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2013 Genentech USA, Inc. All rights reserved.
Disclosure/Disclaimer
The Molecular Basis of Breast Cancer slide presentation is not an
independent educational program, and no CME credits will be provided.
This program is not intended to promote any cancer agent
or class approved by the FDA/EMA or currently
under clinical development.
The contents of this slide presentation are owned solely by Genentech;
any unauthorized uses are prohibited.
This program is presented on behalf of Genentech and the information
presented is consistent with FDA guidelines.
The following slides are selected samples from a complete presentation.
They are for educational purposes only.
BIO00020782001
2013 Genentech USA, Inc. All rights reserved.
Granulosa
Sex hormone biology and its role in breast carcinoma
Adrenal glands
ESTRONE
ESTRADIOL
Corpus luteum
Ovaries
PREMENOPAUSAL
POSTMENOPAUSAL Breast adipose
tissue
AROMATASE Breast
PeripheryAROMATASE
(peripheral)
ANDROSTENEDIONE
Fabian CJ. Int J Clin Pract. 2007;61:2051-2063. 2
2013 Genentech USA, Inc. MBoC Program
HER2 protein expression measured by IHC
IHC 0 IHC 1+ IHC 2+ IHC 3+
HER2 expression and prognosis in breast cancer
Shortened median survival in patients with HER2 overexpression (combined adjuvant and metastatic):
• HER2+ 2 to 3 years
• HER2 normal 6 to 7 yearsHER=human epidermal growth factor receptor; IHC=immunohistochemistry.Andrulis IL, et al. J Clin Oncol. 1998;16:1340-1349. Ellis CM, et al. J Clin Pathol. 2005;58:710-714. Banerjee R, et al. J Pharmacol Exp Ther. 2010;334:9-20. Images courtesy of Genentech. 3
2013 Genentech USA, Inc. MBoC Program 4
BRCA1 and BRCA2 have important roles in DNA repair
DNA damage
Cancer
Failed repair of checkpoint genes
Accumulation of mutations
Cell-cycle progression despite damage
Mutations in BRCA1 or BRCA2
BRCA=breast cancer.Venkitaraman AR. J Cell Sci. 2001; 114:3591-3598.
BRCA2
RAD51
BRCA1
Germline mutations in BRCA1 and BRCA2 genes predispose women to an increased risk of breast and ovarian cancers.
References:Venkitaraman AR. Functions of BRCA1 and BRCA2 in the biological response
to DNA damage. J Cell Sci. 2001;114:3591-3598.
Notes
2013 Genentech USA, Inc. All rights reserved.5
HER3
The HER2 signaling pathway and anti-HER2monoclonal antibodies
Cell-cyclecontrol
Proliferation
↑Survival
Ras Sos Grb2 Shc
MEK
Angiogenesis
Raf
Cyclin D1
p27
BAD
GSK3b
NFκBmTOR
MAPK
↓Apoptosis
AktPDK1
PI3K
HER=human epidermal growth factor receptor; Ras=rat sarcoma; Sos=son of sevenless; Grb2=growth factor receptor-bound 2; PI3K=phosphatidylinositol 3-kinase; PDK=phosphoinositide-dependent kinase; PTEN=phosphatase and tensin homolog; Raf=rapidly accelerating fibrosarcoma; MEK=mitogen-activated protein kinase kinase; MAPK=mitogen-activated protein kinase; mTOR=mammalian target of rapamycin; BAD=Bcl-2–associated death promoter; NFκB=nuclear factor kappa–light-chain-enhancer of activated B-cells; GSK=glycogen synthase kinase.Adjei AA, Hidalgo M. J Clin Oncol. 2005;23:5386-5403.
PTEN
HER2
HER3
Domain IV
A strategy to stem proliferative signaling in cancer cells is to target the extracellular region of growth receptors with monoclonal antibodies.
Reference:Adjei AA, Hidalgo M. Intracellular signal transduction pathway proteins as targets for cancer therapy. J Clin Oncol. 2005;23:5386- 5403.
Notes
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