Japanese Journal of Clinical Oncology 31:259-262 (2001)
© 2001 Foundation for Promotion of Cancer Research
Validation and Problems of St-Gallen Recommendations of Adjuvant Therapy for Node-negative Invasive Breast Cancer in Japanese Patients
Breast Surgery Division, National Cancer Center Hospital, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: The objectives of this study were to confirm the favorable outcome of invasive breast cancer in Japanese patients without lymph node metastasis who did not receive adjuvant therapies and to validate the St-Gallen recommendations in this population.
Methods: The subjects were a consecutive series of 920 node-negative invasive breast cancer patients who underwent surgery between 1987 and 1994 at our hospital. These patients did not receive adjuvant chemotherapy. Ten-year disease-free (DFS) and overall survival (OS) rates were analyzed by the St-Gallen risk categories (Minimal/Low, Intermediate, High).
Results: The median age of the patients at surgery was 52 years and the median follow-up period of patients was 10.2 years. At 10 years, the respective DFS and OS rates of all patients were 84.6 and 86.7%. The DFS and OS of patients in the Minimal/Low risk category (25 patients) both showed 100%. The DFS and OS of patients in the Intermediate risk category (356 patients) showed 92.0 and 93.1%, respectively. The DFS and OS of patients in the High risk category (539 patients) showed 79.4 and 82.2%, respectively, indicating a significant difference between those in the Minimal/Intermediate risk category (381 patients) (p < 0.001, p < 0.001, respectively). The DFS and OS of patients who had one pathological lymph node metastasis (775 patients) showed 72.7 and 75.2%, respectively, which indicated a non-significant difference between those in the High risk category (381 patients) (p = 0.10). These data support the validation of adjuvant therapy for high-risk node-negative breast cancers in Japanese patients. However, quality control is needed to define the histological grade included in the risk categories.
Conclusion: Japanese patients with invasive breast cancer without lymph node metastasis showed a survival advantage compared with their Caucasian counterparts. However, patients in the High risk group as defined by St-Gallen recommendations should be indicated for adjuvant therapy.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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It has been suggested that Japanese breast cancer patients tend to show better survival rates than their Caucasian counterparts (1–4). The prognosis of breast cancer patients with no histological lymph node metastasis, treated with surgery alone, were relatively good in Japanese patients (1). The effects of postoperative adjuvant therapy on the prognosis of node-negative invasive breast cancer patients are controversial (2,3). In 1998, St-Gallen recommendations were established for the indication of postoperative adjuvant therapy for node-negative breast cancer (2). The objectives of the present study were to confirm the favorable outcome of invasive breast cancer in Japanese patients without lymph node metastasis and to validate the risk categories advocated by the St-Gallen recommendations in this population.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The subjects were a consecutive series of 920 node-negative invasive breast cancer patients who underwent surgery between 1987 and 1994 at our hospital. All patients were treated with surgery alone with or without any adjuvant therapy. Ten-year disease-free survival (DFS) and overall survival (OS) rates were analyzed by St-Gallen risk categories (Minimal/Low, Intermediate, High) (Table 1). Patients with bilateral breast cancers (synchronous or asynchronous) or second primary malignancies were included in the analyses. All patients were followed up for at least 5 years. The practicalities of the follow-up procedures have been reported previously (5). History and physical examinations as well as blood tests were performed at least once every 6 months over 10 years. Blood tests included investigations of liver function and tumor markers (ST-439, CEA and CA15-3). Chest X-rays, abdominal ultrasound examinations and bone scintigrams were performed annually for 5 years. T was the histopathological size of the invasive component. The histological grades of invasive carcinomas were defined as documented previously (6). Briefly, the histological grading of the primary tumor was a summed score comprising the degree of structural atypia, the number of mitotic figures and the degree of nuclear atypia. Individualized cases were categorized as grade 1 when the sum of the scores was 3 or 4, as grade 2 when the sum was 5, 6 or 7 and as grade 3 when the sum was 8 or 9. The number of mitotic figures was counted per 10 high-power fields (x400). Estrogen receptor (ER) and progesterone receptor (PgR) levels were measured by an enzyme immunoassay (7), with cut-off values of 10 fmol/mg protein and 13 fmol/mg protein for ER and PgR, respectively. DFS and OS rates were calculated for the entire patient series and also after stratification by the risk categories advocated by the St-Gallen recommendations (Minimal/Low, Intermediate, High). All data including pathological and clinical data were retrieved from the patients’ medical records. With regard to background factors, complete data were not available for every patient because pieces of information were missing or certain tests had not been performed. Survival curves were obtained by the Kaplan–Meier method (8) and differences between the survival curves were investigated using the log-rank test (9).
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The clinicopathological characteristics of the patients are shown in Table 2. The median age of the patients at surgery was 52 years (range 21–88 years) and the median follow-up period of those patients known to have survived was 10.2 years. At 10 years, the respective DFS and OS rates of all patients were 84.6 and 86.7% (Fig. 1). The DFS and OS of patients in the Minimal/Low risk category (25 patients) both showed 100%. As shown in Fig. 2, the DFS and OS of patients in the Intermediate risk category (356 patients) showed 92.0 and 93.1%, respectively. The DFS and OS of patients in the High risk category (539 patients) showed 79.4 and 82.2%, respectively, indicating a significant difference between those in the Minimal/Intermediate risk category (381 patients) (p < 0.001, p < 0.001, respectively.) (Fig. 3). In addition, as shown in Fig. 4, the DFS and OS of patients who had one pathological lymph node metastasis (775 patients) showed 72.7 and 75.2%, respectively, indicating a non-significant difference between those in the High risk category (381 patients) (p = 0.10). These data support the validation of adjuvant therapy for the high-risk node-negative breast cancers in Japanese patients. However, quality control is needed to define the histological grade in the risk categories.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The prognosis of breast cancer patients, particularly those with node-positive disease, has improved recently (2,3). However, it is likely that the outcome of treatment for node-negative breast cancer has reached a plateau. The proportion of node-negative invasive breast cancer patients who can be cured by adjuvant therapies remains controversial (2,3), mainly because useful prognostic factors have not been established for node-negative patients. We previously reported that histological grade, combined with examinations for the presence of certain gene and chromosomal alterations, are effective in identifying node-negative breast cancer patients at high risk of early recurrence (10,11). However, in these previous studies, the number of patients was small, the methods used to evaluate genetic alterations were complicated for routine use in a community hospital and the follow-up period was relatively short.
In the present study, to validate the risk categories advocated by the St-Gallen recommendations for node-negative breast cancers, we evaluated a large series of node-negative breast cancer patients over an extended follow-up period (median: 10.2 years) at a single institute. At 10 years, the respective DFS and OS rates for node-negative invasive breast cancer patients were 84.6 and 86.7%. The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) reported that 5-year DFS and OS of all node-negative breast cancer patients were 67–84 and 81–89%, respectively (3). These data indicate a better treatment outcome for node-negative invasive breast cancer patients in Japan than in Western countries. It is possible that breast cancers in Japanese women are biologically less aggressive, although there is no direct evidence for this hypothesis. Considering the relatively low incidence of breast cancer in the Japanese population, certain genetic and/or environmental factors could contribute to these ethnic differences in breast carcinomas (12).
The present study also confirmed the validation of the St-Gallen recommendations, particularly for patients in the High risk category. We therefore consider adjuvant chemotherapy to be justified in node-negative invasive breast cancer patients in the High risk category. However, the indication of adjuvant therapies for the Intermediate risk group remains controversial in node-negative Japanese breast cancer patients. In addition, quality control of histopathology is needed to define the risk category. The pathology departments of each hospital should standardize the subjective criteria used for histological/nuclear grading of breast cancers. Repeated slide conferences are considered effective for improving inter-observer agreement when judging histological grade including nuclear atypia (13).
In conclusion, invasive breast cancer in Japanese patients without lymph node metastasis showed a survival advantage compared with their Caucasian counterparts. However, patients in the High risk group as defined by the St-Gallen recommendations should be indicated for adjuvant therapy.
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FOOTNOTES |
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+ For reprints and all correspondence: Takashi Fukutomi, Breast Surgery Division, National Cancer Center Hospital, 1–1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. E-mail: tfukutom@gan2.ncc.go.jp
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REFERENCES |
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1 Saimura M, Fukutomi T, Tsuda H, Sato H, Miyamoto K, Akashi-Tanaka S, et al. Prognosis of a series of consecutive node-negative breast cancer patients without adjuvant therapy: analysis of clinicopathological prognostic factor. J Surg Oncol 1999;71:101–5.[Medline]
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Received January 12, 2001; accepted March 5, 2001.
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