Remission of Macroglobulinemia during Anastrozole Treatment for Breast Cancer
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《新英格兰医药杂志》
To the Editor: Waldenstr?m's macroglobulinemia is a lymphoproliferative disorder characterized by a lymphoplasmacytic bone marrow infiltrate and high levels of a monoclonal IgM in serum.1 A number of chemotherapeutic agents and, more recently, monoclonal antibodies have resulted in complete or partial remissions, but the disease remains incurable, with a median survival of five years.1
We first saw our patient in 1996, when she was 71 years of age and had an elevated IgM paraprotein level, which had been found two years earlier. She was asymptomatic, and her lymph nodes and spleen were not enlarged. The IgM level was 22.2 g per liter. A bone marrow aspirate from the posterior iliac crest was diagnostic of Waldenstr?m's macroglobulinemia. Over the course of the next seven years, she remained asymptomatic, with IgM paraprotein levels ranging from 17.5 to 25.0 g per liter.
In December 2003, the patient was found to have a focally invasive, grade 3 ductal carcinoma of the breast, with positive axillary lymph nodes. After lumpectomy and axillary dissection, the patient received 5000 cGy of radiation to the right breast, followed by treatment with anastrozole (1 mg daily by mouth) from January 2004 to the present time. When we next saw her, in July 2004, the IgM level had plunged to 0.19 g per liter. The IgM levels were measured monthly for the next eight months, and all measured values were 0.19 g per liter or less, including those obtained from blood drawn and tested at 37°C. The other immunoglobulin levels remained in the normal range. A bone marrow aspirate obtained from the posterior iliac crest in December 2004 showed no sign of macroglobulinemia by morphologic analysis or flow cytometry. Her anastrozole therapy appears to have had no untoward side effects.
Anastrozole is a nonsteroidal aromatase inhibitor that blocks the conversion of androgens to estrogens; it has been in use for the treatment of breast cancer since 1995.2 We are unaware of other reports of the use of this agent in Waldenstr?m's macroglobulinemia. In vitro studies of a related condition, multiple myeloma, have shown the presence of estrogen and progesterone receptors on human myeloma cells lines,3 and Kahr et al. have reported a case that suggests a role for androgen deficiency in myeloma proliferation.4 Our patient's clinical course suggests that anastrozole may have had a role in the remission of her Waldenstr?m's macroglobulinemia, and we believe that further investigation is warranted.
Crystal Chettle, B.Sc.
Michael A. Baker, M.D.
University Health Network
Toronto, ON M5G 2C4, Canada
michael.baker@uhn.on.ca
References
Ghobrial IM, Gertz MA, Fonseca R. Waldenstrom macroglobulinemia. Lancet Oncol 2003;4:679-685.
Baum M, Buzdar AU, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Lancet 2002;359:2131-2139.
Otsuki T, Yamada O, Kurebayashi J, et al. Estrogen receptors in human myeloma cells. Cancer Res 2000;60:1434-1441.
Kahr WH, Al-Homadhi A, Meharchand J, Bailey DJ, Stewart AK. Testicular plasmacytoma following chemical orchiectomy: potential role of hypogonadism in myeloma proliferation. Leuk Lymphoma 1998;28:437-442.
We first saw our patient in 1996, when she was 71 years of age and had an elevated IgM paraprotein level, which had been found two years earlier. She was asymptomatic, and her lymph nodes and spleen were not enlarged. The IgM level was 22.2 g per liter. A bone marrow aspirate from the posterior iliac crest was diagnostic of Waldenstr?m's macroglobulinemia. Over the course of the next seven years, she remained asymptomatic, with IgM paraprotein levels ranging from 17.5 to 25.0 g per liter.
In December 2003, the patient was found to have a focally invasive, grade 3 ductal carcinoma of the breast, with positive axillary lymph nodes. After lumpectomy and axillary dissection, the patient received 5000 cGy of radiation to the right breast, followed by treatment with anastrozole (1 mg daily by mouth) from January 2004 to the present time. When we next saw her, in July 2004, the IgM level had plunged to 0.19 g per liter. The IgM levels were measured monthly for the next eight months, and all measured values were 0.19 g per liter or less, including those obtained from blood drawn and tested at 37°C. The other immunoglobulin levels remained in the normal range. A bone marrow aspirate obtained from the posterior iliac crest in December 2004 showed no sign of macroglobulinemia by morphologic analysis or flow cytometry. Her anastrozole therapy appears to have had no untoward side effects.
Anastrozole is a nonsteroidal aromatase inhibitor that blocks the conversion of androgens to estrogens; it has been in use for the treatment of breast cancer since 1995.2 We are unaware of other reports of the use of this agent in Waldenstr?m's macroglobulinemia. In vitro studies of a related condition, multiple myeloma, have shown the presence of estrogen and progesterone receptors on human myeloma cells lines,3 and Kahr et al. have reported a case that suggests a role for androgen deficiency in myeloma proliferation.4 Our patient's clinical course suggests that anastrozole may have had a role in the remission of her Waldenstr?m's macroglobulinemia, and we believe that further investigation is warranted.
Crystal Chettle, B.Sc.
Michael A. Baker, M.D.
University Health Network
Toronto, ON M5G 2C4, Canada
michael.baker@uhn.on.ca
References
Ghobrial IM, Gertz MA, Fonseca R. Waldenstrom macroglobulinemia. Lancet Oncol 2003;4:679-685.
Baum M, Buzdar AU, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Lancet 2002;359:2131-2139.
Otsuki T, Yamada O, Kurebayashi J, et al. Estrogen receptors in human myeloma cells. Cancer Res 2000;60:1434-1441.
Kahr WH, Al-Homadhi A, Meharchand J, Bailey DJ, Stewart AK. Testicular plasmacytoma following chemical orchiectomy: potential role of hypogonadism in myeloma proliferation. Leuk Lymphoma 1998;28:437-442.