Lobular Breast Carcinoma with an Isolated Bladder Metastasis: A Case Report

Metastasis of the bladder is an exceptionally rare occurrence in primary breast cancer. We report the case of a 68-year-old woman with a history of lobular breast carcinoma who developed metastatic bladder involvement ten years after her initial treatment. Cystoscopy and biopsy confirmed submucosal infiltration by carcinoma with an immunohistochemical profile consistent with lobular breast carcinoma, featuring estrogen receptor-positive and human epidermal growth factor receptor 2 (HER-2) negative. The therapeutic decision recommended was to start first-line treatment with Fulvestrant plus Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors.

Introduction

Breast cancer is considered the most common cancer in women worldwide [1] and is the leading cause of cancer-related mortality, mainly due to metastatic extension to the liver, lung, and brain [2]. Metastatic localization to the bladder remains rare in general and exceptional from primary breast cancer. 2% of bladder tumors are metastases from other primary sites, mainly observed in gastric cancer, lung cancer, and melanoma, and very uncommon in breast cancer. Since 1950, approximately 107 cases of bladder metastasis from various primary cancers have been documented. Around 50 cases of bladder metastasis from breast cancer have been reported [3], [4].

Case Report

We report the case of a 68-year-old female patient who was diagnosed in 2014 with right lobular breast carcinoma. She underwent a right mastectomy with lymph node dissection. One out of 17 nodes was positive. She had staged T2N1a. Receptors were positive for estrogen and progesterone, and HER-2 was negative (score 0).

She then received adjuvant chemotherapy with 3 cycles of 5-Fluoro-Uracile, Epirubicin, and Cyclophosphamide (FEC) followed by 3 cycles of Docetaxel and adjuvant radiotherapy.

After radiation therapy, the patient started endocrine therapy with Letrozole and proceeded with annual surveillance. In December 2023, while still under Letrozole, she consulted for right hypochondrium pain with no urinary symptoms. Abdominal and Pelvic CT imaging revealed an image compatible with acute cholecystitis and suspicious thickening with enhancement of the left bladder wall (Fig. 1).

Fig. 1. Pelvic CT scan showing thickening of the bladder wall.

Cystoscopy was performed, revealing the presence of polyps. The suspicious lesion was biopsied, and a histopathological examination showed an infiltration of the submucosa by a carcinoma. The immuno-histochemical profile was consistent with lobular breast carcinoma. Tumor cells expressed CK7, GATA3 (Fig. 2), estrogen receptor (Fig. 3), and HER-2 expression was negative. CA15,3 tumor marker was high at 150 U/ml.

Fig. 2. Immunohistochemical image of GATA3 positive.

Fig. 3. Immunohistochemical image of ER Positive.

The workup was completed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), which showed no clear focus of suspicious hypermetabolism. The case was discussed at a multidisciplinary meeting, and the decision was made to initiate Fulvestrant plus CDK4/6 inhibitors.

Discussion

Breast cancer commonly metastasizes to lymph nodes, lungs, liver, bone, and brain. However, uncommon sites such as the bladder, stomach, and retroperitoneum are more frequently associated with invasive lobular breast carcinoma. Bladder metastasis is rare. In 1950, the first case was reported in an autopsy study [4].

Lobular breast carcinoma represents 5% to 15% of breast carcinoma, the second most frequent after ductal carcinoma. It metastasizes preferentially to serous tissue, particularly the peritoneum, and rarely to the urinary system [5].

Routine examination for bladder metastasis is not standard practice in breast cancer management but should be considered, especially in patients presenting urinary symptoms such as frequent urination or hematuria. Early detection can significantly impact treatment decisions and outcomes [6].

The relapse diagnosis of Invasive lobular breast cancer is considered difficult due to the lack of specificity both clinically and on imaging, which makes it hard to detect using conventional imaging and frequently shows less avidity to FDG PET/CT [7], [8].

Invasive lobular carcinoma (ILC) exhibits unique patterns of metastasis compared to invasive ductal carcinoma (IDC). ILC cells often exhibit loss of E-cadherin expression, which may facilitate dissemination to uncommon sites such as the bladder. The diagnostic challenge is compounded by the submucosal pattern of infiltration, often leading to late detection [9], [10].

For patients with a history of ILC presenting urinary symptoms, a thorough urological evaluation, including imaging and cystoscopy, should be considered. Immunohistochemical profiling is crucial in differentiating primary bladder carcinoma from metastatic lesions [11]. GATA-3 is a newly described marker that labels urothelial and breast carcinoma and is rarely positive in bladder adenocarcinomas [12].

Systemic therapy is generally required for the management of metastatic breast disease, including urinary localisations. In this case, the patient’s treatment regimen was adjusted to include Fulvestrant and CDK4/6 inhibitors, reflecting current therapeutic strategies targeting hormone receptor-positive and HER2-negative metastatic breast cancer [13].

Conclusion

This report highlights a rare case of a 68-year-old woman presenting a late relapse of lobular breast cancer at an unusual site. The main purpose lies in increasing awareness of atypical secondary sites of breast cancer, particularly the lobular type. Understanding and recognizing such rare occurrences can help in early diagnosis and appropriate treatment strategies to improve prognosis.