The impact of oophorectomy on survival after breast cancer in BRCA1-positive breast cancer patients.

The aim of the study is to identify treatments which predict survival for women with a BRCA1 mutation, including oophorectomy and chemotherapy. 476 women with stage I to stage III breast cancer who carried a BRCA1 mutation were followed from diagnosis until April 2015. Information on treatment was obtained from chart review and patient questionnaires. Dates of death were obtained from the Poland vital statistics registry. Survival curves were compared for different subgroups according to treatment received. Predictors of overall survival were determined using the Cox proportional hazards model. The ten-year overall survival was 78.3 % (95 % CI 74.2-82.6 %) and the ten-year breast cancer-specific survival was 84.2 % (95 % CI 80.5-88.0 %). Sixty-two patients died of breast cancer, 14 patients died of ovarian cancer, and 2 patients died of peritoneal cancer. Oophorectomy was associated with a significant reduction in all-cause mortality in the entire cohort (adjusted HR = 0.41; 95 % CI 0.24-0.69; p = 0.0008) and in breast cancer-specific mortality among ER-negative breast cancer patients (HR = 0.44; 95 % CI 0.22-0.89; p = 0.02). Among women with breast cancer and a BRCA1 mutation, survival is greatly improved by oophorectomy due to the prevention of deaths from both breast and ovarian cancer.

Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland.

BACKGROUND: Mutations in the BRCA1, BRCA2 and PALB2 genes are well-established risk factors for the development of breast and/or ovarian cancer. The frequency and spectrum of mutations in these genes has not yet been examined in the population of Southern Poland. METHODS: We examined the entire coding sequences of the BRCA1 and BRCA2 genes and genotyped a recurrent mutation of the PALB2 gene (c.509_510delGA) in 121 women with familial and/or early-onset breast or ovarian cancer from Southern Poland. RESULTS: A BRCA1 mutation was identified in 11 of 121 patients (9.1 %) and a BRCA2 mutation was identified in 10 of 121 patients (8.3 %). Two founder mutations of BRCA1 accounted for 91 % of all BRCA1 mutation carriers (c.5266dupC was identified in six patients and c.181 T > G was identified in four patients). Three of the seven different BRCA2 mutations were detected in two patients each (c.9371A > T, c.9403delC and c.1310_1313delAAGA). Three mutations have not been previously reported in the Polish population (BRCA1 c.3531delT, BRCA2 c.1310_1313delAAGA and BRCA2 c.9027delT). The recurrent PALB2 mutation c.509_510delGA was identified in two patients (1.7 %). CONCLUSIONS: The standard panel of BRCA1 founder mutations is sufficiently sensitive for the identification of BRCA1 mutation carriers in Southern Poland. The BRCA2 mutations c.9371A > T and c.9403delC as well as the PALB2 mutation c.509_510delGA should be included in the testing panel for this population.

Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients.

The aim of this study is to estimate the frequency of pathologic complete response (pCR) after neoadjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation. One hundred and seven women with breast cancer and a BRCA1 mutation, who were diagnosed with stage I to III breast cancer between December 2006 and June 2014, were treated with cisplatin 75 mg/m(2) every 3 weeks for four cycles, followed by mastectomy and conventional chemotherapy. Information was collected on clinical stage, grade, hormone receptor status, and Her2neu status prior to treatment. pCR was determined by review of surgical specimens. One hundred and seven patients were enrolled in the study, including 93 patients who were treated for first primary breast cancer and 14 patients who had previously received treatment for a prior cancer. A pCR was observed in 65 of the 107 patients (61 %). Platinum-based chemotherapy is effective in a high proportion of patients with BRCA1-associated breast cancer.

Survival from breast cancer in patients with CHEK2 mutations.

The purpose of this study is to estimate 10-year survival rates for patients with early onset breast cancer, with and without a CHEK2 mutation and to identify prognostic factors among CHEK2-positive breast cancer patients. 3,592 women with stage I to stage III breast cancer, diagnosed at or below age 50, were tested for four founder mutations in the CHEK2 gene. Information on tumor characteristics and on treatments received was retrieved from medical records. Dates of death were obtained from the Poland Vital Statistics Registry. Survival curves were generated for the mutation-positive and -negative sub-cohorts. Predictors of survival were determined among CHEK2 carriers using the Cox proportional hazards model. 3,592 patients were eligible for the study, of whom 140 (3.9 %) carried a CHEK2-truncating mutation and 347 (9.7 %) carried a missense mutation. The mean follow-up was 8.9 years. The 10-year survival for all CHEK2 mutation carriers was 78.8 % (95 % CI 74.6-83.2 %) and for non-carriers was 80.1 % (95 % CI 78.5-81.8 %). Among women with a CHEK2-positive breast cancer, the adjusted hazard ratio associated with ER-positive status was 0.88 (95 % CI 0.48-1.62). Among women with an ER-positive breast cancer, the adjusted hazard ratio associated with a CHEK2 mutation was 1.31 (95 % CI 0.97-1.77). The survival of women with breast cancer and a CHEK2 mutation is similar to that of patients without a CHEK2 mutation.

Clinical characteristics of breast cancer in patients with an NBS1 mutation.

To identify characteristic features of breast cancers associated with an NBS1 mutation. To estimate and to compare 10-year survival rates for patients with early-onset breast cancer, with and without an NBS1 mutation. 4,566 women with stage I to stage III breast cancer, diagnosed at or below age 50, were tested for a founder mutation in the NBS1 gene. Information on tumor characteristics and on treatments received was retrieved from medical records. Dates of death were obtained from the Poland vital statistics registry. Survival curves for the mutation-positive and negative sub-cohorts were generated and were compared and the effect of an NBS1 mutation on survival was determined using the Cox proportional hazards model. 4566 patients were enrolled in the study, of whom 53 (1.2 %) carried a NBS1 mutation. Mutation carriers were similar to non-carriers in terms of tumor receptor status, grade, and lymph node status. The 10-year survival for NBS1 mutation carriers was 81.2 % (95 % CI 70.1-94.1 %) and for non-carriers was 79.4 % (95 % CI 78.0-80.9 %). The presence of an NBS1 mutation is not associated with prognosis (HR = 1.21; 95 % 0.67-2.19). The survival of women with breast cancer and a NBS1 mutation is similar to that of patients without a NBS1 mutation.

Breast cancer predisposing alleles in Poland.

Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors.

Factors determining the post-operative hypo-albuminaemia in cancer patients--stepwise regression analysis.

AIM: To investigate factors influencing post-operative hypo-albuminaemia in cancer patients, with special reference to low dose albumin and/or immunoglobulins administration. PATIENTS AND METHODS: In 270 patients with malignant neoplasms, who underwent extensive chest and/or abdominal surgery, albumin concentrations on the first four postoperative days were examined. One hundred and three high-risk patients received human immunoglobulins intravenously; 44 were given albumin. Univariate and multivariate regression analyses were used to determine the factors influencing albuminaemia on the first four postoperative days. RESULTS: Mean nadir of hypo-albuminaemia occurred on the third postoperative day. In the multivariate analysis, a positive correlation was found between postoperative albuminaemia and pre-operative albuminaemia (b = 0.4919; p = 0.0000) as well as male gender (b = 2.0939; p = 0.0025). A negative correlation was found with the duration of surgery (b = -0.0416; p = 0.0212), pre-operative plasma protein (b = -0.2118, p = 0.0130) and postoperative immunoglobulin administration (b = -1.8858, p = 0.0074). CONCLUSIONS: Postoperative albuminaemia is positively correlated with pre-operative albuminaemia and male gender and negatively correlated with the duration of surgery, pre-operative proteinaemia and postoperative Ig administration.