Gastrointestinal metastases from breast cancer: a case report. (Case Report).

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Breast cancer is the most frequently encountered cancer in women and the second leading cause of cancer death. Distant metastases are present in about 60% of the patients at the time of diagnosis. (1) The lymph nodes, lung, bone, liver, peritoneal cavity, and brain are the usual sites for metastases of breast carcinoma, while gastrointestinal (GI) involvement is rare. (2) Upper GI tract metastases are more frequent than lower GI tract metastases. We herein report a case of upper and lower GI tract metastases occurring many years after the diagnosis of breast carcinoma.

Discussion

GI metastasis is an underdiagnosed complication of breast cancer. Breast cancer is among the most common primary malignancies metastasizing to the GI tract, along with melanoma, ovary, and bladder. (3,4) Gastric lesions seem to be slightly more frequent (6-18% versus 8-12%) than colorectal ones in postmortem examinations. (5) Median interval between breast cancer and the diagnosis of GI metastasis may vary from a few months to many years (>12 yr). (6-8) Besides gastric and colorectal metastases, reported cases of metastatic breast cancer also present as cholecystitis (9) or as an unusual cause of biliary obstruction due to pancreatic metastasis. (10) Presenting symptoms are sparse, nonspecific, and frequently attributed to the secondary effects of chemotherapy. Among breast cancer histologies, infiltrating lobular cancer is the predominant type to metastasize to the colon and rectum; (11) mixed type and infiltrating ductal cancer are rarely the source for GI metastasis.

Many studies showed a mainly diffuse linitis plasticalike infiltration: (12) diffuse thickening of the gastric and colorectal wall causing rigidity of the involved segment. Pathologic criteria include infiltration of the serosal, muscular, and submucosal layers by small cells with monomorphic, round nuclei and vacuolated cytoplasm typically arrayed in chords, named "Indian files." This pattern of infiltration provokes an intense fibrous reaction from the tissues, macroscopically evident as linitis plastica, which occurs both in the stomach and in the rectum. (13) In addition, the "signet ring" morphology of lobular carcinoma may mimic other primary tumors (ie, gastric carcinoma). Correct interpretation of "signet ring" cells as metastatic, most likely from the breast or stomach, is helpful in diagnosis and management. (14) The lack of dysplasia or atypia of the rectal epithelium and the glands surrounding the malignant cells is often helpful in the differential diagnosis between a primary and a metastatic le sion. (11) Immunohistochemistry is the most useful tool to reach the correct diagnosis. Metastatic breast carcinomas are usually positive for gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7, carcinoembryonic antigen, estrogen receptor, and progesterone receptors, and negative for cytokeratin 20. (14-17)

Systemic treatment (chemotherapy and/or hormonal therapy) is usually used. (18) Surgery is indicated mainly in cases of stenosis or complete obstruction. Results are variable. Taal et al (6) reported in detail the different therapeutic modalities employed (surgery and/or radiotherapy and/or hormone or chemotherapy); in this series, the overall response rate was 53% (9 patients). (17)

Our patient had a relapse of her breast cancer 14 years after the initial diagnosis. She consulted for constipation and was found to have colonic stenotic lesion and a second ulcerating lesion. Although she was at increased risk for a second primary breast cancer, colonic metastasis from her breast cancer was suspected. She underwent surgery after she developed intestinal occlusion. This is a rare and unusual case of GI relapse many years after the first presentation for a breast adenocarcinoma.

Accepted October 2, 2002.

References

(1.) Winer EP, Morrow M, Osborne CK, Harris JR. Malignant tumors of the breast, in DeVita VT Jr, Hellman S, Rosenberg SA (eds): Cancer: Principles & Practice of Oncology. Philadelphia, Lippineott Williams & Wilkins, 2001, vol 2, ed 6, pp 1651-1716.

(2.) Jam S, Fisher C, Smith P, Millis RR, Rubens RD. Patterns of metastatic breast cancer in relation to histological type. Eur J Cancer 1993;29A: 2155-2157.

(3.) Washington K, McDonagh D. Secondary tumors of the gastrointestinal tract: Surgical pathologic findings and comparison with autopsy survey. Mod Pathol 1995;8:427-433.

(4.) Meyers MA, McSweency J. Secondary neoplasms of the bowel. Radiology 1972;105:l-11.

(5.) CifuentesN, Pickren JW. Metastases from carcinoma of mammary gland: An autopsy study. J Surg Oncol 1979;11:193-205.

(6.) Taal BG, den Hartog Jager FC, Steinmetz R, Peterse H. The spectrum of gastrointestinal metastases of breast carcinoma: Part II--The colon and rectum. Gastrointest Endose 1992;38: 136-141.

(7.) Schwarz RE, Klimstra DS, Tumbull AD. Metastatic breast cancer masquerading as gastrointestinal primary. Am J Gestroenterol 1998;93: 111-114.

(8.) Van Trappen P, Serreyn R, Elewaut AE, Cocquyt V, Van Belle S. Abdominal pain with anorexia in patients with breast carcinoma. Ann Oncol 1998;9: 1243-1245.

(9.) Crawford DL, Yeh IT, Moore JT. Metastatic breast carcinoma presenting as cholecystitis. Am Surg 1996;62:745-747.

(10.) Mountney I, Maury AC, Jackson AM, Coleman RE, Johnson AG. Pancreatic metastases from breast cancer: An unusual cause of biliary obstruction. Eur J Surg Oncol 1997;23:574-576.

(11.) Bamias A, Baltayiannis G, Kamina S, Fatouros M, Lymperopoulos E, Agnanti N, et al. Rectal metastases from lobular carcinoma of the breast: Report of a case and literature review. Ann Oncol 2001;12:715-718.

(12.) Clavien PA, Laffer U, Torhost I, Harder F. Gastro-intestinal metastases as first clinical manifestation of the dissemination of a breast cancer. Eur J Surg Oncol 1990;16:121-126.

(13.) Cormier WI, Gaffey TA, Welch JM, Welch IS, Edmonson JH. Linitis plastica caused by metastatic lobular carcinoma of the breast. Mayo Clin Proc 1980;55:747-753.

(14.) Pambuccian SE, Bachowski GJ, Twiggs LB. Signet ring cell lobular carcinoma of the breast presenting in a cervicovaginal smear: A case report. Acta Cytol 2000;44:824-830.

(15.) Raju U, Ma CK, Shaw A. Signet ring variant of lobular carcinoma of the breast: A clinicopathologic and immunohistoehemical study. Mod Pathol 1993;6:516-520.

(16.) Kaufmann O, Deidesheimer T, Muehlenbcrg M, Deicke P, Dietel M. Immunohistochemical differentiation of metastatic breast carcinomas from metastatic adenocarcinomas of other common primary sites. Histopathology 1996;29:233-240.

(17.) Lagendijk JH, Mullink H, van Diest PJ, Meijer GA, Meijer CJ. Immunohistochemical differentiation between primary adenocareinomas of the ovary and ovarian metastases of colonic and breast origin: Comparison between a statistical and an intuitive approach. J Clin Pathal 1999; 52:283-290.

(18.) Taal BG. Peterse H, Boot H. Clinical presentation, endoscopic features, and treatment of gastric metastases from breast carcinoma. Cancer 2000; 89:2214-2221.

RELATED ARTICLES: Key Points

* The use of different cytokeratin stains helped to confirm the diagnosis of metastasis from the breast.

* Metastasis from the breast to the colon must be considered in the presence of bowel symptoms.

* The aromatase inhibitor letrozole is an effective agent against advanced hormone-positive breast cancer in postmenopausal women.

Case Report

A 68-year-old woman had a moderately differentiated infiltrating ductal carcinoma of a right-sided accessory mammary gland, diagnosed in October 1984. She underwent a re-excision of the tumor bed, including a partialmastectomy, with a right-sided axillary nodal dissection. No residual tumor or extensions to the axillary nodes were found. The diagnosis was a T2N0M0 right sided mammary cancer. She received adjuvant radiotherapy, ending in February 1985.

In September 1999, a 1-year-old, left-sided deltoid mass was resected. The pathology examination revealed a 3.5 X 2 cm metastatic, poorly differentiated adenocarcinoma, strongly positive for hormone receptors, positive for Ca 15-3 immunohistochemistry, and negative for c-erb B2 (HER2/neu) protein. The workup, including a chest x-ray and computed tomography (CT) of the thorax, abdomen, and pelvis, was normal. Bilateral mainmogram and bone scan were unremarkable. Serum Ca 15-3, alkaline phosphatase, and [gamma]-glutamyltransferase values were normal. A daily treatment of 20 mg tamoxifen was started. Two months later (November 1999), she developed severe constipation. Colonoscopic examination revealed a stenotic, rigid sigmoid and an ulcerated stenotic lesion at the hepatic angle. The biopsy of the sigmoid was unremarkable, whereas the biopsy of the ulcerated lesion showed a submucosal metastatic mammary adenocarcinoma. Two months later, she started to have diffuse, cramping abdominal pain; a normal CT scan of the abdomen was obtained but her Ca 15-3 serum level went up. One month later she developed intestinal occlusion and underwent a total colectomy, wedge resection of the gastric antrum, and total hysterectomy with bilateral salpingo-oophorectomy because of perioperative findings of uterine metastasis. The final pathology examination showed metastasized, poorly differentiated adenocarcinoma involving the antrum, the colon at multiple sites, the omentum, the serosa of the appendix, the uterus, the cervix, the bilateral fallopian tubes, and the ovaries. The immunoperoxidase stain done on the patient's biopsy was positive for cytokeratin 7, negative for cytokeratin 20, and positive for estrogen receptors, indicating these lesions had metastasized from the primary breast cancer. She received 6 cycles of Adriamycin-Docetaxel combination, followed by a daily 2.5-mg dose of letrozole. She remains alive and well 2 years after completion of chemotherapy.

From the Department of Medical Oncology, St. Georges Hospital, Beirut; the Pathology Department and the Hematology-Oncology Division, Lebanese University Medical School, Beirut, Lebanon; and the Hematology-Oncology Division, University of Utah and Salt Lake City Medical Centers, Salt Lake City, UT.

Reprint requests to Michel Saade, MD, Hematology-Oncology Division, St. Georges Hospital, Beirut, Lebanon. Email: [e-mail]

Copyright [c] 2003 by The Southern Medical Association