Association of breast cancer and immune thrombocytopenic purpura.
ABSTRACT: Immune thrombocytopenic purpura immune thrombocytopenic purpura
See idiopathic thrombocytopenic purpura.
immune thrombocytopenic purpura Idiopathic thrombocytopenic purpura, see there (ITP ITP - Intent to Package ) and breast cancer are common disorders. Only six cases in which patients have had both diseases have been reported. We describe a 40-year-old woman who had ITP while responding to therapy for metastatic breast cancer. Given the few reported cases, the diverse presentations of thrombocytopenia Thrombocytopenia Definition
Thrombocytopenia is an abnormal drop in the number of blood cells involved in forming blood clots. These cells are called platelets. during the course of each patient's breast cancer and the variable therapeutic responses of ITP, the association of breast cancer and ITP is probably coincidental.
IMMUNE THROMBOCYTOPENIC PURPURA (ITP), the most common autoimmune disorder, results from accelerated platelet destruction after the binding of autoreactive antibodies to platelets. It is estimated that this entity affects approximately 1 in 10,000 people among the general population. (1) Most patients with ITP have detectable immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against platelet glycoprotein complexes on their platelets or in their plasma. (2)
Although ITP is often associated with lymphoproliferative disorders, the medical literature has only occasionally linked ITP with solid tumors. (3-9) To date, only 6 cases of ITP have been reported in patients with breast cancer. (4-8) Carcinoma of the breast is the most common malignancy in women; a woman has a 1 in 8 (12.2%) chance of having breast cancer in her lifetime. (10) We present a patient who had ITP while responding to chemotherapy for metastatic breast cancer.
A 40-year-old African American woman was seen on May 18, 2000, because of an enlarging right breast mass. A needle core biopsy of the lesion revealed moderately differentiated invasive ductal carcinoma. Estrogen-progesterone receptors were positive. She had no history of any autoimmune disorders. Her only medication was a fentanyl fentanyl /fen·ta·nyl/ (fen´tah-nil) an opioid analgesic; the citrate salt is used as an adjunct to anesthesia, in the induction and maintenance of anesthesia, in combination with droperidol (or similar agent) as a neuroleptanalgesic, and patch. Positive physical findings included a large mass in the right breast and palpable right supraclavicular and right axillary lymph nodes The Axillary lymph nodes are of large size, vary from twenty to thirty in number, and may be arranged in the following groups:
n a diagnostic clinical laboratory test to determine the number and types of leukocytes present in a measured sample of blood. Overall the normal number of leukocytes ranges from 5000 to 10,000/mm3. (WBC WBC white blood cell; see leukocyte.
white blood cell
n stands for white
cell. ) of 5,200/[mm.sup.3].
A combination of cyclophosphamide cyclophosphamide /cy·clo·phos·pha·mide/ (-fos´fah-mid) a cytotoxic alkylating agent of the nitrogen mustard group; used as an antineoplastic, as an immunosuppressant to prevent transplant rejection, and to treat some diseases (600 mg/[m.sup.2]) and doxorubicin (60 mg/[m.sup.2]) was initiated for treatment of metastatic invasive ductal breast cancer on May 25, 2000. Three more courses were given at attenuated doses because of severe mucositis. Follow-up was erratic because she had problems with transportation and social support.
The patient was seen on October 19, 2000, for her fifth cycle of chemotherapy, 6 weeks after her previous treatment. She had no specific complaints. Physical examination showed a reduction in the right breast mass. No residual lymphadenopathy lymphadenopathy /lym·phad·e·nop·a·thy/ (-op´ah-the) disease of the lymph nodes.
angioimmunoblastic lymphadenopathy , angioimmunoblastic lymphadenopathy with dysproteinemia , hepatosplenomegaly, ecchymoses Ecchymosis (plural, ecchymoses)
The medical term for a bruise. Ecchymoses may develop around the eyes following a nasal fracture.
Mentioned in: Nasal Trauma , or petechiae Petechiae
Tiny purple or red spots on the skin associated with endocarditis, resulting from hemorrhages under the skin's surface.
Mentioned in: Endocarditis, Hantavirus Infections, Hemorrhagic Fevers, Idiopathic Thrombocytopenic Purpura
were found. Repeated CT revealed resolution of mediastinal mediastinal /me·di·as·ti·nal/ (-as-ti´n'l) of or pertaining to the mediastinum.
of or pertaining to the mediastinum. lymphadenopathy and liver hypodensities. Pertinent laboratory values included hemoglobin, 10.1 g/dL; platelet count, 8,000/[mm.sup.3]; WBC, 4,600/[mm.sup.3] (59% neutrophils, 32% lymphocytes, 8% monocytes monocytes,
n.pl the largest of the white blood cells. They have one nucleus and a large amount of grayish-blue cytoplasm. Develop into macrophages and both consume foreign material and alert T cells to its presence. , and 1% eosinophils Eosinophils
A leukocyte with coarse, round granules present.
Mentioned in: Histiocytosis X
eosinophils ); reticulocyte count, 2.2%; and mean cell volume (MCV MCV mean corpuscular volume.
mean corpuscular volume
Mean corpuscular volume (MCV)
A measure of the average volume of a red blood cell. ), 80.1/[micro][m.sup.3]. The peripheral smear showed no granulocytic granulocytic
pertaining to granulocytes.
see myelocytic leukemia.
extramedullary growth of multiple, focal granulocytic neoplasm. They may be neutrophilic or eosinophilic. precursors, nucleated red cells, or schistocytes. Urinalysis revealed numerous red blood cells Red blood cells
Cells that carry hemoglobin (the molecule that transports oxygen) and help remove wastes from tissues throughout the body.
Mentioned in: Bone Marrow Transplantation
red blood cells , but results of renal function tests and electrolyte levels were normal. The activated partial thromboplastin time Activated partial thromboplastin time
Partial thromboplastin time test that uses activators to shorten the clotting time, making it more useful for heparin monitoring. and prothrombin time were normal. Tests for antinuclear antibody (ANA) and platelet antibodies were negative. The pati ent did not consent to human immunodeficiency virus human immunodeficiency virus
Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans. (HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. ) testing, but HIV serology had been negative 2 years before. On September 1, 2000, the day of her fourth chemotherapy treatment, her platelet count had been 103,000/[mm.sup.3]. Bone marrow aspirate as·pi·rate
To take in or remove by aspiration.
A substance removed by aspiration.
The removal by suction of a fluid from a body cavity using a needle. and biopsy specimens showed maturing hematopolesis and an increase in megakaryocytes but no evidence of metastatic carcinoma. The diagnosis of ITP was established, and prednisone therapy (1 mg/kg per day) was initiated. The platelet count increased to 51,000/[mm.sup.3] over 2 days. By the following week, it had increased to 165,000/[mm.sup.3]. Chemotherapy was resumed. Her initial response to therapy was followed by progression of breast cancer. Docetaxel therapy was initiated in December 2000. Prednisone therapy was tapered while the platelet count was 198,000/[mm.sup.3] in February 2001. The platelet count decreased to 4,000/[mm.sup.3] 1 week after prednisone therapy had been discontinued. By that time, a second response of the breast cancer had been achiev ed with docetaxel. One week after reinitiation of prednisone therapy, the platelet count increased to 435,000/[mm.sup.3]. The patient maintained an adequate platelet count and continued to receive both chemotherapy and prednisone at a maintenance dose of 40 mg daily.
Thrombocytopenia frequently occurs during the course of treatment in patients with solid tumors. Chemotherapy-induced myelosuppression, chemotherapy-induced myelodysplasia, and bone marrow involvement by cancer cells are the most common causes for low platelet counts in these patients. Thrombotic microangiopathies associated with cancer and chemotherapy have also been described in a small number of patients. Our patient's clinical presentation and the course of her disease suggested an autoimmune etiology.
The relationship between ITP and carcinoma has rarely been reported in the literature (3-9) Investigators have shown the presence of circulating immune complexes that may interact with platelets; however, the clinical significance of this observation remains unproven. (11)
Uncommon before the age of 30, breast cancer incidence increases with age. From an incidence of 117 per 100,000 women aged 40 to 44 years, breast cancer strikes 296 per 100,000 aged 55 to 59 years. (10) Chronic ITP most commonly affects women between 30 and 50 years of age, (12) but the association of both diseases has been reported in only six patients. Five of them were 40 to 60 years of age, and the remaining two were 69 and 72 years of age, respectively, when ITP was detected (Table).
Of the 6 previously described patients who had ITP during the course of breast cancer, 5 had metastatic or recurrent breast cancer when ITP was diagnosed (Table). (4-8) All but 1 of them were successfully managed with commonly used therapies for ITP, including steroids, intravenous immunoglobulin (IVIG IVIG Intravenous immunoglobulin, see there ), and/or splenectomy Splenectomy Definition
Splenectomy is the surgical removal of the spleen, which is an organ that is part of the lymphatic system. The spleen is a dark-purple, bean-shaped organ located in the upper left side of the abdomen, just behind the bottom of the . The remaining patient was treated solely for breast cancer with radiotherapy and tamoxifen, and her platelet count returned to normal. (6) On the basis of available information, there remains no demonstrable relationship between ITP and breast cancer. Immune thrombocytopenic purpura has apparently responded to therapy directed against breast cancer in only 1 of these 6 cases. (6) The appearance of ITP in the course of breast cancer has been variable. Among some individuals, ITP became manifested simultaneously with the initial presentation of breast cancer. For others, it appeared at the time of a late recurrence or during the course of treatment for advanced disease, as in our case (Tabl e) (4-7). In another case report from our center, Jillella et a1 (8) described ITP manifested after high-dose chemotherapy and autologous stem-cell rescue in a patient with high-risk breast cancer. (8) Four of the 6 previously reported patients had bone marrow metastases, and 2 had diffuse splenic splenic /splen·ic/ (splen´ik) pertaining to the spleen.
Of, in, near, or relating to the spleen.
pertaining to the spleen. involvement (Table).
Our patient became thrombocytopenic thrombocytopenic
of the nature of or pertaining to thrombocytopenia. after the fourth cycle of chemotherapy; however, her leukocyte count was normal, and her hemoglobin level had remained stable over four treatment cycles. The evaluation of her bone marrow biopsy Bone marrow biopsy
A procedure in which cellular material is removed from the pelvis or breastbone and examined under a microscope to look for the presence of abnormal blood cells characteristic of specific forms of leukemia and lymphoma. confirmed the absence of myelosuppression and myelodysplasia. Results of a bone marrow biopsy showed no evidence of metastatic breast cancer. The number of megakaryocytes was increased. There was no history of blood transfusion or use of drugs that can cause thrombocytopenia and no evidence of a thrombotic microangiopathy or consumptive con·sump·tive
Of, relating to, or afflicted with consumption. coagulopathy. Thrombocytopenia recurred immediately after prednisone therapy was discontinued. Solid tumors may cause low-grade disseminated intravascular coagulation disseminated intravascular coagulation
Abbr. DIC A hemorrhagic disorder that occurs following the uncontrolled activation of clotting factors and fibrinolytic enzymes throughout small blood vessels, resulting in tissue necrosis and (DIG) that can lead to thrombocytopenia. (13) Our patient did not have superficial venous thrombosis or migratory venous thrombosis, however, and her thrombocytopenia responded twice to prednisone, which is not effective in the treatment of chronic DIG. We ruled out other disorders ass ociated with thrombocytopenia and established a diagnosis of ITP in our patient using the guidelines of the American Society of Hematology. (14) We did not test for antibodies against platelets in her serum; however, the antiplatelet antibody assay has a predictive value of only 46% and a negative predictive value The negative predictive value is the proportion of patients with negative test results who are correctly diagnosed. Worked example
(as determined by "Gold standard")
True False of 82%. (1 The diagnosis and relapse of ITP were not associated with progression of breast cancer.
At present, seven cases of ITP in breast cancer patients have been reported. Most have responded to treatment directed toward the autoimmune process rather than to the primary cancer treatment. The presentations of thrombocytopenia during the course of each patient's breast cancer were varied. The diagnosis of ITP in our patient was established while her breast cancer was responding to treatment; treatment with prednisone increased the platelet count. Because both are common disorders in the general population, and considering the low number of reported cases of concurrence, the diverse presentations of thrombocytopenia during the course of each patient's breast cancer, and the variable therapeutic responses of ITP, we suggest that the association of breast cancer and ITP may be only a coincidence.
After an initial partial response to docetaxel, the patient's breast cancer has remained stable, and she continues to receive chemotherapy. In January 2002, candidal esophagitis esophagitis /esoph·a·gi·tis/ (e-sof?ah-ji´tis) inflammation of the esophagus.
chronic peptic esophagitis reflux e. developed, and the patient consented to a repeat HIV test that was positive. With the known association of corticosteroid responsive thrombocytopenia and HIV infection, our patient's clinical course supports the premise that breast cancer and ITP may be only a coincidence and that other causes of ITP should be considered.
TABLE Summary of Reported Cases of Breast Cancer and Immune Thrombocytopenic Purpura (ITP) Interval Between Breast Cancer Stage of Breast Reference, Year Age/Sex and ITP Cancer Schwartz et al, (4) 1982 44, F - IV Cummings and Mazur; (5) 1992 46, F 6 years IV, recurrent 59, F 6 months IV Igarashi et al, (6) 1998 72, F At time of III, recurrent relapse Poratta et al, (7) 1999 69, M 13 months IV Jillella et al, (8) 2000 58, F 7 months III Present case 40, F 5 months IV recurrent Site of Reference, Year Metastases Therapy for ITP Schwartz et al, (4) 1982 Cortical bone, Prednisone bone marrow Cummings and Mazur; (5) 1992 Cortical bone, bone Splenectomy marrow, spleen Spleen, bone Splenectomy marrow Igarashi et al, (6) 1998 - None Poratta et al, (7) 1999 Cortical bone, bone Prednisone marrow, lung Jillella et al, (8) 2000 - Prednisone Present case Cortical bone, Prednisone lung, liver IVIG = Intravenous immunoglobulin.
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Idiopathic thrombocytopenic purpura, or ITP, is a bleeding disorder caused by an abnormally low level of platelets in the patient's blood. in adults. Blood 1989; 74:2309-2317
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(3.) Bellone JD, Kunicki TJ, Aster RH: Immune thrombocytopenia associated with carcinoma. Ann Intern Med 1983; 99:470-472
(4.) Schwartz KA, Slichter SJ, Harker LA: Immune-mediated platelet destruction and thrombocytopenia in patients with solid tumors. Br] Haematol 1982; 51:17-24
(5.) Cummings OW, Mazur MT: Breast carcinoma diffusely metastatic to the spleen. a report of two cases as idiopathic thrombocytopenic purpura. Am J Clin Pathol 1992; 97:484489
(6.) Igarashi T, Itoh K, Fujii H, et al: Successful treatment by radiation and hormone therapy of isolated local recurrence of breast cancer 24 years after mastectomy accompanied by immune thrombocytopenia: a case report. Jpn J Clin Oncol 1998; 28:270-275
(7.) Porrata LF, Alberts 5, Hook C, et al: Idiopathic thrombocytopenic purpura associated with breast cancer: a case report and review of the literature. Am J Clin Oncol 1999; 22:411-413
(8.) Jillella AP, Kallab AM, Kutlar A: Autoimmune thrombocytopenia following autologous hematopoietic cell transplantation: review of literature and treatment options. Bone Marrow Transplant bone marrow transplant: see bone marrow. 2000; 26:925-927
(9.) Demirer T, Celebi H, Arat M, et al: Autoimmune thrombocytopenia in a patient with small cell lung cancer Lung Cancer, Small Cell Definition
Small cell lung cancer is a disease in which the cells of the lung tissues grow uncontrollably and form tumors.
Lung cancer is divided into two main types: small cell and non-small cell. developing after chemotherapy and resolving following autologous peripheral blood stem cell transplantation Stem Cell Transplantation Definition
Stem cells are basic human cells that reproduce (replicate) easily, providing a continuous source of new, sometimes different types of cells. . Bone Marrow Transplant 1999; 24:335-337
(10.) Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review, 1973-1996. Bethesda, Md, National Cancer Institute, 1999
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(12.) Stasi R, Stipa E, Masi M, et al: Long-therm observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med 1995; 98:436-442
(13.) Sack OH, Levin J, Bell WR: Trousseau's syndrome and other maifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine 1977; 56:1-37
(14.) George JN, Woolf SH, Raskob GE, et al: Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996; 88:3-40
(15.) Kelton JG, Powers PJ, Carter CJ: A prospective study of the usefulness of the measurement of platelet-associated IgG for the diagnosis of idiopathic thrombocytopenic purpura Blood 1982; 60:1050-1053
RELATED ARTICLE: KEY POINTS
* Despite the fact that immune thrombocytopenic purpura (ITP) and breast cancer are common among women, the association of both diseases has rarely been reported.
* Among the published cases, no common findings suggest a causal relationship between these 2 disorders.
* The response of ITP to treatment appears unrelated to the clinical course of breast cancer; conventional approaches are often successful.
From the Department of Internal Medicine, Section of Hematology/Oncology, Medical College of Georgia In 1828, it was chartered by the state of Georgia as the Medical Academy of Georgia, with plans to offer a single course of lectures leading to a bachelor's degree. It opened the following year on October 1st at the Augusta hospital. , Augusta.
Reprint requests to Paul Dainer, MD, Medical College of Georgia, Department of Medicine, Section of Hematology/Oncology, 1120 15th St, BAA 5407, Augusta, GA 30912-3125.