Surgical Resection and Outcome of Synchronous and Metachronous Primary Lung Cancer in Breast Cancer Patients

Discussion

In this study, we reported the frequency of synchronous and metachronous surgically-resected lung cancer and breast cancer (total, 14 patients; 1.3% with breast cancer and 2.1% with lung cancer).

In Europe, several large cancer registry-based studies have reported the risk of lung cancer in breast cancer patients (11-14); however, few similar studies have been conducted in Asia (3, 4). In particular, no study has reported both incidence and surgical outcome of second primary lung cancer in women with breast cancer. Therefore, we described a series of female patients with breast cancer undergoing surgical resection for synchronous or metachronous lung cancer in a single institution. Evans et al. (11) summarized five cancer registry-reported studies of female breast cancer patients and showed an increased risk for lung cancer after breast cancer (relative risk, 1.4-1.7), although the reasons for the association are unknown. In contrast, Kwast et al. (14) suggested that chemotherapy for breast cancer was associated with a decreased risk of second primary cancers including lung cancer, although radiotherapy and endocrine therapy were not associated with a decreased risk. Also, some studies suggest that radiotherapy for breast cancer is a risk factor for developing a second primary lung cancer (15, 16). In our series, all eight (100%) metachronous patients received adjuvant therapies including chemotherapy, radiotherapy, hormonal therapy, anti-HER2 therapy, or a combination of these modalities. In addition, 4/8 (50%) metachronous patients with postoperative recurrence of breast cancer in our study received chemotherapy, hormonal therapy, or anti-HER2 therapy. However, the sample size in our series was too small to detect differences between these therapies and the risk of lung cancer. According to the histological type, 16 lung cancer lesions in 14 patients (94.1%) were adenocarcinomas and one (5.9%) was squamous cell carcinoma, which is similar to a previous report stating that the most common pathological lung cancer subtype (27/38 patients) was adenocarcinoma in breast cancer patients (17).

In our five synchronous cases, all patients had both lung and breast cancers detected at the same time and underwent concurrent surgery for both cancers. Breast cancer surgery consisted of partial or total mastectomy with/without axillary lymph node dissection. Lung cancer surgery consisted of pulmonary lobectomy with lymph node dissection. There were no serious postoperative complications, and the perioperative course was uneventful in all patients undergoing concomitant surgery. Therefore, concomitant surgical resection of both lung cancer and breast cancer may be feasible and safe.

At the time of this report, as of the most recent follow-up, all 14 patients were alive. In our series, 4/14 (28.6%) patients had recurrent breast cancer and 1/14 (7.1%) patients had recurrent lung cancer. In synchronous cases, no patients had postoperative breast cancer recurrence, although 1/5 (20%) patients had postoperative recurrence of lung cancer. In metachronous cases, 4/8 (50%) patients had postoperative breast cancer, although none had postoperative recurrence of lung cancer. Kim et al. (4) studied metachronous primary cancers after treatment for breast cancer, and reported that lung cancer was the fifth leading second primary organ cancer detected with breast cancer (0.19%, 5/2657). The study also showed that the mean time to diagnosis of a second primary lung cancer was 89.1±45.9 months. Four of five second primary lung cancer patients were diagnosed 5 years after diagnosis of breast cancer. However, the 5-year survival rate after diagnosis of the second primary lung cancer was 22.2%, although the lung cancer stages were not shown. In a review of lung cancer risk and time elapsed since breast cancer treatment (15), several lung cancers were coincidentally found within 5 years from breast cancer treatment, with many studies showing that the risk of lung cancer after breast cancer treatment increases with time. In the present study, all metachronous lung cancers tended to be detected within 3 years after surgery for breast cancer, and the pathological stage for all lung cancer was early. The reason for the early detection may be the result of routine CT screening after surgery for breast cancer. As a result, careful follow-up for postoperative breast cancer may contribute to the early detection of lung cancer.

Finally, based on the imaging features of preoperative CT, we presented the radiological features of lung cancer in breast cancer. It is important to distinguish primary lung cancer and metastatic lung tumor from breast cancer. It is well known that pure-GGO pathological findings highly suggest that the tumor is primary lung cancer. A previous study demonstrated that no metastatic lung tumor from breast cancer was identified as pure-GGO (18). Our series showed that pure-GGO was seen in approximately 44% of primary lung cancer cases with the remaining 56% of lung cancers classed as part- or pure-solid, similar to a previous study showing that most primary lung cancers demonstrated part- or pure-solid features (18). Therefore, it may be difficult to diagnose exactly whether a tumor is primary or metastatic lung cancer based solely on preoperative CT imaging features. Some investigations of mammary carcinogenesis or metastasis using animal models have been demonstrated (19, 20). In addition, several studies that genotype/phenotype can be used for novel diagnostic markers have been reported, which may provide the best strategies and targets in early detection and prediction the susceptibility and outcomes in breast cancer patients (21-24). Thus, further basic researches are also necessary.

In conclusion, we report a series of patients with synchronous or metachronous lung cancer and breast cancer in a single institution. Concomitant surgery for synchronous lung and breast cancer was safe. In metachronous cases, lung cancer tended to be detected within 3 years after surgery for breast cancer, and the pathological stage of all lung cancers was early. Careful follow-up for postoperative breast cancer may contribute to the detection of early-stage lung cancer.