Search

Objective: To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment. Methods: A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained. Results: Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR =2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR =1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR =1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR =1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR =1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR =1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR =1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR =1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR =2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions: Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

Objective: To identify the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1~2 positive axillary sentinel lymph node (SLN) and construct an accurate prediction model. Methods: Retrospective chart review was performed in 917 breast cancer patients who underwent surgery treatment between 2002 and 2017 and pathologically confirmed 1-2 positive SLNs. According to the date of surgery, patients were divided into training group (497 cases) and validation group (420 cases). A nomogram was built to predict nSLN metastasis and the accuracy of the model was validated. Results: Among the 917 patients, 251 (27.4%) had nSLN metastasis. Univariate analysis showed tumor grade, lymphovascular invasion (LVI), extra-capsular extension (ECE), the number of positive and negative SLN and macro-metastasis of SLN were associated with nSLN metastasis (all P <0.05). Multivariate Logistic regression analysis showed the numbers of positive SLN, negative SLN and macro-metastasis of SLN were independent predictors of nSLN metastasis (all P <0.05). A nomogram was constructed based on the 6 factors. The area under the receiver operating characteristic curve was 0.718 for the training group and 0.742 for the validation group. Conclusion: We have developed a nomogram that uses 6 risk factors commonly available to accurately estimate the likelihood of nSLN metastasis for individual patient, which might be helpful for radiation oncologists to make a decision on regional nodal irradiation.

Objective: To evaluate the incidence of early cardiac injury in patients with left-sided breast cancer receiving hypofractionated radiotherapy after breast conserving surgery, and to investigate the correlation between cardiac injury and hypofractionated radiotherapy dose. Methods: We prospectively enrolled 103 breast cancer patients who received whole breast with or without regional nodal irradiation after breast conserving surgery using either deep inspiration breath-hold (DIBH) or free breathing (FB) radiotherapy technique. Cardiac examinations that included N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and myocardial perfusion imaging were performed routinely before and after radiotherapy. The effects of heart dose, systemic therapy and individual factors (Framingham score) on the incidence of cardiac events were analyzed. Results: The median age was 48 years. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) were 4.0, 16.9, 6.3, and 4.4 Gy, respectively. With a median follow-up of 13.4 months, no patient had clinical cardiac abnormalities. The incidence rates of subclinical cardiac events at 1- 6- and 12-month were 23.5%, 31.6%, and 41.3%, respectively. The DIBH group had a lower mean dose, maximum dose, and V5-V40 in the heart, LAD, LV, and RV than the FB group ( P <0.001). Univariate analysis showed an increased incidence of subclinical cardiac events with heart Dmean >4 Gy, LAD V40 > 20%, LV Dmean >6 Gy, RV Dmean >7 Gy, or cumulative doses of anthracycline or taxane > 300 mg/m(2) (All P <0.05). Anti-HER2 targeted therapy, endocrine therapy and Framingham score were not associated with the incidence of subclinical cardiac events (all P >0.05). Multivariate analysis demonstrated that Dmean of LV and RV were independently associated with the increased incidence of subclinical cardiac events. Conclusions: Early subclinical heart injury are found in patients with left-sided breast cancer after hypofractionated radiotherapy. The increased incidence of subclinical cardiac events after radiotherapy is positively associated with the cardiac radiation doses.

Objective: To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients compared to 7th edition. Methods: a total of 1 823 female patients with T1-2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log-rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic (ROC) analyses and the concordance index (C-index). Results: 5-year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5-year distant metastasis (DM) rate was 11.5%, 5-year disease-free survival (DFS) was 85.0%, and 5-year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS ( P <0.05). Compared with stage by 7th edition, 1 278(70.1%) were assigned to a different prognostic stage group: 1 088 (85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stage ⅠA, ⅠB, ⅡA, ⅡB and ⅢA according to 8th edition of the AJCC staging system( P <0.001). Prognostic stage had significantly higher C-indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system ( P <0.001). Conclusion: The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1-2N1M0 breast cancer, and has better clinical therapeutic guidance value.

Objective: To investigate the overall efficacy of early breast cancer after breast-conserving treatment. To analyze risk factors affecting local regional recurrence (LRR), distant metastasis (DM) and survival. Methods: 1 791 breast cancer patients treated with breast-conserving surgery were retrospectively analyzed. The inclusion criteria were pathologic diagnosis of invasive breast cancer without supraclavicular and internal mammary node metastasis, T1-2N0-3M0, and no neoadjuvant therapy. Univariate analysis of survival was performed by Kaplan-Meier method and log rank test. Cox regression model was used for multivariate analysis. Results: The median follow-up time was 4.2 years. For all patients, the 5-year LRR, DM, disease-free survival(DFS) and overall survival(OS) rates were 3.6%, 4.6%, 93.0% and 97.4%, respectively. The LRR rates of patients with Luminal A, Luminal B1, Luminal B2, HER-2 over-expressed and triple-negative breast cancer were 2.0%, 6.1%, 5.9%, 0 and 10.0%, while the DM rates were 3.2%, 6.7%, 8.3%, 4.8% and 7.3%, respectively. Among the N0 patients, axillary dissection was performed in 689 cases and sentinel lymph node biopsy in 652 cases. The 5-year LRR rates were 3.3% and 3.2% ( P =0.859), and the OS rates were 98.2% and 98.3% ( P =0.311) respectively, which showed no statistically significant. There were 1 576 patients that underwent postoperative radiotherapy. Postoperative radiotherapy significantly reduced the 5-year LRR compared with surgery alone (2.5% vs 12.9%). The 5-year LRR rates of patients who received conventional fractionated radiotherapy and hypo-fractionated radiotherapy were 2.7% and 3.1%, respectively. But the difference was not statistically significant ( P =0.870). Multivariate analysis showed that age, lymphovascular invasion, pathological T staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors of LRR in breast cancer patients (all P <0.05). Histological grade and pathological N staging were independent factors of DM (all P <0.05). The age, lymphovascular invasion, pathological T and N staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors for DFS (all P <0.05). Histological grade, pathological N staging, ER/PR status and endocrine therapy were factors for OS (all P <0.05). Conclusions: With contemporary standard treatment, the recurrence rate of early breast cancer after breast conserving treatment is less than 10%. Node-negative patients after sentinel lymph node biopsy did not need axillary dissection. The overall utilization of radiotherapy after breast conserving surgery is satisfactory. Hypofractionated radiotherapy is as effective as conventional fractionated radiotherapy. Local regional recurrence and distant metastasis have different risk factors.

Objective: To analyze the clinical features and prognosis of the ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery. Methods: From 1999 to 2013, 63 women with IBTR after breast conserving surgery were retrospectively reviewed. All patients had adequate information on tumor location both at first presentation and at recurrence, with or without regional recurrence or distant metastasis. The histologic changes between true local recurrence and elsewhere recurrence groups were compared. The local recurrence, the overall survival after IBTR (IBTR-OS), the disease-free survival after IBTR (IBTR-DFS) were also compared. Results: All patients had undergone lumpectomy, including 38 cases with additional axillary lymph node dissection and 13 cases with sentinel lymph node biopsy. There were 11.3% (7/63) cases received neoadjuvant systemic therapy, 68.3% (43/63) had adjuvant radiotherapy, 60.3% (38/63) underwent adjuvant chemotherapy and 47.6% (30/63) received hormonal therapy. Forty-five cases (71.4%) had recurrence in the same quadrant, and 18 cases (28.6%) had elsewhere recurrence. Compared with histology at presentation, 10.3% of the patients (6/58) had different ones at recurrence and 28.9% of patients (13/45) had different molecular subtypes. The conversion rate of estrogen receptor status (33.3% vs 9.5%, P =0.012) and progesterone receptor status (56.3% vs 19.0%, P =0.005) in patients with elsewhere recurrence was significantly higher than that in patients with same quadrant recurrence. Fifty-nine cases had undergone surgery after IBTR, with 48 cases of secondary breast-conserving surgery and 11 cases of salvage mastectomy. The median time to IBTR of same quadrant recurrence and elsewhere recurrence groups were 26 months and 62 months ( P =0.012), respectively. There were 84.4% and 44.4% cases who had local recurrence within 5 years after breast conserving surgery, respectively. Of all cases, the overall 5-year IBTR-OS and 5-year IBTR-DFS rates were 79.4% and 60.4%, respectively. There were no significant differences in 5-year IBTR-OS (77.4% vs. 83.6%, P =0.303) or 5-year IBTR-DFS (60.0% vs. 62.8%, P =0.780) between same quadrant recurrence and elsewhere recurrence groups. Univariate analysis showed that pN0-1 ( P <0.001), luminal subtype ( P =0.026), adjuvant endocrine therapy ( P =0.007) at first presentation, recurrent tumor < 3 cm ( P =0.036) and having surgery after IBTR( P =0.002) were favorable factors of IBTR-OS. pN0-1 ( P <0.001) at first presentation, recurrent tumor stage Ⅰ-Ⅱ ( P <0.001) and having surgery after IBTR( P =0.001) were favorable factors of IBTR-DFS. There was no significant difference between second breast-conserving surgery and salvage mastectomy in IBTR-OS and IBTR-DFS ( P >0.05). Conclusions: The IBTR after breast conserving surgery mainly occurred at the original quadrant. Second breast-conserving surgery did not affect patient's prognosis. There were significant differences in biological features between the same quadrant recurrence and elsewhere recurrence, requiring different therapeutic strategies in the future.

Objective: To establish a risk-adapted postmastectomy radiotherapy strategy based on local-regional recurrence for intermediate-risk breast cancer (T1~2N1M0 stage). Methods: A total of 2413 patients with T1-2N1M0 breast cancer were retrospectively reviewed. Of them, 588 patients (24.4%) received postmastectomy radiotherapy (PMRT), while 1 825 (75.6%) patients did not. A comprehensive comparative study was performed by using multivariable and propensity score-matched (PSM) analyses. Results: The median follow-up time was 67.0 months, the 5-year local region recurrence free-survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were 93.8%, 85.7% and 93.3%, respectively. The 5-year local region recurrence (LRR) was 6.1%. For patients without PMRT, multivariable analysis indicated that age, tumor localization, molecular subtype, pathologic T stage and number of positive lymph node were independent factors for LRRFS (all of P <0.05). Patients with T1-2N1 breast cancer were classified into low-risk group (0-1 risk factor, 768 patients), intermediate-risk group (2 risk factors, 690 patients) and high-risk groups (≥3 risk factors, 544 patients) based on the five independent factors mentioned above. The 5-year LRRFS, DFS and OS were significantly different among the three groups ( P <0.001). In low- and intermediate-risk groups, there were no significant differences in LRRFS, DFS and OS of patients who received PMRT or not ( P >0.05). In high-risk group, the DFS of patients received PMRT or not were 79.8% and 74.4%, respectively ( P =0.127), the OS of them were 86.8% and 87.1%, respectively ( P =0.174), and the LRRFS were 93.3% and 84.3%, respectively ( P =0.002). After PSM adjustment, no significant differences in LRRFS, DFS and OS were observed between PMRT-received subgroup and no PMRT subgroup of low-risk group ( P >0.05). In intermediate-risk group, the LRRFS of patients received PMRT or not were 95.2% and 91.0%, respectively ( P =0.037). However, in the high-risk group, the LRRFS, DFS and OS of patients received PMRT were 93.3%, 79.7% and 86.6%, respectively, while those of patients did not receive PMRT were 78.5% ( P <0.001), 69.5% ( P =0.038) and 85.7% ( P =0.080), respectively. Conclusions: The local-regional recurrence risks of patients with pT1-2N1 breast cancer are viable and risk-adapted PMRT is available for them. Better prognoses can be achieved by the patients of intermediate and high-risk group. More samples on this subject are needed to validate the results.

Objective: To analyze the outcomes of clinical T1-3N1M0 breast cancer patients with pathological negative axillary lymph nodes (ypN0) after neoadjuvant chemotherapy (NAC) and mastectomy, and investigate the role of postmastectomy radiotherapy (PMRT). Methods: A total of 185 patients with clinical T1-3N1M0 breast cancer treated between 1999 and 2013 were retrospectively reviewed. All patients were treated with NAC and mastectomy, and achieved ypN0. Of them, 89 patients received additional PMRT and 96 patients did not. 101 patients had clinical stage Ⅱ disease. 84 patients had clinical stage Ⅲ disease. The rates of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and differences were compared using the log-rank test. Univariate analysis was used to interpret the impact of clinical features and treatment on patients' outcome. Results: The 5-year rates of LRR, DM, DFS, and OS for all patients were 4.5%, 10.4%, 86.6%, and 97.1%, respectively. For patients with and without PMRT, the 5-year LRR rates were 1.1% and 7.5% ( P =0.071), the 5-year DM rates were 5.1% and 15.0% ( P =0.023), the 5-year DFS rates were 95.0% and 79.0% ( P =0.008), and the 5-year OS rates were 100.0% and 94.5% ( P =0.089) respectively. In univariate analysis, lymph-vascular space invasion (LVSI) was poor prognostic factor of LRR ( P =0.001), < 40 years old and lack of PMRT was a poor prognostic factor for DM ( P <0.05), lack of PMRT was a poor prognostic factor for DFS ( P =0.008), primary lesion residual and mild-moderate pathological response to NAC were poor prognostic factors for OS ( P <0.05). In the subgroup of Stage Ⅲ disease, for patients with and without PMRT, the 5-year LRR rates were 1.9% and 14.4% ( P =0.041), the 5-year DFS rates were 91.9% and 67.4% ( P =0.022), respectively. In the subgroup of Stage Ⅱ disease, for patients with and without PMRT, the 5-year DM rates were 0 and 11.5% ( P =0.044), the 5-year DFS rates were 100.0% and 84.9% ( P =0.023), respectively. Conclusions: The LRR rate of clinical T1-3N1M0 breast cancer patients who achieved ypN0 after NAC and mastectomy was low. PMRT decreased the DM rate and increased DFS rate in all patients, and significantly decreased the LRR rate in Stage Ⅲ disease. PMRT should be considered for patients with Stage Ⅲ disease, and further research is warranted to investigate the benefit of PMRT for Stage Ⅱ disease.

Objective: To evaluate the prognostic value of sequencing of adjuvant radiotherapy and chemotherapy following breast-conserving surgery for patients with breast cancer. Methods: A total of 1 154 patients withT1-2N0-3M0 breast cancer retrospectively reviewed. All patients received sequential radiotherapy and chemotherapy following breast-conserving surgery. Among them, 603 patients received radiotherapy first and 551 patients received chemotherapy first. Log-rank tests were used to determine significance of disease-free survival (DFS) and overall survival (OS) rates in the Kaplan-Meier curve. Results: The 5-year DFS and OS rates for all patients were 93.0% and 97.8%. The 5-year OS rate was 98.6% in the radiotherapy first group and 96.4% in the chemotherapy first group ( P =0.191), and the corresponding DFS rate was 92.7% and 93.2% ( P =0.430), respectively. Among the patients with Luminal A subtype, the 5-year OS rate was 99.6% in the radiotherapy first group and 97.8% in the chemotherapy first group ( P =0.789). Among the patients with Luminal B subtype, the 5-year OS rate was 94.2% and 96.0%, respectively ( P =0.680). Among the patients with triple negative breast cancer, the 5-year OS rate was 100% and 90.9%, respectively, with statistically significant differences ( P =0.019). Among the patients with HER-2 positive breast cancer, The 5-year DFS rate was 80.1% and 100%, respectively ( P =0.045). Conclusions: The OS and DFS rates in the chemotherapy first group are not significantly different from those of radiotherapy first group after breast-conserving surgery. Patients with HER-2 positive breast cancer in chemotherapy first group have a much higher DFS rate than that of radiotherapy first group, whereas patients with triple negative breast cancer in radiotherapy first group have a better OS rate than that of chemotherapy first group. Further research is warranted to investigate the benefit of different molecular types in different sequencing of radiotherapy and chemotherapy after breast-conserving surgery.

Objective: To find phenotypic subgroups of patients with pT1-2N0 invasive breast cancer by means of cluster analysis and estimate the prognosis and clinicopathological features of these subgroups., Methods: From 1999 to 2013, 4979 patients with pT1-2N0 invasive breast cancer were recruited for hierarchical clustering analysis. Age (≤40, 41-70, 70+ years), size of primary tumor, pathological type, grade of differentiation, microvascular invasion, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were chosen as distance metric between patients. Hierarchical cluster analysis was performed using Ward's method. Cophenetic correlation coefficient (CPCC) and Spearman correlation coefficient were used to validate clustering structures., Results: The CPCC was 0.603. The Spearman correlation coefficient was 0.617 (P<0.001), which indicated a good fit of hierarchy to the data. A twelve-cluster model seemed to best illustrate our patient cohort. Patients in cluster 5, 9 and 12 had best prognosis and were characterized by age >40 years, smaller primary tumor, lower histologic grade, positive ER and PR status, and mainly negative HER-2. Patients in the cluster 1 and 11 had the worst prognosis, The cluster 1 was characterized by a larger tumor, higher grade and negative ER and PR status, while the cluster 11 was characterized by positive microvascular invasion. Patients in other 7 clusters had a moderate prognosis, and patients in each cluster had distinctive clinicopathological features and recurrent patterns., Conclusions: This study identified distinctive clinicopathologic phenotypes in a large cohort of patients with pT1-2N0 breast cancer through hierarchical clustering and revealed different prognosis. This integrative model may help physicians to make more personalized decisions regarding adjuvant therapy.