p53 protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer.

Clahsen, P. C.; Velde, C.J. van de; Duval, Christian; Pallud, C.; Mandard, A.M.; Delobelle-Deroide, A; Broek, L. van den; Sahmoud, Tarek; Vijver, Marc J. van de

doi:10.1200/jco.1998.16.2.470

Cited by 147 publications

(63 citation statements)

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“…In this series, we have shown previously that premenopausal node-negative breast cancer patients whose tumours show p53 accumulation have a poor response to one cycle of adjuvant chemotherapy, whereas patients whose tumours have no accumulation of p53 benefit from adjuvant chemotherapy. In addition, we showed Ki-67 overexpression, negative ER status, and young age (o43 years) to be associated with worse prognosis (Clahsen et al, 1998). apy given directly after surgery yields better results in terms of treatment outcome than surgery alone.…”

mentioning

confidence: 73%

“…Previously, tumour sections had been stained and analysed for oestrogen and progesterone receptor status, Ki-67 positivity, P53 expression, HER2 expression, and mitotic index (Clahsen et al, 1998).…”

Section: Other Tumour Markersmentioning

confidence: 99%

“…Tumours were histologically typed and graded (Elston et al, 1991) centrally by one pathologist; immunohistochemistry to assess the expression of various proteins has been performed. Results of these studies have been reported previously (Clahsen et al, 1998). For the present study, assays were reviewed simultaneously by two investigators (MJ Van de Vijver, JA Van der Hage) who had to come to an agreement in case of any uncertainties.…”

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confidence: 95%

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Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients

et al. 2004

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The RPS6KB1 gene is amplified and overexpressed in approximately 10% of breast carcinomas and has been found associated with poor prognosis. We studied the prognostic significance of P70 S6 kinase protein (PS6K) overexpression in a series of 452 nodenegative premenopausal early-stage breast cancer patients (median follow-up: 10.8 years). Immunohistochemistry was used to assess PS6K expression in the primary tumour, which had previously been analysed for a panel of established prognostic factors in breast cancer. In a univariate analysis, PS6K overexpression was associated with worse distant disease-free survival as well as impaired locoregional control (HR 1.80, P 0.025 and HR 2.50, P 0.006, respectively). In a multivariate analysis including other prognostic factors, PS6K overexpression remained an independent predictor for poor locoregional control (RR 2.67, P 0.003). To our knowledge, P70 S6 kinase protein is the first oncogenic marker that has prognostic impact on locoregional control and therefore may have clinical implications in determining the local treatment strategy in early-stage breast cancer patients. The treatment of breast cancer is guided by risk factors. Approximately 70% of all node-negative breast cancer patients can be cured by locoregional therapy alone. This automatically implies that the remaining 30% of these patients will develop a recurrence despite adequate locoregional therapy. Currently, treatment strategy in breast cancer is based upon tumour stage, grade, and hormone receptor status. Additional prognostic factors are greatly needed, first to select those patients who might benefit from adjuvant systemic therapy and second to optimise locoregional therapy in order to avoid locoregional recurrences.The prognostic significance of a considerable number of tumour markers has already been investigated but to date, none of these factors can be used to guide the treatment of primary breast cancer.A recent study by Barlund et al (2000a) demonstrated that amplification of a putative tumour marker called P70 S6 kinase protein (PS6K) might be associated with poor outcome in breast cancer. In addition, the authors reported that RPS6KB1 gene amplification and PS6K overexpression are significantly correlated.The RPS6KB1 gene is located at 17q23 and amplified in approximately 10% of all primary breast cancer cases. PS6K is a ribosomal protein that is involved in the progression from the G1 to S phase of the cell cycle. It is rapidly activated in response to mitogenic stimuli, for example, growth factors, cytokines, and oncogene products (Grove et

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confidence: 73%

Section: Other Tumour Markersmentioning

confidence: 99%

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confidence: 95%

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Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients

et al. 2004

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“…It also appears that Topo IIa expression is often correlated to Her-2/neu overexpression in breast carcinoma. This complex relationship between the two genes may explain the altered sensitivity to anthracyclines of Her-2/neu-amplified breast carcinomas (Bitran et al, 1996;MacGrogan et al, 1996a;Niskanen et al, 1997;Clahsen et al, 1998;Jarvinen et al, 1998;Paik et al, 1998;Thor et al, 1998;Vincent-Salomon et al, 2000). Most previous studies regarding the effect of Topo IIa poisons in relation to the cellular level of Topo IIa expression were either performed in vitro or on breast tumour fragments without analysis of the direct in vivo effect (Gudkov et al, 1993;Asano et al, 1996a, b;Vassetzky et al, 1996;Withoff et al, 1996a, b;Zhou et al, 1999;Stacey et al, 2000).…”

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confidence: 99%

DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

MacGrogan

Rudolph²,

Mascarel

et al. 2003

Br J Cancer

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The a isoform of Topoisomerase IIa (Topo IIa) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIa expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T 2 43 cm and T 3 N 0 -1 M 0 breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIa. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (415%) was associated with tumour regression under chemotherapy (OR ¼ 2.88, CI: 1.3 -6.4, P ¼ 0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR ¼ 3.34, CI: 1.41 -7.93, P ¼ 0.006), together with tumour size of less than 40 mm (OR ¼ 3.82, CI: 1.58 -9.25, P ¼ 0.002) and negative oestrogen receptor (ER) status (OR ¼ 3.35, CI: 1.43 -7.86, P ¼ 0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIa expression and tumour chemosensitivity and thus may have important practical implications.

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“…Some immunohistochemical studies have indicated that p53 accumulation does not predict a survival benefit with chemotherapy (1,9,10). In the study by Elledge et al (1), the patients were randomly selected to adjuvant chemotherapy or no systemic treatment.…”

Section: Discussionmentioning

confidence: 99%

Mutation and accumulation of p53 related to results of adjuvant therapy of postmenopausal breast cancer patients

Askmalm¹,

Carstensen²,

Nordenskjöld³

et al. 2004

Acta Oncologica

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p53 protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer.

Abstract: p53 accumulation was associated with a poor response to one perioperative course of FAC chemotherapy. Ki-67, ER-IA, and age are important prognostic factors in premenopausal women with node-negative breast cancer.

Cited by 147 publications

References 29 publications

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients

DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

Mutation and accumulation of p53 related to results of adjuvant therapy of postmenopausal breast cancer patients

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