breast cancer , first described as early as 3000 b.c . by edwin smith papyrus of egypt , comprises 23% of all female malignancies ( excluding non  melanomatous skin cancer ) [ 1 , 2 ] . in 2008 ,
the number of deaths from breast cancer totaled 460,000 patients ; it is a global concern accounting for 14% of all cancer deaths in females .
it is the most common invasive cancer in women with an incidence that ranges between 19.3 per 100,000 in eastern africa to 89.7 per 100,000 in western europe [ 4 , 5 ] .
the mortality in breast cancer patients is attributed to metastatic disease [ 3 , 6 ] .
it is known to metastasize to numerous organs including lymph nodes , lung , bone , liver , skin , kidneys , brain , adrenal , thyroid , and heart [ 3 , 6 , 7 , 8 ] .
breast cancer metastasizing to the urinary bladder has only been reported sporadically totaling 41 cases in the english medical literature [ 3 , 913 ] .
bladder metastasis from breast cancer as the only organ involved is very rare , with only eight cases reported worldwide [ 3 , 11 , 12 , 14 ] .
we herein present a patient who presented with bladder metastasis from breast cancer with the bladder being the only organ involved .
a 64year  old female patient , a non  smoker known to have hypertension , diabetes mellitus , dyslipidemia , supraventricular tachycardia , and osteoporosis was diagnosed in 2005 with left breast intraductal carcinoma .
ten out of 23 nodes were positive ; she was staged as t2 ( 4 cm ) n3 m0 disease .
the patient was treated with eight cycles of chemotherapy , adriamycin , cytoxan , and taxol and 25 sessions of radiation therapy ( total dose of 50 grays ) , and completed a 5year treatment with an aromatase inhibitor .
she had no evidence of disease until march 2010 , when she presented to our clinic with recurrent urinary tract infections and urinary incontinence that failed to resolve with antibiotics alone .
workup included a computed tomography ( ct ) scan of her abdomen and pelvis , which showed diffuse thickening of the urinary bladder wall with surrounding fat streaking of the pelvis and retroperitoneum ( figure 1 ) .
there was evidence of mild right hydroureteronephrosis with no evidence of obstructing urinary tract calculi ( figure 1 ) .
a , b. diffuse thickening of the urinary bladder wall ( arrows ) with surrounding fat streaking of the pelvis .
a pocket of gas is noted c , d. mild right hydroureteronephrosis ( arrowheads ) .
pathology showed an unremarkable bladder mucosa , but a submucosal nest of carcinoma cells was found .
the cells were plasmacytoid with marked nuclear pleomorphism , frequent mitotic figures and multiple foci suggestive of lymphovascular invasion were present .
the tumor cells were positive for estrogen receptor and e  cadherin ; they were negative for progesterone receptors .
a. h&e sections of the urinary bladder biopsy revealing a dense submucosal infiltrate ( mag .
b. the cells are cohesive , plasmacytoid with an abundant eosinophilic cytoplasm and eccentric nucleus ( mag .
the cells demonstrate positive immunostaining with anti  estrogen receptor ( er ) antibody ( c , mag .
chest ct scan and bone scan were performed as part of the full work  up and failed to show any evidence of other distant metastasis .
one week after receiving the first cycle of chemotherapy , the patient developed hematuria and clot retention .
several attempts of irrigation failed so the decision was made to perform cystoscopy in order to fulgurate all bleeders .
the cystoscopy identified a large clot in the bladder , which was removed and all bleeding areas were fulgurated .
. however , a few days after the third chemotherapy cycle she developed severe dyspnea and was found to have pneumonia that progressed to septic shock .
the patient passed away from cardiorespiratory arrest one year after the diagnosis of the bladder metastasis .
until 2012 , 41 cases of bladder metastasis from breast cancer have been reported and they were mostly associated with systemic dissemination and multiple organ involvement .
only eight cases of solitary bladder metastasis from primary breast cancer have been documented and our case represents the ninth in the english medical literature [ 3 , 11 , 12 , 14 ] ( table i , in bold ) .
macroscopically , bladder metastasis may appear as a mass , irregular lesion , mucosal nodularity , abnormally thickened bladder wall , or plaque with telangiectasias .
cystoscopy was performed based on the suspicious ct scan findings , and it revealed an abnormal bladder wall thickening and inflammation , which were both subsequently biopsied .
abbreviations : gu  genitourinary , nr  not reported , mets  metastasis , ln  lymph node , sb  small bowels , lb  large bowels , ilc invasive lobular carcinoma , idc  invasive ductal carcinoma , er  estrogene receptors , pr 
progesterone receptors the breast primary tumor subtype was invasive intraductal carcinoma while in the previously published reports , the most common histology of the breast primary was invasive lobular ( 10 out of the 15 cases where the breast cancer subtype was determined ) . bates and baithun reported 4.5% incidence of secondary bladder metastasis among all bladder cancer [ 9 , 15 ] , with secondary metastasis to the bladder from breast cancer being approximately 3% [ 16 , 17 ] . when autopsy and pathology are used as mainstay for diagnosis , the incidence ranges from 0% to 7% .
bladder metastasis from previously diagnosed breast cancer is reported in the literature to vary from 2% to 14% .
the most common primary tumors metastasizing to the bladder are : stomach , lung , skin / melanoma , and breast .
it is only when the mucosa is involved by the disease will symptoms become clinically detectable .
since mucosal involvement is the last stage of metastatic invasiveness into the bladder , the prognosis is very poor with a mean survival of two to three years , although a 5year survival of two patients out of the 41 was reported in the literature [ 14 , 20 ] . as a consequence , early stages of breast cancer metastasizing to the bladder
the most common findings in patients with secondary bladder metastasis are lower urinary tract symptoms ( luts ) , flank or abdominal pain , hydronephrosis , and the painless hematuria that is in many cases the most common initial symptom ( microscopic being more frequent than gross ) .
hematuria as a sign of bladder involvement following primary breast cancer is considered sensitive , but not specific for tumor metastasis .
gross hematuria with a history of breast cancer needs to be thoroughly investigated , keeping in mind the side effects of cyclophosphamide as treatment of the primary breast cancer , regardless of time or duration of treatment .
suprapubic and bilateral flank pain was later the major disabling symptom that warranted the investigation through ct scan imaging .
ca 153 is one method to follow up breast cancer recurrence or metastasis , but strong evidence are lacking on its clinical usefulness .
the positron emission tomography ( pet ) scan has been showed to have increasing usage after suspecting bladder involvement in a breast cancer patient ; however , its cost effectiveness is yet to be determined .
breast metastasis to the bladder has been shown to have a worse prognosis than metastasis to bone .
the time interval between primary tumor diagnosis and detection of metastasis is highly variable between 0 month and 30 years with an average of 6.2 years ( table 1 ) .
bladder metastases in our patient were identified five years after the initial diagnosis of primary breast carcinoma .
conduction of the proper investigations prevented the delay in the diagnosis of the metastatic disease .
the patient survived one year from the time she first presented with urinary symptoms , and there was no evidence that her death was related to the bladder metastasis .
only 8% of all breast cancer is lobular carcinoma , however , it is the most common type of breast cancer type involving the bladder ( 33% of secondary bladder metastasis ) followed by ductal carcinoma , which accounts for the majority of primary breast cancer ( 66% ) and metastasizes mostly to the lung parenchyma .
one hypothesis is that lobular carcinoma is of the serosal type , which gives it a predilection to spread to the gastrointestinal and gynecological systems .
it is part of the seeding soil hypothesis : the interaction of tumor with specific host factors in the metastasized organ .
another culprit is concomitant steroid therapy , which is thought to be due to exacerbation of the immunosuppressive effect .
estrogen , progesterone , and her2 receptors are the three main receptors studied in breast cancer .
discrepancy between receptors is not uncommon between the primary and the secondary tumor ( reported between 30 and 39% ) .
bladder metastases from our case were positive for estrogen receptors , which was also true for the patient 's known primary cancer of the breast .
however , progesterone receptors were only present in the malignant breast cells and not the secondary bladder metastasis .
one hypothesis is that the polyclonicity of breast tumor cells is affected by treatment modalities ( hormonal therapy may select some and suppress others ) , which manifests itself later in case of bladder metastasis .
it has been shown that if receptors convert from positive in the breast to negative in the bladder , it is associated with decrease survival [ 17 , 24 ] . even with receptor  negative secondary bladder metastasis , a trial of anti 
receptor therapy has been used with promising results in controlling disease . reported cases of bladder metastasis were managed through surgery , chemotherapy , radiotherapy , hormonal therapy , or a combination of those . in our patient ,
we report a rare case of breast cancer with solitary urinary bladder metastasis that was diagnosed several years after the initial presentation .
secondary malignancies of the bladder are difficult to distinguish from non  transitional cell primary bladder cancer .
a high level of suspicion and extensive investigation are warranted if a known primary cancer already exists .
we emphasize the need to be more aware of the possible metastatic nature of every urinary symptom that shows in a breast cancer patient .
 breast cancer is the most common malignancy in woman . 
 the urinary bladder is an unusual site for metastasis from primary tumors of the breast , especially when it is the only organ involved . 
 we present the case of a female patient with known breast cancer stage t2n3m0 who developed isolated bladder metastasis five years after the primary diagnosis . 
 we reviewed the literature for similar cases and discussed the clinical presentation , pathophysiology , and prognosis of this entity . 
INTRODUCTION
CASE REPORT
DISCUSSION
CONCLUSIONS