BACKGROUND: Breast cancer is associated with a relatively good prognosis. Prognostic factors examined to date are related to early recurrence while those related to late recurrence and their countermeasures remain unclear. Therefore, we examined the factors related to late recurrence. PATIENTS AND METHODS: From January 1980 to August 2012, 4,774 patients who underwent primary treatment and estrogen (ER) and progesterone receptor (PgR) assessment were enrolled in this study. The patients were divided into two groups, those with a follow-up period <10 years and those without any recurrence at 10 years but who continued follow-up examinations. Recurrence occurred in 711 patients followed up for <10 years and in 51 patients for ≥10 years. RESULTS: The overall 10-year cumulative disease-free survival rate was 79.5%, and the recurrence rate at ≥10 years was 5.8%. A multivariate analysis revealed that the factors related to late recurrence were PgR positivity and positive nodes. This result differed from that for early recurrence in terms of ER/PgR, Ki-67 index and p53 overexpression. CONCLUSION: PgR positivity and lymph node metastases significantly correlated with late recurrence. Therefore, it is important to evaluate appropriate measures such as treatment period and treatment regimen for hormone-sensitive patients.
The choice of adjuvant systemic therapy is based on targeted therapy in line with the St. Gallen Consensus meeting. In addition to the traditional parameters, the panel recommended the use of proliferation markers and multigene assays. The purpose of the present study was to evaluate the clinical significance of proliferative activity using the Ki-67 index as a prognostic marker and as a predictor of recurrence time in breast cancer patients. The Ki-67 index was measured in 3,652 cases with primary breast cancer from 1987 to 2009. Out of these patients, 2,638 cases were evaluated simultaneously for estrogen receptor, progesterone receptor and HER2 from 1997, and these were analyzed as a prognostic factor according to their subtypes. The Ki-67 index exhibited a wide range of 1-99%, with a median of 20%, and cases were divided into 2 or 3 index groups; <20% and ≥20% (and ≥50%). The median Ki-67 index of tumors with luminal A was 17%, and that of luminal B type tumors was 29%. The Ki-67 index of HER2 tumors was 40% and that of triple negative tumors was 50%. A higher Ki-67 index significantly correlated with a higher grade of malignancy. Patients with a higher Ki-67 index had significantly lower disease-free survival (DFS) and overall survival rates. Moreover, there was a significant difference in the recurrence time. Multivariate analysis revealed that the Ki-67 index was a significant factor for DFS, irrespective of nodal status, and that Ki-67 was a significant marker only in luminal A type tumors. Furthermore, luminal A type cases with high Ki-67 had a similar DFS as the luminal B type cases. A higher Ki-67 index (≥20%) significantly correlated with other biological markers, poorer prognosis and early recurrence, particularly in luminal A type tumors. It is important to take the Ki-67 index into consideration in the treatment and follow-up of breast cancer patients.
BACKGROUND: The clinical features of ipsilateral breast tumor recurrence (IBTR) after breast conserving therapy (BCT) for early stage breast cancer were analyzed from long-term follow-up of BCT in Japan. The purpose of this study was to clarify risk factors of IBTR and the impact of IBTR on development of distant metastases in this ethnic group. METHODS: Patients (N = 1901)with unilateral breast cancer < or = 3 cm in diameter who underwent BCT at 18 Japanese major breast cancer treatment institutes from 1986 to 1993 were registered in this study. Survival rates, the incidences of IBTR and distant metastases, and annual rates of IBTR and distant metastases after primary operation were calculated by the Kaplan-Meier method. A Cox proportional hazards model was used to estimate the risks of IBTR and distant metastases. A Cox model was also used to estimate the risks of distant metastases after IBTR in the group of IBTR. RESULTS: At a median follow-up time of 107 months, the 10-year overall and disease-free survival rates were 83.9% and 77.8%, respectively. The 10-year cumulative rates of IBTR were 8.5% in the patients with postoperative irradiation and 17.2% in the patients without irradiation. The 10-year cumulative distant metastasis rate was 10.9%. On multivariate analysis, young age, positive surgical margin, and omission of radiation therapy were significant predictors of IBTR. In addition, IBTR significantly correlated with subsequent distant metastases (hazard ratio, 3.93; 95% confidence interval, 2.676-5.771; P < 0.0001). Among patients who developed IBTR, initial lymph node metastases and short interval to IBTR were significant risk factors for subsequent distant metastasis. CONCLUSIONS: Young age, positive surgical margin, and omission of radiation therapy seemed to be important factors in relation to local control. The authors' results also indicated that IBTR is significantly associated with subsequent distant metastasis. Patients with positive nodal status at primary operation or with short interval from primary operation to IBTR are at especially high risk of distant metastasis. It remains unclear, however, whether IBTR is an indicator or a cause of subsequent distant metastases.