Triple-negative breast cancer (TNBC) is proposed to be an immunohistochemical surrogate of the basal-like breast cancer subtype. In spite of the relative chemosensitivity of this cancer subtype, it is characterized by aggressive clinical behavior; therefore, a further subclassification of TNBC is required to develop new targeted treatment. In previous studies, a strong correlation between BRCA1 mutation-associated tumors and TNBC has been identified. The aim of the present study was to investigate the prognostic significance of carrying two germline BRCA1 founder mutations (4153delA and 5382insC) in patients with TNBC in the Latvian population. A total of 78 consecutive BRCA1 mutation-negative and 38 BRCA1 mutation-positive invasive TNBC patients in stage I–IV with no history of ovarian or other primary advanced cancers, who had undergone definitive surgery and genetic testing between 2005 and 2011, were deemed eligible for study. Relapse rates and breast cancer-specific survival (BCS) outcomes were compared between mutation carriers and non-carriers. Univariate and multivariate analyses Cox proportional-hazards models were used to compute independent predictors of survival outcomes. No statistically significant differences were identified in relation to tumor size, T stage, stage, Ki-67 status and tumor differentiation grade between the two groups. The median follow-up period was 36 months for mutation carriers and 41 months for non-carriers. A higher proportion of BRCA1 mutation non-carriers experienced distant recurrence compared with that of mutation carriers (P<0.03). BRCA1 mutation carriers had a significantly higher BCS than non-carriers (94.9 vs. 76.9%; P<0.02). In the univariate analyses, BRCA1-positive status was associated with decreased risk of distant recurrence (HR, 0.228; 95% Cl, 0.052–0.997; P<0.049) and breast cancer-specific mortality (HR, 0.209; 95% Cl, 0.048–0.902; P<0.036). In the multivariate analysis Cox proportional-hazards model, BRCA1-positive status was an independent favorable prognostic factor for distant recurrence-free survival (HR, 3.301; 95% Cl, 1.102–9.893; P<0.033). In conclusion, results of the present study demonstrate that positive BRCA1 founder mutation status in TNBC, with no evidence of ovarian or other cancer type in advanced stage, significantly improves prognosis.

We would like to present a patient with a classical phenotype of a rare disorder - Cowden syndrome, its diagnostics and management challenges. A breast surgeon has to be aware of this rare condition when treating a patient with breast manifestations of Cowden syndrome and has to refer the patient to a clinical geneticist for further evaluation. Sequencing of the PTEN gene showed the Asp24Gly mutation. According to the latest literature data, the lifetime risk of breast cancer for Cowden syndrome patients is 81% and surgery is a justified option to reduce the risk of breast cancer. Bilateral risk-reducing mastectomy with immediate reconstruction was performed to eliminate further risk of breast cancer. 3 years after the risk-reducing breast surgery the patient is satisfied with the outcome. This is to our best knowledge the first reported Cowden syndrome case with follow-up data after risk-reducing measures have been taken.

IntroductionIt has not been established whether CHEK2 and NOD2 variants are present in Latvia and whether inherited variation in these genes influences cancer risk in this population.Aim of the studyTo evaluate the role of CHEK2 and NOD2 mutations in breast and colorectal cancers in the population of Latvia.Materials and methodsPeripheral venous blood samples were collected from 185 breast cancer and 235 colorectal cancer consecutive hospital-based cases from 11/2003 to 06/2005. The population control group included blood samples from the clamped distal part of the umbilical cord from 978 consecutive anonymous newborns born between 03/2005 and 08/2005. All cases and controls were tested for the presence of NOD2 3020insC mutation and CHEK2 I157T mutation.ResultsNOD2 3020insC was present in 7.7% (18/235) of CRC cancers, in 9.2% (17/185) of breast cancers and in 7.7% (75/974) of controls. CHEK2 I157T variant was found in 7.6% (14/185) of breast cancer cases, 10.2% (24/235) of colon cancer cases and in 6.4% (63/978) of population controls. NOD2 3020insC variant was associated with increased risk of breast cancer (OR = 2.5, p < 0.05) for cases diagnosed at age between 51 and 60 years. CHEK2 I157T variant was associated with increased risk of colorectal cancer (OR = 1.7, p < 0.05) with the highest OR = 2.0 for cases diagnosed at age >70 yrs.ConclusionsNOD2 3020insC, CHEK2 I157T variants may be associated with increased risk of colorectal and breast cancers in Latvia.

IntroductionThe aim of the study is to evaluate the incidence and phenotype-genotype characteristics of hereditary breast and ovarian cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by this syndrome.Materials and methodsIn 2002-2004 in two Latvian oncology hospitals (Liepãja Oncology Hospital and Daugavpils Oncology Hospital) cancer family histories were collected from 287 consecutive patients with breast and ovarian cancer. In all cases, when it was possible to obtain the blood sample, DNA testing for founder mutations in the BRCA1 gene was performed.ResultsAmong 287 family cancer histories analysed in 8 (2.8%) cases criteria of hereditary breast cancer (HBC) were fulfilled and in 5 (1.7%) cases hereditary breast and ovarian cancer (HBOC) was diagnosed. In 50 (17.4%) cases we have suspicion of hereditary breast cancer (HBC susp.) and in 8 (2.8%) cases - suspicion of hereditary breast and ovarian cancer (HBOC susp.). We have one (0.3%) case with hereditary ovarian cancer (HOC). DNA testing of founder mutations in the BRCA1 gene (exon 20 (5382 insC) exon 5 (300T/G), exon 11, 17 (4153delA)) for 178/287 (62%) patients was performed. In 9/287 (4.9%) cases we found a mutation in the BRCA1 gene. 4 mutations were detected in exon 11, 17 (4153delA) and 4 mutations in exon 20 (5382 insC) and 1 in exon 5.ConclusionsExisting pedigree/clinical data suggest that in Latvia the clinical frequency of hereditary breast and ovarian cancer is around 5% of consecutive breast and ovarian cancer patients and suspicion of the syndrome is observed in another 20% of cases. Frequency of BRCA1 founder mutations is 5% of all consecutive breast and ovarian cancers. Considerable geographical differences in the clinical and molecular frequency of hereditary breast ovarian cancer have been observed in Latvia.

Human Dirofilariasis in Latvia - the First Case in Surgical PracticeThough dirofilariasis in humans occurs rarely, the number of cases due toDirofilaria repenshas been increasing worldwide over the last decade. Climatic changes and animal migration extend geographic area of human dirofilariasis, now including Latvia. The diagnosis is based on histopathological features. Surgical excision is the only curative treatment. Practitioners should bear in mind the possibility of human dirofilariasis in residents of Latvia.

Management ofBRCA1Mutation Carrier with Breast CancerBRCA1gene mutation carriers face high lifetime risk of breast cancer therefore specific diagnostic features should be considered and individualized treatment strategies should be applied. ForBRCA1mutation carriers with already developed breast cancer, extensive surgery - bilateral mastectomy - could be indicated due to the cancer risk in the contralateral breast.

No abstract

Contributed by Jânis GardovskisThe aim of the study was to determine epidemiological, clinical and molecular features of hereditary breast-ovarian, colorectal, endometrial, prostate Only 22.0 % of patients were diagnosed with stage I or II disease. The majority of ovarian cancers (78.0 %) were diagnosed with stage III or IV disease. Therefore, it is very important to identify the group at risk from breast and ovarian cancers in order to employ prevention or early detection of cancer in patients and their family members.The majority of breast and ovarian cancers are considered sporadic. Approximately 15-20% of all breast and ovarian cancers are hereditary (Ford et al., 1998;Vasen et al., 2001;Jacobi et al., 2003). The incidence of hereditary breast and ovarian cancer may vary considerably among different populations and ethnic groups. In the last ten years, mutations in both BRCA1 and BRCA2 genes have been shown to be responsible for the development of hereditary breast and ovarian cancer. The aim of the study was to determine clinical and molecular and pathological features of hereditary breast and ovarian cancer in Latvia. There is continuing interest in identifying DNA variants associated with moderately increased risk of cancer. Several studies have suggested an increased risk of cancer in individuals who carry a mutation in the CHEK2 gene, one of the genes in the DNA damage signaling pathway. Originally, a single founder allele in CHEK2, 1100delC, was reported to be a low penetrance breast cancer susceptibility allele in several studies, and in many ethnic groups (Jarvinen, 1992;Bülow et al., 1996; Gorski et al., 2000;Chapelle, 2004). Then, a positive association was found between CHEK2 variants and prostate cancer in the USA, Finland and Poland (Bisgaard et al, 2004;Aretz et al., 2007;Anonîms, 2007). Recently, it was reported that individuals with a single common founder allele in Poland (the I157T missense variant) have increased risk of cancer development in many organs including the breast, prostate, thyroid, kidney and colon (Kilpivaara et al., 2003). The NOD2 gene is associated with susceptibility to inflammatory bowel disease, in particular, with Crohn's disease . It was reported that a single truncating mutation in NOD2, 3020insC, may confer increased risk of late onset colorectal cancer (Ogura et al., 2001) and then that a NOD2 mutation may be associated with increased susceptibility to lung, ovarian, early-onset laryngeal cancer and early onset breast cancer (Lichtenstein et al., 2000). It has not been established whether CHEK2 and NOD2 variants are present in Latvia and whether inherited variation in these genes influences cancer risk in this population.The aim of the study was to investigate the clinical and molecular features of hereditary colorectal cancer syndromes in Latvia in order to offer and provide predictive genetic testing of the affected families.Endometrial cancer. Endometrial cancer (EC) is among the three most common cancers in females in Latvia. There are approximately 390 new c...