A Case-Control Study on Risk Factors for Local Recurrences or Distant Metastases in Breast Cancer Patients Treated with Breast-Conserving Surgery

Noguchi, Shinzaburo; Koyama, Hiroki; Kasugai, Tsutomu; Tsukuma, Hideaki; Tsuji, Naoko; Tsuda, Hitoshi; Akiyama, Futoshi; Motomura, Kazuyoshi; Inaji, Hideo

doi:10.1159/000227605

Cited by 29 publications

(16 citation statements)

References 14 publications

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“…After evaluation of several clinico-pathological factors and biomarkers in a case-control study of 66 patients with LR following breast conserving therapy, p53 was found to be an independent predictor of LR [17]. Similar results have been obtained in the study by Turner et al [18] In DCIS, there are not many studies that describe the relation between p53 immunoreactivity and LR.…”

Section: Discussionsupporting

confidence: 72%

p53 Overexpression is a Predictor of Local Recurrence After Treatment for Both in situ and Invasive Ductal Carcinoma of the Breast

Roos

Bock

Vries

et al. 2007

Journal of Surgical Research

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p53 overexpression is a predictor of local recurrence after treatment for both in situ and invasive ductal carcinoma of the breast de Roos, M.A.; de Bock, G.H.; de Vries, J; van der Vegt, Bert; Wesseling, J. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Background. Several biological markers have been related to prognosis in mammary ductal carcinoma. The aim of the study was to determine biological markers that could predict local recurrence following treatment for all stages of primary operable ductal carcinoma of the breast.Materials and methods. A consecutive series of patients treated for pure ductal carcinoma in situ (DCIS, n ‫؍‬ 110) and invasive ductal carcinoma (IDC, n ‫؍‬ 243) was studied. Twenty-three patients with DCIS were excluded because of lack of original paraffin embedded tissue. All patients had been treated between July 1996 and December 2001. Median follow-up was 49.8 mo. From the original paraffin embedded tumors, tissue microarrays (TMAs) were constructed. On these TMAs, immunohistochemistry was performed for estrogen-receptor (ER), progesterone-receptor (PR), Her2/neu, p53, and cyclin D1. Main outcome was the event of LR. All analyses were stratified for diagnosis (DCIS or IDC) and pathological grade.Results. In univariate analyses, Her2/neu overexpression (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.1-8.7, P ‫؍‬ 0.032) and p53 overexpression (HR 3.5, 95% CI 1.3-9.3, P ‫؍‬ 0.014) were associated with LR in patients treated for both DCIS and IDC. In multivariate analysis, p53 overexpression (HR 3.0, 95% CI 1.1-8.2, P ‫؍‬ 0.036 and HR 4.4, 95% CI 1.5-12.9, P ‫؍‬ 0.008) and adjuvant radiotherapy (HR 0.2, 95% CI 0.1-0.8, P ‫؍‬ 0.026) were independent common predictors of LR in patients who had received treatment for both DCIS and IDC.Conclusions. p53 overexpression is a common predictor of LR following treatment for all stages of primary operable ductal carcinoma of the breast. This marker may help in planning optimal treatment and follow-up.

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Section: Discussionsupporting

confidence: 72%

p53 Overexpression is a Predictor of Local Recurrence After Treatment for Both in situ and Invasive Ductal Carcinoma of the Breast

Roos

Bock

Vries

et al. 2007

Journal of Surgical Research

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“…In addition, 5-year follow-up results concerning the impact of P53 and PS6K status on locoregional control Several studies have examined the relation between P53 overexpression and local breast tumour recurrence. A case -control study of 66 women with local breast tumour relapse following lumpectomy and radiation therapy showed that p53 overexpression was an independent predictive factor for ipsilateral breast tumour recurrence (IBTR) (Noguchi et al, 1997). Recent studies conducted by Turner et al (2000) and Zellars et al (2000) demonstrated predictive significance of P53 overexpression for locoregional recurrence in patients who underwent breast-conserving therapy, as well as in patients who underwent mastectomy.…”

Section: Discussionmentioning

confidence: 99%

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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“…They found that bcl-2 negativity carried a 17 times higher risk of local recurrence in patients >50 yr (10). Noguchi et al (9) and Turner et al (15) conducted similar case-control studies and noted the association between local recurrence and p53 positivity. However, a case-control approach has the limitation of inevitable biases in selecting control cases although the process is random.…”

Section: Discussionmentioning

confidence: 81%

“…Aforementioned case-control studies noted a higher risk of distant metastases in patients with p53 expression (9,15). Again, however, consecutive populationbased studies failed to verify the relationship, despite the larger number of patients and events (11,17).…”

Section: Probability (%)mentioning

confidence: 99%

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Prognostic Value of p53 and bcl-2 Expression in Patients Treated With Breast Conservative Therapy

Chie

Kim

Han

et al. 2007

International Journal of Radiation Oncology*Biology*Physics

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Prognostic value of p53 and bcl-2 expression on treatment outcome in breast cancer patients has been extensively evaluated, but the results were inconclusive. We evaluated the prognostic significance of these molecular markers in patients treated with breast conserving surgery and radiotherapy. One hundred patients whose immunostaining of p53 and bcl-2 expression was available among 125 patients who underwent radiotherapy after breast conserving surgery and axillary lymph node dissection were enrolled into this study. Eighty-seven patients also received adjuvant chemotherapy and/or hormonal therapy. Conventional clinicopathologic variables and treatment-related factors were also considered. The 5-yr loco-regional relapse-free and distant metastasis-free survival rates were 91.7% and 90.9%, respectively. On univariate analysis, age, T stage and the absence of bcl-2 & estrogen receptor (ER) expression were associated with loco-regional relapse-free survival. When incorporating these variables into Cox proportional hazard model, only bcl-2(-)/ER(-) phenotype was an adverse prognostic factor (P=0.018). As for the distant metastasis-free survival, age, T stage, and p53 expression were significant on univariate analysis. However, p53 expression was the only prognosticator on multivariate analysis (P=0.009). A bcl-2(-)/ER(-) phenotype and p53 expression are useful molecular markers predicting loco-regional relapse-free and distant metastasis-free survival, respectively, in patients treated with breast conserving surgery and radiotherapy.

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A Case-Control Study on Risk Factors for Local Recurrences or Distant Metastases in Breast Cancer Patients Treated with Breast-Conserving Surgery

Cited by 29 publications

References 14 publications

p53 Overexpression is a Predictor of Local Recurrence After Treatment for Both in situ and Invasive Ductal Carcinoma of the Breast

p53 Overexpression is a Predictor of Local Recurrence After Treatment for Both in situ and Invasive Ductal Carcinoma of the Breast

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

Prognostic Value of p53 and bcl-2 Expression in Patients Treated With Breast Conservative Therapy

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