Article ID: 2025-0008-CR
The incidence of breast cancer in patients with pre-existing interstitial lung disease has been rarely reported. Consequently, evidence supporting the safety of chemotherapy in this population remains limited. This report describes the case of a 55-year-old woman with a history of cryptogenic organizing pneumonia who received adjuvant chemotherapy for the management of breast cancer. The chemotherapy regimen comprised the administration of epirubicin/cyclophosphamide followed by the weekly administration of paclitaxel. This regimen was selected based on the findings of previous studies that assessed the utility of chemotherapy regimens for the treatment of lung cancer in patients with interstitial lung disease. Chemotherapy was completed without worsening of the cryptogenic organizing pneumonia or the appearance of new abnormal lung fields. Therefore, the administration of epirubicin/cyclophosphamide followed by the weekly administration of paclitaxel may be safe in patients with pre-existing interstitial lung disease. This regimen may be a suitable choice for the perioperative management of this population.
Interstitial lung disease is a risk factor for the incidence of chemotherapy-induced acute interstitial disease.1 Interstitial lung disease often precedes the commencement of treatment in patients with lung cancer.2,3 Several prospective studies have assessed the utility of chemotherapy regimens in patients with lung cancer who have a history of interstitial lung disease.4,5,6,7,8,9,10,11,12,13 Therefore, the choice of the chemotherapy regimen used to treat lung cancer depends on the risk of worsening interstitial lung disease. However, reports of cases wherein interstitial lung disease preceded the diagnosis of breast cancer are rare. This report describes the case of a woman with a history of cryptogenic organizing pneumonia who received adjuvant chemotherapy for the treatment of breast cancer.
The pathological findings of a 55-year-old woman who had undergone breast-conserving surgery with axillary lymph node dissection for the management of early stage breast cancer were suggestive of invasive ductal carcinoma (pStage IIB [pT2, pN1a, M0], estrogen receptor-positive [90%], progesterone receptor-positive [5%], and HER2 1+ according to IHC). The Ki-67 labeling index determined using the average method was 15% (approximately 60% using the hot spot method). The tumor was f+, lymphovascular invasion positive (Ly1, V1), and extensive intraductal component invasion negative, with nuclear grade 1 and Nottingham histological grade 2. The patient had been receiving prednisolone daily since being diagnosed with cryptogenic organizing pneumonia at the age of 54 years. The dose of prednisolone was tapered off such that the patient was receiving 8 mg/day postoperatively.
The adjuvant chemotherapy regimen involved the administration of 75 mg/m2 of docetaxel and 600 mg/m2 of cyclophosphamide on day 1 at 3-week intervals. Four cycles of adjuvant chemotherapy were planned. However, we searched for prospective and retrospective studies of anti-cancer treatment in patients with lung cancer who had a history of interstitial lung disease and collected information regarding the incidence of interstitial lung disease among patients with breast cancer receiving chemotherapy. Based on the information collected, we recommended commencing treatment with 90 mg/m2 of epirubicin and 600 mg/m2 of cyclophosphamide on day 1 at 3-week intervals for a total of four cycles, followed by 12 cycles of weekly administration of 80 mg/m2 of paclitaxel. The administration of epirubicin/cyclophosphamide followed by the weekly administration of paclitaxel was initiated on day 55 after surgery.
Adjuvant chemotherapy was completed without treatment delays or interruptions caused by adverse events. No respiratory symptoms were reported, and the SpO2 was maintained at 95%–99% during the treatment period. The degree of consolidation at the base of both lungs and bronchiectasis before breast conservation surgery and after the completion of chemotherapy were similar on chest radiographs and computed tomography (CT) images (Fig. 1). No new pulmonary opacities were noted, and no significant changes were observed in the blood test results, including those for Krebs von den Lungen-6, after the start of chemotherapy (Fig. 2). Verbal consent was obtained from the patient for publication of the case details.
Radiograph and computed tomography (CT) images of the chest before and after the completion of chemotherapy for breast cancer.
(A) Chest radiograph acquired 551 days before breast conservation surgery (at the time of cryptogenic organizing pneumonia diagnosis); (B) 36 days before surgery; and (C) 14 days after administering the last dose of paclitaxel. (D) Corresponding CT images were acquired 532 days before breast conservation surgery (at the time of cryptogenic organizing pneumonia diagnosis); (E) 40 days before surgery; and (F) 27 days after administering the last dose of paclitaxel.
Changes in blood test values related to cryptogenic organizing pneumonia and changes in prednisolone dosage.
Day 0 is the day of breast conservation surgery. COP, cryptogenic organizing pneumonia; CT, computed tomography; KL-6, Krebs von den Lungen-6; LDH, lactate dehydrogenase; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; PSL, prednisolone.
The findings of this report indicate that the administration of epirubicin/cyclophosphamide followed by weekly administration of paclitaxel is safe in patients with breast cancer who have a history of cryptogenic organizing pneumonia. The choice of treatment in patients with breast cancer who have a history of interstitial lung disease must be based on the findings of previous studies, such as those assessing the utility of chemotherapy regimens for the treatment of lung cancer in patients with interstitial lung disease.
The incidence of interstitial pneumonia has been reported in less than 1% of patients receiving perioperative chemotherapy for the treatment of breast cancer in most clinical trials.14,15 Literature review revealed no reports of chemotherapy for the treatment of breast cancer in patients with interstitial lung disease. Therefore, this is the first case report to demonstrate that the administration of epirubicin/cyclophosphamide followed by the weekly administration of paclitaxel is safe in patients with breast cancer who have a history of cryptogenic organizing pneumonia.
Prospective studies have evaluated the utility of chemotherapy regimens for the treatment of lung cancer in patients with a history of interstitial lung disease.4,5,6,7,8,9,10,11,12,13 Notably, the rate of acute exacerbation of interstitial lung disease among patients receiving carboplatin/etoposide for small cell lung cancer and carboplatin/S-1, carboplatin/nanoparticle albumin-bound paclitaxel, and carboplatin/paclitaxel for non-small cell lung cancer was less than 10% in most of these studies.4,6,7,8,9,10,11,12 Consequently, these regimens are frequently selected for the treatment of lung cancer in patients with interstitial lung disease. Several retrospective studies have also evaluated the utility of different chemotherapy regimens for the treatment of lung cancer in patients with interstitial lung disease.16,17,18,19,20,21,22,23,24 The incidence of interstitial lung disease was 25.9% among cases of non-small cell lung cancer treated with docetaxel wherein pre-treatment CT imaging revealed pre-existing interstitial changes. This incidence is higher than that observed in cases without such changes.21 These findings indicate that compared with docetaxel, paclitaxel may be associated with a lower risk of exacerbation of interstitial pneumonia in patients with interstitial lung disease; however, evidence supporting this association remains limited. Literature on the effects of anthracyclines on interstitial lung disease remains scarce.25 However, most clinical trials have reported that interstitial pneumonia occurs in less than 1% of patients.14 Cyclophosphamide increases the risk of mortality in patients experiencing idiopathic pulmonary fibrosis exacerbations.26 Nevertheless, it is commonly used for the management of interstitial pneumonia.27 Therefore, epirubicin/cyclophosphamide and doxorubicin/cyclophosphamide may be considered relatively safe for the treatment of breast cancer in patients with interstitial lung disease. In this case, we suggested the use of the regimen comprising the administration of epirubicin/cyclophosphamide followed by the weekly administration of paclitaxel, which was deemed to exhibit a therapeutic effect equal to or greater than that of docetaxel/cyclophosphamide and a lower risk of developing acute interstitial pneumonia than docetaxel/cyclophosphamide, based on the findings of previous studies. The findings of previous studies, such as those assessing the risk of occurrence of acute interstitial pneumonia among patients with interstitial lung disease who developed lung cancer, may aid in selecting an appropriate regimen for the treatment of breast cancer in patients with interstitial lung disease.
Our findings suggest that the administration of epirubicin/cyclophosphamide followed by the weekly administration of paclitaxel may be safe in patients with cryptogenic organizing pneumonia who develop breast cancer. Furthermore, the choice of treatment in this population must be based on the findings of previous studies, such as those assessing the utility of chemotherapy regimens for the treatment of lung cancer in patients with interstitial lung disease. The administration of epirubicin/cyclophosphamide followed by the weekly administration of paclitaxel should be considered as perioperative chemotherapy for the treatment of breast cancer in patients with pre-existing interstitial lung disease. Cryptogenic organizing pneumonia has exhibited a relatively good prognosis among patients with idiopathic interstitial pneumonia.28 Furthermore, it has exhibited a good response to steroids. However, whether the risk of acute exacerbation among patients with cryptogenic organizing pneumonia differs from that among those with other types of idiopathic interstitial pneumonia remains unclear. Further studies must be conducted in the future to assess the risk of acute exacerbation of interstitial lung disease for each classification of interstitial lung disease and chemotherapy regimen.
We thank Editage (www.editage.jp) for English language editing.
The authors declare that no conflict of interest exists.
