| 1. |
- Ronowicz, Anna, et al.
(author)
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Concurrent DNA Copy-Number Alterations and Mutations in Genes Related to Maintenance of Genome Stability in Uninvolved Mammary Glandular Tissue from Breast Cancer Patients
- 2015
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:11, s. 1088-1099
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Journal article (peer-reviewed)abstract
- Somatic mosaicism for DNA copy-number alterations (SMC-CNAs) is defined as gain or loss of chromosomal segments in somatic cells within a single organism. As cells harboring SMC-CNAs can undergo clonal expansion, it has been proposed that SMC-CNAs may contribute to the predisposition of these cells to genetic disease including cancer. Herein, the gross genomic alterations (>500 kbp) were characterized in uninvolved mammary glandular tissue from 59 breast cancer patients and matched samples of primary tumors and lymph node metastases. Array-based comparative genomic hybridization showed 10% (6/59) of patients harbored one to 359 large SMC-CNAs (mean: 1,328 kbp; median: 961 kbp) in a substantial portion of glandular tissue cells, distal from the primary tumor site. SMC-CNAs were partially recurrent in tumors, albeit with considerable contribution of stochastic SMC-CNAs indicating genomic destabilization. Targeted resequencing of 301 known predisposition and somatic driver loci revealed mutations and rare variants in genes related to maintenance of genomic integrity: BRCA1 (p.Gln1756Profs*74, p.Arg504Cys), BRCA2 (p.Asn3124Ile), NCOR1 (p.Pro1570Glnfs*45), PALB2 (p.Ser500Pro), and TP53 (p.Arg306*). Co-occurrence of gross SMC-CNAs along with point mutations or rare variants in genes responsible for safeguarding genomic integrity highlights the temporal and spatial neoplastic potential of uninvolved glandular tissue in breast cancer patients.
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| 2. |
- Holmberg, Lars, et al.
(author)
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Increased risk of recurrence after hormone replacement therapy in breast cancer survivors
- 2008
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 100:7, s. 475-482
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Journal article (peer-reviewed)abstract
- BACKGROUND: Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up. METHODS: HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and chi(2) tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone. RESULTS: Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = .51, log-rank test). CONCLUSION: After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.
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| 3. |
- Woniacki, Piotr, et al.
(author)
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The impact of the Polish mass breast cancer screening program on prognosis in the Pomeranian Province
- 2017
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In: Archives of Medical Science. - : TERMEDIA PUBLISHING HOUSE LTD. - 1734-1922 .- 1896-9151. ; 13:2, s. 441-447
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Journal article (peer-reviewed)abstract
- Introduction: Mammographic screening results in diagnosis of less advanced breast cancer (BC). A meta-analysis of randomized clinical trials confirmed that BC screening reduces mortality. In 2007, the National Breast Cancer Screening Program (NBCSP) was established in Poland with the crucial aim of reducing mortality from BC. The purpose of this study was to assess the impact of participation in the NBCSP on prognosis. Material and methods: A single institution, non-randomized retrospective study was undertaken. The study population comprised 643 patients with BC treated in the Department of Surgical Oncology (DSO) at the Medical University of Gdansk over a 4-year period, from 01.01.2007 until 31.12.2010. Patients were divided into two groups: group A-patients who participated in the NBCSP (n = 238, 37.0%); and group B-patients who did not participate in the NBCSP (n = 405, 63.0%). Results: Statistical analysis revealed that group A displayed a less advanced MCC stage (more patients in AJCC stage I, p = 0.002), lower tumor diameter (more patients with pT1, p = 0.006, and pT < 15 mm, p = 0.008) and a lower incidence of metastases to axillary lymph nodes (more patients with pNO, p = 0.01). From 2009 to 2010 the NBCSP revealed a statistically significant benefit significantly more patients in stage 0 + I (60.7% vs. 48.8%, p = 0.018) and with tumors pT < 15 mm (48.8% vs. 35.1%, p = 0.011) were observed in group A. Conclusions: The study results revealed the beneficial impact of the NBCSP. Superior prognostic factors and favorable staging were observed in women who participated in the NBCSP.
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