Basal biomarkers nestin and INPP4b identify intrinsic subtypes accurately in breast cancers that are weakly positive for oestrogen receptor

Asleh, Karama; Sheffield, Brandon S.; Kos, Zuzana; Won, Jennifer; Wang, Xiu Qing; Gao, Dongxia; Wolber, Robert; Gilks, C Blake; Bernard, Philip S.; Chia, Stephen; Nielsen, Torsten O.

doi:10.1111/his.13038

Cited by 14 publications

(32 citation statements)

References 37 publications

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“…Among luminal tumours, CK14 was the only positive basal marker in 88 cases. Other basal markers such as CK17, vimentin, nestin and p63 [ 1,2 ] could have increased the number of tumours with basal traits in this material.…”

Section: Discussionmentioning

confidence: 89%

Basal markers and prognosis in luminal breast cancer

Engstrøm

Valla

Bofin

2017

Breast Cancer Res Treat

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PurposeBasal marker expression in triple negative breast cancers identifies basal like tumours, and thus separates the TN group into two prognostic groups. However, the expression and prognostic significance of basal markers in luminal breast cancers are poorly described. The aim of this study was to investigate the expression and prognostic value of basal markers (CK5, CK14 and EGFR) in luminal breast cancer.

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Section: Discussionmentioning

confidence: 89%

Basal markers and prognosis in luminal breast cancer

Engstrøm

Valla

Bofin

2017

Breast Cancer Res Treat

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“…Scoring of biomarkers was performed by pathologists who did not have any access to clinical or molecular data. The scoring method used prespecified published criteria for nestin and for INPP4B as previously reported by others and validated by our group . Nestin expression was considered positive if cytoplasmic staining of any intensity above background was observed in ≥1% of invasive breast carcinoma cells.…”

Section: Methodsmentioning

confidence: 99%

“…Representative positive and negative stains for nestin and INPP4B have been shown in previous publications. 23,37 PAM50 nCounter intrinsic subtyping…”

Section: Tissue Microarrays and Ihc Biomarker Assessmentmentioning

confidence: 99%

Basal biomarkers nestin and INPP4B predict gemcitabine benefit in metastatic breast cancer: Samples from the phase III SBG0102 clinical trial

Asleh

Carstensen

Jørgensen

et al. 2018

Intl Journal of Cancer

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In a formal prospective‐retrospective analysis of the phase III SBG0102 clinical trial randomizing metastatic breast cancer patients to gemcitabine‐docetaxel or to single agent docetaxel, patients with basal‐like tumors by PAM50 gene expression had significantly better overall survival in the gemcitabine arm. By immunohistochemistry (IHC), triple negative status was not predictive, but more specific biomarkers have since become available defining basal‐like by nestin positivity or loss of inositol‐polyphosphate‐4‐phosphate (INPP4B). Here, we evaluate their capacity to identify which patients benefit from gemcitabine in the metastatic setting. Nestin and INPP4B staining and interpretation followed published methods. A prespecified statistical plan evaluated the primary hypothesis that patients with basal‐like breast cancer, defined as “nestin+ or INPP4B−”, would have superior overall survival on gemcitabine‐docetaxel when compared to docetaxel. Interaction tests, Kaplan–Meier curves and forest plots were used to assess prognostic and predictive capacities of biomarkers relative to treatment. Among 239 cases evaluable for our study, 36 (15%) had been classified as basal‐like by PAM50. “Nestin+ or INPP4B−” was observed in 41 (17%) of the total cases and was significantly associated with PAM50 basal‐like subtype. Within an estimated median follow‐up of 13 years, patients assigned as IHC basal “nestin+ or INPP4B‐” had significantly better overall survival on gemcitabine‐docetaxel versus docetaxel monotherapy (HR = 0.31, 95%CI: 0.16–0.60), whereas no differences were observed for other patients (HR = 0.99), p‐interaction < 0.01. In the metastatic setting, women with IHC basal breast cancers defined as “nestin+ or INPP4B‐” have superior overall survival when randomized to gemcitabine‐containing chemotherapy compared to docetaxel alone. These findings need to be validated using larger prospective‐retrospective phase III clinical trials series.

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“…INPP4b is a tumour suppressor protein that reportedly acts through inhibition of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B pathway, a signalling pathway whose activity is frequently increased in breast cancer. The absence of INPP4b expression shows high specificity for the basal‐like breast cancer subtype …”

Section: Methodsmentioning

confidence: 99%

“…Epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5 stains were interpreted as positive if ≥1% of tumour cells showed membranous or cytoplasmic staining, respectively . Nestin positivity was defined as cytoplasmic staining in ≥1% of tumour cells, and INPP4b positivity was defined as cytoplasmic expression in ≥5% of tumour cells …”

Section: Methodsmentioning

confidence: 99%