Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in <i>BRCA1/2</i> Mutation Carriers

Broek, Alexandra J. van den; Veer, Laura J. van ’t; Hooning, Maartje J.; Cornelissen, Sten; Broeks, Annegien; Rutgers, Emiel J.; Smit, Vincent T.H.B.M.; Cornelisse, Cees J.; Beek, M. van; Janssen‐Heijnen, M.L.G.; Seynaeve, Caroline; Westenend, Pieter J.; Jobsen, Jan J.; Siesling, Sabine; Tollenaar, Rob A.E.M.; Leeuwen, Flora E. van; Schmidt, Marjanka K.

doi:10.1200/jco.2015.62.3942

Cited by 91 publications

(74 citation statements)

References 52 publications

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“…Distant metastasis and therapeutic failure have been the major challenges in the treatment of human breast cancer [3]. Thus, we need to unravel more markers to predict responsiveness of treatment, tumor progression, and use the knowledge to develop novel targets and therapies for breast cancer [4]. Epithelial-mesenchymal transition (EMT) has been demonstrated to promote cell invasion, leading to tumor cell metastasis in various cancers, including breast cancer [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

Lv¹,

Wang

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Epithelial-mesenchymal transition (EMT) is recognized as a crucial mechanism in breast cancer progression and metastasis. Paired-related homeobox 2 (Prrx2) has been identified as a new EMT inducer in cancer, but the underlying mechanisms are still poorly understood. Methods: The expression of Prrx2 was assessed by immunohistochemistry in breast cancer tissues to evaluate the clinicopathological significance of Prrx2, as well as the correlation between Prrx2 and EMT. Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2, detecte the expression of Wnt/β-catenin signaling and EMT-associated proteins, and observe cell proliferation, invasion and migration abilities in vitro and in vivo. Results: Clinical association studies showed that Prrx2 expression was related to tumor size, lymph node metastasis, tumor node metastasis stages, EMT and poor survival. Results also showed that knockdown of Prrx2 could alter cell morphology, suppressed the abilities of cell proliferation, invasion and migration in breast cancer. Moreover, silencing of Prrx2 induced the mesenchymal-epithelial transition and prevented nuclear translocation of β-catenin, inhibited wnt/β-catenin signaling pathway. Conclusion: Our study indicated that Prrx2 may be an important activator of EMT in human breast cancer and it can serve as a molecular target of therapeutic interventions for breast cancer.

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Section: Introductionmentioning

confidence: 99%

Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

Lv¹,

Wang

Liu

et al. 2017

Cell Physiol Biochem

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“…This finding has important implications, since nodal staging was the main outcome predictor: detection of BRCA1 mutation carriers among young relatives of high familial risk BC patients may lead to appropriate schedule of surveillance in order to promptly detect early stage BC before nodal spread occur . BRCA status was not associated with the occurrence of secondary contralateral tumors: however, this result might be influenced by prophylactic mastectomy in one‐third of patients.…”

Section: Discussionmentioning

confidence: 97%

BRCA mutation in breast cancer patients: Prognostic impact and implications on clinical management

et al. 2018

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BRCA1/2 mutations are involved in breast cancer (BC) susceptibility but their influence on outcome is unclear. We reviewed BC patients tested for BRCA to determine biological features and influence on outcome. BRCA-1 was correlated to younger age (P = 0.035), nodal involvement (P = 0.030), higher tumor grade (P = 0.0022) and Ki-67 (P = 0.014), ER/PgR negative status (P = 0.00042 and 0.0091, respectively), and use of adjuvant chemotherapy (P = 0.000038); BRCA was neither predictive for chemotherapy administration nor resulted in impaired outcome or occurrence of secondary BC. BRCA status did not influence outcome despite higher biological aggressiveness and younger age at presentation.

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“…These results were in line with the majority of published studies that derived the conclusion of no difference in local recurrence, 36 whereas increased incidence of CBC was associated with BRCA1/2 mutation. 4,22,[37][38][39][40][41] Till now, comprehensive research has been administrated to seek optimum prevention of CBC in BRCA mutation carriers.…”

Section: Discussionmentioning

confidence: 99%

Outcomes and risk of subsequent breast events in breast‐conserving surgery patients with BRCA1 and BRCA2 mutation

Huang

Lang

et al. 2020

Cancer Medicine

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Purpose Previous studies provide inconsistent interpretations of the effect of inherited genetic factors on the survival and prognosis of patients with breast cancer. The aim of this study was to examine the effect of germline BRCA1 and BRCA2 mutation on survival and subsequent breast events in Chinese women who underwent breast‐conserving surgery. Methods A retrospective review of the clinical and pathological records was performed in patients diagnosed with primary invasive breast cancer between 2005 and 2018 in the cancer registry database. Clinicopathological data and data regarding treatment and outcomes, including date and site of disease progression, were collected. The survival outcomes and independent risk factors were conducted using SPSS. Results Overall, a total of 501 patients who underwent breast‐conserving surgery were identified and subjected to analyses, of which 63 cases with BRCA1 or BRCA2 mutation. The median age at diagnosis was 41 (range, 24‐74) for carriers and 37 (range, 17‐84) for noncarriers. After a median follow‐up time of 61 months (range, 8‐161) and 70 months (range, 0‐153), respectively, in carriers and noncarriers, the overall survival (P = .173) and disease‐free survival (P = .424) were not significantly different. Analogously, there was no significant difference between the two groups about the outcomes of ipsilateral breast tumor recurrence (P = .348), yet the contralateral breast cancer (CBC) was overt worse than noncarriers (P < .001). When adjusted to confounding factors, BRCA mutation was the only independent risk factors to CBC (HR = 7.89, P = .01). Conclusion In this study, BRCA mutation carriers have higher risk of CBC. And, BRCA mutation is the only independent risk factor to CBC. Therefore, intensive surveillance and follow‐up as well as more effective individual prevention are urgent. Decisions on alternatively effective prevention, especially the prevention of CBC, are urgent and should take into account patient prognosis and preferences.

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Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in BRCA1/2 Mutation Carriers

Abstract: Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers. Considering the available evidence, age-specific risk estimates should be included in counseling.

Cited by 91 publications

References 52 publications

Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

BRCA mutation in breast cancer patients: Prognostic impact and implications on clinical management

Outcomes and risk of subsequent breast events in breast‐conserving surgery patients with BRCA1 and BRCA2 mutation

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