Pathology findings and clinical outcomes after risk reduction salpingo-oophorectomy in BRCA mutation carriers: a multicenter Spanish study.

OBJECTIVE: To determine the incidence of serous tubal intraepithelial carcinoma (STIC) after risk reduction salpingo-oophorectomy(RRSO), and to describe oncological outcomes after RRSO. MATERIALS AND METHODS: BRCA pathogenic mutation carriers who had undergone an RRSO were evaluated in this retrospective multicenter observational study. Patients were only included when fallopian tubes were analyzed following the protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Surgeries were performed between June 2010 and April 2017 at eight Spanish hospitals. RESULTS: A total of 359 patients met the inclusion criteria. STIC was diagnosed in 3 (0.8%) patients; one of them underwent surgical staging due to positive peritoneal washing, with absence of disease at the final pathology report. None of the three patients received adjuvant chemotherapy and were free of disease at last follow-up. Fallopian tube and ovarian carcinoma were diagnosed in 5 (1.4%) and 1 (0.3%), respectively. At a median (range) follow-up time of 29 (3-92) months, five patients had a newly diagnosed breast cancer. Other types of cancer, which were diagnosed during the follow-up time, included: serous primary peritoneal carcinoma (n = 1), serous endometrial carcinoma (n = 1), colon (n = 1), pancreas (n = 1), jaw (n = 1), and lymphoma (n = 1). Seven patients died due to different types of cancer: breast (n = 4), pancreas (n = 1), jaw (n = 1), and colon (n = 1). CONCLUSION: The incidence of STIC after RRSO in BRCA mutation carriers is low (0.8%) and it presents an excellent oncological outcome. Patients after RRSO, however, run the risk to develop other types of cancer during follow-up and should be properly advised before the prophylactic surgery.

Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

Validation of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish Oncologic Genitourinary Group (SOGUG) SPAZO study.

BACKGROUND: Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. PATIENTS AND METHODS: Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. RESULTS: According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. CONCLUSION: Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.

BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study.

Male breast cancer (MBC) is a rare disease that represents <1% of all breast cancers (BCs). We analyze the results of a multicenter study performed in Spanish familial MBC including family history of hereditary breast and ovarian cancer syndrome (HBOCS) and clinicopathological features. We also study the relationship between BRCA1/BRCA2 mutational status in male relatives affected with cancer (MAC) and, family history and tumor types. The study included 312 men index cases with family history of HBOCS and 61 MAC BRCA1/2 mutation-carriers. Family history, histological grade (HG), clinicopathological and immunohistochemistry data were collected. BRCA1/2 mutation analyses were performed by direct sequencing or screening methods and the large rearrangements by multiplex ligation dependent probe amplification. We found 49 mutation-carriers (15.7%), 95.9% with BRCA2 mutations. BRCA2 mutation-carriers were associated with families with at least one MBC and one BC in female (type II; p = 0.05). Strong association were found between the presence of pathogenic mutations in MBCs and the advanced HG (p = 0.003). c.658_659delTG, c.2808_2811delACAA, c.6275_6276delTT and c.9026_9030delATCAT were the most prevalent mutations. In 61 MAC we found 20 mutations in BRCA1 and 41 in BRCA2. For MAC we show that mutational status was differentially associated with family history (p = 0.018) and tumor type, being BRCA2 mutations linked with BC and prostatic cancer (p = 0.018). MBC caused by BRCA1/2 mutations define two types of MBCs. The most frequent caused by BRCA2 mutation linked to type II families and the rarest one attributed to BRCA1 mutation. Tumor associated with MAC suggest that only BRCA2 mutations have to do with a specific type of cancer (BC and prostatic cancer); but the linkage to tumors is questionable for BRCA1 mutations .

Asymmetry of coding versus noncoding strand in coding sequences of different genomes.

We have used the asymmetry between the coding and noncoding strands in different codon positions of coding sequences of DNA as a parameter to evaluate the coding probability for open reading frames (ORFs). The method enables an approximation of the total number of coding ORFs in the set of analyzed sequences as well as an estimation of the coding probability for the ORFs. The asymmetry observed in the nucleotide composition of codons in coding sequences has been used successfully for analysis of the genomes completed at the time of this analysis.