BRCA1-associated breast cancer is considered an unique clinical entity with its own specific histopathological characteristics. Several recently published large studies have shown that overall survival of BRCA1 mutation carriers having breast cancer is similar to sporadic breast cancer patients. It was also suggested that better response to chemotherapy is one of the most important factors that improves the clinical outcome of breast cancers with unfavorable histopathological subtypes in BRCA1 mutation carriers. Adjuvant! Online and PREDICT are web-based prognostic tools that estimate the survival benefit of adjuvant chemotherapy in primary breast cancer patients. These tools have been extensively validated in different populations; however, the accuracy of the predictions made by Adjuvant! Online and PREDICT among BRCA1 mutation carriers has not yet been investigated. In this study we have found, that predictions of overall and breast cancer-specific survival obtained from Adjuvant! Online and PREDICT were significantly lower than the observed survival percentages in the study population [predicted--observed difference for 10-year overall survival: -9.75%, P < 0.0001 (Adjuvant! Online); -10.21%, P < 0.0001 (PREDICT)]. Thus this study suggests that Adjuvant! Online and PREDICT should be used with caution in this group of patients. Further updating of adjuvant therapy benefit calculation tools by inclusion of the information about inherited genetic alterations should be considered to improve the performance of the prognostic programs among hereditary breast cancer patients.

BackgroundMutations in the high penetrance breast and ovarian cancer susceptibility gene BRCA1 account for a significant percentage of hereditary breast and ovarian cancer cases. Genotype-phenotype correlations of BRCA1 mutations located in different parts of the BRCA1 gene have been described previously; however, phenotypic differences of specific BRCA1 mutations have not yet been fully investigated. In our study, based on the analysis of a population-based series of unselected breast and ovarian cancer cases in Latvia, we show some aspects of the genotype-phenotype correlation among the BRCA1 c.4034delA (4153delA) and c.5266dupC (5382insC) founder mutation carriers.MethodsWe investigated the prevalence of the BRCA1 founder mutations c.4034delA and c.5266dupC in a population-based series of unselected breast (n = 2546) and ovarian (n = 795) cancer cases. Among the BRCA1 mutation carriers identified in this analysis we compared the overall survival, age at diagnosis and family histories of breast and ovarian cancers.ResultsWe have found that the prevalence of breast and ovarian cancer cases (breast: ovarian cancer ratio) differs significantly among the carriers of the c.5266dupC and c.4034delA founder mutations (OR = 2.98, 95%CI = 1.58 to 5.62, P < 0.001). We have also found a difference in the prevalence of breast and ovarian cancer cases among the 1st and 2nd degree relatives of the c.4034delA and c.5266dupC mutation carriers. In addition, among the breast cancer cases the c.4034delA mutation has been associated with a later age of onset and worse clinical outcomes in comparison with the c.5266dupC mutation.ConclusionsOur data suggest that the carriers of the c.4034delA and c.5266dupC founder mutations have different risks of breast and ovarian cancer development, different age of onset and prognosis of breast cancer.

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.