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Journal of Clinical Oncology, Vol 25, No 27 (September 20), 2007: pp. 4308-4310 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.12.9379
Urinary Bladder Metastasis From Breast Cancer With Heterogeneic Expression of Estrogen and Progesterone ReceptorsDepartment of Radiology, China Medical University Hospital, Taichung, Taiwan A 68-year-old woman was admitted to our hospital after experiencing left flank pain for 1 week. Abdomen ultrasonography revealed left hydronephrosis. Further intravenous pyelography failed to demonstrate the obstruction level due to delayed function of the left kidney and nonopacification of the left ureter, but an indentation was noted in the bladder base. In addition, occult blood was noted in the microscopic examination of the urine. Oligouria and then anuria occurred 2 weeks later. Hydronephrosis of both kidneys were demonstrated during the follow-up abdominal ultrasonography and emergent bilateral percutaneous nephrostomies were performed. Abdominal computed tomography (CT) revealed diffuse nodular thickening of the urinary bladder wall (Fig 1A; arrows). Urine cytology was negative for malignant cells. Urethrocystoscopy discovered some irregular mucosa in the proximal third urethra and multiple nodular lesions in the bladder, especially in the bladder neck and the trigonal region (Figs 1B and 1C). Under the impression of transitional cell carcinoma or metastases from the breast carcinoma, transurethral bladder biopsies were performed in the trigone, the bladder neck, and the proximal urethra.
After asking for her medical history, it was determined that she had received a partial mastectomy of the right breast with axillary lymph node dissection for invasive ductal carcinoma (pT1, pN0, M0) 3 years prior. The largest diameter of the tumor was approximately 1.5 cm and all of the dissected lymph nodes in level I and level II were free of malignancy. The resection margin was free from tumor involvement. The tumor was poorly differentiated. No lymphovascular permeation or perineural invasion was seen. Immunohistochemical stains for estrogen receptor (ER) and progesterone receptor (PR) were negative but positive for human epidermal growth factor receptor-2 (HER-2). Postoperative adjuvant radiation therapy was administrated. A regular postoperative follow-up with chest x-ray, bone scan, mammography, and breast and abdominal ultrasonography did not reveal any evidence of recurrence or metastasis until the bladder nodules were found in the recent CT survey. The pathological analysis of the bladder tumor (Fig 2A) demonstrated invasive carcinoma of the urinary bladder with moderately to poorly differentiated pleomorphic tumoral cells arranged in solid nests involving the stroma and the lamina propria of the urinary bladder (hematoxylin and eosin stain; original magnification x200). Foci of lymphovascular permeation and perineural invasion were noted. The immunohistochemical studies disclosed not only positive reaction for ER, but also positive for PR and HER-2/neu (original magnification x400; Figs 2B and 2C) and gross cyst disease fluid protein 15. These pathological features were consistent with metastatic invasive ductal carcinoma of the breast.
After the definite diagnosis of breast carcinoma with urinary bladder metastasis, a comprehensive imaging work-up to exclude any possibility of metastatic lesions in other anatomic locations was performed using chest x-ray, whole body bone scan, breast ultrasonography, chest and abdominal CT, and whole body positron emission tomography scan. However, all imaging studies showed negative findings except increased [18F]fluorodeoxyglucose uptake was noted in the urinary bladder in positron emission tomography (Fig 3). After palliative chemotherapy with taxotere and trastuzumab (Herceptin; Genentech Inc, South San Francisco, CA), the patient is currently alive—more than 2 years after the diagnosis of urinary bladder metastasis and 5 years after the initial diagnosis of breast carcinoma without evidence of further metastatic disease.
Breast cancer metastases can occur in almost any organ. Common sites of metastasis include lymph nodes, lung, liver, and bone.1 However, brain, meninges, thyroid, heart, skin, adrenal glands, kidney, ovary, uterus, omentum, peritoneum, small and large bowel, spleen, pancreas, liver, and gallbladder metastases are also reported.1-3 Urinary bladder is an uncommon site of breast carcinoma metastasis. Most are discovered during autopsy reports.2,4-7 Although breast cancer with bladder metastasis was occasionally reported in the literature, only two of these patients had no other metastases even axillary nodes—the same as our case.8,9 It once was hypothesized that distant metastasis may be mediated by the first metastasis of regional lymph nodes. However, sole remote metastasis in the urinary bladder seems to support the recent hypothesis of cancer cells metastases to various sites simultaneously more.10 ER- and PR-positive tumors respond to hormone therapy and are predicted to have a higher disease-free survival than patients with ER-negative tumors. The expression of ER and PR in the metastatic bladder tumor was expected to be like the primary breast tumor. However, heterogeneic expression of ER between the primary breast tumor and the metastatic lesions is not uncommon. In a study of 35 patients, ER expression was discordant between the primary tumor and the involved lymph nodes in approximately 24% of the breast cancers evaluated.10 A large retrospective study comparing primary with metastatic tumor with ER and PR content from 200 metastatic breast cancer patients also showed that although there was a significant correlation between both the ER and PR in the primary and metastatic lesion, discordance of ER and PR expression between the primary and the metastatic site was still noted in 30% and 39% patients, respectively. Patients with tumors that changed from positive primary to negative metastasis (positive/negative) experienced significantly shorter median survival compared with positive/positive or compared with negative/positive.11 Discordant expression of the ER and PR status in primary breast carcinoma and metastatic bladder lesions, as reported in our patient, had been found in four patients in the literature.12-15 The hypotheses of the heterogeneous ER and PR expression in the primary tumor and metastatic lesions in the same patient include: the breast cancer cells are polyclonal; and ER and PR expression may change after endocrine therapy, due to the elimination and growth of ER- and PR-positive or -negative cells or due to gene mutations.10 HER-2–positive breast cancer tends to be more aggressive than other types of breast cancer and less responsive to hormone treatment. Fortunately, the success in the application of trastuzumab in HER-2–positive breast cancer has led to its widespread use. The combination of trastuzumab and chemotherapy is significantly superior to chemotherapy alone in terms of both response rates and survival.16 In a study of metastatic breast cancer to the bladder, it was found that previous patient survival, ranging from 1 month to 2 years after bladder metastasis was diagnosed, was improved with recently developed better adjuvant systemic chemotherapy or hormone therapy.17 AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Holland JF, Frei E: Cancer Medicine. Philadelphia, PA, Lea & Febiger, 1973, pp 1773–1774 2. Abrams HL, Spiro R, Goldstein N: Metastases in carcinoma: Analysis of 1000 autopsied cases. Cancer 3:74-85, 1950[CrossRef][Medline] 3. Murguia E, Quiroga D, Canteros G, et al: Gallbladder metastases from ductal papillary carcinoma of the breast. Hepatobiliary Pancreat Surg 13:591-593, 2006[CrossRef] 4. Ganem EJ, Batal JT: Secondary malignant tumors of the urinary bladder metastatic from primary foci in distant organs. J Urol 75:965-972, 1956[Medline] 5. Perez-Mesa C, Pickren JW, Woodruff MN, et al: Metastatic carcinoma of the urinary bladder from primary tumors in the mammary gland of female patients. Surg Gynecol Obstet 21:813-818, 1965 6. Goldestein AG: Metastatic carcinoma to the bladder. J Urol 98:209-215, 1967[Medline] 7. Grabstald H, Kaufman R: Hydronephrosis secondary to ureteric obstruction by metastatic breast cancer. J Urol 102:569-576, 1969[Medline] 8. Silverstein LI, Plaine L, Davies JE: Breast carcinoma metastasis to bladder. Urology 29:544-547, 1987[CrossRef][Medline] 9. Choudhary M, Ahmed AA, Williamson JG: Sole bladder metastasis from breast cancer. J Obstet Gynaecol 23:212, 2003[Medline] 10. Iguchi C, Nio Y, Itakura M: Heterogeneic expression of estrogen receptor between the primary tumor and the corresponding involved lymph nodes in patients with node-positive breast cancer and its implications in patient outcome. J Surg Oncol 83:85-93, 2003[CrossRef][Medline] 11. Lower EE, Glass EL, Bradle DA, et al: Impact of metastatic estrogen receptor and progesterone receptor status on survival. Breast Cancer Res Treat 90:65-70, 2005[CrossRef][Medline] 12. Feldman P, Madeb R, Naroditsky I, et al: Metastatic breast cancer to the bladder: A diagnostic challenge and review of the literature. Urology 59:138, 2002[Medline] 13. Elia G, Stewart S, Makhuli ZN, et al: Metastatic breast cancer diagnosed during a work-up for urinary incontinence: A case report. Int Urogynecol J Pelvic Floor Dysfunct 10:39-42, 1999[CrossRef][Medline] 14. Lawrentschuk N, Chan Y, Bolton D: Metastatic breast cancer to the bladder. Breast J 11:143, 2005[CrossRef][Medline] 15. Zagha RM, Hamawy JK: Solitary breast cancer metastasis to the bladder: An unusual occurrence. Urol Oncol 25:236-239, 2007[Medline] 16. Buzdar AU, Ibrahim NK, Francis D, et al: Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: Results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 23:3676-3685, 2005 17. Poulakis V, Witzsch U, de Vries RE, et al: Metastatic breast carcinoma to the bladder: 5-year follow up. J Urol 165:905, 2001[CrossRef][Medline]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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