Serum HER‐2/<i>neu</i> conversion to positive at the time of disease progression in patients with breast carcinoma on hormone therapy

Lipton, Allan; Leitzel, Kim; Ali, Suhail M.; Demers, Laurence M.; Harvey, Harold A.; Chaudri-Ross, D.E.P. Hilary A.; Evans, Dean B.; Lang, Raquel; Hackl, Wolfgang; Hamer, Peter; Carney, Walter P.

doi:10.1002/cncr.21202

Cited by 93 publications

(63 citation statements)

References 53 publications

(67 reference statements)

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“…Such requirements may explain why some groups have been unable to detect EGFR increases in equivalent clinical material where conventional analysis of growth factor receptor expression positivity is employed. In support of our data, however, HER2 amplification has been reported by others on relapse with antihormonal treatment, while one study showed that 25% of patients treated with firstline hormonal therapy converted from serum HER2 negative to positive on relapse (Lonn et al 1996, Lipton et al 2003. Verification of the role of modestly increased EGFR signalling in acquired tamoxifen resistance should be achievable from the various ongoing clinical trials employing gefitinib in such breast cancers (Nicholson et al 2004b).…”

Section: Introductionsupporting

confidence: 82%

Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer

Gee

Robertson²,

Gutteridge³

et al. 2005

Endocr Relat Cancer

189

173

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Breast cancer models of acquired tamoxifen resistance, oestrogen receptor (ER) + /ER -de novo resistance and gene transfer studies cumulatively demonstrate the increased importance of growth factor receptor signalling, notably the epidermal growth factor receptor (EGFR)/HER2, in tamoxifen resistance. Our recent in vitro studies also suggest that EGFR signalling productively cross-talks with insulin-like growth factor receptor (IGF-1R) and, where present, activates ER on key AF-1 serine residues to facilitate acquired tamoxifen-resistant growth. This paper presents our immunohistochemical evidence that EGFR/HER2 signalling (i.e. transforming growth factor (TGF)a, EGFR and HER2 expression; phosphorylation of EGFR, HER2 and ERK1/2 MAP kinase) is also prominent in clinical de novo resistant and modestly increased in acquired tamoxifen-resistant states, suggesting that anti-EGFR/HER2 strategies may prove valuable treatments. Primary breast cancer samples employed were obtained for (1) patients subsequently treated with tamoxifen for advanced disease where endocrine response and survival data were available and (2) ER + elderly patients during tamoxifen response and relapse. We also present our clinical immunohistochemical findings that IGF-1R expression, its phosphorylation on tyrosine 1316, and also phosphorylation on serine 118 of ER are not only prominent in ER + tamoxifen-responsive disease, but are also detectable in ER + de novo and acquired tamoxifen-resistant breast cancer, where there is evidence of EGFR/ER cross-talk. Our data suggest that agents to deplete effectively ER or IGF-1R signalling may be of value in treating ER + de novo/acquired tamoxifen resistance in addition to tamoxifenresponsive disease in vivo. IGF-1R inhibitors may also prove valuable in ER -patients, since considerable IGF-1R signalling activity was apparent within 50% of such tumours.Endocrine-Related Cancer (2005) 12 S99-S111

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Section: Introductionsupporting

confidence: 82%

Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer

Gee

Robertson²,

Gutteridge³

et al. 2005

Endocr Relat Cancer

189

173

View full text Add to dashboard Cite

show abstract

“…There are also data showing that HER2 status may change, related to previous hormonal treatment, even if the analyses in that study were carried out on circulating tumor cells [21]. We strongly believe that it is very important to identify these patients, as survival could be prolonged substantially for each patient and unnecessary over treatment might be avoided [3,4].…”

Section: Discussionmentioning

confidence: 94%

HER2 status in a population-derived breast cancer cohort: discordances during tumor progression

Wilking

Karlsson

Skoog

et al. 2010

Breast Cancer Res Treat

103

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“…In particular, a few recent provocative clinical studies suggest that acquired resistance to tamoxifen may also be associated with an increase in HER2 gene amplification and/ or expression in patients with breast cancer (Meng et al 2004, Gutierrez et al 2005, Lipton et al 2005.…”

Section: Er Functions and Crosstalk With Growth Factor Receptor Pathwaysmentioning

confidence: 99%

Resistance to endocrine therapy in breast cancer: exploiting estrogen receptor/growth factor signaling crosstalk

Massarweh¹,

Schiff²

2006

Endocr Relat Cancer

142

129

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Targeting the estrogen receptor (ER) is the oldest form of molecular targeted therapy, and the widespread use of the selective estrogen receptor modulator tamoxifen in breast cancer is responsible for major improvements in cure rates, quality of life, and disease prevention in the last 25 years. Newer forms of endocrine therapy now available for the management of endocrine responsive breast cancer include a new generation of aromatase inhibitors, which lower the estrogen ligand for ER, and pure ER antagonists which destroy the receptor. Despite these recent clinical advances, intrinsic and acquired resistance to these endocrine therapies is still a common feature that limits the success of this therapeutic strategy. Recent research into the molecular biology of ER signaling has revealed a remarkably complex interactive signaling with other growth factor signaling pathways in breast cancer cells, potentially explaining some of the reasons behind endocrine therapy action as well as resistance. This view of a more complex ER signaling system has uncovered new molecular targets which, if present in a cancer cell, might be additionally targeted using various signal transduction inhibitors to overcome or prevent resistance to endocrine therapy. In addition, the dynamic inverse relationship between the expression of ER and growth factor receptors brings more excitement to the potential of restoring ER expression in apparently ER-negative cells by inhibition of growth factor signaling. Ongoing clinical trials of endocrine therapy combined with growth factor pathway inhibitors or their downstream signaling elements promise to further improve the present care for breast cancer patients.

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Serum HER‐2/neu conversion to positive at the time of disease progression in patients with breast carcinoma on hormone therapy

Cited by 93 publications

References 53 publications

Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer

Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer

HER2 status in a population-derived breast cancer cohort: discordances during tumor progression

Resistance to endocrine therapy in breast cancer: exploiting estrogen receptor/growth factor signaling crosstalk

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