Ann Thorac Surg 2005;79:1711-1714
© 2005 The Society of Thoracic Surgeons
Original articles: General thoracic
Surgery for Pulmonary Nodules in Breast Cancer Patients
Fumihiro Tanaka, MD, PhDa,*,
Mio Li, MDa,
Nobuharu Hanaoka, MD, PhDa,
Toru Bando, MD, PhDa,b,
Tatsuo Fukuse, MD, PhDa,
Seiki Hasegawa, MD, PhDa,c,
Hiromi Wada, MD, PhDa
a Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan
b Department of Thoracic Surgery, Otsu Red-cross Hospital, Otsu, Japan
c Department of Thoracic Surgery, Hyogo College of Medicine, Hyogo, Japan
Accepted for publication October 20, 2004.
* Address reprint requests to Dr Tanaka, Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Shogoin-kawahara-cho 54, Sakyo-ku, Kyoto, 606–8507 Japan; (E-mail: ftanaka{at}kuhp.kyoto-u.ac.jp).
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Abstract
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BACKGROUND: The nature of pulmonary nodules that appeared in patients who had received surgery for breast cancer, as well as the role of surgery for such pulmonary nodules, remains unclear.
METHODS: A total of 52 consecutive patients who underwent surgery for pulmonary nodules between 1992 and 2001 after curative operation for breast cancer were reviewed.
RESULTS: The pathologic diagnoses of pulmonary nodules were pulmonary metastases of breast cancer in 39 patients, primary lung cancer in 6, and other diagnoses in 7 (tuberculosis and hamartoma in 2 each; sclerosing hemangioma, organizing pneumonia, and paragohimiasis in 1 each). The incidence of multiple pulmonary nodules was significantly higher in metastatic breast cancer patients (64.1%), but 33.3% of primary lung cancer patients and 28.6% of other histology patients had multiple pulmonary nodules. The average disease-free interval from the initial mastectomy was significantly shorter in metastatic breast cancer patients (66.8 months), but disease-free intervals were longer than 5 years in 41.0% of metastatic breast cancer patients. The 5-year survival rate after pulmonary metastectomy of metastatic breast cancer patients was 30.8%, which was not better than those documented in metastatic breast cancer patients treated with modern chemotherapy. There was no significant difference in postmetastectomy survival according to the number or sites of pulmonary metastases or the disease-free interval.
CONCLUSIONS: Pulmonary metastectomy may not be the primary therapeutic option in metastatic breast cancer patients, and patients should be treated principally with chemotherapy. As pulmonary nodules that appear in breast cancer patients are not always pulmonary metastases, the pathologic diagnosis should be confirmed, and surgery is an option for the pathologic confirmation.
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Introduction
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Pulmonary metastases are common features in patients with breast cancer [1, 2]. Patients with metastatic breast cancer including pulmonary metastases of breast cancer are usually treated with systemic chemotherapy [1], but some clinical studies have suggested that surgical resection of pulmonary metastases should be an option of treatment in selected patients with pulmonary metastases of breast cancer [2–5]. Recently more effective chemotherapy including an anti-HER2 antibody, trastuzumab, has been developed, and the prognosis of metastatic breast cancer patients has been greatly improved [6]. Thus the role of surgery for pulmonary metastases of breast cancer may not be established. In addition, pulmonary nodules that appear in patients who underwent mastectomy for breast cancer are usually pulmonary metastases; sometimes they are not metastases, but other histologic types such as primary lung cancer and pulmonary tuberculosis. We conducted a retrospective review to reveal the nature of pulmonary nodules in breast cancer patients as well as the role of surgery for pulmonary metastases.Fig 1
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Fig 1. Survival curve of patients who underwent an operation for pulmonary metastases of breast cancer.
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Patients and Methods
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A total of 52 consecutive patients who underwent surgery for pulmonary nodules at Kyoto University Hospital from January 1, 1992 through December 31, 2001 after curative operation for breast cancer were retrospectively reviewed (Table 1). All patients were female patients, and the mean age was 55.8 years (median, 55.5 years; range, 35 to 80). Pathologic diagnosis had not been confirmed in any patient. Fine-needle aspiration biopsy had not been performed in any patient. There was no apparent metastasis in any other organ. Before 1997, all surgical procedures for pulmonary nodules were performed through open thoracotomy. Since 1998, video-assisted thoracic surgery has been used for diagnosis of pulmonary nodules; open thoracotomy was performed when the nodules proved to be malignant tumors such as pulmonary metastases and primary lung cancer.
For all patients, the inpatient medical records, chest roentgenogram films, whole-body computed tomographic films, bone scanning data, and records of surgery were reviewed. Follow-up of the postoperative clinical course was conducted by outpatient medical records and by telephone or letter inquiries.
The 
2 was used to compare counts. Continuous data were compared using Student's t test if the distribution of samples was normal, or by the Mann-Whitney U test if the sample distribution was asymmetrical. The postoperative survival rate was analyzed by the Kaplan-Meier method, and the differences in survival rates were assessed by the log-rank test. Differences were considered significant for p < 0.05. All statistical manipulations were performed using the SPSS for Windows software (SPSS Inc, Chicago, IL).
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Results
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Pathological Diagnosis of Pulmonary Nodules
Pathological diagnosis of pulmonary nodules was listed in Table 1. For 39 patients with pulmonary metastases of breast cancer, pulmonary metastectomy for all nodules was tried through open thoracotomy; complete resection was actually achieved in 33 patients (84.6%). For 6 patients with primary lung cancer, lobectomy along with nodal dissection was performed, and complete resection was achieved in all patients. For 1 patient with sclerosing hemangioma, a segmentectomy was performed. For the other patients, a partial lung resection was performed.
Among 39 patients with pulmonary metastases of breast cancer, 24 patients (64.1%) showed multiple pulmonary nodules. The median number of pulmonary nodules for all metastatic breast cancer patients was two (range, 1 to 30), and for multiple metastases patients the median was 5. The incidence of multiple nodules in metastatic breast cancer patients was significantly higher than that in primary lung cancer patients (33.3%) or that in patients with other histologies (28.6%; p = 0.045) (Table 2). Table 3Among 6 primary lung cancer patients, 2 patients had multiple pulmonary nodules, 1 patient had two nodules (one adenocarcinoma and one atypical adenomatous hyperplasia), and 1 patient had eight nodules (one adenocarcinoma and 7 atypical adenomatous hyperplasia). One patient with pulmonary tuberculosis and 1 patient with organizing pneumonia also had multiple pulmonary nodules.
The average time from the initial mastectomy for breast cancer to the occurrence of pulmonary nodules (disease-free interval [DFI]) in metastatic breast cancer patients was 66.8 months, which was significantly shorter than that in primary lung cancer patients (average DFI, 272.0 months) or that in other histology patients (average DFI, 131.8 months) (p < 0.001) (Table 2). In 16 of 39 patients (41.0%) with pulmonary metastases of breast cancer, the DFI was longer than 5 years.
Postoperative Survival After Pulmonary Metastectomy for Metastatic Breast Cancer
For all patients with pulmonary metastases of breast cancer, the median overall survival time from pulmonary metastectomy was 32 months, and the 5-year survival rate was 30.8% (Fig 1). There was no significant difference in postmetastectomy survival according to the number of pulmonary metastases (single or multiple), sites of pulmonary metastases (unilateral or bilateral), or DFI (
5 years or > 5 years) (Table 3).
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Comment
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The majority of pulmonary nodules that appeared in patients who underwent mastectomy for breast cancer were pulmonary metastases, which were also demonstrated in the present study (pulmonary metastases of breast cancer in 39 of 52 patients [75.0%]). However, more importantly, the other 13 patients (25.0%) in the present series showed other histologic diagnoses including nonmalignant lesions. Thus, pulmonary nodules that appear in patients who underwent mastectomy for the breast may not always be pulmonary metastases, and a decision-making in the treatment should be made only after the pathologic diagnosis is confirmed. When nonsurgical diagnosis such as transbronchial biopsy fails to reveal a pathological diagnosis, video-assisted thoracic surgery should be considered as an option for the diagnosis. It may be possible that multiple pulmonary nodules in 1 patient did not show the same histology. However, in clinical practice a pathologic diagnosis of one typical pulmonary nodule may be enough to decide the treatment. When a treatment is not effective for some nodules, but is effective for others, a re-exploration for pathologic diagnosis may be considered.
In accordance with the slow progressive nature of breast cancer, the average time from an initial mastectomy to identification of pulmonary nodules, or DFI, was as long as 60.8 months in the present study. In fact, the average DFI for patients with pulmonary metastases of breast cancer was significantly shorter than that in primary lung cancer patients or that in other histology patients. In addition, the incidence of multiple lung nodules was significantly more frequent in metastatic breast cancer patients in the present study. Can we predict a diagnosis of pulmonary nodules that appear in patients who underwent mastectomy for breast cancer based on the DFI or the number of pulmonary nodules, or both? As described in the present study, patients with primary lung cancer may have multiple nodules (eg, eight nodules in 1 patient). In addition, the DFI was < 2 years in 1 patient with primary lung cancer and in 2 patients with nonmalignant diseases. Pulmonary metastases appeared > 10 years after mastectomy in 7 patients with pulmonary metastases of breast cancer. Considering these results, we should emphasis again that pathologic diagnosis is essential for pulmonary nodules that appear in patients who underwent breast cancer surgery. In addition, to distinguish between primary lung cancer and pulmonary metastases, an immunohistochemical staining against thyroid tissue factor-1, a marker of primary lung cancer, is useful, although this was not performed on any patient in the present study.
The 5-year survival rate and the median survival time after pulmonary metastectomy of patients with metastatic breast cancer in the present series were 30.8% and 32 months, respectively. Lanza and colleagues [3] and Ludwig and colleagues [7] reported more favorable results in patients who received pulmonary metastectomy (the 5-year survival rate, 49.5% and 53%, respectively; the median survival time, 47 months and 96.9 months, respectively). They concluded that pulmonary metastectomy should be an effective therapy in selected patients with pulmonary metastases of breast cancer. In a larger study, the 5-year survival rate after pulmonary metastectomy of 467 metastatic breast cancer patients was 38% [5], which was almost the same as that in the present series. These results documented in patients who received pulmonary metastectomy might be better than those documented in patients treated with chemotherapy or radiotherapy, or both for pulmonary metastases of breast cancer (median survival time after pulmonary metastases, 12 months) [8]. However, modern chemotherapy has dramatically improved survival of metastatic breast cancer patients, and the median survival times reported are 2 to 3 years [1]. Considering such favorable prognosis in medically treated metastatic breast cancer patients, surgery should not be a primary option of therapy for pulmonary metastases of breast cancer. In the present study, there was no significant difference in postoperative prognosis according to number of pulmonary metastases, sites of metastases, or DFI after mastectomy. We failed to identify patients who experienced a significant benefit from pulmonary metastectomy. Thus, surgery, especially video-assisted thoracic surgery, is a useful modality to confirm pathologic diagnosis of pulmonary nodules that appear in patients who received mastectomy for breast cancer. Fine-needle aspiration biopsy has been recently established as a useful diagnostic modality for pulmonary nodules, whereas fine-needle aspiration biopsy had not been performed before surgery in any patient of the present study. Fine-needle aspiration biopsy should be initially performed for diagnosis of pulmonary nodules, and surgical biopsy should be performed when failed.
In conclusion, pulmonary nodules in patients with breast cancer should be treated after pathologic confirmation, and surgical resection of pulmonary nodules should be considered as an option of the diagnosis. Once the pathologic diagnosis of pulmonary metastases is confirmed, patients should be treated principally with chemotherapy.
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Acknowledgments
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We thank Seiko Sakai for her helpful assistance in the preparation of this article. This work was supported by Grant-in-Aid No. 14370410 to Dr Tanaka and Grant-in-Aid No. 15390411 to Drs Tanaka and Wada for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. Part of this work was also supported by The Japanese Foundation for Multidisciplinary Treatment of Cancer.
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References
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- Lanza LA, Natarajan G, Roth JA, Putnam Jr JB. Ann Thorac Surg 1992;54:244-247.[Abstract]
- Staren ED, Salerno C, Rongione A, Witt TR, Faber LP. Pulmonary resection for metastatic breast cancer Arch Surg 1992;127:1232-1234.[Abstract]
- Friedel G, Pastorino U, Ginsberg RJ, et al. Results of lung metastectomy from breast cancer: prognostic criteria on the basis of 467 cases of the international registry of lung metastases Eur J Cardiothorac Surg 2002;22:335-344.[Abstract/Free Full Text]
- Carlsson J, Nordgren H, Sjostrom J, et al. HER2 expression in breast cancer primary tumours and corresponding metastasesOriginal data and literature review. Br J Cancer 2004;90:2344-2348.[Medline]
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- Patanaphan V, Salzar OM, Risso R. Breast cancer: metastatic patterns and their prognosis South Med J 1988;81s:1109-1112.
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Abstract
Introduction
