Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy

Malamou‐Mitsi, Vassiliki; Gogas, Helen; Dafni, Urania; Bourli, Antonia; Fillipidis, T; Sotiropoulou, Maria; Vlachodimitropoulos, Dimitrios; Papadopoulos, Savvas; Tzaida, Olympia; Kafiri, Georgia; Kyriakou, Vassiliki; Markaki, S.; Papaspyrou, Irene; Karagianni, Evangelia; Pavlakis, Kitty; Toliou, T.; Scopa, C D; Papakostas, Pavlos; Bafaloukos, Dimitrios; Christodoulou, C.; Fountzilas, George

doi:10.1093/annonc/mdl147

Cited by 46 publications

(32 citation statements)

References 41 publications

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“…As we observed in human primary tumors, NK-1R and SP are highly expressed in those of the HER2 þ subtype, and SP can activate HER2 in primary cultures derived from human tumors with and without HER2 overexpression. In addition to HER2 overexpression, our current results identify NK-1R and SP as two new markers associated with other clinicopathologic characteristics related to a poor prognosis such as p53 overexpression, ER negativity expression, high proliferation, and a high histologic grade (38,39). In addition, the relevance of SP signaling in breast cancer could be context dependent.…”

Section: Discussionmentioning

confidence: 66%

Substance P Autocrine Signaling Contributes to Persistent HER2 Activation That Drives Malignant Progression and Drug Resistance in Breast Cancer

et al. 2013

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ERBB receptor transmodulation by heterologous G-protein-coupled receptors (GPCR) generates functional diversity in signal transduction. Tachykinins are neuropeptides and proinflammatory cytokines that promote cell survival and cancer progression by activating several GPCRs. In this work, we found that the pain-associated tachykinin Substance P (SP) contributes to persistent transmodulation of the ERBB receptors, EGFR and HER2, in breast cancer, acting to enhance malignancy and therapeutic resistance. SP and its high-affinity receptor NK-1R were highly expressed in HER2 þ primary breast tumors (relative to the luminal and triple-negative subtypes) and were overall correlated with poor prognosis factors. In breast cancer cell lines and primary cultures derived from breast cancer samples, we found that SP could activate HER2. Conversely, RNA interference-mediated attenuation of NK-1R, or its chemical inhibition, or suppression of overall GPCR-mediated signaling, all strongly decreased steady-state expression of EGFR and HER2, establishing that their basal activity relied upon transdirectional activation by GPCR. Thus, SP exposure affected cellular responses to anti-ERBB therapies. Our work reveals an important oncogenic cooperation between NK-1R and HER2, thereby adding a novel link between inflammation and cancer progression that may be targetable by SP antagonists that have been clinically explored. Cancer Res; 73(21); 6424-34. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 66%

Substance P Autocrine Signaling Contributes to Persistent HER2 Activation That Drives Malignant Progression and Drug Resistance in Breast Cancer

et al. 2013

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“…TP53 mutation is one of the most common genetic abnormalities in breast cancer (40,41) and associates with more aggressive disease and a poor clinical outcome (40)(41)(42)(43). Although the overall frequency of TP53 mutation is 20%-30%, the incidence is much higher in certain breast cancer subtypes.…”

Section: Figurementioning

confidence: 99%

Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models

et al. 2012

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“…p53 was also assessed by IHC at the Department of Pathology, University of Ioannina School of Medicine, as has been described recently [26]. Both HER-1/EGFR and p53 data were available in 307 patients.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the Prognostic and Predictive Value of HER-1/EGFR in Breast Cancer Patients Participating in a Randomized Study with Dose-Dense Sequential Adjuvant Chemotherapy

Tzaida

Gogas²,

Dafni³

et al. 2007

Oncology

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Background: To assess the prognostic and predictive significance of HER-1/EGFR protein levels in high-risk patients with breast cancer treated with dose-dense sequential adjuvant chemotherapy. Methods: 595 high-risk breast cancer patients were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy (E-CMF vs. E-T-CMF). Disease-free survival (DFS) was the primary end point. HER-1/EGFR was assessed by immunohistochemistry (IHC) in 312 patients. Results: HER-1/EGFR expression was detected in 54 of 312 patients (17%). Positive expression of HER-1/EGFR was significantly associated with negative receptor status (52 vs. 17%, p < 0.001), worse histological grade (70 vs. 45%, p = 0.001), HER-2 overexpression (46 vs. 27%, p = 0.01) and positive p53 expression (48 vs. 19%, p < 0.001). With a median follow-up of 7 years, the total number of relapses was 105 (34%), and the total number of deaths 69 (22%). The analysis for DFS provides significant evidence that the HER-1/EGFR effect on the risk of disease progression was different according to treatment (interaction p = 0.02). Regarding overall survival, a trend towards a significant difference for an interaction of HER-1/EGFR and treatment was found (p = 0.07). Conclusion: The present study demonstrated a differential effect of positive HER-1/EGFR expression in the two treatment groups, with HER-1/EGFR being a negative prognostic marker in the absence of paclitaxel.

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Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy

Abstract: For both treatments, p53 positive expression was a significant negative prognostic factor for OS and DFS while Bcl-2 was not. No predictive ability of p53 status or Bcl-2 status for paclitaxel treatment was evident.

Cited by 46 publications

References 41 publications

Substance P Autocrine Signaling Contributes to Persistent HER2 Activation That Drives Malignant Progression and Drug Resistance in Breast Cancer

Substance P Autocrine Signaling Contributes to Persistent HER2 Activation That Drives Malignant Progression and Drug Resistance in Breast Cancer

Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models

Evaluation of the Prognostic and Predictive Value of HER-1/EGFR in Breast Cancer Patients Participating in a Randomized Study with Dose-Dense Sequential Adjuvant Chemotherapy

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