Immunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen

Khoshnoud, Mahmoud R.; Löfdahl, Britta; Fohlin, Helena; Fornander, Tommy; Stål, Olle; Skoog, Lambert; Bergh, Jonas; Nordenskjöld, Bo

doi:10.1007/s10549-010-1202-7

Cited by 57 publications

(58 citation statements)

References 32 publications

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“…Cut-off level for ER positivity was 0.05 fmol/μg DNA. Isoelectric focusing/EIA and IHC data have been shown to be comparable [15]. Human epidermal growth factor receptor 2 (HER2) protein was quantified retrospectively by flow cytometry as described previously [16] and HER2 amplification was determined with quantitative Real-Time PCR [17].…”

Section: Evaluation Of Er Her2 Pik3ca and Paktmentioning

confidence: 99%

Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer

Karlsson

Veenstra

Emin

et al. 2015

Breast Cancer Res Treat

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Gene copy loss of PTPN2 was detected in 16% (34/215) of the tumours and this was significantly correlated with lower levels of PTPN2 mRNA. PTPN2 gene loss and lower mRNA levels were associated with activation of AKT and a poor prognosis. Furthermore, PTPN2 gene loss was a significant predictive marker of poor benefit from tamoxifen treatment.In conclusion, genomic loss of PTPN2 may be a previously unknown mechanism of PI3K/AKT upregulation in breast cancer. PTPN2 status is a potential new clinical marker of endocrine treatment benefit which could guide further individualised therapies in breast cancer.

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Section: Evaluation Of Er Her2 Pik3ca and Paktmentioning

confidence: 99%

Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer

Karlsson

Veenstra

Emin

et al. 2015

Breast Cancer Res Treat

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“…Among postmenopausal women, earlier studies have shown a significant trend in reduction of recurrence rate with higher ER levels among tamoxifen treated, supporting the significance of stronger ER content in endocrine treatment [5][6][7][8].…”

Section: Discussionmentioning

confidence: 92%

“…Remaining research questions include the benefit of LHRH agonists, in addition to tamoxifen, and if LHRH agonists have a role among those not achieving amenorrhea during cytotoxic chemotherapy. Moreover, efficacy of endocrine treament in relation to estrogen receptor (ER) status is mainly established among postmenopausal women, and the different endocrine milieu in premenopausal women may affect the predictive ability of ER status [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Interaction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer

Sverrisdóttir

Johansson

et al. 2011

Breast Cancer Res Treat

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Interaction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer. Breast Cancer Research and Treatment, Springer Verlag, 2011, 128 (3) Abstract: Ovarian ablation improves survival in premenopausal early breast cancer, but the potential added value by luteinizing hormone-releasing hormone (LHRH) agonists to tamoxifen, is still not clear. The purpose of our study is to examine the efficacy of the LHRH agonist goserelin for adjuvant therapy of premenopausal breast cancer, the role of interaction between goserelin and tamoxifen, and the impact of estrogen receptor (ER) content. A total of 927 patients were included in the Stockholm part of the Zoladex in Premenopausal Patients (ZIPP) trial. They were randomly allocated in a 2 x 2 factorial study design to goserelin, tamoxifen, the combination of goserelin and tamoxifen or no endocrine therapy for 2 years, with or without chemotherapy. This is formally not a preplanned subset analysis presenting the endpoint first event. In this Stockholm sub-study, at a median follow up of 12.3 years, goserelin reduced the risk of first event by 32 % (P = 0.005) in the absence of tamoxifen, and tamoxifen reduced the risk by 27 % (P = 0.018) in the absence of goserelin. The combined goserelin and tamoxifen treatment reduced the risk by 24 % (P = 0.021) compared to no endocrine treatment. In highly ER positive tumours, there were 29% fewer events among goserelin treated (P = 0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, P = 0.007). In conclusion, goserelin as well as tamoxifen, reduces the risk of recurrence in endocrine responsive premenopausal breast cancer. Women with strongly ER positive tumours may benefit more from goserelin treatment. The combination of goserelin and tamoxifen is not superior to either modality alone. With the limitations of a subset trial, these data have to be interpreted cautiously.

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“…A number of studies have shown a direct linear relationship between er concentration and survival 3,8,14,16,18,[23][24][25][26] . However, very few studies have supported the use of antihormonal treatment in breast cancer patients whose tumours are weakly positive for er (3-9 fmol/mg cytosol protein by lba or 1%-9% by ihc assay).…”

Section: Discussionmentioning

confidence: 99%

“…Pts = patients; HR = hazard ratio; CI = confidence interval. those used in most previous studies (femtomoles per microgram of dna rather than femtomoles per milligram of cytosol protein) 26 .…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Predictive Value of Low Estrogen Receptor Expression in Breast Cancer

et al. 2017

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Purpose Anti-hormonal therapy (tamoxifen) is recommended for estrogen receptor (er)-positive breast cancer (bca); however, its effect on low-receptor cancers is unclear. We retrospectively evaluated the effect of adjuvant tamoxifen in patients with weakly er-positive bca. MethodsWe identified 2221 bca patients who had been er-tested by ligand-based assay (lba) during [1976][1977][1978][1979][1980][1981][1982][1983][1984][1985][1986][1987][1988][1989][1990][1991][1992][1993][1994][1995] and who had been treated and followed until 2008. Cox proportional hazards models adjusted for age, body mass index, tumour size, nodal status, surgery, and chemotherapy were used to assess the effect of er level on bca survival in patients who received tamoxifen.Results Overall, 17% (383) of patients were within 0-3 fmol/mg cytosol protein, and 12% (266) were within 4-9 fmol/mg cytosol protein. Patients with er levels of 0-3, 4-9, 10-19, 20-49, and 50 fmol/mg or more cytosol protein had 20-year bca survival rates of 56%, 56%, 63%, 71%, and 60% respectively. Of the 2221 patients studied, 661 (29.8%) received anti-hormonal therapy. Within the latter group, er levels of 0-3, 4-9, 10-19, 20-49, and 50 fmol/mg or more cytosol protein were associated with a hazard ratio for lower bca mortality: respectively, 1.00 (reference), 0.59 (p = 0.09), 0.19 (p < 0.0001), 0.26 (p < 0.0001), and 0.31 (p < 0.0001)-the risk reduction being significant only for er levels of 10 fmol/mg or more cytosol protein. ConclusionsTamoxifen use in bca patients with a weakly positive er status (4-9 fmol/mg cytosol protein), compared with those having higher er levels (≥10 fmol/mg cytosol protein), is not associated with a significantly lower bca-specific mortality. Our results do not support treatment with anti-hormonal therapy for bca patients with a weakly positive er status as identified by lba.

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Immunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen

Cited by 57 publications

References 32 publications

Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer

Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer

Interaction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer

Prognostic and Predictive Value of Low Estrogen Receptor Expression in Breast Cancer

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