neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.

The objectives of this study were to determine the prognostic significance of subgrouping estrogen receptor (ER)-positive breast tumors into low-and high-risk luminal categories using Ki67 index, TP53, or progesterone receptor (PR) status. The study group comprised 540 patients with lymph node negative, invasive breast carcinoma. Luminal A subtype was defined as being ER positive, HER2 negative, and Ki67 low (o14% cells positive) and luminal B subtype as being ER positive, HER2 negative, and Ki67 high (Z14% cells positive). Luminal tumors were also subgrouped into risk categories based on the PR and TP53 status. Survival analysis was performed. Patients with luminal B tumors (n ¼ 173) had significantly worse disease-free survival compared to those with luminal A tumors (n ¼ 186) (log rank P-value ¼ 0.0164; univariate Cox regression relative risk 2.00; 95% CI, 1.12-3.58; P ¼ 0.0187). Luminal subtype remained an independent prognostic indicator on multivariate analysis including traditional prognostic factors (relative risk 2.12; 95% CI, 1.16-3.88; P ¼ 0.0151). Using TP53 status or PR negativity rather than Ki67 to classify ER-positive luminal tumors gave similar outcome results to those obtained using the proliferation index. However, it was a combination of the three markers, which proved the most powerful prognostically. Ki67 index, TP53 status, or PR negativity can be used to segregate ERpositive, HER2-negative tumors into prognostically meaningful subgroups with significantly different clinical outcomes. These biomarkers particularly in combination may potentially be used clinically to guide patient management.

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“…18 Written informed consent was obtained from all participants. Patients were followed for recurrence and death.…”

Section: Patient Cohort and Clinical Follow-upmentioning

confidence: 99%

Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

et al. 2014

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“…Moreover, ampli®cation and consequent overexpression prognosticates a poor clinical prognosis in both lymph node positive (Hynes and Stern, 1994;Mansour et al, 1994;Ravdin, 1995) and node-negative (Andrulis et al, 1998) breast cancer patients. It is felt that ErbB-2 overexpression leads to an aggressive tumor phenotype as elevated ErbB-2 expression is detected in many in situ and invasive human ductal carcinomas, yet is rarely observed in benign breast disorders (hyperpla-*Correspondence: WJ Muller sias and dysplasias) (Allred et al, 1992;reviewed in Mansour et al, 1994).…”

Section: Erbb-2 Plays a Causal Role In Mammary Tumorigenesismentioning

confidence: 99%

Signal transduction in mammary tumorigenesis: a transgenic perspective

Dankort

Muller

2000

Oncogene

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“…Loss of oestrogen or progesterone receptor expression was the first molecular feature recognised to associate with poor survival in breast cancer (Chevallier et al, 1988). C-erbB-2 expression has been linked to resistance to chemotherapy and poor outcome (Andrulis et al, 1998), while apoptosis-related proteins such as p53 and bcl-2 have been related to disease-free interval and survival of breast cancer patients (Thor et al, 1992;Gasparini et al, 1995). Similarly, a large body of clinicopathological studies support the important and independent prognostic role of the tumour angiogenic ability in operable breast cancer (Locopo et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of local relapse in high-risk breast cancer patients: can radiotherapy fractionation and time factors make a difference?

et al. 2003

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Large primary breast tumours and extensive lymph node involvement are linked to a high rate of local recurrence after surgery. In 10 -20% of such high-risk breast cancer patients, local relapse will occur despite postoperative radiotherapy. In the present study, we investigated whether molecular features, such as angiogenesis, cancer cell proliferation, steroid receptor expression, c-erbB-2 oncoprotein overexpression, p53 protein nuclear accumulation or bcl-2 antiapoptotic protein expression, can predict failure of local therapy. We further examined as to which subgroups of patients could benefit from altered fractionation schemes of radiotherapy. In univariate analysis, high intratumoural angiogenesis, c-erbB overxpression and mutant-p53 nuclear accumulation were significantly associated with increased relapse rate (P ¼ 0.0002, 0.009 and 0.05, respectively). In multivariate analysis, the microvessel density and the c-erbB-2 status were independent and significant factors related to local relapse (P ¼ 0.001, t-ratio 3.36 and P ¼ 0.02, t-ratio 2.26, respectively). Hypofractionated and accelerated radiotherapy supported with amifostine (HypoARC regimen) was significantly more effective than standard radiotherapy in cases with high cancer cell proliferation index, c-erbB-2 and p53 overexpression. High angiogenesis, however, was linked with local relapse regardless of the radiotherapy regimen.

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neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.

Cited by 396 publications

References 29 publications

Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

Signal transduction in mammary tumorigenesis: a transgenic perspective

Molecular analysis of local relapse in high-risk breast cancer patients: can radiotherapy fractionation and time factors make a difference?

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