4-IHC classification of breast cancer subtypes in a large cohort of a clinical cancer registry: use in clinical routine for therapeutic decisions and its effect on survival

Inwald, Elisabeth C.; Koller, Michael; Klinkhammer‐Schalke, Monika; Zeman, Florian; Hofstädter, Ferdinand; Gerstenhauer, M.; Brockhoff, Gero; Ortmann, O.

doi:10.1007/s10549-015-3572-3

Cited by 54 publications

(47 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the diagnostic evaluation of breast cancer, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and Ki-67 are routinely used for the classification of breast tumors into distinct subtypes [1, 2]. …”

Section: Introductionmentioning

confidence: 99%

“…Based on the report from the Clinical Cancer Registry Regensburg in Bavaria, Germany, among 4480 patients with non metastatic breast cancers, these immunohistochemical results divided tumors in Luminal A (found in 48.4% patients), Luminal B (24.8% patients), HER2-like (17.8% patients) and Basal-like (found in 9.0% patients) [2]. In another report, among 267 patients with invasive breast carcinomas, 44.9% of tumors were Luminal B type, 21.7% Luminal A tumors, 18.7% triple-negative and 14.6% of pure HER2 type [4].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distribution of Ki-67 values within HER2 & ER/PgR expression variants of ductal breast cancers as a potential link between IHC features and breast cancer biology

et al. 2017

View full text Add to dashboard Cite

BackgroundUnexpected differences in Ki-67 values among HER2 & ER/PgR defined subgroups were found. This study aims to detect possible subdivisions beyond the conventional breast cancer types.MethodsOne thousand one hundred eighty consecutive patients with invasive ductal breast carcinoma were included and distributed in 16 subgroups (four HER2 phenotypes (0+, 1+, 2+ and 3+) times four ER/PgR phenotypes). Complex distributions of Ki-67 values were tested by expectation maximization (EM) clustering.ResultsPooled Ki67 values of all patients showed the presence of three EM clusters (defined as LMA-low mitotic activity, IMA-intermediate mitotic activity and HMA-high mitotic activity) with expected mean Ki-67 values of 1.17%, 40.45% and 77.79%, respectively. Only ER-PgR- tumors significantly dispersed in three clusters (29.75% tumors in LMA, 46.95% in IMA and 23.30% in the HMA cluster), while almost no detected HMA tumors were of ER + PgR+ or ER + PgR- phenotypes.Among 799 ER + PgR+ patients distribution in clusters was HER2 dependent (p = 0.000243), due to increased number of IMA HER2 3+ tumors on the expense of LMA HER2 3+ tumors (52 IMA out of 162 HER2 3+ patients versus113 IMA out of 637 HER2 < 3+ patients). This was not found among ER + PgR- patients (p = 0.186968).Among ER-PgR- patients, HER2 overexpression also increased number of IMA tumor, but by reducing the number of HMA tumors (p < 0.000001). Here, difference between HER2 absent (0+) and HER2 3+ patients was evident (10 HMA out of 125 HER2 3+ patients versus 42 HMA out of 103 HER2 0+ patients).ConclusionsResults suggest that distributions of breast cancers in three clusters of mitotic activity depend on different mechanisms for ER + PgR+ and ER negative tumors. Although HER2 overexpression increases number of IMA tumors in both settings, in the former it is done by reducing number of LMA tumors, while in the latter it reduces the number of HMA tumors. Mitotic activity of ER + PgR- tumors seems unrelated to the HER2 status, possibly as an indicator that ER dysfunctionality in cancers that lack PgR expression. Among ER negative tumors, the absence of HER2 (0+) might be as important as the HER2 overexpression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3212-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distribution of Ki-67 values within HER2 & ER/PgR expression variants of ductal breast cancers as a potential link between IHC features and breast cancer biology

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In addition, clinical examination of axillary lymph nodes is recommended together with ultrasound and ultrasound‐guided FNAB in the diagnostic phase. The pathological report should include histopathological subtype, grade, and the immunohistochemical (IHC) status of oestrogen receptor (ER), progesterone receptor (PgR), Ki67, and human epidermal growth factor receptor 2 (HER2), in order to define patient prognosis and tailor treatment . In patients with operable nodular lesions, FNAB‐derived cell blocks may be sufficient to make the diagnosis, as FNAB cytology and CNB have similar accuracy in terms of specificity, and both show good clinical performance.…”

Section: Introductionmentioning

confidence: 99%

“…The pathological report should include histopathological subtype, grade, and the immunohistochemical (IHC) status of oestrogen receptor (ER), progesterone receptor (PgR), Ki67, and human epidermal growth factor receptor 2 (HER2), in order to define patient prognosis and tailor treatment. 7,8 In patients with operable nodular lesions, FNAB-derived cell blocks may be sufficient to make the diagnosis, as FNAB cytology and CNB have similar accuracy in terms of specificity, and both show good clinical performance. Although the sensitivity of CNB is higher than that of FNAB, the latter is perhaps the most suitable for evaluation of suspicious non-palpable breast lesions.…”

Section: Introductionmentioning

confidence: 99%

Are fine‐needle aspiration biopsy‐derived cell blocks a useful surrogate for tissue samples in breast cancer?

et al. 2018

View full text Add to dashboard Cite

show abstract

“…1,2 It is a heterogeneous disorder that can be categorized into 5 different groups-luminal A, luminal B, HER2, basal and normal types dependent on the expression of markers for hormone-receptors [estrogen receptor (ER) and progesterone receptor (PR)], human ErbB2 [HER2] and Ki67. [3][4][5][6][7] In a separate thought, intrinsic subtypes of BCs were determined by GeneChip Microarrays of 18001 genes for categorization. 8,9 These subtype classifications of BCs have been used to predict patient outcomes and responsiveness to treatments.…”

mentioning

confidence: 99%

Oncogenic and tumor-suppressive mouse models for breast cancer engaging HER2/neu

2016

View full text Add to dashboard Cite

The human c-ErbB2 (HER2) gene is amplified in ~20 % of human breast cancers (BCs), but the protein is overexpressed in ~30% of the cases indicating that multiple different mechanisms contribute to HER2 overexpression in tumors. It has long been used as a molecular marker of BC for sub-categorization for the prediction of prognosis, and determination of therapeutic strategies. In comparison to ER(+) BCs, HER2(+) BCs are more invasive, but the patients respond to monoclonal antibody therapy with trastuzumab or tyrosine kinase inhibitors at least at early stages. To understand the pathophysiology of HER2-driven carcinogenesis and test HER2-targeting therapeutic agents in vivo, numerous mouse models have been created that faithfully reproduce HER2(+) BCs in mice. They include MMTV-neu (active mutant or wild type, rat neu or HER2) models, neu promoter-driven neuNT-transgenic mice, neuNT-knock-in mice at the neu locus, and doxycycline-inducible neuNT-transgenic models. HER2/neu activates the Phosphatidylinositol-3 kinase-AKT-NF-κB pathway to stimulate the mitogenic cyclin D1/Cdk4-Rb-E2F pathway. Of note, overexpression of HER2 also stimulates the cell autonomous Dmp1-Arf-p53 tumor suppressor pathway to quench oncogenic signals to prevent the emergence of cancer cells. Hence tumor development by MMTV-neu mice was dramatically accelerated in mice that lack Dmp1, Arf or p53 with invasion and metastasis. Expressions of neuNT under the endogenous promoter underwent gene amplification, closely recapitulating human HER2(+) BCs. MMTV-HER2 models have been shown to be useful to test humanized monoclonal antibodies to HER2. These mouse models will be useful for the screening of novel therapeutic agents against BCs with HER2 overexpression.

show abstract

4-IHC classification of breast cancer subtypes in a large cohort of a clinical cancer registry: use in clinical routine for therapeutic decisions and its effect on survival

Cited by 54 publications

References 35 publications

Distribution of Ki-67 values within HER2 & ER/PgR expression variants of ductal breast cancers as a potential link between IHC features and breast cancer biology

Distribution of Ki-67 values within HER2 & ER/PgR expression variants of ductal breast cancers as a potential link between IHC features and breast cancer biology

Are fine‐needle aspiration biopsy‐derived cell blocks a useful surrogate for tissue samples in breast cancer?

Oncogenic and tumor-suppressive mouse models for breast cancer engaging HER2/neu

Contact Info

Product

Resources

About