Browsing by Subject "Triple-negative breast cancer"

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  • Kiiski, Johanna I.; Tervasmäki, Anna; Pelttari, Liisa M.; Khan, Sofia; Mantere, Tuomo; Pylkäs, Katri; Mannermaa, Arto; Tengström, Maria; Kvist, Anders; Borg, Åke; Kosma, Veli-Matti; Kallioniemi, Anne; Schleutker, Johanna; Bützow, Ralf; Blomqvist, Carl; Aittomäki, Kristiina; Winqvist, Robert; Nevanlinna, Heli (2017)
    The FANCM c.5101C > T nonsense mutation was previously found to associate with breast cancer in the Finnish population, especially among triple-negative cases. Here, we studied the prevalence of three other FANCM variants: c.5791C > T, which has been reported to predispose to familial breast cancer, and the c.4025_4026delCT and c.5293dupA variants recently identified in Finnish cancer patients. We genotyped the FANCM c.5791C > T mutation in 4806 invasive breast cancer patients, including BRCA1/2 mutation negative familial cases and unselected cases, and in 2734 healthy population controls from four different geographical areas of Finland. The association of the mutation with breast cancer risk among patient subgroups was statistically evaluated. We further analyzed the combined risk associated with c.5101C > T and c.5791C > T mutations. We also genotyped 526 unselected ovarian cancer patients for the c.5791C > T mutation and 862 familial breast cancer patients for the c.4025_4026delCT and c.5293dupA variants. The frequency of the FANCM c.5791C > T mutation was higher among breast cancer cases than in controls (OR 1.94, 95% CI 0.87-4.32, P = 0.11), with a statistically significant association with triple-negative breast cancer (OR 5.14, 95% CI 1.65-16.0, P = 0.005). The combined analysis for c.5101C > T and c.5791C > T carriers confirmed a strong association with breast cancer (OR 1.86, 95% CI 1.32-2.49, P = 0.0002), especially among the triple-negative patients (OR 3.08, 95% CI 1.77-5.35, P = 0.00007). For the other variants, only one additional c.4025_4026delCT carrier and no c.5293dupA carriers were observed. These results support the role of FANCM as a breast cancer susceptibility gene, particularly for triple-negative breast cancer.
  • O'Loughlin, Mark; Andreu, Xavier; Bianchi, Simonetta; Chemielik, Ewa; Cordoba, Alicia; Cserni, Gabor; Figueiredo, Paulo; Floris, Giuseppe; Foschini, Maria P.; Heikkilä, Paivi; Kulka, Janina; Liepniece-Karele, Inta; Regitnig, Peter; Reiner, Angelika; Ryska, Ales; Sapino, Anna; Shalaby, Aliaa; Stovgaard, Elisabeth Specht; Quinn, Cecily; Walsh, Elaine M.; Zolota, Vicky; Glynn, Sharon A.; Callagy, Grace (2018)
    Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value <0.001). Agreement was less when a 25% threshold was used (ICC 0.509, 95% CI 0.416-0.614, p-value <0.001) and for lymphocyte predominant breast cancer (LPBC) (ICC 0.504, 95% CI 0.412-0.610, p-value <0.001). Intra-observer agreement was strong for absolute sTIL values (Spearman rho = 0.727); fair for sTILs >= 25% (kappa = 0.53) and for LPBC (kappa = 0.49), but poor for sTILs as 10% increments (kappa = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.
  • Tumiati, Manuela; Hietanen, Sakari; Kauppi, Liisa (2018)
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