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- De Lara, Shahin, 1966, et al.
(författare)
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The prognostic relevance of FOXA1 and Nestin expression in breast cancer metastases: a retrospective study of 164 cases during a 10-year period (2004-2014)
- 2019
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCurrent prognostic markers cannot adequately predict the clinical outcome of breast cancer patients. Therefore, additional biomarkers need to be included in routine immune panels. FOXA1 was a significant predictor of favorable outcome in primary breast cancer, while Nestin expression is preferentially found in triple-negative tumors with increased rate of nodal metastases, and reduced survival. No studies have investigated the prognostic value of FOXA1 and Nestin expression in breast cancer metastases.MethodsBreast cancer metastases (n=164) from various anatomical sites were retrospectively analyzed by immunohistochemistry for FOXA1, Nestin and GATA3 expression. Cox regression analysis assessed the prognostic value of FOXA1 and Nestin expression.ResultsIn breast cancer metastases, FOXA1 expression was associated with Nestin-negativity, GATA3-positivity, ER-positivity, HER2-positivity and non-triple-negative status (P<0.05). In contrast, Nestin expression was associated with FOXA1-negative, GATA3-negative, ER-negative, and triple-negative metastases (P<0.05). Univariate Cox regression analysis showed FOXA1 expression was predictive of overall survival (OS, P=0.00048) and metastasis-free survival (DMFS, P=0.0011), as well as, distant metastasis-free survival in ER-positive patients (P=0.036) and overall survival in ER-negative patients (P=0.024). Multivariate analysis confirmed the significance of FOXA1 for both survival endpoints in metastatic breast cancer patients (OS, P=0.0033; DMFS, P=0.015).ConclusionsIn our study, FOXA1 was expressed mostly in ER-positive breast cancer metastases. Expression of Nestin was related to triple-negative metastases, where brain was the most frequent metastatic site. These findings highlight the clinical utility of FOXA1 and Nestin expression and warrant their inclusion in routine immunohistochemical panels for breast carcinoma.
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- Nyqvist, Jenny, et al.
(författare)
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Metachronous and synchronous occurrence of 5 primary malignancies in a female patient between 1997 and 2013 : A case report with germline and somatic genetic analysis
- 2017
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Ingår i: Case Reports in Oncology. - : S. Karger AG. - 1662-6575. ; 10:3, s. 1006-1012
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Tidskriftsartikel (refereegranskat)abstract
- The number of patients with multiple primary malignancies has been increasing steadily in recent years. In the present study, we describe a unique case of an 81-year-old woman with 5 metachronous and synchronous primary malignant neoplasms. The patient was first diagnosed with an endometrium adenocarcinoma in 1997 and a colon adenocarcinoma in 2002. Eleven years after her colon surgery, in 2013, the patient presented with 3 other primary malignancies within a 4-month time span: An invasive malignant melanoma on the lower leg, an invasive mucinous breast carcinoma in the right breast, and a pleomorphic spindle cell sarcoma on the left upper arm. Subsequent routine medical checkups in 2013-2017 revealed no metastases of the primary malignancies. The patient mentioned a familial aggregation of malignant tumors, including 2 sisters with breast cancer and a brother with lung cancer. Interestingly, next-generation sequencing analysis of the patient's blood sample detected no mutations in the BRCA1, BRCA2, TP53, PTEN, CDH1, PALB2, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MUTYH, STK11, BMPR1A, SMAD4, PTEN, POLE, POLD1, GREM1, and GALNT12 genes. Therefore, whole genome sequencing is warranted to identify cancer-related genetic alterations in this patient with quintuple primary malignancies.
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- Tobin, N. P., et al.
(författare)
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Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival
- 2015
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 26:1, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and beta-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and beta-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information.
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