human
***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: Two hundred patients with node positive stage II breast cancer were r and omised to four groups after radical mastectomy and axillary evacuation : ( 1 ) Postoperative radiotherapy , ( 2 ) Adjuvant chemotherapy with eight courses of CAFt ( cyclophosphamide 500 mg m-2 + doxorubicin 40 mg/m-2 + ftorafur 20 mg kg-1 orally day 1 - 14 ) every fourth week , ( 3 ) Postoperative radiotherapy and adjuvant chemotherapy and ( 4 ) postoperative radiation , adjuvant chemotherapy and tamoxifen 40 mg daily for 2 years . Thirty-two per cent of the patients discontinued treatment due to GI-toxicity , while 26 % required dose reductions due to leukopenia . Radiation pneumonitis was more frequent after the combination of postoperative radiotherapy with chemotherapy . There was a better relapse-free survival in the groups receiving chemotherapy compared to radiotherapy alone ( P = 0.05 ) , which was highly significant in a multivariate Cox analysis ( P = 0.004 ) . No significant survival differences were seen . Tamoxifen had no clear overall effect but there were better relapse-free ( P = 0.04 ) and overall ( P = 0.004 ) survival with tamoxifen in estrogen receptor positive patients , while estrogen receptor negative patients had a somewhat poorer survival ( P = 0.07 ) after tamoxifen .  Local control was better ( NS ) after the combination ( 93 % ) radiotherapy and chemotherapy compared to either treatment alone ( 76 % with radiotherapy and 74 % with chemotherapy at 5 years ) In a prospect i ve study of 622 women with breast cancer , those with one to three histologically positive axillary lymph nodes were r and omised after mastectomy  to receive cyclophosphamide 100 mg/m2 orally on days 1 - 14 , methotrexate 40 mg/m2 intravenously on days 1 and 8 , and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles ( CMF x six ) , or for twelve cycles of the same chemotherapy ( CMF x 12 ) . Those with > or = four positive nodes were r and omised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy ( RT ) followed by six cycles of the same chemotherapy ( RT + CMF x six ) . With about 10 years median follow-up , there was no significant difference in survival or disease-free survival among the three groups . There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six ( relative risk 0.53 , P = 0.067 ) . Multivariate analysis indicated that the presence of > or = four positive nodes ( negatively ) and the percentage of ideal ( full ) dose of CMF received ( positively ) were the strongest factors predictive of survival . This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes . There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes OBJECTIVE To provide information and recommendations for women and their physicians when making decisions about the management of lymphedema related to breast cancer . OPTIONS Compression garments , pneumatic compression pumps , massage and physical therapies , other physical therapy modalities , pharmaceutical treatments . OUTCOMES Symptom control , quality of life , cosmetic results . EVIDENCE Systematic review of English- language literature retrieved primarily from MEDLINE ( 1966 to April 2000 ) and CANCERLIT ( 1985 to April 2000 ) . Non systematic review of breast cancer literature published to October 2000 . RECOMMENDATIONS Pre- and postoperative measurements of both arms are useful in the assessment and diagnosis of lymphedema . Circumferential measurements should be taken at 4 points : the metacarpal-phalangeal joints , the wrists , 10 cm distal to the lateral epicondyles and 15 cm proximal to the lateral epicondyles . Clinicians should elicit symptoms of heaviness , tightness or swelling in the affected arm . A difference of more than 2.0 cm at any of the 4 measurement points may warrant treatment of the lymphedema , provided that tumour involvement of the axilla or brachial plexus , infection and axillary vein thrombosis have been ruled out . Practitioners may want to encourage long-term and consistent use of compression garments by women with lymphedema . One r and omized trial has demonstrated a trend in favour of pneumatic compression pumps  compared with no treatment . Further r and omized trials are required to determine whether pneumatic compression provides additional benefit over compression garments alone . Complex physical therapy , also called complex decongestive physiotherapy , requires further evaluation in r and omized trials . In one r and omized trial no difference in outcomes was detected between compression garments plus manual lymph drainage versus compression garments alone . Clinical experience supports encouraging patients to consider some practical advice regarding skin care , exercise and body weight . [ A patient version of these guidelines appears in Appendix 2 . ] VALIDATION An initial draft of this document was developed by a task force sponsored by the BC Cancer Agency . It was up date d and revised substantially by a writing committee and then su bmi tted for further review , revision and approval by the Steering Committee for Clinical Practice Guidelines for the Care and Treatment of Breast Cancer . SPONSOR The steering committee was convened by Health Canada . COMPLETION DATE : October 2000 UNLABELLED A prospect i ve r and omized study was made of 270 patients with unilateral stage I or II invasive breast cancer treated by segmental resection , axillary dissection and radiation at the University Hospital of Tampere , Finl and , between 1989 and 1991 . The aim of the study was to determine whether there is any advantage or disadvantage if the internal mammary chains ( IMC ) are included in the radiation target volume . The medial and lateral two-field technique was used and the target volumes were determined r and omly either to include the internal mammary chain ( IMC-RT ) or not ( no-IMC-RT ) . The prevalence of radiation pneumonitis was 16 % and there was no significant difference between the IMC- and no-IMC-groups ( 18 vs. 14 % ) . Skin reactions were equal in both groups . Lung fibrosis was more common in the IMC-RT group . IN CONCLUSION radiation of internal mammary chain after conservative surgery does not lead to an increase in clinical ly important skin or pulmonary complications . Whether it prevents recurrences or new primaries of the opposite breast is too early to say because of the short follow-up time Summary 158 evaluable patients with stage II , lymph node positive , carcinoma of the breast were r and omized to adjuvant therapy with either melphalan ( L-PAM ) or cyclophosphamide , methotrexate , and fluorouracil ( CMF ) after mastectomy . In addition , patients were r and omized to be treated with or without post-operative irradiation therapy ( RT ) in addition to their chemotherapy . At a median follow-up time of 11 years , there is no difference in time to relapse ( P=0.69 ) or survival ( P=0.55 ) among the four treatment groups . Multivariate analysis including treatment arm , age , race , tumor size , histologic type , performance status , time to onset of treatment , menopausal status , and number of positive nodes , revealed that only the number of positive nodes ( < 4 vs ≥ 4 ) was related to disease-free and overall survival . Ten year relapse-free survival for patients with < 4 positive nodes compared to those with ≥4 positive nodes was 63 % versus 30 % , and overall survival 63 % versus 41 % , respectively . Patients who received post-operative radiation therapy had significantly less local recurrence than those treated with chemotherapy alone ( P=0.03 ) but without improvement in relapse-free or overall survival . In this trial , post-operative radiation therapy when added to chemotherapy  decreased the risk of local recurrence without adverse effects on survival . Treatment outcome was not influenced by chemotherapy regimen , but differences may have been obscured by the small sample size We studied loco-regional recurrence during follow-up ( median observation time 8 years ) in 1,153 patients , who underwent modified mastectomy and were r and omly assigned to one of the following postoperative treatments ; Premenopausal patients : radiotherapy , cyclophosphamide , or both ; Post-menopausal patients : radiotherapy , tamoxifen , or both .  Recurrence occurred in a total of 419 patients , 123 of whom had loco-regional recurrence with or without distant metastasis . The loco-regional recurrence rate was 7 % in the irradiated subgroups and 17 % in the non-irradiated subgroups , the corresponding cure rates being 43 % and 58 % . Complete remission of all local recurrence was obtained after the first treatment in 67 % of the cases , and was persistent in 67 % of them ( 44 % overall ) . Complete remission was obtained in all patients with local recurrence who received local treatment only , and was persistent in 65 % . Of local recurrences treated with a combination of surgery , radiotherapy and hormone therapy , complete response was obtained in 94 % of the patients , and was persistent in 94 % of them ( 88 % overall ) . Complete remission of all regional recurrence was obtained after the first treatment in 58 % of the patients and was persistent in 67 % of them ( 39 % overall ) . Postoperative radiotherapy reduced not only the total number of loco-regional recurrences but also the number of uncontrolled loco-regional recurrences . Aggressive local treatment would appear to yield both satisfactory initial control and , when combined with the hormone therapy , a high rate of persistent loco-regional control The efficacy of adjuvant treatment with tamoxifen was evaluated in protocol DBCG 77 C. Postmenopausal high risk patients ( tumor greater than 5 cm , positive axillary nodes , or invasion to skin/fascia ) were r and omized after total mastectomy and axillary sampling to postoperative radiotherapy ( control ) or to radiotherapy plus treatment with tamoxifen ( TAM ) , 30 mg daily for 1 year . A total of 1,716 patients entered the study . At 8 years of follow-up , ( 7 years median time of observation ) , we observed a significant increase of recurrence-free survival for the TAM treated group and a reduction in mortality , which is significant for patients less than 70 years of age . Retrospectively , an increased recurrence-free survival in TAM treated patients was significant in the following subgroups : tumor less than 5 cm , positive lymph nodes , anaplasia grade II and estrogen receptor level greater than 100 fmol/mg cytosol protein . In the subsequent trial ( DBCG 82 C ) , 1,347 postmenopausal patients less than 70 years were r and omized to one of the following 3 regimens : radiotherapy + tamoxifen , 30 mg daily for 1 year ( TAM ) , TAM alone , or TAM + CMF ( CMF i.v . day 1 every 4 weeks x 9 ) . The survival is similar in the 3 groups at 4 years ( 2 years median time of observation ) The purpose of this study was to test the role of radiotherapy following total mastectomy , axillary dissection , and adjuvant systemic therapy in the management of operable locally advanced breast carcinoma BACKGROUND Tamoxifen is an anti-estrogen with proven efficacy and low toxicity in the treatment of breast cancer . However , tamoxifen has been shown to exert a number of nonhormonal as well as hormonal effects . One nonhormonal effect of tamoxifen is the induction of transforming growth factor-beta ( TGF-beta ) secretion . TGF-beta has been implicated in the pathogenesis of radiation-induced fibrosis . PURPOSE We investigated the development of lung fibrosis in breast cancer patients who were treated after mastectomy with radiotherapy , with or without simultaneous adjuvant treatment with tamoxifen .  METHODS Data from 196 women were included in the analysis . Eighty-four women were postmenopausal patients who participated in a r and omized trial testing tamoxifen as an adjuvant to postmastectomy radiotherapy .  The radiotherapy technique employed an 8-MV photon field covering the axillary and the infraclavicular and supraclavicular regions of the affected side of the chest ; the chest wall was treated with an abutted electron field . Optical density changes in pretreatment and post-treatment chest x-ray films were used to monitor the development of lung fibrosis ; lung reactions were assessed in the photon-irradiated field only . Logistic regression analysis was used to explore relationships between radiation dose and the development of lung fibrosis in patients either receiving or not receiving tamoxifen . All P values are from two-sided tests . RESULTS Among the 84 women who participated in the r and omized trial of radiotherapy plus tamoxifen ( n = 38 ) versus radiotherapy alone ( n = 46 ) , there was a significant association between tamoxifen treatment and the incidence of marked lung fibrosis ( relative risk = 2.0 ; 95 % confidence interval [ CI ] = 1.2 - 3.5 ; P = .01 ) . When logistic regression analysis was used to evaluate data from all 196 patients , a highly significant relationship was found between the incidence of lung fibrosis and total 
    Output:
    
agent
Locoregional PMRT is recommended for women with 4 or more positive axillary lymph nodes .
The role of PMRT in women with 1 to 3 positive axillary lymph nodes is unclear .
Locoregional PMRT is generally not recommended for women who have tumours that are less than 5 cm in diameter and who have negative axillary nodes .
***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: Two hundred patients with node positive stage II breast cancer were r and omised to four groups after radical mastectomy and axillary evacuation : ( 1 ) Postoperative radiotherapy , ( 2 ) Adjuvant chemotherapy with eight courses of CAFt ( cyclophosphamide 500 mg m-2 + doxorubicin 40 mg/m-2 + ftorafur 20 mg kg-1 orally day 1 - 14 ) every fourth week , ( 3 ) Postoperative radiotherapy and adjuvant chemotherapy and ( 4 ) postoperative radiation , adjuvant chemotherapy and tamoxifen 40 mg daily for 2 years . Thirty-two per cent of the patients discontinued treatment due to GI-toxicity , while 26 % required dose reductions due to leukopenia . Radiation pneumonitis was more frequent after the combination of postoperative radiotherapy with chemotherapy . There was a better relapse-free survival in the groups receiving chemotherapy compared to radiotherapy alone ( P = 0.05 ) , which was highly significant in a multivariate Cox analysis ( P = 0.004 ) . No significant survival differences were seen . Tamoxifen had no clear overall effect but there were better relapse-free ( P = 0.04 ) and overall ( P = 0.004 ) survival with tamoxifen in estrogen receptor positive patients , while estrogen receptor negative patients had a somewhat poorer survival ( P = 0.07 ) after tamoxifen .  Local control was better ( NS ) after the combination ( 93 % ) radiotherapy and chemotherapy compared to either treatment alone ( 76 % with radiotherapy and 74 % with chemotherapy at 5 years ) In a prospect i ve study of 622 women with breast cancer , those with one to three histologically positive axillary lymph nodes were r and omised after mastectomy  to receive cyclophosphamide 100 mg/m2 orally on days 1 - 14 , methotrexate 40 mg/m2 intravenously on days 1 and 8 , and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles ( CMF x six ) , or for twelve cycles of the same chemotherapy ( CMF x 12 ) . Those with > or = four positive nodes were r and omised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy ( RT ) followed by six cycles of the same chemotherapy ( RT + CMF x six ) . With about 10 years median follow-up , there was no significant difference in survival or disease-free survival among the three groups . There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six ( relative risk 0.53 , P = 0.067 ) . Multivariate analysis indicated that the presence of > or = four positive nodes ( negatively ) and the percentage of ideal ( full ) dose of CMF received ( positively ) were the strongest factors predictive of survival . This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes . There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes OBJECTIVE To provide information and recommendations for women and their physicians when making decisions about the management of lymphedema related to breast cancer . OPTIONS Compression garments , pneumatic compression pumps , massage and physical therapies , other physical therapy modalities , pharmaceutical treatments . OUTCOMES Symptom control , quality of life , cosmetic results . EVIDENCE Systematic review of English- language literature retrieved primarily from MEDLINE ( 1966 to April 2000 ) and CANCERLIT ( 1985 to April 2000 ) . Non systematic review of breast cancer literature published to October 2000 . RECOMMENDATIONS Pre- and postoperative measurements of both arms are useful in the assessment and diagnosis of lymphedema . Circumferential measurements should be taken at 4 points : the metacarpal-phalangeal joints , the wrists , 10 cm distal to the lateral epicondyles and 15 cm proximal to the lateral epicondyles . Clinicians should elicit symptoms of heaviness , tightness or swelling in the affected arm . A difference of more than 2.0 cm at any of the 4 measurement points may warrant treatment of the lymphedema , provided that tumour involvement of the axilla or brachial plexus , infection and axillary vein thrombosis have been ruled out . Practitioners may want to encourage long-term and consistent use of compression garments by women with lymphedema . One r and omized trial has demonstrated a trend in favour of pneumatic compression pumps  compared with no treatment . Further r and omized trials are required to determine whether pneumatic compression provides additional benefit over compression garments alone . Complex physical therapy , also called complex decongestive physiotherapy , requires further evaluation in r and omized trials . In one r and omized trial no difference in outcomes was detected between compression garments plus manual lymph drainage versus compression garments alone . Clinical experience supports encouraging patients to consider some practical advice regarding skin care , exercise and body weight . [ A patient version of these guidelines appears in Appendix 2 . ] VALIDATION An initial draft of this document was developed by a task force sponsored by the BC Cancer Agency . It was up date d and revised substantially by a writing committee and then su bmi tted for further review , revision and approval by the Steering Committee for Clinical Practice Guidelines for the Care and Treatment of Breast Cancer . SPONSOR The steering committee was convened by Health Canada . COMPLETION DATE : October 2000 UNLABELLED A prospect i ve r and omized study was made of 270 patients with unilateral stage I or II invasive breast cancer treated by segmental resection , axillary dissection and radiation at the University Hospital of Tampere , Finl and , between 1989 and 1991 . The aim of the study was to determine whether there is any advantage or disadvantage if the internal mammary chains ( IMC ) are included in the radiation target volume . The medial and lateral two-field technique was used and the target volumes were determined r and omly either to include the internal mammary chain ( IMC-RT ) or not ( no-IMC-RT ) . The prevalence of radiation pneumonitis was 16 % and there was no significant difference between the IMC- and no-IMC-groups ( 18 vs. 14 % ) . Skin reactions were equal in both groups . Lung fibrosis was more common in the IMC-RT group . IN CONCLUSION radiation of internal mammary chain after conservative surgery does not lead to an increase in clinical ly important skin or pulmonary complications . Whether it prevents recurrences or new primaries of the opposite breast is too early to say because of the short follow-up time Summary 158 evaluable patients with stage II , lymph node positive , carcinoma of the breast were r and omized to adjuvant therapy with either melphalan ( L-PAM ) or cyclophosphamide , methotrexate , and fluorouracil ( CMF ) after mastectomy . In addition , patients were r and omized to be treated with or without post-operative irradiation therapy ( RT ) in addition to their chemotherapy . At a median follow-up time of 11 years , there is no difference in time to relapse ( P=0.69 ) or survival ( P=0.55 ) among the four treatment groups . Multivariate analysis including treatment arm , age , race , tumor size , histologic type , performance status , time to onset of treatment , menopausal status , and number of positive nodes , revealed that only the number of positive nodes ( < 4 vs ≥ 4 ) was related to disease-free and overall survival . Ten year relapse-free survival for patients with < 4 positive nodes compared to those with ≥4 positive nodes was 63 % versus 30 % , and overall survival 63 % versus 41 % , respectively . Patients who received post-operative radiation therapy had significantly less local recurrence than those treated with chemotherapy alone ( P=0.03 ) but without improvement in relapse-free or overall survival . In this trial , post-operative radiation therapy when added to chemotherapy  decreased the risk of local recurrence without adverse effects on survival . Treatment outcome was not influenced by chemotherapy regimen , but differences may have been obscured by the small sample size We studied loco-regional recurrence during follow-up ( median observation time 8 years ) in 1,153 patients , who underwent modified mastectomy and were r and omly assigned to one of the following postoperative treatments ; Premenopausal patients : radiotherapy , cyclophosphamide , or both ; Post-menopausal patients : radiotherapy , tamoxifen , or both .  Recurrence occurred in a total of 419 patients , 123 of whom had loco-regional recurrence with or without distant metastasis . The loco-regional recurrence rate was 7 % in the irradiated subgroups and 17 % in the non-irradiated subgroups , the corresponding cure rates being 43 % and 58 % . Complete remission of all local recurrence was obtained after the first treatment in 67 % of the cases , and was persistent in 67 % of them ( 44 % overall ) . Complete remission was obtained in all patients with local recurrence who received local treatment only , and was persistent in 65 % . Of local recurrences treated with a combination of surgery , radiotherapy and hormone therapy , complete response was obtained in 94 % of the patients , and was persistent in 94 % of them ( 88 % overall ) . Complete remission of all regional recurrence was obtained after the first treatment in 58 % of the patients and was persistent in 67 % of them ( 39 % overall ) . Postoperative radiotherapy reduced not only the total number of loco-regional recurrences but also the number of uncontrolled loco-regional recurrences . Aggressive local treatment would appear to yield both satisfactory initial control and , when combined with the hormone therapy , a high rate of persistent loco-regional control The efficacy of adjuvant treatment with tamoxifen was evaluated in protocol DBCG 77 C. Postmenopausal high risk patients ( tumor greater than 5 cm , positive axillary nodes , or invasion to skin/fascia ) were r and omized after total mastectomy and axillary sampling to postoperative radiotherapy ( control ) or to radiotherapy plus treatment with tamoxifen ( TAM ) , 30 mg daily for 1 year . A total of 1,716 patients entered the study . At 8 years of follow-up , ( 7 years median time of observation ) , we observed a significant increase of recurrence-free survival for the TAM treated group and a reduction in mortality , which is significant for patients less than 70 years of age . Retrospectively , an increased recurrence-free survival in TAM treated patients was significant in the following subgroups : tumor less than 5 cm , positive lymph nodes , anaplasia grade II and estrogen receptor level greater than 100 fmol/mg cytosol protein . In the subsequent trial ( DBCG 82 C ) , 1,347 postmenopausal patients less than 70 years were r and omized to one of the following 3 regimens : radiotherapy + tamoxifen , 30 mg daily for 1 year ( TAM ) , TAM alone , or TAM + CMF ( CMF i.v . day 1 every 4 weeks x 9 ) . The survival is similar in the 3 groups at 4 years ( 2 years median time of observation ) The purpose of this study was to test the role of radiotherapy following total mastectomy , axillary dissection , and adjuvant systemic therapy in the management of operable locally advanced breast carcinoma BACKGROUND Tamoxifen is an anti-estrogen with proven efficacy and low toxicity in the treatment of breast cancer . However , tamoxifen has been shown to exert a number of nonhormonal as well as hormonal effects . One nonhormonal effect of tamoxifen is the induction of transforming growth factor-beta ( TGF-beta ) secretion . TGF-beta has been implicated in the pathogenesis of radiation-induced fibrosis . PURPOSE We investigated the development of lung fibrosis in breast cancer patients who were treated after mastectomy with radiotherapy , with or without simultaneous adjuvant treatment with tamoxifen .  METHODS Data from 196 women were included in the analysis . Eighty-four women were postmenopausal patients who participated in a r and omized trial testing tamoxifen as an adjuvant to postmastectomy radiotherapy .  The radiotherapy technique employed an 8-MV photon field covering the axillary and the infraclavicular and supraclavicular regions of the affected side of the chest ; the chest wall was treated with an abutted electron field . Optical density changes in pretreatment and post-treatment chest x-ray films were used to monitor the development of lung fibrosis ; lung reactions were assessed in the photon-irradiated field only . Logistic regression analysis was used to explore relationships between radiation dose and the development of lung fibrosis in patients either receiving or not receiving tamoxifen . All P values are from two-sided tests . RESULTS Among the 84 women who participated in the r and omized trial of radiotherapy plus tamoxifen ( n = 38 ) versus radiotherapy alone ( n = 46 ) , there was a significant association between tamoxifen treatment and the incidence of marked lung fibrosis ( relative risk = 2.0 ; 95 % confidence interval [ CI ] = 1.2 - 3.5 ; P = .01 ) . When logistic regression analysis was used to evaluate data from all 196 patients , a highly significant relationship was found between the incidence of lung fibrosis and total 
    Output:
    