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Predicting Breast Cancer Recurrence Following Breast-Conserving Therapy: A Single-Institution Analysis Consisting of 764 Chinese Breast Cancer Cases
chart review to abstract data on age at initial diagnosis and at recurrence, time to recurrence, histologic subtype, histologic grade, hormonal receptor status of IBTR, location of IBTR relative to the index lesion, and details of treatment, including the extent of surgery, surgical margin status, systemic therapy, and radiotherapy. The 10-year estimates of survival endpoints, including distant recurrence-free survival, BCSS, and OS, were calculated from the data associated with patients’ pathological diagnoses of IBTR. These estimates were then computed for patient- and IBTR-related factors using KaplanMeier methods and were compared using the log-rank test. Multivariate analysis was performed with the use of Cox proportional hazards regression modeling. On univariate analysis, the authors found several factors, such as
time to IBTR of 48 months or less, lymphovascular invasion (LVI), estrogen receptor (ER)-negative status, high grade, clinical IBTR detection, biopsy alone, and close or positive margins, to be significantly associated with diminished OS and BCSS. However, on multivariate analysis, only some of the factors, including time to IBTR of 48 months or less, LVI, ERnegative status, high grade, and close or positive margins, were significantly associated with diminished OS. The 10-year OS rate was 70.4% for patients with 1 adverse factor, 35.8% for those with 2 adverse factors, and 19.9% for those with 3 or more factors. The authors concluded that time to IBTR of 48 months or less, LVI, ER-negative status, high grade, and close or positive margins were independent prognostic indicators of survival in women with IBTR and that the presence of 2 or more
of these high-risk factors would be associated with a lower survival rate. The study by Panet-Raymond and colleagues included the largest series of IBTR patients to date in whom clinicopathologic factors were systematically examined in order to stratify patients into various prognostic groups. The importance of performing a thorough pathological examination of the recurrent tumor and evaluating patients for the high-risk adverse factors identified in this study, including time to IBTR of 48 months or less, LVI, ER-negative status, high grade, and close or positive margins, cannot be overemphasized when stratifying patients into prognostic groups and selecting the most appropriate treatment for these patients.
Predicting Breast Cancer Recurrence Following BreastConserving Therapy: A SingleInstitution Analysis Consisting of 764 Chinese Breast Cancer Cases
in Shanghai Cancer Center between 1995 and 2008. Univariate and multivariate analysis were performed to identify independent risk factors for locoregional recurrence (LRR) and all the recurrence events. Logistic regression was used to construct a recurrence prediction model, which was further evaluated by receiver operating characteristics (ROC) curves. Results.dThe 5-year locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) rates were 90.8 and 88.4%, respectively. Multivariate analysis revealed 1 independent predictive factor for LRRFS (lymph node, P ¼ .0049) and three independent predictive factors for RFS (lymph node, P ¼ .0036; molecular subtype, P ¼ .0021; histological grade, P ¼.041). These three variables entered into logistic regression to establish a recurrent prediction model. ROC curve
showed that the area under the curve (AUC) of the established model was 0.70 (95% confidence interval: 0.61e 0.78). This model could classify patients into “high-risk recurrence” and “low-risk recurrence” groups and could successfully predict their prognosis (P < .00001). Conclusions.dThe information of lymph node status, molecular subtype, and grade may help doctors to evaluate recurrence risk of a woman treated with BCT. Our new model might be helpful in clinical practice for recurrence prediction after BCT in Chinese patients, though further validation studies are needed.
Li S, Yu K-D, Fan L, et al (Fudan Univ, Shanghai, People’s Republic of China) Ann Surg Oncol 18:2492-2499, 2011
Background.dThe purpose of this study was to identify prognostic factors related to recurrence in women treated with breast-conserving surgery (BCS) and to predict the recurrence following breast-conserving therapy (BCT) by constructing a prediction model. Methods.dThe retrospective analysis included 764 consecutive invasive breast cancer patients treated with BCT
S. Krishnamurthy, MD
Breast cancer care was revolutionized when the results of the Milan and NSABP B-06 trials demonstrated similar low recurrence rates in patients undergoing total mastectomy
Breast Diseases: A Year BookÒ Quarterly Vol 23 No 2 2012
199
and those undergoing BCT with irradiation.1,2 Patient and tumor characteristics associated with an increased risk of recurrence have previously been identified,3-5 and advances in multidisciplinary breast cancer treatment have continued to lower recurrence rates in patients undergoing BCT.6 In this study reported by Li and colleagues, the authors identified variables associated with LRRFS and RFS in patients undergoing BCT. A predictive model was then developed. A total of 764 patients undergoing BCT comprised the study cohort. The follow-up time was 41.5 months. LRRFS was significantly associated with lymph node status, HER2 status, and molecular subtype on univariate analysis. However, lymph node status was the only independent variable associated with LRRFS on multivariate analysis. Furthermore, lymph node status; estrogen receptor, progesterone receptor, and HER2 status; molecular subtype; histologic grade; and endocrine therapy were significantly associated with RFS on univariate analysis. Consistent with previous reports, lymph node status, molecular subtype, and histologic grade were independent factors predictive of RFS on multivariate analysis. The authors reported the predictive model to have the best accuracy at an R (probability of recurrence) value of 10%, with a sensitivity of 78% and specificity of 67%. The short follow-up and exclusion of patients receiving trastuzumab are
200
significant limitations of this study. The majority of patients in this study had estrogen receptorepositive disease, which is known to have a delayed recurrence of 9 years or more. Moreover, the addition of trastuzumab in systemic therapy has reduced the recurrence rate by 50%.7 The exclusion of these patients could have significantly influenced the outcomes of the analysis and, subsequently, the predictive model. In addition, molecular subtype recurrence rates can be affected when use of trastuzumab in the luminal B and ERBB2+ subgroups is omitted from the analysis. Advances such as trastuzumab use have contributed to patients undergoing BCT having recurrence rates as low as 1.3%.6 Many Chinese women are diagnosed with breast cancer in the fourth decade of life. Recent studies have shown a decrease in ipsilateral breast tumor recurrence from 9.1% to 1.4% in women age 50 years or younger.6 A predictive model such as this can provide a platform for clinicians to discuss the best surgical options for women presenting with breast cancer. However, a more comprehensive cohort with respect to multidisciplinary treatment is necessary for the model to be applicable to the majority of women with breast cancer. J. L. Wagner, DO
References 1. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-
Breast Diseases: A Year BookÒ Quarterly Vol 23 No 2 2012
conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227-1232. 2. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347: 1233-1241. 3. Huang EH, Tucker SL, Strom EA, et al. Predictors of locoregional recurrence in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62:351-357. 4. Miles RC, Gullerud RE, Lohse CM, Jakub JW, Degnim AC, Boughey JC. Local recurrence after breastconserving surgery: multivariable analysis of risk factors and the impact of young age. Ann Surg Oncol. 2012; 19:1153-1159. 5. Wallgren A, Bonetti M, Gelber RD, et al; International Breast Cancer Study Group Trials I through VII. Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII. J Clin Oncol. 2003;21:1205-1213. 6. Cabioglu N, Hunt KK, Buchholz TA, et al. Improving local control with breast-conserving therapy: a 27-year single-institution experience. Cancer. 2005;104:20-29. 7. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2positive breast cancer. N Engl J Med. 2005;353:1673-1684.
time to IBTR of 48 months or less, lymphovascular invasion (LVI), estrogen receptor (ER)-negative status, high grade, clinical IBTR detection, biopsy alone, and close or positive margins, to be significantly associated with diminished OS and BCSS. However, on multivariate analysis, only some of the factors, including time to IBTR of 48 months or less, LVI, ERnegative status, high grade, and close or positive margins, were significantly associated with diminished OS. The 10-year OS rate was 70.4% for patients with 1 adverse factor, 35.8% for those with 2 adverse factors, and 19.9% for those with 3 or more factors. The authors concluded that time to IBTR of 48 months or less, LVI, ER-negative status, high grade, and close or positive margins were independent prognostic indicators of survival in women with IBTR and that the presence of 2 or more
of these high-risk factors would be associated with a lower survival rate. The study by Panet-Raymond and colleagues included the largest series of IBTR patients to date in whom clinicopathologic factors were systematically examined in order to stratify patients into various prognostic groups. The importance of performing a thorough pathological examination of the recurrent tumor and evaluating patients for the high-risk adverse factors identified in this study, including time to IBTR of 48 months or less, LVI, ER-negative status, high grade, and close or positive margins, cannot be overemphasized when stratifying patients into prognostic groups and selecting the most appropriate treatment for these patients.
Predicting Breast Cancer Recurrence Following BreastConserving Therapy: A SingleInstitution Analysis Consisting of 764 Chinese Breast Cancer Cases
in Shanghai Cancer Center between 1995 and 2008. Univariate and multivariate analysis were performed to identify independent risk factors for locoregional recurrence (LRR) and all the recurrence events. Logistic regression was used to construct a recurrence prediction model, which was further evaluated by receiver operating characteristics (ROC) curves. Results.dThe 5-year locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) rates were 90.8 and 88.4%, respectively. Multivariate analysis revealed 1 independent predictive factor for LRRFS (lymph node, P ¼ .0049) and three independent predictive factors for RFS (lymph node, P ¼ .0036; molecular subtype, P ¼ .0021; histological grade, P ¼.041). These three variables entered into logistic regression to establish a recurrent prediction model. ROC curve
showed that the area under the curve (AUC) of the established model was 0.70 (95% confidence interval: 0.61e 0.78). This model could classify patients into “high-risk recurrence” and “low-risk recurrence” groups and could successfully predict their prognosis (P < .00001). Conclusions.dThe information of lymph node status, molecular subtype, and grade may help doctors to evaluate recurrence risk of a woman treated with BCT. Our new model might be helpful in clinical practice for recurrence prediction after BCT in Chinese patients, though further validation studies are needed.
Li S, Yu K-D, Fan L, et al (Fudan Univ, Shanghai, People’s Republic of China) Ann Surg Oncol 18:2492-2499, 2011
Background.dThe purpose of this study was to identify prognostic factors related to recurrence in women treated with breast-conserving surgery (BCS) and to predict the recurrence following breast-conserving therapy (BCT) by constructing a prediction model. Methods.dThe retrospective analysis included 764 consecutive invasive breast cancer patients treated with BCT
S. Krishnamurthy, MD
Breast cancer care was revolutionized when the results of the Milan and NSABP B-06 trials demonstrated similar low recurrence rates in patients undergoing total mastectomy
Breast Diseases: A Year BookÒ Quarterly Vol 23 No 2 2012
199
and those undergoing BCT with irradiation.1,2 Patient and tumor characteristics associated with an increased risk of recurrence have previously been identified,3-5 and advances in multidisciplinary breast cancer treatment have continued to lower recurrence rates in patients undergoing BCT.6 In this study reported by Li and colleagues, the authors identified variables associated with LRRFS and RFS in patients undergoing BCT. A predictive model was then developed. A total of 764 patients undergoing BCT comprised the study cohort. The follow-up time was 41.5 months. LRRFS was significantly associated with lymph node status, HER2 status, and molecular subtype on univariate analysis. However, lymph node status was the only independent variable associated with LRRFS on multivariate analysis. Furthermore, lymph node status; estrogen receptor, progesterone receptor, and HER2 status; molecular subtype; histologic grade; and endocrine therapy were significantly associated with RFS on univariate analysis. Consistent with previous reports, lymph node status, molecular subtype, and histologic grade were independent factors predictive of RFS on multivariate analysis. The authors reported the predictive model to have the best accuracy at an R (probability of recurrence) value of 10%, with a sensitivity of 78% and specificity of 67%. The short follow-up and exclusion of patients receiving trastuzumab are
200
significant limitations of this study. The majority of patients in this study had estrogen receptorepositive disease, which is known to have a delayed recurrence of 9 years or more. Moreover, the addition of trastuzumab in systemic therapy has reduced the recurrence rate by 50%.7 The exclusion of these patients could have significantly influenced the outcomes of the analysis and, subsequently, the predictive model. In addition, molecular subtype recurrence rates can be affected when use of trastuzumab in the luminal B and ERBB2+ subgroups is omitted from the analysis. Advances such as trastuzumab use have contributed to patients undergoing BCT having recurrence rates as low as 1.3%.6 Many Chinese women are diagnosed with breast cancer in the fourth decade of life. Recent studies have shown a decrease in ipsilateral breast tumor recurrence from 9.1% to 1.4% in women age 50 years or younger.6 A predictive model such as this can provide a platform for clinicians to discuss the best surgical options for women presenting with breast cancer. However, a more comprehensive cohort with respect to multidisciplinary treatment is necessary for the model to be applicable to the majority of women with breast cancer. J. L. Wagner, DO
References 1. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-
Breast Diseases: A Year BookÒ Quarterly Vol 23 No 2 2012
conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227-1232. 2. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347: 1233-1241. 3. Huang EH, Tucker SL, Strom EA, et al. Predictors of locoregional recurrence in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62:351-357. 4. Miles RC, Gullerud RE, Lohse CM, Jakub JW, Degnim AC, Boughey JC. Local recurrence after breastconserving surgery: multivariable analysis of risk factors and the impact of young age. Ann Surg Oncol. 2012; 19:1153-1159. 5. Wallgren A, Bonetti M, Gelber RD, et al; International Breast Cancer Study Group Trials I through VII. Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII. J Clin Oncol. 2003;21:1205-1213. 6. Cabioglu N, Hunt KK, Buchholz TA, et al. Improving local control with breast-conserving therapy: a 27-year single-institution experience. Cancer. 2005;104:20-29. 7. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2positive breast cancer. N Engl J Med. 2005;353:1673-1684.