Pulmonary Nodule in Patients with Breast Cancer

Abstract & commentary

By William B. Ershler, MD

Synopsis: Of 34 breast cancer patients with pulmonary nodules and no other evidence for metastatic disease, progression occurred in only 3 (of the 26) whose nodules were < 1 cm in diameter, compared with all 8 in whom the nodules were > 1 cm. The data suggest that sub-centimeter pulmonary nodules in those without apparent metastatic disease elsewhere are unlikely themselves to represent metastases and such patients should not be excluded from curative-intent adjuvant therapy protocols.

Source: Lee B, et al. The clinical significance of radiologically detected silent pulmonary nodules in early breast cancer. Ann Oncol. 2008;19:2001-2006.

Clinical oncologists utilize neoadjuvant chemotherapy before surgery or adjuvant chemotherapy, radiotherapy, or hormonal therapy after surgery to reduce the risk of recurrence and improve overall survival. For patients who present with evidence for systemic metastases, treatment strategies are often administered with less intensity and with palliative intention. Thus, the pre-treatment assessment of tumor stage remains critical. Computerized tomography (CT) is commonly employed and, not infrequently, pulmonary nodules are visualized without the presence of other metastatic lesions. To the extent that these represent a process other than metastatic breast cancer, such patients would be more aptly approached with "curative intent" adjuvant treatments. Even in today's environment of aggressive interventional techniques, many of these nodules are sufficiently small, or are centrally located and not amenable to needle biopsy. Thus, Lee et al from the United Kingdom performed a retrospective review examining clinical outcomes in patients with early breast cancer found to have radiologically detected pulmonary nodules, with no other evidence for metastatic disease.

For this, medical records of breast cancer patients who underwent thoracic CT scans at a single institution (Charring Cross Hospital, London) between the years 2002 and 2008 were analyzed. Those with obvious metastatic disease were excluded. Patients were identified using the radiology database by searching for the terms: "suspicious lung metastases" and "indeterminate nodules."

Of the 1,578 new patients assessed from 2002 to 2008, there were 802 staging CT scans. Sixty-five cases (8.1%) were identified with pulmonary, but approximately half were excluded because the primary findings could be attributed to infection (n = 3), effusion (n = 6), sarcoma of the breast (n = 3), other metastatic disease (n = 5), or were normal (n = 14). The remaining 34 cases were considered "indeterminate" and were subdivided on the basis of size and number. At a median follow-up of 18 months, there were no changes in lesion size in six of the seven (86%) patients, with a solitary nodule < 1 cm in 17 of 19 (89%) patients with multiple sub-centimeter nodules. In contrast, in 100% of cases with pulmonary nodules > 1 cm, the nodules had progressed at follow-up (p = 0.004).

Commentary

There remains no consensus on the management of 'indeterminate' pulmonary nodules. In earlier studies in which such nodules were detected by chest X-ray or early CT scan, many were found to be cancerous. For example, a report published in 1984 examined the nature of solitary pulmonary nodules in breast cancer patients, and found that 95% harbored malignancy (either metastatic breast cancer in 43% or lung cancer in 52%).1 In another study of 64 breast cancer patients with pulmonary nodules that were biopsied, 10 were found to have metastatic disease.2 In that study, the size of the nodules was not described, but the fact that biopsies were accomplished suggests they were larger than in the current report.

CT-discovered small (< 1 cm) pulmonary nodules have been the focus of interest in those studying the feasibility and efficacy of lung cancer screening. Recommendations for management of non-calcified nodules of < 0.5 cm include annual CT follow-up. For lesions between the sizes of 0.6 and 0.8 cm, scanning should occur at six-month intervals the first year, then at two years, whereas for those with lesions > 0.8 cm, they should be followed-up by contrast-enhanced dynamic CT scanning at 3, 9, and 24 months.3 PET scanning is recognized to be of diagnostic value in solitary pulmonary nodules of > 1 cm in which the standardized uptake value (SUV) of > 3 has proven to be both a sensitive and specific indicator of cancer.4 However, if a nodule is < 1 cm, sensitivity and specificity decline.5

Thus, the current report suggests breast cancer cases with subcentimeter pulmonary lesions and no evidence of metastases elsewhere are unlikely to represent metastatic disease. This, however, is based not upon histological evidence but on a lack of change over a median follow-up of 18 months during which most patients received some sort of anti-breast cancer therapy. Nonetheless, it is hard to argue with Lee et al's conclusion, based upon their findings, that such patients should be treated with curative intent, and that their entry into clinical trials should not be excluded.

References

1. Casey JJ, et al. The solitary pulmonary nodule in the patient with breast cancer. Surgery. 1984;96:801-805.

2. Khokhar S, et al. Significance of non-calcified pulmonary nodules in patients with extrapulmonary cancers. Thorax. 2006;61:331-336.

3. Henschke CI, et al. CT screening for lung cancer: suspiciousness of nodules according to size on baseline scans. Radiology. 2004;231:164-168.

4. Gould MK, et al. Accuracy of positron emission tomo-graphy for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA. 2001;285:914-924.

5. Goldsmith SJ, Kostakoglu L. Nuclear medicine imaging of lung cancer. Radiol Clin North Am. 2000;38: 511-524.