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- Aaltonen, Kirsimari, et al.
(författare)
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High cyclin B1 expression is associated with poor survival in breast cancer
- 2009
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 100:7, s. 1055-60
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Tidskriftsartikel (refereegranskat)abstract
- Cyclin B1 regulates the G(2)-M transition of the cell cycle. Cyclin B1 expression is higher in premalignant and malignant than normal breast lesions. Correlation of cyclin B1 expression with other histopathological variables and prognostic role in breast cancer are not fully understood. Traditionally used prognostic criteria identify large subset of patients to receive adjuvant chemotherapy and to be exposed to adverse effects. A reliable and simple method helping prognostic evaluation in breast cancer is needed. We analysed cyclin B1 expression on 1348 invasive breast cancers and studied correlations with other histopathological variables and survival. High cyclin B1 correlated with high tumour grade, large tumour size and positive nodal status, oestrogen and progesterone receptor negativity, positive HER2 and p53 status, young age at diagnosis, and high cyclin E, cyclin A and Ki67 expression. Among patients not given adjuvant chemotherapy high cyclin B1 was a strong predictor of shorter overall and metastasis-free survival (RR 3.74, P<0.0005 and RR 3.51, P<0.0005, respectively), and remained as an independent prognostic factor also in multivariate analysis (RR 1.80, P=0.04 and RR 2.31, P=0.02, respectively). This study suggests high cyclin B1 associates with aggressive phenotype and is an independent prognostic factor in breast cancer.
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| 2. |
- Heikkinen, Tuomas, et al.
(författare)
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The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype
- 2009
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 15:9, s. 3214-22
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine the effect of the breast cancer susceptibility mutation PALB2 1592delT on tumor phenotype and patient survival. EXPERIMENTAL DESIGN: We defined the PALB2 mutation status in 947 familial and 1,274 sporadic breast cancer patients and 1,079 population controls, and compared tumor characteristics and survival in mutation carriers relative to other familial and sporadic cases and to 79 BRCA1 and 104 BRCA2 mutation carrier cases. RESULTS: The PALB2 1592delT mutation was found in 19 familial [2.0%; odds ratio, 11.03; 95% confidence interval (95% CI), 2.65-97.78; P < 0.0001] and eight sporadic patients (0.6%; odds ratio, 3.40; 95% CI, 0.68-32.95; P = 0.1207) compared with two (0.2%) control individuals. Tumors of the PALB2 mutation carriers presented triple negative (estrogen receptor negative/progesterone receptor negative/HER negative) phenotype more often (54.5%; P < 0.0001) than those of other familial (12.2%) or sporadic (9.4%) breast cancer patients. They were also more often of higher grade (P = 0.0027 and P = 0.0017, respectively) and had higher expression of Ki67 (P = 0.0004 and P = 0.0490, respectively). Carrying a PALB2 mutation was also associated with reduced survival, especially in familial cases (hazard ratio, 2.30; 95% CI, 1.01-5.24; P = 0.0466) and among familial patients with HER2-negative tumors (hazard ratio, 4.57; 95% CI, 1.96-10.64; P = 0.0004). Carrying a BRCA2 mutation was also found to be an independent predictor of poor survival at 10-year follow-up (P = 0.04). CONCLUSIONS: The PALB2 1592delT mutation has a strong effect on familial breast cancer risk. The tumors rising in patients carrying this mutation manifest a phenotype associated with aggressive disease. Our results also suggest a significant impact of carrying a BRCA2 mutation on long-term breast cancer survival.
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