***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: We characterized BRCA1 and BRCA2 status ( mutation/methylation ) in a consecutive series of cases of ovarian carcinoma in order to identify differences in clinicopathological features , molecular characteristics , and outcome between the pelvic high- grade serous cancers with ( i ) germline or somatic mutations in BRCA1 or BRCA2 , ( ii ) methylation of BRCA1 , and ( iii ) normal BRCA1 or BRCA2 . In all , 131 women were identified prospect ively , who were undergoing surgical staging and agreed to germline testing for BRCA1 and BRCA2 mutations .  Histopathology , germline and somatic BRCA1 or BRCA2 mutations , BRCA1 methylation , and BRCA1 and BRCA2 mRNA expression levels distinguished four subgroups . In all , 103 cases were high- grade serous carcinoma and of these 31 ( 30 % ) had germline or somatic BRCA1 or BRCA2 mutations ( 20 % BRCA1 and 10 % BRCA2 ) ( group 1 ) , 21 ( 20 % ) had methylation of BRCA1 ( group 2 ) , and in 51 ( 50 % ) there was no BRCA loss ( group 3 ) . Group 4 consisted of 28 cases of non-high- grade serous , none of which had BRCA loss . BRCA1 and BRCA2 mRNA expression levels correlated with design ated group ( P=0.0008 ) . Among high- grade serous carcinomas , there were no differences between groups 1–3 with respect to stage , ascites , CA125 level , platinum sensitivity , cytoreduction rate , neoadjuvant chemotherapy , or survival . Tumors with BRCA1 or BRCA2 mutations had increased immune infiltrates ( CD20 and TIA-1 ) compared with high- grade serous without mutations ( P=0.034 , 0.027 ) . TP53 expression differed between groups ( P<0.0001 ) , with abnormal TP53 expression in 49/50 tumors from groups 1 and 2 . Wild-type TP53 expression was associated with worse outcome in high- grade serous ( P<0.001 ) . BRCA loss ( mutation/methylation ) is a common event in the pelvic high- grade serous ( 50 % ) . TP53 abnormalities and increased immune cell infiltrates are significantly more common in high- grade serous with germline and somatic mutations in BRCA1 or BRCA2 , compared with tumors lacking BRCA abnormalities This multi-centre UK study assesses the impact of predictive testing for breast and ovarian cancer predisposition genes ( BRCA1/2 ) in the clinical context . In the year following predictive testing , 261 adults ( 59 male ) from nine UK genetics centres participated ; 91 gene mutation carriers and 170 noncarriers .  Self-report question naires were completed at baseline ( pre-genetic testing ) and 1 , 4 and 12 months following the genetic test result . Men were assessed for general mental health ( by general health question naire ( GHQ ) ) and women for general mental health , cancer-related worry , intrusive and avoidant thoughts , perception of risk and risk management behaviour . Main comparisons were between female carriers and noncarriers on all measures and men and women for general mental health . Female noncarriers benefited psychologically , with significant reductions in cancer-related worry following testing ( P<0.001 ) . However , younger female carriers ( < 50 years ) showed a rise in cancer-related worry 1 month post-testing ( P<0.05 ) . This returned to pre-testing baseline levels 12 months later , but worry remained significantly higher than noncarriers throughout ( P<0.01 ) . There were no significant differences in GHQ scores between males and females ( both carriers and noncarriers ) at any time point . Female carriers engaged in significantly more risk management strategies than noncarriers in the year following testing ( e.g. mammograms ; 92 % carriers vs 30 % noncarriers ) . In the 12 months post-testing , 28 % carriers had bilateral risk-reducing mastectomy and 31 % oophorectomy . Oophorectomy was confined to older ( mean 41 yrs ) women who already had children . However , worry about cancer was not assuaged by surgery following genetic testing , and this requires further investigation . In all , 20 % of female carriers reported insurance problems . The data show persistent worry in younger female gene carriers and confirm changes in risk management consistent with carrier status . Men were not adversely affected by genetic testing in terms of their general mental health This prospect i ve multicentre study assesses long-term impact of genetic testing for breast/ovarian cancer predisposition in a clinical cohort . Areas evaluated include risk management , distress and insurance problems 3 years post-testing . Participants are adults unaffected with cancer from families with a known BRCA1/2 mutation . One hundred and ninety-three out of 285 ( 70 % response ) participants at nine UK clinical genetics centres completed assessment s at 3 years : 80 % female ; 37 % carriers of a BRCA1/2 mutation . In the 3 years , post-genetic testing carriers reported more risk management activities than non-carriers . Fifty-five per cent of female carriers opted for risk reducing surgery ; 43 % oophorectomy ; and 34 % mastectomy . Eighty-nine per cent had mammograms compared with 47 % non-carriers . Thirty-six per cent non-carriers ⩾50 years did not have a mammogram post-test . Twenty-two per cent male carriers had colorectal and 44 % prostate screening compared with 5 and 19 % non-carriers respectively . Seven per cent carriers and 1 % non-carriers developed cancer . Distress levels did not differ in carriers and non-carriers at 3-year follow-up . Forty per cent of female carriers reported difficulties with life and /or health insurance . Given the return to pre-test levels of concern among female non-carriers at 3 years and a substantial minority not engaging in recommended screening , there appears to be a need to help some women underst and the meaning of their genetic status Objective Opportunistic bilateral salpingectomy is now promoted for women at the time of hysterectomy for a benign disease , consequent to the fimbrial end of the fallopian tube emerging as the primary site for carcinogenesis in high- grade serous carcinomas . In high-risk women with an identified germ line mutation , bilateral salpingo-oophorectomy offers the greatest risk reduction for ovarian cancer . Currently , no prospect i ve evidence exists with respect to the effectiveness of opportunistic salpingectomy alone in preventing ovarian cancer . Although it is thought that there is no direct connection between the ovary and its adjacent fallopian tube , we often find remnants of the fimbria adherent to the ovary at the time of surgery . If this tubo-ovarian interface is not separate , then practice s such as salpingectomy and radical fimbriectomy may be incomplete , and the effectiveness of this technique as a prophylactic strategy may need reconsideration . We aim ed to establish whether there might exist a direct attachment of the fimbria to the ovary by examining this interface in surgically removed specimens . Methods The tubes and ovaries of 20 women undergoing risk-reducing salpingo-oophorectomy  were examined using the Sectioning and Extensively Examining the Fimbriated End of the Tubes protocol and p53 immunohistochemistry for lesions suspicious of serous intraepithelial tubal carcinoma . Results Three specimens showed fimbria adherent to the ovary at the histopathological analysis . One p53 signature was identified , but there were no occult cancers or serous intraepithelial tubal carcinomas . Conclusions Although only a small study , the findings show that microscopic fimbriae are adherent to the ovary . This relationship challenges the recommendation for bilateral salpingectomy alone for risk-reducing surgery because the primary site of carcinogenesis may be left on the ovary to later develop into a high- grade serous carcinoma . A larger study is needed to assess our findings related to the tubo-ovarian interface and its implication s for long-term ovarian cancer development . Until then , caution on using this technique alone in the high-risk patient should be adopted OBJECTIVES Considerable morbidity persists among survivors of breast cancer ( BC ) including high levels of psychological stress , anxiety , depression , fear of recurrence , and physical symptoms including pain , fatigue , and sleep disturbances , and impaired quality of life . Effective interventions are needed during this difficult transitional period . METHODS We conducted a r and omized controlled trial of 84 female BC survivors ( Stages 0-III ) recruited from the H. Lee Moffitt Cancer and Research Institute . All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and /or chemotherapy .  Subjects were r and omly assigned to a 6-week Mindfulness-Based Stress Reduction ( MBSR ) program design ed to self-regulate arousal to stressful circumstances or symptoms ( n=41 ) or to usual care ( n=43 ) . Outcome measures compared at 6 weeks by r and om assignment included vali date d measures of psychological status ( depression , anxiety , perceived stress , fear of recurrence , optimism , social support ) and psychological and physical subscales of quality of life ( SF-36 ) . RESULTS Compared with usual care , subjects assigned to MBSR(BC ) had significantly lower ( two-sided p<0.05 ) adjusted mean levels of depression ( 6.3 vs 9.6 ) , anxiety ( 28.3 vs 33.0 ) , and fear of recurrence ( 9.3 vs 11.6 ) at 6 weeks , along with higher energy ( 53.5 vs 49.2 ) , physical functioning ( 50.1 vs 47.0 ) , and physical role functioning ( 49.1 vs 42.8 ) . In stratified analyses , subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning . CONCLUSIONS Among BC survivors within 18 months of treatment completion , a 6-week MBSR(BC ) program result ed in significant improvements in psychological status and quality of life compared with usual care BACKGROUND Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2 mutation carriers . The aims of this study were to derive penetrance estimates for breast cancer , ovarian cancer , and contralateral breast cancer in a prospect i ve series of mutation carriers and to assess how these risks are modified by common breast cancer susceptibility alleles . METHODS Prospect i ve cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2 carriers from the United Kingdom . Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline , 1509 women were unaffected by ovarian cancer , and 651 had been diagnosed with unilateral breast cancer .  Cumulative risks were obtained using Kaplan-Meier estimates . Associations between cancer risk and covariables of interest were evaluated using Cox regression . All statistical tests were two-sided . RESULTS The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60 % ( 95 % confidence interval [ CI ] = 44 % to 75 % ) for breast cancer , 59 % ( 95 % CI = 43 % to 76 % ) for ovarian cancer , and 83 % ( 95 % CI = 69 % to 94 % ) for contralateral breast cancer . For BRCA2 carriers , the corresponding risks were 55 % ( 95 % CI = 41 % to 70 % ) for breast cancer , 16.5 % ( 95 % CI = 7.5 % to 34 % ) for ovarian cancer , and 62 % ( 95 % CI = 44 % to 79.5 % ) for contralateral breast cancer . BRCA2 carriers in the highest tertile of risk , defined by the joint genotype distribution of seven single nucleotide polymorphisms associated with breast cancer risk , were at statistically significantly higher risk of developing breast cancer than those in the lowest tertile ( hazard ratio = 4.1 , 95 % CI = 1.2 to 14.5 ; P = .02 ) . CONCLUSIONS Prospect i ve risk estimates confirm that BRCA1 and BRCA2 carriers are at high risk of developing breast , ovarian , and contralateral breast cancer . Our results confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers Purpose : To investigate the medical and psychosocial factors determining the time to prophylactic surgery of unaffected women carriers of a deleterious BRCA1/2 mutation . Methods : Prospect i ve study on a French national cohort of unaffected BRCA1/2 carriers ( N = 244 ) ; multivariate Cox proportional hazard modeling . Results : Median follow-up time was 2.33 years ( range , 0.04–6.84 years ) . Time to surgery was shorter when the psychological impact of BRCA1/2 result disclosure was stated to be higher ( P ≤ 0.01 ) . Those who intended to opt for prophylactic surgery before being tested did so faster and more frequently after test disclosure than those who were undecided/opposed . The older the women were , the faster their uptake of risk-reducing salpingo-oophorectomy  ( adjusted hazard ratio > 2.95 ; P < 0.001 ) was ; the uptake of those with at least two children was also faster ( adjusted hazard ratio = 2 
    Output:
    
Other outcome measures on the Female Sexual Function Index and the Female Sexual Distress Scale showed no significant differences between the two groups .