LETTER TO THE EDITOR
Intensive Postoperative Surveillance using Chest CT and Bone Scan in Patients with Locally Advanced Breast Cancer To the Editor: Breast cancer, the most commonly occurring malignancy in American women, accounts for 29% of all cancer (1). Locally advanced breast cancer (LABC), which includes all patients with stage III disease, poses a significant clinical challenge due to its high prevalence of early disease recurrence. Current guidelines recommend regular physical examinations and mammography for postoperative surveillance for the patients (2,3). Bone scan, ultrasound examination, or advanced imaging modalities (CT, MRI, PET/CT) are not recommended in asymptomatic patients since there has been no evidence of survival benefit. However, the imaging techniques to detect minute lesions and therapeutic options have shown remarkable advancement. Therefore, early detection of recurrence in patients with LABC may have a beneficial impact on survival. We here to evaluate the recurrence pattern and survival outcomes in LABC patients who underwent intensive postoperative surveillance using chest CT and bone scan. We retrospectively investigated 195 consecutive patients with LABC who received curative surgery at Gachon University Gil Hospital (Incheon, Korea) between January 2005 and November 2010. Postoperative surveillance in LABC patients consisted of physical examination, chest CT/bone scan every 6 months for the first 3 years and annually thereafter, and annual mammography. Recurrence detected solely by chest CT or bone scan without any symptoms or abnormal findings on physical/mammographic examination was regarded as detected by intensive surveillance. If patients had any suspicious recurrent symptoms, abnormal findings on physical examinations/mammography Address correspondence and reprint requests to: Heung Kyu Park, MD, Department of Surgery, Gachon University Gil Hospital, 1198, Guwol-dong, Namdong-gu, Incheon 405-760, Korea, or e-mail: [email protected] 1 These authors contributed equally to this article. DOI: 10.1111/tbj.12326 © 2014 Wiley Periodicals, Inc., 1075-122X/14 The Breast Journal, Volume 20 Number 5, 2014 558–559
at the routine follow-up date, or unscheduled visit due to these reasons, the recurrence was regarded as detected by minimal surveillance, even though the concurrent chest CT and bone scan confirmed the recurrence. We verified the diagnostic performance of chest CT for detection of recurrence within the thoracoabdominal area. When suspicious lesions detected on the chest CT, the histologic confirmation was performed whenever possible, or additional imaging studies (PET/CT, MRI) or short-term follow-up CT examinations were recommended. Recurrence-free survival (RFS) was calculated from the date of surgery to the date of recurrence, or death from any cause. After a median follow-up of 50.7 months (range 4.6–96.8), 44 (23%) patients had recurrence. Fiveyear RFS rate was 74% and median time to recurrence was 24.7 months (range 4.7–60.3). There was no significant difference in baseline characteristics between patients with and without recurrence, except for histologic subtypes and operation; recurrence was frequent in patients with triple negative breast cancer (7/19, 37%), compared to those with other types of breast cancer (37/176, 21%; p = 0.15) and in patients who underwent mastectomy, rather than breast conserving surgery (35/128, 27% versus 9/66, 14%, p = 0.03). Loco-regional recurrence occurred in seven patients, and distant metastasis was found in 39 patients (bone metastases [n = 23], pulmonary metastases [n = 17], hepatic metastases [n = 7], and others [n = 4]; Table 1). Thirty-eight patients (86%) had recurrence on multiple sites at the time of the first recurrence. Six patients with a solitary recurrence (five with loco-regional recurrence, and one with solitary pulmonary metastasis) underwent radiotherapy and metastasectomy for curative intent. For patients with recurrence, the median survival after the diagnosis of recurrence was 50.2 months (95% CI 16.1–84.3). A total of 32 (73%) patients was detected by intensive surveillance as follows; loco-regional recurrence (n = 5), bone/pulmonary/hepatic metastases (n = 14, 13, 4, respectively). All recurrences in patients with
Letter to the Editor • 559
Table 1. Distribution of Recurrence Recurrence Distant Bone, thoracic Bone, extrathoracic Lung, pleura, mediastinal lymph node Liver Others Loco-regional
Total (n = 44) 39 19 4 17 7 5 7
By intensive surveillance (n = 32) 28 13 1 13
(72%) (68%) (25%) (77%)
4 (57%) 0 (0%) 5 (71%)
triple negative breast cancer (n = 7) was detected by intensive surveillance. Chest CT was able to detect all of the recurrent lesions in the thoraco-abdominal area, except for three patients who had intrathoracic bone metastases, which were detected by concurrent bone scan. There were three cases of false-positive recurrent lesions detected by chest CT (hematoma in the mastectomy bed [n = 1], hepatic hemangioma [n = 1], and reactive mediastinal lymph node [n = 1]). On a per-patient basis, the overall sensitivity, specificity, and accuracy of chest CT were 92.5%, 98.0%, and 97.0%, respectively. Several recent studies have reported that local therapy for loco-regional recurrence and solitary metastatic lesions yielded unexpectedly promising results (4,5). In addition, an increasing number of randomized clinical trials have documented survival benefit in metastatic breast cancers with newer chemotherapeutic agents (6,7). These results may support early detection of recurrence has beneficial effect on survival. The postoperative surveillance should be based on knowledge of recurrence patterns and the diagnostic performance of the examinations; patients with positive regional lymph nodes have a high recurrence rate (up to 75%), and skeleton is the most common site of the first recurrence, followed by loco-regional failure, pulmonary, and hepatic metastases (2). In addition, triple negative breast cancer has shorter RFS and a tendency toward visceral metastases, compared to other types of breast cancer (8). Based on these findings, we have performed intensive surveillance in LABC patients; Chest CT, and bone scan enabled early detection of asymptomatic recurrence in a significant number of the patients. The diagnostic performance of chest CT was excellent and three cases of false-negative intrathoracic bone metastases on chest CT could be detected by concurrent bone scan. Our
study also demonstrated a slightly higher recurrence rate in triple negative breast cancer and all recurrences in triple negative breast cancers were detected by intensive surveillance, which implies that this patient group may have more benefit from intensive surveillance. Further investigations regarding the survival benefit would be needed. Young Saing Kim, MD*,1 Eun Young Kim, MD†,1 Heung Kyu Park, MD‡ Hee Kyung Ahn, MD* Junshik Hong, MD* Eun Kyung Cho, MD* Hye-Young Choi, MD† *Division of Hematology and Oncology Gachon University Gil Hospital Incheon Korea; † Department of Radiology Gachon University Gil Hospital Incheon Korea; and ‡Department of Breast Surgery Gachon University Gil Hospital Incheon Korea REFERENCES 1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11–30. 2. Khatcheressian JL, Wolff AC, Smith TJ, et al. American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 2006;24:5091–7. 3. NCCN. NCCN Clinical practice guidelines in oncology (NCCN Guidelines) version 3. 2013. Available at: http://www.nccn. org/professionals/physician_gls/pdf/breast.pdf (accessed July 30, 2013). 4. Sofi AA, Mohamed I, Koumaya M, Kamaluddin Z. Local therapy in metastatic breast cancer is associated with improved survival. Am J Ther 2013;20:487–92. 5. Noguchi M, Nakano Y, Ohno Y, Kosaka T. Local therapy and survival in breast cancer with distant metastases. J Surg Oncol 2012;105:104–10. 6. Johnston SR. The role of chemotherapy and targeted agents in patients with metastatic breast cancer. Eur J Cancer 2011;47(Suppl 3):S38–47. 7. Perez EA, Spano JP. Current and emerging targeted therapies for metastatic breast cancer. Cancer 2012;118:3014–25. 8. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007;13:4429–34.
Intensive Postoperative Surveillance using Chest CT and Bone Scan in Patients with Locally Advanced Breast Cancer To the Editor: Breast cancer, the most commonly occurring malignancy in American women, accounts for 29% of all cancer (1). Locally advanced breast cancer (LABC), which includes all patients with stage III disease, poses a significant clinical challenge due to its high prevalence of early disease recurrence. Current guidelines recommend regular physical examinations and mammography for postoperative surveillance for the patients (2,3). Bone scan, ultrasound examination, or advanced imaging modalities (CT, MRI, PET/CT) are not recommended in asymptomatic patients since there has been no evidence of survival benefit. However, the imaging techniques to detect minute lesions and therapeutic options have shown remarkable advancement. Therefore, early detection of recurrence in patients with LABC may have a beneficial impact on survival. We here to evaluate the recurrence pattern and survival outcomes in LABC patients who underwent intensive postoperative surveillance using chest CT and bone scan. We retrospectively investigated 195 consecutive patients with LABC who received curative surgery at Gachon University Gil Hospital (Incheon, Korea) between January 2005 and November 2010. Postoperative surveillance in LABC patients consisted of physical examination, chest CT/bone scan every 6 months for the first 3 years and annually thereafter, and annual mammography. Recurrence detected solely by chest CT or bone scan without any symptoms or abnormal findings on physical/mammographic examination was regarded as detected by intensive surveillance. If patients had any suspicious recurrent symptoms, abnormal findings on physical examinations/mammography Address correspondence and reprint requests to: Heung Kyu Park, MD, Department of Surgery, Gachon University Gil Hospital, 1198, Guwol-dong, Namdong-gu, Incheon 405-760, Korea, or e-mail: [email protected] 1 These authors contributed equally to this article. DOI: 10.1111/tbj.12326 © 2014 Wiley Periodicals, Inc., 1075-122X/14 The Breast Journal, Volume 20 Number 5, 2014 558–559
at the routine follow-up date, or unscheduled visit due to these reasons, the recurrence was regarded as detected by minimal surveillance, even though the concurrent chest CT and bone scan confirmed the recurrence. We verified the diagnostic performance of chest CT for detection of recurrence within the thoracoabdominal area. When suspicious lesions detected on the chest CT, the histologic confirmation was performed whenever possible, or additional imaging studies (PET/CT, MRI) or short-term follow-up CT examinations were recommended. Recurrence-free survival (RFS) was calculated from the date of surgery to the date of recurrence, or death from any cause. After a median follow-up of 50.7 months (range 4.6–96.8), 44 (23%) patients had recurrence. Fiveyear RFS rate was 74% and median time to recurrence was 24.7 months (range 4.7–60.3). There was no significant difference in baseline characteristics between patients with and without recurrence, except for histologic subtypes and operation; recurrence was frequent in patients with triple negative breast cancer (7/19, 37%), compared to those with other types of breast cancer (37/176, 21%; p = 0.15) and in patients who underwent mastectomy, rather than breast conserving surgery (35/128, 27% versus 9/66, 14%, p = 0.03). Loco-regional recurrence occurred in seven patients, and distant metastasis was found in 39 patients (bone metastases [n = 23], pulmonary metastases [n = 17], hepatic metastases [n = 7], and others [n = 4]; Table 1). Thirty-eight patients (86%) had recurrence on multiple sites at the time of the first recurrence. Six patients with a solitary recurrence (five with loco-regional recurrence, and one with solitary pulmonary metastasis) underwent radiotherapy and metastasectomy for curative intent. For patients with recurrence, the median survival after the diagnosis of recurrence was 50.2 months (95% CI 16.1–84.3). A total of 32 (73%) patients was detected by intensive surveillance as follows; loco-regional recurrence (n = 5), bone/pulmonary/hepatic metastases (n = 14, 13, 4, respectively). All recurrences in patients with
Letter to the Editor • 559
Table 1. Distribution of Recurrence Recurrence Distant Bone, thoracic Bone, extrathoracic Lung, pleura, mediastinal lymph node Liver Others Loco-regional
Total (n = 44) 39 19 4 17 7 5 7
By intensive surveillance (n = 32) 28 13 1 13
(72%) (68%) (25%) (77%)
4 (57%) 0 (0%) 5 (71%)
triple negative breast cancer (n = 7) was detected by intensive surveillance. Chest CT was able to detect all of the recurrent lesions in the thoraco-abdominal area, except for three patients who had intrathoracic bone metastases, which were detected by concurrent bone scan. There were three cases of false-positive recurrent lesions detected by chest CT (hematoma in the mastectomy bed [n = 1], hepatic hemangioma [n = 1], and reactive mediastinal lymph node [n = 1]). On a per-patient basis, the overall sensitivity, specificity, and accuracy of chest CT were 92.5%, 98.0%, and 97.0%, respectively. Several recent studies have reported that local therapy for loco-regional recurrence and solitary metastatic lesions yielded unexpectedly promising results (4,5). In addition, an increasing number of randomized clinical trials have documented survival benefit in metastatic breast cancers with newer chemotherapeutic agents (6,7). These results may support early detection of recurrence has beneficial effect on survival. The postoperative surveillance should be based on knowledge of recurrence patterns and the diagnostic performance of the examinations; patients with positive regional lymph nodes have a high recurrence rate (up to 75%), and skeleton is the most common site of the first recurrence, followed by loco-regional failure, pulmonary, and hepatic metastases (2). In addition, triple negative breast cancer has shorter RFS and a tendency toward visceral metastases, compared to other types of breast cancer (8). Based on these findings, we have performed intensive surveillance in LABC patients; Chest CT, and bone scan enabled early detection of asymptomatic recurrence in a significant number of the patients. The diagnostic performance of chest CT was excellent and three cases of false-negative intrathoracic bone metastases on chest CT could be detected by concurrent bone scan. Our
study also demonstrated a slightly higher recurrence rate in triple negative breast cancer and all recurrences in triple negative breast cancers were detected by intensive surveillance, which implies that this patient group may have more benefit from intensive surveillance. Further investigations regarding the survival benefit would be needed. Young Saing Kim, MD*,1 Eun Young Kim, MD†,1 Heung Kyu Park, MD‡ Hee Kyung Ahn, MD* Junshik Hong, MD* Eun Kyung Cho, MD* Hye-Young Choi, MD† *Division of Hematology and Oncology Gachon University Gil Hospital Incheon Korea; † Department of Radiology Gachon University Gil Hospital Incheon Korea; and ‡Department of Breast Surgery Gachon University Gil Hospital Incheon Korea REFERENCES 1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11–30. 2. Khatcheressian JL, Wolff AC, Smith TJ, et al. American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 2006;24:5091–7. 3. NCCN. NCCN Clinical practice guidelines in oncology (NCCN Guidelines) version 3. 2013. Available at: http://www.nccn. org/professionals/physician_gls/pdf/breast.pdf (accessed July 30, 2013). 4. Sofi AA, Mohamed I, Koumaya M, Kamaluddin Z. Local therapy in metastatic breast cancer is associated with improved survival. Am J Ther 2013;20:487–92. 5. Noguchi M, Nakano Y, Ohno Y, Kosaka T. Local therapy and survival in breast cancer with distant metastases. J Surg Oncol 2012;105:104–10. 6. Johnston SR. The role of chemotherapy and targeted agents in patients with metastatic breast cancer. Eur J Cancer 2011;47(Suppl 3):S38–47. 7. Perez EA, Spano JP. Current and emerging targeted therapies for metastatic breast cancer. Cancer 2012;118:3014–25. 8. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007;13:4429–34.
