Relationship Between Quantitative Estrogen and Progesterone Receptor Expression and Human Epidermal Growth Factor Receptor 2 (HER-2) Status With Recurrence in the Arimidex, Tamoxifen, Alone or in Combination Trial

Dowsett, Mitch; Allred, Craig; Knox, Jill; Quinn, Emma M.; Salter, Janine; Wale, Chris; Cuzick, Jack; Houghton, J; Williams, NR; Mallon, Elizabeth; Bishop, Hugh; Ellis, Ian O.; Larsimont, Denis; Sasano, Hironobu; Carder, P J; Llombart-Cussac, Antonio; Knox, Fiona; Speirs, Valerie; Forbes, John F.; Buzdar, Aman U.

doi:10.1200/jco.2007.12.9437

Cited by 419 publications

(293 citation statements)

References 17 publications

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“…Most studies analyzing predictive or prognostic factors in ER-positive breast cancer have been performed in postmenopausal women, mainly using patients and samples in adjuvant aromatase inhibitor trials [3,4,23]. In premenopausal women, however, even the clinical role of PgR has been little analyzed so far.…”

Section: Discussionmentioning

confidence: 99%

“…Estrogen receptor (ER) is essential for estrogen-dependent growth, and its level of expression is considered a crucial determinant of response to endocrine therapy and prognosis in ER-positive breast cancer [1][2][3][4]. On the other hand, the clinical role of progesterone receptor (PgR) in ER-positive breast cancer remains controversial, although testing of PgR by immunohistochemistry (IHC) has become routine [5].…”

Section: Introductionmentioning

confidence: 99%

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Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer

Hosoda

Yamamoto

Nakano

et al. 2014

Breast Cancer Res Treat

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Estrogen receptor (ER) is essential for estrogen-dependent growth, and its level of expression is considered a crucial determinant of response to endocrine therapy and prognosis in ER-positive breast cancer. On the other hand, the clinical role of progesterone receptor (PgR) in ER-positive breast cancer remains controversial, although testing of PgR by immunohistochemistry (IHC) has become routine. Recent studies indicated that plasma estradiol levels were related to expression levels of estrogen-responsive genes in ER-positive breast cancer tissues in both preand postmenopausal women. In this study, we analyzed expression levels of estrogen-responsive genes (PgR and TFF1), a progesterone-responsive gene (RANKL), ER-related genes (FOXA1 and GATA3), HER2, Ki67 and p53 in ER-positive, HER2-negative breast cancer tissues by IHC.Correlations between expression levels of these molecular markers and clinicopathological factors, including prognosis, were compared between pre-and postmenopausal women. Serum levels of estrone, estradiol, progesterone and testosterone were also measured. Expression levels of PgR, TFF1, RANKL and GATA3 were significantly higher in premenopausal women than in postmenopausal women. Serum estradiol levels were positively correlated with Ki67 labeling index (LI) in premenopausal women, but not in postmenopausal women. High expression of FOXA1 and GATA3 was significantly associated with improved disease-free survival in premenopausal women, but not in postmenopausal women, whereas high expression of PgR and low expression of p53 was significantly correlated with improved disease-free survival in postmenopausal women, but not in premenopausal women. Moreover, the best cutoff points of 3 Ki67 LI for disease-free survival were 30% for premenopausal women and 14% for postmenopausal women. Expression levels of ER, TFF1 and RANKL were not associated with disease-free survival in either pre-or postmenopausal women. Our results suggest that the mechanisms of development and estrogen-dependent growth of ER-positive breast cancer might differ according to menopausal status.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer

Hosoda

Yamamoto

Nakano

et al. 2014

Breast Cancer Res Treat

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“…6 In two randomized controlled trials of tamoxifen therapy versus no treatment supported the use of tamoxifen as adjuvant therapy. 7 As it has been demonstrated that time to recurrence varies inversely with hormone receptor expression, 8 each patients' likelihood of benefiting from hormonal therapy depends significantly on the degree of ER and PR expression. [9][10][11][12][13][14][15] As tamoxifen has been associated with increased incidence of thromboembolic events and endometrial cancer, it is necessary to evaluate risk versus benefit for each patient.…”

Section: Discussionmentioning

confidence: 99%

Semi-quantitative immunohistochemical assay versus oncotype DX® qRT-PCR assay for estrogen and progesterone receptors: an independent quality assurance study

et al. 2012

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Estrogen receptor (ER) status is a strong predictor of response to hormonal therapy in breast cancer patients. Presence of ER and level of expression have been shown to correlate with time to recurrence in patients undergoing therapy with tamoxifen or aromatase inhibitors. Risk reduction is also known to occur in ERnegative, progesterone receptor (PR)-positive patients treated with hormonal therapy. Since the 1990s, immunohistochemistry has been the primary method for assessing hormone receptor status. Recently, as a component of its oncotype DX s assay, Genomic Health began reporting quantitative estrogen and PR results determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of an ongoing quality assurance program at our institution, we reviewed 464 breast cancer cases evaluated by both immunohistochemistry and oncotype DX s assay for estrogen and PR. We found good correlation for ER status between both assays (98.9% concordance), with immunohistochemistry being slightly more sensitive. Concordance for PR was 94.2% between immunohistochemistry and qRT-PCR with immunohistochemistry again more sensitive than RT-PCR. The results also showed linear correlation between immunohistochemistry H-scores and qRT-PCR expression values for ER (correlation coefficient of 0.579), and PR (correlation coefficient of 0.685). Due to the higher sensitivity of hormone receptor immunohistochemistry and additional advantages (ie preservation of morphology, less expensive, faster, more convenient), we conclude immunohistochemistry is preferable to qRT-PCR for determination of estrogen and PR expression.

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“…Breast cancer patients with oestrogen receptor-positive tumours revealing HER-2 amplification have been shown to respond poorly to endocrine therapy with aromatase inhibitors as well as tamoxifen. 147 Adding trastuzumab 148 or lapatinib 149 in concert improves response to aromatase inhibitors. The finding that mTOR inhibition may reverse resistance to endocrine agents in breast cancer MCF-7 cells 150,151 is consistent with clinical findings; recently, two studies reported addition of the mTOR inhibitor everolimus to endocrine therapy with the aromatase inhibitor exemestane 152 or the anti-oestrogen tamoxifen, 153 to significantly improve response to therapy in cancers nonamplified for HER-2.…”

Section: Activating Mutations In the Pten/pi3k/mtor Pathway As A Causmentioning

confidence: 99%

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Lønning

Knappskog

2013

Oncogene

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Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer. Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms. Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair. As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel. Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms.

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Relationship Between Quantitative Estrogen and Progesterone Receptor Expression and Human Epidermal Growth Factor Receptor 2 (HER-2) Status With Recurrence in the Arimidex, Tamoxifen, Alone or in Combination Trial

Cited by 419 publications

References 17 publications

Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer

Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer

Semi-quantitative immunohistochemical assay versus oncotype DX® qRT-PCR assay for estrogen and progesterone receptors: an independent quality assurance study

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

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