| Japanese Journal of Clinical Oncology | Pages |
Detection of the First Recurrence During Intensive Follow-up of Breast Cancer Patients
Introduction
Patients and Methods
Results
Discussion
References
Detection of the First Recurrence During Intensive Follow-up of Breast Cancer Patients
Background: Breast cancer patients are routinely followed after primary treatment. Many intensive diagnostic methods (tumor markers, chest X-ray, mammography, liver echography, bone scans) are performed periodically. However, it remains to be determined how often attempts should be made to detect the first recurrence of breast cancer by these methods.
Methods: To evaluate the effect of imaging diagnosis and tumor markers, we analyzed methods of detection of first recurrence sites during intensive follow-up of breast cancer patients.
Results: Of 550 female patients who had been surgically treated between July 1992 and December 1996, 65 recurrent cases had been diagnosed as of December 1997. Thirty cases (46%) had been found as a result of symptoms related to the site of recurrence and 14 cases (22%) were detected by physical examination. In the remaining 21 cases (32%), detection was by other methods: in eight cases by imaging diagnosis, in three cases based on abnormal tumor markers and in 10 cases by imaging diagnosis and abnormal tumor markers. Twenty-nine cases (45%) followed every 1-3 months had presented with symptoms at routine or interval appointments. There was a significant difference between first recurrence sites (loco-regional, bone and viscera) and the methods of detection (symptoms, physical examination and other diagnostic methods) (P < 0.0001). However, no statistical difference in overall survival after operation was observed between the 30 cases found as a result of symptoms and the 35 cases detected by physical examination or other diagnostic methods.
Conclusions: Taken together with ASCO's surveillance guidelines (J Clin Oncol 1997;15:2149-56), intensive follow-up of breast cancer patients should be limited to high-risk breast cancer patients, especially those who enter randomized clinical trials. A careful history and physical examination are in practice indicated every 3-6 months for 3 years and then every 6 months for the following 2 years.
INTRODUCTION
Surgical, medical and radiological treatments can prolong the disease-free survival of operable breast cancer patients (1). Once breast cancer has recurred, it is generally considered incurable. Breast cancer surveillance is necessary to detect early recurrence. One reason is that the sooner any recurrence is detected, the more effectively medical or other treatment may be administered. However, there has been no clear evidence whether intensive follow-up of breast cancer patients results in survival benefit. The optimum cost-benefit relationship of follow-up of breast cancer also remains to be determined (2,3). The surveillance guidelines recommended by the American Society of Clinical Oncology (ASCO) in 1997 (4) caused us to reflect on the usual follow-up methods. ASCO's expert panel recommended monthly breast self-examination, annual mammography, a careful history and physical examination every 3-6 months for 3 years, then every 6-12 months for the following 2 years. The value of intensive diagnostic methods (tumor markers, chest X-ray, liver echography and bone scans) could not be confirmed. To evaluate the effect of imaging diagnosis and tumor markers, we retrospectively analyzed methods of detection of first recurrence sites during intensive follow-up of breast cancer patients.
Table 1.
| Characteristics | No. of cases | (%) |
| Recurrent cases | 65 | (100) |
| Age (years) | ||
| <35 | 5 | (8) |
| 36-50 | 32 | (49) |
| 51+ | 28 | (43) |
| Menopausal status | ||
| Premenopause | 37 | (57) |
| Postmenopause | 28 | (43) |
| Stage | ||
| I | 8 | (12) |
| IIA, IIB | 37 | (57) |
| IIIA, IIIB | 20 | (31) |
| Histological subtype | ||
| Invasive ductal carcinoma | 60 | (92) |
| Invasive lobular carcinoma | 2 | (3) |
| Others | 3 | (5) |
| Nodal metastases | ||
| 0 | 15 | (23) |
| 1-9 | 29 | (45) |
| [ge]10 | 21 | (32) |
| Surgical procedure | ||
| Total mastectomy | 59 | (91) |
| Partial mastectomy | 6 | (9) |
| Adjuvant therapy | ||
| No therapy | 6 | (9) |
| Hormonal therapy | 5 | (8) |
| Chemotherapy | 23 | (35) |
| Chemohormonal therapy | 31 | (48) |
| Radiation therapy | 2 | (3) |
| Disease-free interval (days) | ||
| <365 | 24 | (37) |
| 366-730 | 20 | (31) |
| 731+ | 21 | (32) |
| First site detected | ||
| Local lesion (skin, ipsilateral axilla and breast) | 16 | (25) |
| Regional lymph node | 12 | (18) |
| Loco-regional lesions | 1 | (2) |
| Bone | 14 | (22) |
| Lung | 8 | (12) |
| Liver | 5 | (8) |
| Brain | 2 | (3) |
| Multiple organs | 7 | (11) |
PATIENTS AND METHODS
Total mastectomy or partial mastectomy with axillary dissection was performed in 550 cases of stages 0-IIIB female breast cancer between July 1992 and December 1996 in this hospital, including 17 cases of bilateral breast cancer and 11 cases of double primary cancer. Adjuvant chemotherapy and/or hormonal therapy were performed in 358 of the 550 cases (65%) and adjuvant radiation therapy in 61 cases (11%). Regardless of whether adjuvant therapy was performed or not, most patients were scheduled to be followed up at routine appointments every 1-4 months for 2 years after operation and then every 4-6 months for the following 3 years. Patients' complaints were recorded: pain, fatigue, nausea, dyspnea, cough, hoarseness, dizziness, abdominal discomfort, and also whether they had noticed a mass in the chest, breast, axillary or cervical regions. Periodic examinations consisted of a standard history, physical examination, complete blood cell count and blood chemistry studies, including tumor markers (CEA, CA15-3) every 1-4 months, chest X-ray every 6 months, mammogram every 6-24 months and liver echography and bone scans every year. No gynecological examination was usually performed. If any signs or symptoms of recurrence developed, more intensive imaging diagnosis, including computed tomography and magnetic resonance imaging, was carried out. In addition, loco-regional recurrent lesions were confirmed by aspiration biopsy cytology or incisional biopsy. Statistical significance was determined by using the chi-squared test. The overall survival curve after operation was constructed using the Kaplan-Meier method and compared using the log rank test.
RESULTS
As of December 1997, 65 cases had been diagnosed as having first recurrence in this Division. The characteristics of the recurrent cases are shown in Table 1. The range and median of follow-up times after operation and first recurrence in these cases were 196-1806 and 878 days and 15-1151 and 281 days. About one third of recurrent cases were in more advanced clinical stages and had 10 or more nodal metastases. Most patients had received adjuvant chemotherapy and/or hormonal therapy. The first sites detected in the table means lesions diagnosed as recurrence on the basis of symptoms or after routine surveillance without symptoms. The 16 cases of local lesions consisted of 13 cases of chest wall recurrence, one case of axillary lymph node and two cases of conserved breast recurrence. Table 2 shows the correlation between first recurrence sites and methods of detection. Thirty cases (46%) had been found as a result of symptoms at the recurrence sites and 14 cases (22%) had been detected by physical examination. In the remaining 21 cases (32%), detection was by other methods: in eight cases by imaging diagnosis, in three cases based on abnormal tumor markers and in 10 cases by imaging diagnosis and abnormal tumor markers. There was a significant difference between first recurrence sites (loco-regional, bone and viscera) and methods of detection (symptoms, physical examination and other diagnostic methods) (P < 0.0001). Imaging diagnosis and tumor markers were more effective in detecting lung, liver and bone metastases than physical examination. However, 14 cases (22%) of distant metastases were diagnosed as a result of symptoms related to the site of recurrence. In the present study, only two patients had conserved breast recurrence with symptoms. Routine mammograms were performed, but no sign was detected in these cases. The follow-up interval and the clinical features of patients at the time of first recurrence were also analyzed (Table 3). Twenty-nine patients with recurrence (45%) who had been followed every 1-3 months had presented with symptoms. Eleven patients with symptoms (17%) had come to our hospital for an interval appointment. No signs of recurrence could be found in these cases even at short intervals. We compared the clinicopathological features and survival curve of the 30 cases with symptoms and the 35 cases without symptoms detected by physical examination, imaging diagnosis or tumor markers (Table 4). There were no significant differences in age, clinical stage, nodal metastases, adjuvant therapy, disease-free interval or final recurrence sites after systemic surveillance between the two groups. There was no statistical difference between them in overall survival after operation (P = 0.48 for the log rank test) (Fig. 1). The range and median survival times after operation and first recurrence were 196-1711 and 792 days and 37-1128 and 231 days in the 30 cases found as a result of symptoms and 218-1806 and 765 days and 15-1151 and 343 days in the 35 cases detected by physical examination or other diagnostic methods.
Figure 1. Survival curve after operation. There was no statistical difference in overall survival after operation between the 30 cases found as a result of symptoms (dotted line) and the 35 cases detected by physical examination or other diagnostic methods (solid line).
Table 2.
| Method | Loco-regional | Bone | Lung | Liver | Brain | Multiple |
| Symptoms (30) | 16 | 6 | 1 | 1 | 2 | 4 |
| Physical examination (14) | 13 | 1 | 0 | 0 | 0 | 0 |
| Imaging diagnosis (8) | 0 | 2 | 6 | 0 | 0 | 0 |
| Tumor markers (3) | 0 | 1 | 0 | 1 | 0 | 1 |
| Imaging diagnosis and tumor markers (10) | 0 | 4 | 1 | 3 | 0 | 2 |
| Total (65) | 29 | 14 | 8 | 5 | 2 | 7 |
Table 3.
| Follow-up interval (months) | Routine appointment | Interval appointment | ||||
| Symptoms | No symptoms | Symptoms | No symptoms | |||
| PE | ID/TM | PE | ID/TM | |||
| 1 | 3 | 2 | 3 | 5 | 0 | 0 |
| 2 | 8 | 4 | 5 | 1 | 0 | 0 |
| 3 | 7 | 5 | 11 | 5 | 0 | 0 |
| 4-6 | 1 | 3 | 2 | 0 | 0 | 0 |
| Total | 19 | 14 | 21 | 11 | 0 | 0 |
Table 4.
| Characteristics | No. of recurrent cases | P value([chi]2 test) | |
| Symptoms | No symptoms | ||
| Age (years) | |||
| <35 | 2 | 3 | 0.959 |
| 36-50 | 15 | 17 | |
| 51+ | 13 | 15 | |
| Stage | |||
| I | 5 | 3 | 0.607 |
| IIA, IIB | 16 | 21 | |
| IIIA, IIIB | 9 | 11 | |
| Nodal metastases | |||
| 0 | 6 | 9 | 0.869 |
| 1-9 | 14 | 15 | |
| [ge]10 | 10 | 11 | |
| Adjuvant therapy | |||
| No therapy | 4 | 2 | 0.432 |
| Hormonal therapy | 3 | 2 | |
| Chemo(hormonal) therapy | 23 | 31 | |
| Disease-free interval (days) | |||
| <365 | 13 | 11 | 0.554 |
| 366-730 | 9 | 11 | |
| 731+ | 8 | 13 | |
| Final recurrence sites after systemic surveillance | |||
| Loco-regional | 12 | 12 | 0.434 |
| Bone or lung | 9 | 16 | |
| Liver or brain* | 3 | 4 | |
| Multiple organs* | 6 | 3 | |
DISCUSSION
This study is based on a non-randomized, retrospective analysis. The sample size is small and the follow-up period is short. There are many biases in patient characteristics, adjuvant therapy, follow-up interval and surveillance tests. In most cases, physical and diagnostic examinations were performed at routine appointments. Nevertheless, 46% of the patients with recurrences presented with symptoms and 54% of them had been detected by physical examination, imaging diagnosis or abnormal tumor markers. Several other investigators have also reported negative results of systemic surveillance of breast cancer patients (5-8). Symptomatic first recurrences ranged between 77 and 91% in their reports. In contrast, asymptomatic first recurrences detected by physical examination or other diagnostic methods ranged between 9 and 46%.
Distant organ metastases may be more frequently found by chest X-ray, bone scans and other imaging diagnosis (9). Tumor markers may be helpful in evaluating the extent of metastatic breast cancer (10). However, survival benefit derived from intensive follow-up has not been confirmed. In the present cases, overall survivals in the symptomatic and asymptomatic recurrent groups were similar. One explanation may be that many cases had early recurrence within 2 years and early recurrence resulted in more rapid progression. In a randomized trial in Italy, the 5-year overall survival in the intensive follow-up group could not be prolonged compared with the control follow-up group (9). Routine examinations including chest X-ray, bone scans, liver echography, annual mammography and tumor markers failed to result in improvements in the outcome of patients with recurrent breast cancer.
Most patients are usually informed of prognostic factors in resected specimens, such as histological grade, number of nodal metastases and hormonal receptor status. They are also informed of the risk of breast cancer recurrence and whether they need to undergo adjuvant therapy. Many patients, especially those with high-risk breast cancer, may prefer more intensive follow-up for their emotional well-being and for high quality of life. However, a randomized trial demonstrated that the intensive follow-up did not affect health-related quality of life in breast cancer patients, i.e. overall health and quality of life perception, emotional well-being, body image, satisfaction with care, etc. (11).
Taken together with ASCO's surveillance guidelines, systemic surveillance of breast cancer is not always necessary for all breast cancer patients. A careful history and physical examination are in practice recommended every 3-6 months for 3 years and then every 6 months for the following 2 years. At least, intensive follow-up should be limited to high-risk breast cancer patients with positive nodes, high nuclear grade or high histological grade and especially those who enter randomized clinical trials.
References
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Last modification: 16 Oct 1998
Copyright©Japanese Journal of Clinical Oncology, 1998.
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