Clinical investigation: breast
Bronchiolitis obliterans organizing pneumonia syndrome in breast-conserving therapy for early breast cancer: Radiation-induced lung toxicity

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Abstract

Purpose: Breast-conserving surgery and postoperative radiotherapy have played important roles in the treatment of early breast cancer. Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome has recently been reported to be one of the complications of adjuvant radiotherapy. The purpose of this study was to determine the incidence of and risk factors for BOOP syndrome in breast cancer patients.

Methods and Materials: Between January 1996 and December 1998, 157 patients with breast cancer underwent radiotherapy after breast-conserving surgery. The criteria used for the diagnosis of BOOP syndrome were as follows: 1) radiation therapy to the breast within 12 months, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lung infiltrates outside the radiation port, and 4) no evidence of a specific cause.

Results: BOOP syndrome developed in 4 (2.5%) patients, who had fever and nonproductive cough, with patchy infiltrative shadows on chest roentgenograms which emerged between 5 and 6 months after radiotherapy. The symptoms and pulmonary infiltrates were rapidly improved by treatment with prednisone (40 mg/day), which was tapered over 2- to 5-month periods. However, BOOP syndrome relapsed in all cases during the tapering period or after withdrawal of prednisone. The eosinophil and neutrophil counts were increased and the ratios of CD4+ to CD8+ lymphocytes were elevated in bronchoalveolar lavage fluid in all four cases. There were no differences in proportions of patients by age, irradiated breast site, use of tamoxifen and/or chemotherapy, or radiation dose between those with and without BOOP syndrome.

Conclusions: BOOP syndrome is considered an intractable form of lung toxicity after radiotherapy to the breast. An immunologic reaction mediated by eosinophils, neutrophils, and lymphocytes may be responsible for the development of this syndrome. Methods of prevention of BOOP syndrome should be established.

Introduction

Bronchiolitis obliterans organizing pneumonia (BOOP) is a lung disease which is pathologically characterized by the presence of granulation tissue polyps within respiratory bronchioles and alveolar ducts, and patchy areas of organizing pneumonia (1). Most cases of BOOP are idiopathic, but BOOP-like pathological reactions are also caused by pulmonary infection, drugs, rheumatoid disease, and inhalation of toxic fumes (1). Patients with BOOP have a nonproductive cough, dyspnea, fever, malaise, or some combination of these (1).

In 1995, Crestani et al. and Bayle et al. independently reported BOOP after radiotherapy to the breast 2, 3. They suggested the possibility of a relationship between the occurrence of BOOP and adjuvant radiotherapy to the breast. In 1998, Crestani et al. defined BOOP syndrome as the presence of lung infiltrates outside a radiation field, a finding not associated with radiation pneumonitis (4). Since the incidence of and risk factors for BOOP syndrome remain unclear, we evaluated them in our institution.

Section snippets

Study design

Between January 1996 and December 1998, 157 patients with breast cancer underwent radiotherapy after breast-conservative surgery. In surgery, wide excision including a margin of 2–3 cm macroscopically normal breast tissue around palpable tumors and axillary dissection up to levels I and II were performed. When the tumor was not palpable at surgery, the mammary gland, including the original tumor site and surrounding area, were excised. In radiotherapy, the entire breast was irradiated with 6-MV

Clinical courses of patients with BOOP syndrome

Four women were diagnosed with BOOP syndrome; the complication rate of this syndrome was therefore 2.5% (4/157). The four women were 44, 48, 50, and 67 years old. Three had right breast cancers and one had left breast cancer. They were all nonsmokers. Two of the four women had a history of possibly allergy-related symptoms; one had an episode of exanthema when she took a drug (incident unknown in detail), while the other had itching on her lips when she took an antipyrine agent. Radiation doses

Discussion

One of the most important complications of radiation therapy to the breast is pneumonitis. The concept of radiation-primed BOOP syndrome was proposed by Crestani et al. in 1998 (4). Arbetter et al. also reported this complication as “radiation-induced pneumonitis in the nonirradiated lung” in 1999 (6). Differentiation of common BOOP from classical radiation pneumonitis appears to be easy. Patchy consolidation and ground-glass opacity are frequently observed in both of these diseases 7, 8. In

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Current affiliation: Second Department of Medicine, Okayama University Medical School, Okayama, Japan.

Current affiliation: Division of Hematology and Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.

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