Can Patients' Likelihood of Benefiting from Primary Chemotherapy for Breast Cancer Be Predicted Before Commencement of Treatment?

Ogston, Keith N.; Miller, Iain D.; Schofield, Andrew Craig; Spyrantis, Andreas; Pavlidou, Eleni; Sarkar, T. K.; Hutcheon, A. W.; Payne, Simon; Heys, Steven Darryll

doi:10.1023/b:brea.0000032986.00879.d7

Cited by 31 publications

(15 citation statements)

References 41 publications

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“…Bcl2 is positively regulated by HR in BC and its expression has been reported to provide an independent predictor of BC outcome [164,167]. Bcl2 has been reported to predict pathological response to a neoadjuvant anthracycline/docetaxel-based regimen [168]. In a previous study of Bcl2 and p53 expression in BC, we have demonstrated that a combination of both markers provides independent prognostic value with p53?/Bcl2-phenotype was independent predictor of a worse prognosis in multivariate analysis.…”

Section: Additional Markersmentioning

confidence: 60%

Combinatorial biomarker expression in breast cancer

Rakha

Reis‐Filho

Ellis

2010

Breast Cancer Res Treat

185

140

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Current clinical management of breast cancer relies on the availability of robust clinicopathological variables and few well-defined biological markers. Recent microarray-based expression profiling studies have emphasised the importance of the molecular portraits of breast cancer and the possibility of classifying breast cancer into biologically and molecularly distinct groups. Subsequent large scale immunohistochemical studies have demonstrated that the added value of studying the molecular biomarker expression in combination rather than individually. Oestrogen (ER) and progesterone (PR) receptors and HER2 are currently used in routine pathological assessment of breast cancer. Additional biomarkers such as proliferation markers and 'basal' markers are likely to be included in the future. A better understanding of the prognostic and predictive value of combinatorial assessment of biomarker expression could lead to improved breast cancer management in routine clinical practice and would add to our knowledge concerning the variation in behaviour and response to therapy. Here, we review the evidence on the value of assessing biomarker expression in breast cancer individually and in combination and its relation to the recent molecular classification of breast cancer.

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Section: Additional Markersmentioning

confidence: 60%

Combinatorial biomarker expression in breast cancer

Rakha

Reis‐Filho

Ellis

2010

Breast Cancer Res Treat

185

140

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“…For example, in a study of 104 patients treated with an anthracycline/docetaxel -based chemotherapy regimen before surgery, a lack of bcl-2 expression correlated with a better pathologic response (although this study did not define a favorable pathologic outcome by achievement of pCR; ref. 30). In addition, an earlier study of 55 patients with locally advanced disease treated with neoadjuvant chemotherapy (some of whom were treated with an anthracycline) also found a similar correlation between bcl-2 expression and a poor response to treatment (31).…”

Section: Discussionmentioning

confidence: 77%

The Nuclear Transcription Factor κB/bcl-2 Pathway Correlates with Pathologic Complete Response to Doxorubicin-Based Neoadjuvant Chemotherapy in Human Breast Cancer

Buchholz

Garg

Chakravarti

et al. 2005

Clinical Cancer Research

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Purpose: Molecular factors involved in apoptosis may affect breast cancer response to chemotherapy. Herein, we studied the nuclear factor nB (NF-nB)/bcl-2 pathway to determine whether or not activation of this antiapoptotic pathway was associated with a poor response of human breast cancer to anthracycline-based neoadjuvant chemotherapy. Experimental Design: We studied 82 human breast cancer samples from patients treated with neoadjuvant doxorubicin-based chemotherapy and studied whether or not nuclear location of the transcription factor NF-nB was associated with expression of bcl-2 and bax and whether or not expression of these proteins correlated with chemotherapy response. Protein expression was measured with immunohistochemical staining. A dedicated breast cancer pathologist who was unaware of the clinical outcome data dichotomized the slides as positive or negative based on the presence or absence of cytoplasmic staining for bcl-2 and bax or nuclear staining for NF-nB. Results: Sixty-one percent of the tumors were positive for bcl-2, 85% were positive for bax, and 16% were positive for NF-nB. All bcl-2-positive tumors were also bax positive (P < 0.0001) and all NF-nB-positive tumors were both bcl-2 positive (P = 0.001) and bax positive (P = 0.113). Eleven of the 82 patients (13%) had a pathologic complete response (pCR) to chemotherapy. Patients with positive staining tumors for any of the markers less commonly achieved a pCR to chemotherapy than those with negative tumor staining. The pCR rates were NF-nB positive 0% (0 of 13) versus NF-nB negative13% (11of 69; P = 0.130); bcl-2 positive 4% (2 of 49) versus bcl-2 negative 27% (9 of 33; P = 0.004); and bax positive 6% (4 of 69) versus bax negative 58% (7 of 12; P < 0.001). Conclusion:We conclude that nuclear localization of NF-nB correlates with bcl-2 and bax expression and that the NF-nB/bcl-2 pathway may be associated with a poor response to neoadjuvant doxorubicin-based chemotherapy.

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“…expression and poor prognosis has also been suggested in breast cancer patients [Ogston et al, 2004]. However, there are only a handful of reports on the subject, including some conflicting ones [Bonetti et al, 1998;Bottini et al, 2000], and, therefore, more clinical studies must be done to further our understanding of the subject.…”

Section: Discussionmentioning

confidence: 99%

Plumbagin‐induced apoptosis of human breast cancer cells is mediated by inactivation of NF‐κB and Bcl‐2

Ahmad

Banerjee

Wang

et al. 2008

J of Cellular Biochemistry

143

125

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Breast cancer remains the major cause of cancer-related deaths in women world-wide. The heterogeneity of breast cancer has further complicated the progress of target-based therapies. Triple negative breast cancers, lacking estrogen receptor, progesterone receptor and the Her-2/neu (ErbB2), represent a highly aggressive breast cancer subtype, that are difficult to treat. Pleiotropic agents, such as those found in nature, can target receptor-positive as well as receptor-negative cancer cells, suggesting that such agents could have significant impact in breast cancer prevention and/or therapy. Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone) is one such agent which has anti-tumor activity against several cancers. However, its mechanism of action against breast cancer is not clearly understood. We hypothesized that plumbagin may act as an effective agent against breast cancer especially triple negative breast cancer. We tested our hypothesis using ER-positive MCF-7 and ER-negative MDA-MB-231 (triple negative) breast cancer cells, and we found that plumbagin significantly inhibits the growth of breast cancer cells with no effect on normal breast epithelial cells. We also found that plumbagin induces apoptosis with concomitant inactivation of Bcl-2 and the DNA binding activity of NF-kappaB. Bcl-2 over-expression resulted in attenuation of plumbagin-induced effects, suggesting that the inhibition of cell growth and induction of apoptosis by plumbagin is in part due to inactivation of NF-kappaB/Bcl-2 pathway. To our knowledge, this is the first report, showing mechanistic and cancer cell specific apoptosis-inducing effects of plumbagin in breast cancer cells, suggesting the potential role of plumbagin in the prevention and/or treatment of breast cancer.

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Can Patients' Likelihood of Benefiting from Primary Chemotherapy for Breast Cancer Be Predicted Before Commencement of Treatment?

Cited by 31 publications

References 41 publications

Combinatorial biomarker expression in breast cancer

Combinatorial biomarker expression in breast cancer

The Nuclear Transcription Factor κB/bcl-2 Pathway Correlates with Pathologic Complete Response to Doxorubicin-Based Neoadjuvant Chemotherapy in Human Breast Cancer

Plumbagin‐induced apoptosis of human breast cancer cells is mediated by inactivation of NF‐κB and Bcl‐2

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