The second most common cancer in BC survivors is another BC. The new cancer can develop in the same or the opposite breast in patients treated with breast-conserving surgery [4]. The current patient had undergone modified radical mastectomy on the right side 21 years ago, and the ILC in the bladder might have originated from the left breast. However, we did not conduct any tests for BC, including physical examination, laboratory tests, and imaging, before performing the random biopsy, the results of which indicated metastasis. It was not possible to determine the time of onset for the second BC. It remains possible that the histologic type of the first BC was misdiagnosed due to inadequate pathologic sections or the lack of effective immunostaining markers for diagnostic assistance, since the pathologic diagnosis of ILC is challenging and depends on the quality of the sections.
Common metastatic sites for BC vary depending on the histologic type. Infiltrating ductal carcinoma (IDC) accounts for approximately 90% of all BCs, followed by ILC (approximately 10%), whereas papillary carcinoma accounts for < 1%. Common metastatic sites for IDC are lung, liver, bone, and brain, whereas ILC tends to spread to the gastrointestinal and genitourinary tracts, peritoneum, retroperitoneum, and leptomeninges [5–7]. Secondary urinary bladder tumors from solid tumors are rare, and most are direct extensions from another pelvic tumor. Metastasis from distant organs are extremely rare; the most common original sites are stomach, lung, and skin (malignant melanoma) [3]. In a literature review of metastatic cancers involving the urinary bladder, Velcheti et al. reported that BC was the primary tumor in approximately 8.5% of the cases [8], and only 50 cases has been reported in the last 60 years [3, 8]. The rate of bladder metastasis is higher with ILC than with IDC [3]. In comparison with the IDC, E-cadherin expression is markedly reduced or absent in the great majority of ILCs [9]. The loss of E-cadherin, a cell-to-cell adhesion molecule, may facilitate metastasis. The mechanism of BC metastasis to the urinary bladder remains poorly understood.
Some of patients with metastatic BC in the bladder are asymptomatic, and the tumor is incidentally identified through imaging studies during regular follow-up. Clinical presentation is diverse, including back pain, hematuria, and voiding dysfunction, such as frequency, urgency, incontinence, and nocturia [3]. Detrusor involvement may also lead to ureteral obstruction; several cases of bladder metastasis from BC were reported to present with symptomatic hydronephrosis and renal failure [3]. Comprehensive evaluation with routine urinalysis, urinary culture, and imaging studies such as plain X-ray of the kidneys, ureters, and bladder and CT can aid in the exclusion of urinary tract infection and urolithiasis. In patients with urinary tract symptoms and a history of malignancy, bladder ultrasound is recommended as a first-line screen for suspected bladder metastasis. CT is recommended in patients with persistent symptoms and negative ultrasound findings. Magnetic resonance imaging and positron emission tomography/CT are useful in revealing other metastatic sites. In imaging studies, bladder wall thickening is a common finding of bladder metastasis. Urine cytology findings vary and are not sufficiently specific for definite diagnosis.
Elevated levels of CA15-3, CEA, tissue polypeptide specific antigen, and CA-125 have been shown to be associated with greater tumor size, lymph node metastasis, and aggressive histology in advanced BC [10]. Additionally, the combined evaluation of tumor markers improves diagnostic sensitivity compared to single tumor markers [11]. Therefore, the levels of several tumor markers were evaluated in the current patient; the CA15-3 level was within the normal range, which could have been misleading in the absence of data on the other tumor markers. Indeed, the elevated serum AFP, CEA, CA-125, and CA-199 levels might be an indication of advanced presentation in the current patient.
Definitive diagnosis depends on the pathologic evaluation of tumor biopsy specimens. Transurethral resection of the vesical lesion not only serves as a diagnostic purpose but also ameliorates urinary symptoms and facilitates ureteral stenting to resolve ureteral obstruction [3]. However, in the present case transurethral resection of the bladder tumor was not suitable due to the diffuse thickening of the urinary bladder wall. Therefore, random biopsy specimens of the urinary bladder were collected using cystofibroscopy.
Bladder metastasis from the breast may occur months or years after the initial diagnosis of the primary tumor. The interval between the primary tumor and metastasis can be as long as 30 years, with a mean interval of 90 months [3]. According to 2012 American Society of Clinical Oncology guideline recommendations for surveillance after BC treatment, all women should undergo physical examination every 3–6 months for the first 3 years after primary therapy, then every 6–12 months for the next 2 years, and then annually. Nevertheless, there was no follow-up record since her third year after she underwent modified radical mastectomy. This may be the reason for delayed detection of advanced disease progression.
The management of BC metastasis to the urinary bladder includes symptomatic relief and local and systemic therapy. Transurethral resection of the bladder tumor can alleviate tumor burden and facilitate ureteral stenting for ureteral obstruction. Local radiotherapy can stop vesical bleeding and control local disease. The standard therapy includes chemotherapy and hormonal treatment. ER-positive and PR-positive tumors are more responsive to hormone therapy than those are negative for these receptors and are associated with longer disease-free survival [13]. Generally, patients with metastatic BC in the bladder have a very limited survival, ranging between 1 month to 2 years. The prognosis is usually poor unless bladder is the only metastatic site [3].
The association between second primary BCs and urinary bladder metastases is unknown, based on our search of PubMed, Medline, and the Cochrane Library for reviews and case reports using the keywords “second primary BC” AND “urinary bladder metastasis.”
In summary, the urinary tract is not a common metastatic site for BC and the patients might receive unsuitable treatments. Symptoms may persist or worsen until the original disease is well demonstrated and treated. Despite the ever-evolving technologies that greatly assist in diagnosis, clinicians must remain alert in history-taking. In patients with a history of cancer, the focus should not only be on the currently affected organ but also on the status of the underlying malignancy. The presence of a usual symptom may be due to an unusual metastatic disease.