***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: Gonadotrophin-releasing hormone analogues were investigated as adjuvant treatment for patients with node-negative , hormone-sensitive , premenopausal breast cancer . Patients were r and omised to either three cycles of cyclophosphamide , methotrexate , and 5-fluorouracil ( CMF ) chemotherapy ( n=378 ) or goserelin every 28 d for 2 years ( n=393 ) . During a median follow-up of 4.9 years , 123 events were observed . The first-failure event of CMF versus goserelin , respectively , was ipsilateral locoregional recurrence ( 18 versus 20 ) , contralateral breast cancer ( 7 versus 6 ) , distant failure ( 35 versus 24 ) and death without recurrence ( 2 versus 2 ) . Forty-two ( 23 versus 19 ) deaths of any cause occurred . The estimated adjusted hazard ratio for goserelin versus CMF ( intention-to-treat analysis ) was 0.79 ( 95 % CI=0.54 - 1.14 ; P=0.19 ) . It is concluded that medical ovarian ablation with goserelin represents a valid option for premenopausal patients with node-negative breast cancer Background Single nucleotide polymorphisms ( SNPs ) in the estrogen receptor 1 ( ESR1 ) and cytochrome P450 19A1 ( CYP19A1 ) genes have been associated with breast cancer risk , endocrine therapy response and side effects , mainly in postmenopausal women with early breast cancer . This analysis aim ed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes , sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial ( TEXT ) . Methods Blood was collected from consenting premenopausal women with hormone-responsive early breast cancer , r and omly assigned to 5-years of tamoxifen plus ovarian suppression ( OFS ) or exemestane plus OFS .  DNA was extracted with QIAamp kits and genotyped for two CYP19A1 ( rs4646 and rs10046 ) and three ESR1 ( rs2077647 , rs2234693 and rs9340799 ) SNPs by a real-time pyrosequencing technique . Adverse events ( AEs ) were recorded at baseline and 3-monthly during the first year . Associations of the genotype variants with grade ≥2 early-onset targeted AEs of hot flashes/sweating or musculoskeletal events were assessed using logistic regression models . Results There were 2660 premenopausal patients with breast cancer in the intention-to-treat population of TEXT , and 1967 ( 74 % ) are included in this translational study . The CYP19A1 rs10046 variant T/T , represented in 23 % of women , was associated with a reduced incidence of grade ≥2 hot flashes/sweating ( univariate odds ratio ( OR ) = 0.78 ; 95 % CI 0.63–0.97 ; P = 0.03 ) , more strongly in patients assigned exemestane + OFS ( TT vs CT/CC : OR = 0.65 , 95 % CI = 0.48–0.89 ) than assigned tamoxifen + OFS ( OR = 0.94 , 95 % CI = 0.69–1.27 , interaction P = 0.03 ) . No association with any of the CYP19A1/ESR1 genotypes and musculoskeletal AEs was found . Conclusion The CYP19A1 rs10046 variant T/T favors lower incidence of hot flashes/sweating under exemestane + OFS treatment , suggesting endocrine-mediated effects . Based on findings from others , this SNP may potentially enhance treatment adherence and treatment efficacy . We plan to evaluate the clinical impact of this polymorphism during time , pending sufficient median follow up . Trial registration Clinical Trials.gov NCT00066703 , registered August 6 , 2003 Optimal adjuvant endocrine therapy for premenopausal women with hormone-receptor positive breast cancer has long been debated . In particular , the role of ovarian function suppression in addition to st and ard tamoxifen divided oncologists worldwide , and more recently , the role of aromatase inhibitors as an alternative to tamoxifen in the setting of ovarian suppression became a key question . In 2014 , the long awaited results of the International Breast Cancer Study Group ( IBCSG ) led r and omized , phase 3 trials , Suppression of Ovarian Function Trial ( SOFT ) and Tamoxifen and Exemestane Trial ( TEXT ) , provided additional evidence to inform the discussion . The interpretation of the SOFT and TEXT trial data can facilitate better selection of appropriate endocrine therapy according to individual disease characteristics , recognizing the complexity of the puzzle , which is still not complete The sequential doxorubicin → CMF ( CMF = cyclophosphamide , methotrexate , fluorouracil ) regimen has never been compared to CMF in a r and omised trial . The role of adding goserelin and tamoxifen after chemotherapy is unclear . In all , 466 premenopausal node-positive patients were r and omised to : ( a ) CMF × 6 cycles ( CMF ) ; ( b ) doxorubicin × 4 cycles followed by CMF × 6 cycles ( A → CMF ) ; ( c ) CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years ( CMF → GT ) ; and ( d ) doxorubicin × 4 cycles followed by CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years ( A → CMF → GT ) . The study used a 2 × 2 factorial experimental design to assess : ( 1 ) the effect of the chemotherapy regimens ( CMF vs A → CMF or arms a+c vs b+d ) and ( 2 ) the effect of adding GT after chemotherapy ( arms a+b vs c+d ) . At a median follow-up of 72 months , A → CMF as compared to CMF  significantly improved disease-free survival ( DFS ) with a multivariate hazard ratio (HR)=0.740 ( 95 % confidence interval ( CI ) : 0.556–0.986 ; P=0.040 ) and produced a nonsignificant improvement of overall survival ( OS ) ( HR=0.764 ; 95 % CI : 0.489–1.193 ) . The addition of GT after chemotherapy significantly improved DFS ( HR=0.74 ; 95 % CI : 0.555–0.987 ; P=0.040 ) , with a nonsignificant improvement of OS ( HR=0.84 ; 95 % CI : 0.54–1.32 ) . A → CMF is superior to CMF . Adding GT after chemotherapy is beneficial for premenopausal node-positive patients Background Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression ( OFS ) as part of adjuvant endocrine therapy . If chemotherapy is also given , it is uncertain whether to select concurrent or sequential OFS initiation . Design and methods We analyzed 1872 patients enrolled in the r and omized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive , HER2-negative breast cancer and upon r and omization to an OFS-containing adjuvant endocrine therapy , initiated gonadotropin-releasing-hormone-agonist triptorelin .  Breast cancer-free interval ( BCFI ) was compared between patients who received OFS concurrently with chemotherapy in TEXT ( n = 1242 ) versus sequentially post-chemotherapy in SOFT ( n = 630 ) . Because timing of trial enrollment relative to adjuvant chemotherapy differed , we implemented l and mark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy ( median , 15.5 and 8.1 months from enrollment to l and mark in TEXT and SOFT , respectively ) . As a non-r and omized treatment comparison , we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling . Results Distributions of several clinico-pathologic characteristics differed between groups . Patients who were premenopausal post-chemotherapy in SOFT were younger on average . The median duration of adjuvant chemotherapy  was 18 weeks in both groups . There were 231 ( 12 % ) BC events after post-l and mark median follow-up of about 5 years . Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-l and mark BCFI compared with sequential triptorelin post-chemotherapy , either in the overall population ( HR = 1.11 , 95 % CI 0.72 - 1.72 ; P = 0.72 ; 4-year BCFI 89 % in both groups ) , or in the subgroup of 692 women < 40 years at diagnosis ( HR = 1.13 , 95 % CI 0.69 - 1.84 ) who are less likely to develop chemotherapy-induced amenorrhea . Conclusion Based on comparative-effectiveness modeling of TEXT and SOFT after about 5 years median follow-up , with limited statistical power especially for the subgroup < 40 years , neither detrimental nor beneficial effect of concurrent administration of OFS with chemotherapy on the efficacy of adjuvant therapy that includes chemotherapy was detected . Clinical trials.gov NCT00066690 and NCT00066703 PURPOSE The combination of taxanes and anthracyclines has proven efficacy in node-positive ( N+ ) premenopausal primary breast cancer patients . Ovarian ablation is also associated with better survival outcomes in premenopausal hormone-receptor positive ( HR+ ) patients . Therefore , this trial aims to determine the superiority of combined hormonal treatment of ovarian ablation with tamoxifen ( TMX ) versus TMX alone , in premenopausal N+ , HR + patients receiving adjuvant chemotherapy ( AC ) with taxane and anthracycline . MATERIAL S AND METHODS Premenopausal women who had surgically removed breast cancer with histologically confirmed N + and HR+ were included in the trial . The AC consisted of six cycles of taxotere , adriamycin , cytoxan or taxotere , epirubicin and cytoxan with the completion of radiation therapy . Patients were r and omly assigned to receive TMX 20 mg/day for 5 years or up to menopause or TMX 20 mg/day for 5 years plus goserelin ( GOS ) 3.6 mg injection per month for 2 years . The primary end point was disease-free survival ( DFS ) . RESULTS Between 2003 and 2011 , 101 consecutive patients were allocated to  TMX  ( 51 patients ) and TMX/GOS ( 50 patients ) groups . The mean follow-up period was 52.4 ± 2.8 months . DFS was 43.0 ± 3.6 months versus 49.9 ± 4.22 months ( P = 0.13 ) and overall survival was 51.1 ± 3.8 months versus 53.1 ± 4.2 months ( P = 0.50 ) in the TMX and TMX/GOS groups , respectively . The results showed 9 % absolute risk reduction with respect to DFS in favor of the TMX/GOS group . CONCLUSION This study group was comprised of stage II and III disease patients with high nodal status .  The TMX/GOS combination reduced absolute risk of developing first locoregional or distant relapse by almost 9 % . Longer follow-up is required to justify this protocol for routine use PURPOSE To determine whether the addition of surgical ovariectomy to st and ard chemotherapy prolongs disease-free survival ( DFS ) and overall survival in premenopausal patients with estrogen receptor (ER)-positive operable breast cancer with positive axillary nodes . PATIENTS AND METHODS Three hundred fourteen premenopausal patients with ER-positive , node-positive breast cancer were enrolled between July 1979 and July 1989 . Patients were stratified according to number of involved nodes and type of primary surgery and r and omized to receive either of the following : ( 1 ) cyclophosphamide 60 mg/m2/d by mouth for 1 year , methotrexate 15 mg/m2 intravenously ( i.v . ) weekly for 1 year , fluorouracil ( 5-FU ) 400 mg/m2 i.v . weekly for 1 year , vincristine .625 mg/m2 i.v . weekly for the first 10 weeks , and prednisone weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 ( CMFVP ) ; or ( 2 ) bilateral ovariectomy followed by CMFVP . RESULTS The median follow-up time is 7.7 years and the maximum 13.2 years . Treatment arms are not significantly different with respect to either survival or DFS ( one-sided log-rank , P = .55 and .70 , respectively ) . The 7-year survival rate is 71 % on the CMFVP arm and 73 % on CM 
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This treatment effect was seen when OFS was added to observation , to tamoxifen , or to chemotherapy and tamoxifen .
This review found evidence that supports adding OFS for premenopausal women with early , hormone receptor-positive breast cancers .
The benefit of OFS persisted when compared to observation , and when added to endocrine therapy ( tamoxifen ) or chemotherapy and endocrine therapy ( tamoxifen ) .