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Cases of breast cancer metastasis to the bladder, come and learn!
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Breast cancer is the most prevalent malignancy affecting women and the leading cause of cancer-related deaths in women worldwide. The vast majority of breast cancer-related deaths are caused by metastasis of distant organs, and it has been reported that 30%~40% of patients with early-stage breast cancer still have recurrence and metastasis even with surgery and standard treatment.
It should be noted that in breast cancer patients with recurrence and metastasis, the common metastasis sites are lymph nodes, lungs, bones, brain and liver, but there are fewer reports of rare metastases.
Recently, it has been reported in the literature [1] that the medical community has sorted out the treatment process and disease progress of a rare case of bladder metastasis in a rare primary breast cancer patient, and summarized its clinicopathological characteristics, so as to provide more references for clinical diagnosis and treatment.
▎ Dry goods first:
- The median time from diagnosis of breast cancer to the occurrence of bladder metastases was 5.6 years;
- The main source of bladder cancer metastasis was invasive ductal carcinoma (52.3%), followed by invasive lobular carcinoma (40.9%).
- The primary tumor had the same pathology as bladder metastasis, with a matching rate of 88.9% for ER, 83.3% for PR, and 100% for HER2.
- The main symptoms of bladder metastasis of breast cancer include urinary manifestations (e.g., urinary frequency, urgency, dysuria, urinary incontinence, nocturia, and gross hematuria); Cystoscopy presents primarily with thickening or mass of the bladder wall with a ureteral orifice mass.
Case data
History:
August 012013:
The patient, a 58-year-old female, was diagnosed with breast cancer and underwent radical mastectomy on the left side.
Postoperative pathology showed invasive ductal carcinoma (IDC) of the left breast with metastasis to ipsilateral axillary lymph nodes. Immunohistochemical analysis showed positive expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 antigen (1%). According to the American Joint Committee on Cancer (AJCC) 8th edition staging system, the postoperative pathological stage was determined to be IIIc (pT2N3M0).
Adjuvant chemotherapy was given after surgery, and the regimen was doxorubicin 80 mg + cyclophosphamide 1.0 g every 3 weeks for 4 cycles and docetaxel 130 mg every 3 weeks for 4 cycles. This was followed by 40 Gy/20 sessions of local radiotherapy. After discharge, tamoxifen was given maintenance therapy (10 mg orally twice a day) for 4 years.
February 022018: Multiple bone metastases were found in the thoracic vertebrae and ribs by bone scan due to the patient's chest pain. Local radiotherapy was given to the thoracic spine, followed by oral anastrozole at a dose of 1 mg once daily for 2 years.
03 April 2020:
CT showed progressive bone metastases in the neck, chest, and lumbar spine, and endocrine therapy with fulvestrant (500 mg once weekly).
September 042021: Urology ultrasound showed hydronephrosis in the right kidney, and no obvious abnormalities in the bladder. CT scan showed dilation and hydronephrosis of the right renal pelvis, calyces, and upper ureter, and rough bladder wall (Figs. 1A and B). Venous pyelogram showed poor right kidney function (Figures 1C and D). Cystoscopy showed a normal ureteral orifice, a stenosis of the right ureteral lumen with a diameter of 1 cm, and two raised masses were visible at the left ureteral orifice, one of which was 1.0×0.8 cm in size and the other was 1.2×0.8 cm (Figs. 1E and F). The patient had no gross hematuria, urinary symptoms such as urinary frequency, urgency, and dysuria. Urine occult blood test is negative.
Fig.1 Patient imaging data in September 2021
病理分析显示膀胱粘膜固有层内腺癌细胞浸润生长，符合转移性乳腺浸润癌(图2A)。 免疫组织化学分析显示CD138和CK7阳性染色，CD38、p63、P504S、pax-8、CK20和HER2染色阴性，GATA结合蛋白3、p53、Ki-67、E-cadherin、ER、PR和mammaglobin染色阳性（图2B-F）。
Fig.2 Pathological and immunohistochemical analysis
Subsequently, the patient was treated with palbociclib (125 mg daily for 21 days, 7 days off) + fulvestrant (500 mg every 4 weeks) for 3 months, after which the drug was discontinued due to myelosuppression due to palbociclib. Due to the lack of a standardized treatment regimen for follow-up treatment after the patient was ER- and PR-positive and resistant to endocrine therapy, the patient was finally given a combination of lenvatinib (8 mg once a day) + fulvestrant (500 mg once every 3 weeks) after discussion between the doctor and the patient.
January 052023:
The patient developed meningeal metastases and received nab-paclitaxel (day 1: 300 mg) + carboplatin (day 1: 0.6 g) + bevacizumab (day 1, 600 mg), repeated every 3 weeks.
March 062023
The patient died due to tumor progression.
Case discussion
A total of 55 female patients with bladder metastasis of breast cancer were analyzed through literature review, and the clinical characteristics of patients with breast cancer complicated with bladder metastasis were summarized as follows:
1. Baseline data:
- The median age of onset was 65 years, and the median time from diagnosis of breast cancer to the onset of bladder metastases was 5.6 years;
- Among the 55 patients, 44 had a clear pathological type of primary breast cancer, including 23 cases (52.3%) of invasive ductal carcinoma (IDC), 18 cases (40.9%) of invasive lobular carcinoma (ILC), and 3 cases (6.8%) of mixed type.
- Through the analysis of the pathology of the primary lesion and bladder metastasis, the pathological agreement of 36 reported cases was 100%. In addition, HER2 status was 100% consistent, and the results for ER (88.9%) and PR (83.3%) were consistent.
2. Clinical symptoms:
- The main first symptoms of 55 patients were related to the urinary system, including urinary frequency, urgency, dysuria, urinary incontinence, nocturia, and gross hematuria.
- A small percentage of patients present with low back pain and edema of the lower extremities;
- Some patients do not exhibit significant urinary symptoms, and signs can be detected only by CT scanning, such as cystoscopy, which reveals thickening of the bladder wall, a mass in the bladder wall, or a mass at the ureteral orifice.
3. Transfer:
- In addition to bladder involvement, concurrent metastases to other sites were observed in 46 patients;
- Among them, there were 20 cases (43.5%) with bone metastasis, 7 cases (15.2%) with liver or lymph node metastasis, 5 cases (10.9%) with metastasis to the lungs, brain and meninges, and only 1 case (7 cases in total) from other sites, including peritoneum, ovaries, pleural effusion, pleura, bone marrow, ampullary region and skin.
- Bladder metastases are rare, and distinguishing between primary and metastatic bladder cancers is a diagnostic challenge, and most metastatic bladder cancers are associated with invasion of adjacent tumor types, such as colorectal, cervical, and prostate cancers.
4. Treatment Strategy:
- Before the advent of molecular typing of breast cancer, radiotherapy and chemotherapy were the mainstay of treatment;
- In recent years, endocrine therapy and targeted therapies such as trastuzumab (anti-HER2 therapy) have been incorporated into treatment regimens.
- The patient in this case report was diagnosed with bladder metastases in 2021 and received a range of novel therapeutics, including palbociclib and fulvestrant. The median time from treatment after diagnosis of bladder metastases to final death was 9 months.
Brief summary:
Although bladder metastases can occur with breast cancer, with the continuous advancement of modern medical technology, there are a range of effective imaging techniques and treatments. As long as it is detected in time and receives professional treatment, even if metastases occur, survival can be prolonged and quality of life can be improved.
参考文献：[1] Zhou H, Liu D, Chen L, et al. Metastasis to the bladder from primary breast cancer: A case report and literature review. Oncol Lett. 2024 Apr 5; 27(6):249.
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