Keywords: brain metastases, breast cancer, prognostic factors, whole brain radiotherapy. Correspond enceto: Daniel a Oltean, Emergency Hospital”O. Fodor”, 19-21 Croitorilor Str. , Cluj … … Nap oca, 400162, Roman ia. Tel+40264439995; e-mailolt_daniela@yahoo.com Received November 3,2008; accepted Septemb er 11,2009. Brain metastases secondary to breast cancer: symptoms, prognosis and evolution Daniel a Olte a n1, Tiberius Dicu 2, and Dan Eniu 3 1 Emergency Hospital”O. Fodor”; 2″Babes-Bolyai”University, Faculty of Environmental …698 DOLT EAN, TDICU, DENIU ferenceswe reconsidered statistically significant when P <0.05. Results Themedianageat the diag nos is of breast cancer and brain metastases was respectively 49 years (range, 28-65) and 50years (range, 28-66) , whereas the median interval between both diagnoseswas 21 months (range, 5-122). Them ediansurviv al after diagnosis of brain metastases was 10months. Figure 1 presents the overall survival in 43 patients. only 4 patients we res til la live at last follow-up. Twelve patients had single brain metastases and 31 had multiple brain lesions. Median survival for patients with single metastaseswas 23 months and for pa tients with multi pleb rain metastases, 7 months (Figure 2) (lo- granktest, P =0.0015). Brain metastases were the first si te of me tas tat icin- volvementin 26 cases (60%). in 25 cases (58%) , they were Themed ianfollow-up for these patients was 74 months. Diagnosis of brain m eta stases was made after the pa- ti entscomplained of various symptoms, according to the metastases location, and followinga CT or MRI scan. Incase of 3 patients, pathologic analy sis confirmed there sults oft he stereotactic biopsy. Patient characteristics The most important characteristics of the patients (42 women and 1man) are listed in Table 1. The primary tumor was located in the left breast in 19 cases, in 24 patients the first location was the right breast, and in 4 cases the le- sionaffectedbothb reasts. At the moment of breast cancer diagnosis, 6 patients were stage II, 16 stage III, and 8 stage IV (graded according to UICC criteria). Modified radical mastectomy was performed in 44%oft he breast cancer patients, and chemotherapy was administered in 35%. Hormonal receptor status was negative in 14 and positive in 8patients. Receptors tat us was unknown in 21 patients. Statistical analyses Survival curves were determined by the Kaplan-Meier methodandcompa red using Mantel-Cox statistics (lo- granktest) . All stat is tic ala na lyses were performed using Prism5.0 software (GraphPad, San Diego, CA, USA). Dif- Table 1 -Characteristics of 43 pa tie ntswithbrain metastases from breast cancer Characteristic no. % Age (yr) ?50 25 58 >50 18 42 Treatment of BC Surgery 19 44 Radiotherapy 25 Chemotherapy 15 35 Unknown 7 16 Interval BC-BM (mo) <12 21 49 13-24 12 28 25-36 5 11 37-60 25 >60 37 no. ofBM Single 12 28 Multiple 21 72 BM size (mm) ?40 22 51 >40 8 19 NA 13 30 BM associated with extracranial lesions 18 42 Bone 10 Liver 9 Lung 7 Pleurae 3 Ovary 1 Peritoneum 1 BC, breast cancer; BM, brain metastases; NA, not assessed. Figure1-Over all survival in 43 pa ti en tswithbrainmet as tas es from breast cancer. Median survival was 10 months. Figure 2 -Survival of pa tientswithsoli tary (solid line, n=12) or mul- tip le (da shed line, n=31) brain metastases ( P =0.0015) . 100 80 60 40 20 0 100 80 60 40 20 0 P e r c e n t s u r v i v a l P e r c e n t s u r v i v a l Single brain lesion Multiple brain lesions 0 10 20 30 40 50 Months….. BRAIN METASTASES SECONDARY TO BREAST CANCER 699 of 30,20 or 18Gy; only one pa tientreceivedradia ti onto 12 Gy. For 3cases, data on the treat me ntofbrainmetas- tas es were not available. Fort he second line oft re at- ment, dexamethasone was associated to chemotherapy orradiationin 31 patients (72%). The dosage de pended on the symptoms and on signs of edema. Discussion The causes of brain metastases secondary to breast cancer are not well k nown, but there are so me hyp othe- ses. Car ey et al. 11 formulated three hypotheses about brain metastasescausa lity: first, the blood-brain barrier hypothesis, then meta static longevity, and the possibili- tyofatropismof met astatic breast cancer involvement for the C NS. Management of brain metastases is difficult because the patients have a poor prognosis 3,12,13 . Untreated pa- tientsusually live only for several weeks, where as differ- enttypesof treatment can pro lo ng li fe for as hortperi- od of time, compared to other patients with metastatic breast cancer but without brain involvement. Mu-Tai et al.4 studied 62 patients with brain metastases from breast cancer and reporteda survival rate of 7.3 months. in another study on 30 cases of brain metastases from breast cancer, the median survival was 9 months14. nevertheless, similar studies reported median survivals of 5, 6,13.1 and16.2 months 3,7,15,16 . Some authors consider that breast cancer is more common in younger, premenopausal patients, who tend to have more aggressive forms of malignancy than older patients 2,4,9,17 . in our study, the group aged between 45and54 years had the highest incidence of brain metastases. The study of Nieder et al.18 reported a better survival for patients less than 50 years of age than for those over 50 years and age as asignificantprognos- tic factor. Mu-Tai et al.4 reported a median survival for patients aged under 50 years and over 50 years of 10.2 and 4.3 months, respectively. We compared the two groups of patients, but the difference was not stat ist ical- lysignificant (median, 8 vs 7 months). Symptoms of brain m etas tasesusually reported in previous studies are headache, nausea and vomiting, motor weakness, gait disturbance, mental status changes, seizures, speech, vision or neurologic deficit 5,7,13,19 . in our study, most of the patients had headache, gait disturbance and nausea with vomiting. Tsukada et al. 20 identified 2patientswithat axia, an other 2patientswith aphasia, and 5 pa tient swith an a ff ect- ed cranial nerve, whereas Wronski et al. 16 ha d 15pa- tientswho suffered from hem i paresis. in our study, the presence of systemic disease at the time of brain metas tas es diagnosis reduced median s ur- vivalfrom 9to 6 months. Extracranial m etas tas es decreased median survival (4 months) compared to pa- ti entswithoutsyst emic metastases (16 months) in the the exclusive sites, and the median survival for these pa- tientswas 9months. Most commonly, brain metastases occurred in association with bone (10 cases) or liver metastases (9 cases). These patients had ashortersur- vival (6 months) than patients with solitary brain metas- tas es (9 months). in 16 cases, extracranial metastatic disease was disco ve red before the brain metastases. one patient devel oped late brain me tastases (the yap- pear ed 10 yearsafterthe diagnosis of breast cancer). The patient devel oped multiple brain metastases and survived 24monthsafterthe diagnosis.

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