***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: Initial clinical studies in 32 Senegalese subjects have demonstrated the efficacy of ivermectin in  Onchocerca volvulus infection ( river blindness ) . Although O. volvulus microfilariae in skin snips were not reduced in number after single oral doses of 5 micrograms or 10 micrograms/kg body-weight , they were greatly reduced in all subjects after single oral doses of 30 micrograms or 50 micrograms/kg and were eliminated completely in 6 of th 8 subjects who received the 50 micrograms/kg dose . All subjects tolerated the drug well . Transient pruritus which did not require treatment was observed on the day the dose was given in 2 of the 8 subjects after the 30 micrograms/kg dose and in 4 of the 8 who received the 50 micrograms/kg dose . Ivermectin produced no abnormal laboratory results Background : Progesterone receptor ( PR ) expression assessment in early invasive breast cancer remains controversial . This study sought to re-evaluate PR expression as a potential therapeutic guide in early breast cancer ; particularly in oestrogen receptor (ER)-positive , lymph node (LN)-negative disease . Methods : A population cohort of 1074 patients presenting to a single Cancer Centre over 4 years ( 2000–2004 ) underwent surgery for primary invasive breast cancer with curative intent . Prospect i ve data collection included patient demographics , pathology , ER and PR expression , HER2 status , adjuvant chemotherapy and endocrine therapy .  Progesterone receptor expression was compared with ( all causes ) overall survival ( OS ) , breast cancer-specific survival ( BCSS ) and disease-free survival ( DFS ) . Results : Overall survival was 71.0 % and BCSS was 83.0 % at median follow-up of 8.34 years . Absent PR expression was significantly associated with poorer prognosis for OS , BCSS and DFS ( P<0.0001 , log-rank ) , even within the ER-positive , LN-negative group ( hazard ratio for BCSS 3.17 , 95 % CI 1.43–7.01 ) and was not influenced by endocrine therapy . Cox ’s regression analysis demonstrated that PR expression was an independent prognostic variable . Conclusion : Absence of PR expression is a powerful , independent prognostic variable in operable , primary breast cancer even in ER-positive , LN-negative patients receiving endocrine therapy . Absence of PR expression should be re-evaluated as a biomarker for poor prognosis in ER-positive breast cancer and such patients considered for additional systemic therapy BACKGROUND Evaluations of epidemiologic risk factors in relation to breast cancer classified jointly by estrogen receptor ( ER ) and progesterone receptor ( PR ) status have been inconsistent . To address this issue , we conducted a prospect i ve evaluation of risk factors for breast cancer classified according to receptor status . METHODS During 1 029 414 person-years of follow-up of 66 145 women participating in the Nurses ' Health Study from 1980 through 2000 , we identified 2096 incident cases of breast cancer for which information on ER/PR status was available : 1281 were ER+/PR+ , 318 were ER+/PR- , 80 were ER-/PR+ , and 417 were ER-/PR- . We fit a log-incidence model of breast cancer and used polychotomous logistic regression to compare coefficients for breast cancer risk factors in patients with different ER/PR status . To test for differences in risk factor odds ratios based on marginal ER/PR categories , we evaluated ER status controlling for PR status and vice versa . The predictive ability of our log-incidence model to discriminate between women who would develop ER+/PR+ breast cancer and those who would not ( and similarly for ER-/PR- breast cancer ) was evaluated by using receiver operator characteristic curve analysis . All statistical tests were two-sided . RESULTS We observed statistically significant heterogeneity among the four ER/PR categories for some risk factors ( age , menopausal status , body mass index [ BMI ] after menopause , the one-time adverse effect of first pregnancy , and past use of postmenopausal hormones ) but not for others ( benign breast disease , family history of breast cancer , alcohol use , and height ) . The one-time adverse association of first pregnancy with incidence was present for PR- but not for PR+ tumors after controlling for ER status ( P = .007 ) . However , the association of BMI after menopause with incidence was present for PR+ but not PR- tumors ( P = .005 ) . Statistically significant differences in the incidence of ER+ and ER- tumors were seen with age , both before and after menopause ( P = .003 ) , and with past use of postmenopausal hormones ( P = .01 ) . Area under the receiver operator characteristic curve , adjusted for age , was 0.64 ( 95 % confidence interval [ CI ] = 0.63 to 0.66 ) for ER+/PR+ tumors and 0.61 ( 95 % CI = 0.58 to 0.64 ) for ER-/PR- tumors . CONCLUSIONS Incidence rates and risk factors for breast cancer differ according to ER and PR status . Thus , to accurately estimate breast cancer risk , breast cancer cases should be divided according to the ER and PR status of the tumor PURPOSE Uncertainty about the relative worth of doxorubicin/cyclophosphamide ( AC ) and cyclophosphamide/methotrexate/fluorouracil ( CMF ) , as well as doubt about the propriety of giving tamoxifen ( TAM ) with chemotherapy to patients with estrogen receptor-negative tumors and negative axillary nodes , prompted the National Surgical Adjuvant Breast and Bowel Project to initiate the B-23 study . PATIENTS AND METHODS Patients ( n = 2,008 ) were r and omly assigned to CMF plus placebo , CMF plus TAM , AC plus placebo , or AC plus TAM . Six cycles of CMF were given for 6 months ; four cycles of AC were administered for 63 days . TAM was given daily for 5 years . Relapse-free survival ( RFS ) , event-free survival ( EFS ) , and survival ( S ) were determined by using life-table estimates . Tests for heterogeneity of outcome used log-rank statistics and Cox proportional hazards models to detect differences across all groups and according to chemotherapy and hormonal therapy status . RESULTS No significant difference in RFS , EFS , or S was observed among the four groups through 5 years ( P = .96,.8 , and .8 , respectively ) , for those aged < or = 49 years ( P = .97,.5 , and .9 , respectively ) , or for those aged > or = 50 years ( P = .7,.6 , and .6 , respectively ) . A comparison between all CMF- and all AC-treated patients demonstrated no significant differences in RFS ( 87 % at 5 years in both groups , P = .9 ) , EFS ( 83 % and 82 % , P = .6 ) , or S ( 89 % and 90 % , P = .4 ) . There were no significant differences in RFS , EFS , or S between CMF and AC in patients aged < or = 49 or > or = 50 years . No significant difference in any outcome was observed when chemotherapy-treated patients who received placebo were compared with those given TAM .  RFS in both groups was 87 % ( P = .6 ) , 87 % in patients aged < or = 49 ( P = .9 ) , and 88 % and 87 % , respectively ( P = .4 ) , in those aged > or = 50 years . CONCLUSION There was no significant difference in the outcome of patients who received AC or CMF . TAM with either regimen result ed in no significant advantage over that achieved from chemotherapy alone 
    Output:
    
Conclusions Among patients with hormone receptor-positive breast cancer , patients with either ER+PR− tumours or ER−PR+ tumours have a higher risk of recurrence and a shorter survival time than those with ER+PR+ tumours .