Prognostic Features And Radiotherapy Of Triple-negative Breast Cancer

Part I:Prognostic features and treatment of triple-negative breast cancerObjective:To determine the clinicopathologic and prognostic features for patients with triple-negative breast cancer (TNBC).Material and methods:Clinicohistologic data of1103TNBC treated at our hospital between August1996and December2010were retrospectively analyzed. Eight hundreds and thirty-six patients of early stage TNBC were treated with breast conservative surgery and radiotherapy (BCS+RT), mastectomy (MRM) or MRM followed by RT. Patients and tumor characteristics were compared using the Chi-square test. Locoregional-recurrence-free survival (LRRFS) and overall survival (OS) were estimated using Kaplan-Meier analysis.Results:There are53.4%patients less than50years old,12.1%with lymphnovascular invasion (LVI), and84.4%with pathologic diagnosis invasive ductal carcinoma.55.7%of patients had histologic grade3for795available patients. Eight hundred thirty-six patients (75.8%) had early stage disease,253patients (22.9%) had locally advanced disease and14patients (1.3%) had IV stage disease. There were significant differences in tumor size, LVI, lymph node positivity, disease onset age in836early stage TNBC patients with different treatment groups. With a median follow-up of57months,162patients developed locoregional recurrence (LRR) and187patients died. The5-year LRRFS and OS rates were84.1%and84.2%, respectively.Conclusions:TNBC are associated with young age and large proportion of axillary lymph node positivity and tumor histologic grade3. The most common pathologic diagnosis is invasive ductal carcinoma. Part II:Improved locoregional control comparing radiotherapy following breast conservative surgery with modified radical mastectomy without radiotherapy for patients with T1-2N0-1M0triple-negative breast cancerObjective:To evaluate the effect of radiotherapy following breast conserving surgery (BCS) comparing with modified radical mastectomy (MRM) without radiotherapy for women with T1-2N0-1M0triple-negative breast cancer (TNBC).Material and methods:Seven hundreds and thirty-two patients diagnosed with T1-2N0-1M0TNBC were retrospectively analyzed. Five hundreds and ninety patients had mastectomy without radiotherapy, and142underwent breast conserving surgery and radiotherapy. Locoregional recurrence-free survival (LRRFS) and overall survival (OS) were compared between two groups with or without propensity-score matching methods.Results:With a median follow-up of60months,94patients developed locoregional recurrence (LRR) and75patients died. The5-year LRRFS and OS rates were86.5%and91.1%. The5-year LRRFS and OS rates were95.7%and97.5%for breast conserving surgery and radiotherapy compared with84.4%(P=0.003) and89.5%(P=0.003) for postmastectomy without radiotherapy, respectively. In multivariate analysis, age<50years (HR2.184,95%CI1.394-3.422; P=0.001), T2(HR1.980,95%CI1.282to3.060; P=0.002), Nl (HR1.786,95%CI1.148to2.780; P=0.010) and MRM (HR2.924,95%CI1.324to6.457; P=0.008) were associated with increased LRR in the two unmatched groups. In matched-pair analysis of breast conserving surgery followed by radiotherapy and mastectomy without radiotherapy using propensity-score matching methods, the5-year LRRFS rates were95.7%and83.2%(P=0.006) in the breast conserving therapy and mastectomy groups respectively; the5-year OS rate was97.5%for BCS plus radiotherapy compared with94.3%for MRM (P=0.085). Multivariate analysis indicated that age<50years (HR6.543,95%CI1.472to29.089; P=0.014), T2(HR2.470,95%CI1.064to5.733; P=0.035) and MRM (HR3.130,95%CI1.321to7.420; P=0.010) were the independent prognostic factors associated with increased LRR.Conclusions:Patients with T1-2N0-1MO TNBC treated with MRM without RT appeared to be at an increased risk for LRR compared with those treated with BCS and RT. BCT is the preferred treatment for early TNBC on the basis of equivalent survival and superior LRC when compared with patients treated with mastectomy and a presumed better quality of life. Prospective studies are warranted to investigate the benefit of BCS and RT to improve the outcome of patients compared with mastectomy in T1-2N0-1M0TNBC. Part III:Improved locoregional control with radiotherapy following modified radical mastectomy for patients with T1-2N1M0triple-negative breast cancerObjective:To evaluate the role of radiotherapy (RT) after modified radical mastectomy for women with T1-2N1M0triple-negative breast cancer (TNBC).Material and methods:Two hundreds and fifteen patients diagnosed with T1-2N1M0TNBC were retrospectively analyzed. All patients were treated with modified radical mastectomy (MRM). Of them,66patients received postmastectomy radiotherapy and146patients did not. Locoregional recurrence-free survival (LRRFS) and overall survival (OS) were compared between two groups with or without propensity-score matching methods.Results:With a median follow-up of56months,36patients developed locoregional recurrence (LRR). The5-year LRRFS and OS rates were92.6%and82.8%for MRM compared with76.6%(P=0.01) and84.7(P=0.499) for MRM and RT, respectively. In multivariate analysis, MRM and T2were associated with increased LRR. In matched-pair analysis of radiotherapy and no radiotherapy using propensity-score matching methods, the5-year LRRFS was92.6%for MRM plus RT compared with74.5%for MRM (P=0.008). Multivariate analysis indicated that no radiotherapy was the only independent prognostic factor associated with increased LRR (hazard ratio,3.536;95%CI,1.153to10.844; P=0.027).Conclusions:Patients with T1-2N1M0TNBC treated with MRM without RT appear to be at an increased risk for LRR compared with those treated with MRM and RT. Prospective studies are warranted to investigate the benefit of postmastectomy radiotherapy to improve the outcome of patients in T1-2N1M0TNBC. Part IV:Improved locoregional control and overall survival with radiotherapy following modified radical mastectomy for patients with locally advanced triple-negative breast cancerObjective:To evaluate the role of postmastectomy radiotherapy (PMRT) for women with locally advanced triple-negative breast cancer (TNBC).Material and methods:Two hundreds and thirty-two patients diagnosed with stage III TNBC were retrospectively analyzed. All patients were treated with modified radical mastectomy (MRM). Of them,165patients received postmastectomy radiotherapy (PMRT) and67patients did not. Locoregional recurrence-free survival (LRRFS), overall survival (OS) and event-free survival (EFS) were compared between two groups.Results:With a median follow-up of48months,60patients developed locoregional recurrence (LRR) and85patients died. The5-year LRRFS and OS rates were71.9%and65.5%, respectively. Postmastectomy radiotherapy significantly improved the locoregional control and survivals compared with MRM alone. The5-year LRRFS rate was85.6%for MRM and39.1%for MRM plus RT, P=0.000). The5-year OS rate was67.6%and59.9%(P=0.032), and the corresponding EFS rate was53.4%for PMRT and28.2%for MRM (P=0.000), respectively. In multivariate analysis, MRM (HR5.476,95%CI3.068-9.774, P=0.000), stage IIIC (HR3.285,95%CI1.752-6.160, P=0.000) and less than6cycles chemotherapy (HR1.928,95%CI1.099-3.382, P=0.022)were associated with increased LRR; chemotherapy cycles (<6vs>6cycles, HR,1.837,95%CI1.119-3.016, P=0.016) and tumor stage (IIIC vs IIIA, HR,2.720,95%CI1.608-4.601, P=0.000) were independent prognostic factors associated with OS; MRM (HR,2.012,95%CI1.347-3.007, P=0.001), stage IIIC (HR,3.111,95%CI1.984-4.880, P=0.000) and chemotherapy cycle (<6vs>6cycles, HR,1.675,95%CI1.105-2.538, P=0.015) were independent prognostic factors associated with EFS.Conclusions:Patients with locally advanced TNBC treated with MRM without RT appeared to be at an increased risk for LRR compared with those treated with PMRT. Postmastectomy radiotherapy significant improved the OS and EFS compared with MRM without RT. Part V:Clinicopathologic characteristics and prognosis for patients with metastatic triple-negative breast cancerObjective:To analyze the clinicopathological features, survival and value of locoregional treatment for metastatic triple-negative breast cancer (TNBC).Material and methods:Two hundred and twenty patients with metastastic TNBC were retrospectively analyzed. Of them,206patients with stage I-III disease developed metastatic disease after treatment and14patients presented with stage IV disease at the initial diagnosis. Overall survival (OS) and progression-free survival (PFS) was estimated using Kaplan-Meier analysis from the time of metastatic occurrence. The difference in survivals was compared using Log-rank test.Results:The most common metastatic site was the lung followed by bone. In this cohort,182patients (82.7%) developed visceral organs metastasis. Sixty-three patients (28.6%) developed metastasis located in single organ, whereas182patients (69.5%) with multiple metastatic disease and4patients were unclear. Most patients developed distant metastasis within3years. With a median follow-up of22months, the5-year OS rate was25.0%, with a median survival time of21months. For63patients with single metastasis, locoregional treatment with radiotherapy or surgery significantly improved OS. The5-year OS rate was48.0%for patients who received locoregional treatment compared with29.0%for those who did not (P=0.006).Conclusions:Patients with metastatic triple-negative breast cancer usually presented with visceral metastasis. Patients with single metastasis had better outcome than those with multiple metastases. Patients with bone metastasis had better outcome than those with visceral organs involved. Locoregional treatment significantly improved the overall survival in patients with single metastasis.