor status, PIK3CA mutation status, HER2/HER3 mRNA levels, tumor-infiltrating lymphocyte levels, PD-L1 status, and NanoString data were analyzed. pCR rates by treatment arm were compared across biomarker subgroups. Analyses were descriptive. Results: Biomarker analyses included data from all 444 patients (T-DM1 + P, n = 223; TCH + P, n = 221) enrolled in KRISTINE. Biomarker distribution was balanced across treatment arms. All subgroups with higher HER2 amplification/expression and immune marker levels showed numerically higher pCR rates in both arms. Mutated versus non-mutated PIK3CA tumors were associated with numerically lower pCR rates in the T-DM1 + P arm but not in the TCH + P arm. In a multivariate analysis, Prediction Analysis of Microarray with the 50-gene classifier (PAM50) HER2-enriched subtype, HER2 gene ratio ≥ 4, and PD-L1-positive status positively influenced the pCR rate. Biomarkers associated with lower pCR rates (e.g., low HER2 levels, positive hormone receptor status, mutated PIK3CA) were more likely to co-occur. Dynamic on-treatment biomarker changes were observed. Differences in the treatment effects for T-DM1 + P versus TCH + P were similar to those observed in the intent-to-treat population for the majority of the biomarker subgroups. Conclusions: Although our biomarker analysis did not identify a subgroup of patients that benefited from neoadjuvant T-DM1 + P versus TCH + P, the data revealed that patients with higher HER2 amplification/expression and immune marker levels had improved response irrespective of treatment arm. These analyses confirm the role of HER2 tumor biology and the immune microenvironment in influencing pCR in the neoadjuvant setting and reaffirm the molecular diversity of HER2-positive breast cancer. Trial registration: ClinicalTrials.gov NCT02131064. Registered 06 May 2014.
MeSH term(s)	Female ; Humans ; Ado-Trastuzumab Emtansine/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; B7-H1 Antigen ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/analysis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Class I Phosphatidylinositol 3-Kinases/genetics ; Neoadjuvant Therapy ; Receptor, ErbB-2/genetics ; Standard of Care ; Trastuzumab/therapeutic use ; Tumor Microenvironment/immunology
Chemical Substances	Ado-Trastuzumab Emtansine (SE2KH7T06F) ; B7-H1 Antigen ; Biomarkers, Tumor ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; pertuzumab (K16AIQ8CTM) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2023-01-11
Publishing country	England
Document type	Randomized Controlled Trial ; Clinical Trial, Phase III ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-022-01587-z
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