Oestrogen receptor-negative/progesterone receptor-positive phenotype of invasive breast carcinoma in Japan: re-evaluated using immunohistochemical staining

Kuroda, Hajime; Muroi, Nozomi; Hayashi, Mitsuhiro; Harada, Oi; Hoshi, Kazuei; Fukuma, Eisuke; Abe, Akihito; Kubota, Keiichi; Imai, Yasuo

doi:10.1007/s12282-018-0898-9

Cited by 17 publications

(19 citation statements)

References 23 publications

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“…Such large cohorts are useful to provide data on uncommon subtypes or phenotypes. For example, the prevalence of ER−/PR+ cases in this database is low ( n = 213, 1.7% in the whole ESME cohort), as reported in the literature with a prevalence ranging from 0.3 to 3.4% 27 – 29 .The ER−/PR+ phenotype is still a controversial molecular subtype, as some data suggest that this phenotype might be mainly due to technical artifacts 20 , 30 , while other studies confirmed it as a true but rare biologic subtype 27 – 29 . Moreover, the largest studies to date on this rare phenotype reported a trend for a poorer prognosis (early recurrence, poorer overall and disease free survival) as compared with ER+/PR+ tumors, and more similar to ER-/PR- tumors 28 , 29 .…”

Section: Discussionsupporting

confidence: 45%

Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

et al. 2021

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Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

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Section: Discussionsupporting

confidence: 45%

Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

et al. 2021

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“…The other important nuclear receptor, the progesterone receptor (PR) is expressed in about 70 per cent of ERpositive cases. Whether PR can be expressed in ER-negative cases has long been a point of debate but this phenotype seems to exist rarely [3]. About 20 per cent of breast tumors over-express the HER2/NEU receptor (erbB2) for epidermal growth factor (EGF).…”

Section: Introductionmentioning

confidence: 99%

Time resolved gene expression analysis during tamoxifen adaption of MCF-7 cells identifies long non-coding RNAs with prognostic impact

et al. 2019

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Acquired tamoxifen resistance is a persistent problem for the treatment of estrogen receptor positive, premenopausal breast cancer patients and predictive biomarkers are still elusive. We here analyzed gene expression changes in a cellular model to identify early and late changes upon tamoxifen exposure and thereby novel prognostic biomarkers. Estrogen receptor positive MCF-7 cells were incubated with 4OHtamoxifen (10 nM) and gene expression analyzed by array hybridization during 12 weeks. Array results were confirmed by nCounter-and qRT-PCR technique. Pathway enrichment analysis revealed that early responses concerned mainly amine synthesis and NRF2-related signaling and evolved into a stable gene expression pattern within 4 weeks characterized by changes in glucuronidation-, estrogen metabolism-, nuclear receptor-and interferon signaling pathways. As a large number of long non coding RNAs was subject to regulation, we investigated 5 of these (linc01213, linc00632 linc0992, LOC101929547 and XR_133213) in more detail. From these, only linc01213 was upregulated but all were less abundant in estrogen-receptor negative cell lines (MDA-MB 231, SKBR-3 and UACC3199). In a web-based survival analysis linc01213 and linc00632 turned out to have prognostic impact. Linc01213 was investigated further by plasmid-mediated over-expression as well as siRNA down-regulation in MCF-7 cells. Nevertheless, this had no effect on proliferation or expression of tamoxifen regulated genes, but migration was increased. In conclusion, the cellular model identified a set of lincRNAs with prognostic relevance for breast cancer. One of these, linc01213 although regulated by 4OH-tamoxifen, is not a central regulator of tamoxifen adaption, but interferes with the regulation of migration.

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“…were initially diagnosed with ER-PR+ breast carcinoma, and 7 patients remained ER-PR+ (13). However, another study found that breast carcinoma of ER-PR+ existed, although rare (1.1% of all phenotypes), and had distinct clinicopathologic characteristics (14).…”

Section: Kaplan-meier Curves Of Os and Bcss After Psmmentioning

confidence: 99%

The Prognosis of Single Hormone Receptor-Positive Breast Cancer Stratified by HER2 Status

Zhao

Yang

2021

Front. Oncol.

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Single estrogen receptor (ER)+ and progesterone receptor (PR)+ tumors account for about10% of all breast cancers. However, the prognosis of these single hormone receptor-positive (HR+) tumor remains unclear. We aimed to investigate the characteristics of single HR+ breast tumors according to HER2 status in order to improve the treatment of patients with single HR+. Patients from the SEER program (2010-2016) were divided into ER+PR-, ER-PR+, ER+PR+ and ER-PR- molecular subtypes stratified by HER2 status. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared by Kaplan–Meier curves after propensity score matching (PSM). A total of 203,406 patients were enrolled. Single ER+ and PR+ tumors account for 11.9% of the total population. For HER2- subtype, patients with ER+PR- (n = 16906 pairs) and ER-PR+ (n = 1395 pairs) had worse prognoses than those with ER+PR+ with hazard ratio (HR) and 95% confidence interval (CI) of 1.52 (1.41-1.64) and 2.25 (1.76-2.88) for OS; and 1.94 (1.76-2.14) and 2.57 (1.94-3.40) for BCSS, respectively; ER+PR- showed a better prognosis than ER-PR+ (n = 1394 pairs) and ER-PR- (n = 9626 pairs) with HR (95% CI) of 1.32 (1.06-1.65) and 1.44 (1.33-1.55) for OS, and 1.32 (1.03-1.69) and 1.46 (1.34-1.60) for BCSS, respectively; ER-PR+ had a similar prognosis relative to ER-PR- (n = 1395 pairs) after PSM. For HER2+ subtype, patients with ER-PR+, ER+PR-, and ER-PR- had similar OS and BCSS; ER+PR+ showed a similar prognosis compare with ER-PR+ (n = 535 pairs), but had better OS and BCSS than ER+PR- (n = 5376 pairs) and ER-PR- (n = 8143 pairs) after PSM. In addition, ER+PR+HER2+ showed similar OS and better BCSS compared with ER+PR+HER2- after PSM. In conclusion, single PR+ patients experienced poorer prognoses than single ER+ patients, and may be treated as ER-PR- patients in HER2- subtype. In HER2+ patients, both single ER+ and single PR+ cases showed similar prognoses compared with ER-PR- cases, and may be treated as ER-PR- patients.

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Oestrogen receptor-negative/progesterone receptor-positive phenotype of invasive breast carcinoma in Japan: re-evaluated using immunohistochemical staining

Cited by 17 publications

References 23 publications

Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

Time resolved gene expression analysis during tamoxifen adaption of MCF-7 cells identifies long non-coding RNAs with prognostic impact

The Prognosis of Single Hormone Receptor-Positive Breast Cancer Stratified by HER2 Status

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