How Does the Interval Between Completion of Adjuvant Chemotherapy and Initiation of Radiotherapy Impact Clinical Outcomes in Operable Breast Cancer Patients?

PURPOSE: The aim of this study was to evaluate the impact of time to radiotherapy (TTR) after completion of chemotherapy (CT), and TTR after surgery, in breast cancer (BC) patients. PATIENTS AND METHODS: Continuous breast cancer patients treated with surgery and CT followed by radiotherapy (RT) from 2009 through 2015 were retrospectively reviewed. Patients were categorized into four groups with respect to TTR after CT, i.e. <4, 4-8, 8-12, and >12 weeks, and TTR after surgery, i.e. <147, 147-180, 180-202, and >202 days. The Cox proportional hazards model was used to identify the independent effect of TTRs. RESULTS: Overall, 989 patients were enrolled. Patients with a TTR of >12 weeks after CT showed significantly worse breast cancer-specific survival (BCSS) and overall survival (OS) compared with those who had a TTR of <4 weeks (BCSS: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.1-0.76; OS: HR 0.33, 95% CI 0.13-0.88), 4-8 weeks (BCSS: HR 0.23, 95% CI 0.08-0.66; OS: HR 0.29, 95% CI 0.11-0.8), and 8-12 weeks (BCSS: HR 0.22, 95% CI 0.05-0.96; OS: HR 0.23, 95% CI 0.06-0.99). TTR after surgery showed no significant association with survival outcomes in the entire cohort, except in patients with hormone receptor (HR)-positive disease and those receiving mastectomy. In HR-positive tumors, a TTR after CT of >12 weeks remained an independent predictor for adverse BCSS and OS. CONCLUSION: Initiation of RT beyond 12 weeks after CT might compromise survival outcomes. Efforts should be made to avoid delaying RT, especially after completion of CT and in patients with HR-positive tumors, positive lymph nodes, and those receiving mastectomy.

The Role of the Neo-Bioscore Staging System in Guiding the Optimal Strategies for Regional Nodal Irradiation Following Neoadjuvant Treatment in Breast Cancer Patients with cN1 and ypN0-1.

BACKGROUND: The role of regional nodal irradiation (RNI) in patients with cN1 breast cancer following neoadjuvant treatment (NAT) is still controversial. The Neo-Bioscore staging system has shown promising prospect in assessing individual prognosis after NAT, and we sought to evaluate the role of Neo-Bioscore in guiding RNI following NAT. METHODS: Medical records of 163 women with cN1 and ypN0-1 disease treated with NAT between 2009 and 2014 were retrospectively reviewed and a Neo-Bioscore was assigned to each patient. Survivals were calculated using the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was used to identify independent predictors by using Cox proportional hazards models. RESULTS: The median follow-up after surgery was 59.4 months. Of all 163 patients, 119 received RNI. At surgery, 36 patients (22.1%) had pathological complete response (pCR), while 89 patients (54.6%) achieved ypN0. In the whole cohort, RNI significantly improved distant metastasis-free survival (DMFS) on multivariable analysis. In the subgroup of patients with a Neo-Bioscore of 1-3, RNI significantly improved the 5-year DMFS rate of 97.0% versus 76.9% (p = 0.002), 5-year regional node recurrence-free survival rate of 95.5% versus 76.9% (p = 0.007), and 5-year overall survival rate of 100% versus 89.2% (p = 0.005). No significant difference in outcomes was found between the RNI and non-RNI groups in patients with a score of 4-6. CONCLUSIONS: In patients with cN1 and ypN0-1, RNI was found to significantly improve DMFS following NAT. Patients with a Neo-Bioscore of 1-3 are more likely to benefit from RNI, however a large prospective study is needed to confirm this finding.

The role of post-mastectomy radiotherapy in elderly patients with 1-3 positive lymph nodes breast cancer: An International Retrospective Double-Center Study.

This study evaluated the role of post-mastectomy radiotherapy (PMRT) in 111 patients with 1-3 positive nodes, aged 65 years or above between 2007 and 2013. In total, 64 received PMRT. The PMRT group had more aggressive tumor. Three patients suffered locoregional recurrences in each group at median follow-up of 50 months. PMRT has no significant impact on distant disease-free survival (DDRFS), recurrence-free survival (RFS) and overall survival (OS). In patients with tumors >5 cm, PMRT significantly improved DDRFS, RFS, and marginally prolonged OS. These results supported that PMRT should not be compromised in all elderly patients, especially in those with tumor >5 cm.

Percent Body Fat Change in Chinese Women After Adjuvant Chemotherapy for Breast Cancer.

BACKGROUND Weight gain is a common side effect observed in breast cancer (BC) patients undergoing adjuvant chemotherapy, although the characteristics and mechanism are not been fully understood. This study aimed to investigate percent body fat (%BF) change, and identify the associated risk factors among Chinese women receiving chemotherapy for BC. MATERIAL AND METHODS A prospective longitudinal study was conducted on a cohort of 140 Chinese female patients with BC between June 2016 and October 2017. Data on demographic and clinical features were collected using a standard protocol. Anthropometric parameters including body weight and %BF were measured before and after chemotherapy. Multiple logistic analysis was performed to identify the risk factors for %BF change. RESULTS A total of 52.9% and 58.6% of the 140 patients experienced gains in weight and %BF after chemotherapy, respectively, with mean increases of 2.1±1.9 kg and 1.3±2.2%, respectively. Fifty-eight patients gained %BF over 2.5% of the baseline value. Moreover, premenopausal women had a greater mean %BF gain than postmenopausal women (P=0.018). Logistic analysis showed that premenopausal status, younger age, multi-agent chemotherapy regimen, high-calorie diet, and decreased physical activity were independent variables that inducted %BF gain. CONCLUSIONS %BF gain occurred frequently in Chinese women after adjuvant chemotherapy for BC, especially in premenopausal women. An effort should be made to the management of %BF.

The importance of biopsy in clinically diagnosed metastatic lesions in patients with breast cancer.

BACKGROUND: Receptor status discordance, such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancer and metastatic lesions has been reported. The aim of this study was to evaluate the biopsy of clinically diagnosed metastatic lesions and to determine the changes in hormonal receptor and HER2 status of the metastatic lesions. METHODS: Sixty-three patients with clinically diagnosed metastatic breast cancer underwent an excisional biopsy or core needle aspiration guided by computed tomography/ultrasound. ER, PR and HER2 were assessed by immunohistochemistry (IHC). RESULTS: A total of 48 metastases (76.2%) and nine second primary malignancies (14.3%, seven primary lung cancers and two primary pancreatic cancers) were found. The discrepancies between ER, PR and HER2 status between the primary breast cancer and metastatic lesions were 14.6%, 16.7% and 8.3%, respectively. Six lesions (9.5%) were proved benign upon biopsy. CONCLUSIONS: The biopsy of clinically suspicious metastatic lesions could histologically confirm the diagnosis of metastasis, evaluate discrepancies between ER, PR and HER2 status and exclude secondary malignancy, which might change the therapeutic strategy for breast cancer patients.

[Use of rebiopsy for clinically diagnosed metastatic lesion in patients with breast cancer].

OBJECTIVE: To evaluate the roles of rebiopsy for clinically diagnosed metastatic lesion in detecting the changes of hormonal receptors and second malignancy. METHODS: The metastatic lesions were rebiopsied by core needle aspiration or incision in 42 patients with a clinical diagnosis of metastatic breast cancer by computed tomography or ultrasound. RESULTS: None of major complications occurred. Thirty-one metastases were proved pathologically. The discrepancies between primary breast cancer and metastatic lesions of estrogen receptor(ER), progesterone receptor(PR), HER-2 statuses were 22.6%, 25.8% and 9.7% respectively. And 7 second malignancies were found (16.7%, 5 primary lung and 2 primary pancreas cancers). Four patients showed no relapse through rebiopsy. CONCLUSION: The rebiopsy of clinically diagnosed metastatic breast cancer may find the discrepancies of ER, PR, HER-2 statuses and second malignancy so as to change the therapeutic strategies of patients.

[MRI outstands mammogram in sensitivity of breast ductal carcinoma in situ:an analysis of 122 cases].

OBJECTIVES: To compare the sensitivity of mammogram and breast dedicated MRI in detecting ductal carcinoma in situ with microinvaion (DCIS-MI) and ductal carcinoma in situ (DCIS) lesions, and to further investigate the independent predictive factors of mammogram and MRI sensitivity. METHODS: From August 2009 to November 2011, 122 consecutive confirmed breast cancer patients who had received operations were recruited for this clinical research. These patients were divided into two groups including DCIS (72 cases) and DCIS-MI (50 cases) based on pathologic reports. All the patients were female, with mean ages of 52.6 years and 54.4 years. Preoperative bilateral breast mammogram, breast dedicated MRI depictions and reports as well as histopathological reports were collected. RESULTS: Sensitivity of MRI outstood mammogram in each subgroups: 84.7% vs. 42.4% in DCIS (χ(2) = 27.028, P = 0.000), 94.0% vs. 80.0% in DCIS-MI group (χ(2) = 4.540, P = 0.040). And further analysis showed that MRI was more sensitive to high nuclear grade DCIS and DCIS-MI lesions than low nuclear grade ones (OR = 3.471, P = 0.031). RESULTS: of logistic regression analysis proved microcalcification was an independent predictive factor of mammogram sensitivity (OR = 11.287, P = 0.001). CONCLUSIONS: Sensitivity of breast dedicated MRI is superior to mammogram in detecting DCIS and DCIS-MI groups. Lesions with microcalcifiation is an independent predictive marker which meant that mammogram would achieve high detection rate in cancers presented calcification on mammogram image when compared with non-calcification. Diagnostic performance of breast MRI is less affected by clinical and pathological characteristics of the early stage breast cancer patients but further increased detection rate is observed in DCIS and DCIS-MI with high nuclear grade lesions which indicated that MRI could detect more early stage cancers with relative more aggression biological behaviour and provide these patients with early surgical interventions before possible progression to invasive breast cancers.

The influence of axillary surgery and radiotherapeutic strategy on the risk of lymphedema and upper extremity dysfunction in early breast cancer patients.

PURPOSE: To explore the risk factors for breast cancer-related lymphedema (BCRL) and upper extremity dysfunction (UED) in patients with early breast cancer after modern comprehensive treatment and to compare the toxicity of different treatment strategies. METHODS: From 2017 to 2020, a total of 1369 female patients with pT1-3N0-1M0 breast cancer who underwent adjuvant radiotherapy in our centre were retrospectively reviewed. BCRL and UED were identified by the Norman and QuickDASH questionnaires. The incidence, severity and risk factors for BCRL and UED were evaluated. RESULTS: After a median follow-up of 25 months, a total of 249 patients developed BCRL; axillary lymph node dissection (ALND), increased number of dissected nodes, right-sided and hypofractionated radiotherapy containing RNI were found to be significant risk factors (all p values < 0.05). The sentinel lymph node biopsy (SLNB)+ regional nodal irradiation (RNI) group had a significantly lower BCRL risk than the ALND + RNI group (10.8% vs. 32.5%, HR = 0.426, p = 0.020), while there was no significant difference between ALND vs. ALND + RNI or SLNB vs. SLNB + RNI. A total of 193 patients developed UED, and ALND (p = 0.02) was the only significant risk factor. The SLNB + RNI group had a significantly decreased risk of UED compared with the ALND + RNI group (7.5% vs. 23.9%, HR = 0.260, p = 0.001), and there was no significant difference between SLNB vs. SLNB + RNI or ALND vs. ALND + RNI. CONCLUSION: Aggressive ALND remains the primary risk factor for BCRL and UED while RNI does not. Thus, replacing ALND with tailored radiotherapy would be an effective preventive strategy in early breast cancer patients.

Hippo/YAP signaling choreographs the tumor immune microenvironment to promote triple negative breast cancer progression via TAZ/IL-34 axis.

Growing evidence suggests that the bidirectional interactions between cancer cells and their surrounding environment, namely the tumor microenvironment (TME), contribute to cancer progression, metastasis, and resistance to treatment. Intense investigation of the Hippo pathway, which controls multiple central cellular functions in tumorigenesis, was focused on cancer cells. However, the role of the Hippo pathway in modulating tumor-stromal interactions in triple-negative breast cancer remains largely unknown. Therefore, this study focused on revealing the effects of Hippo-YAP/TAZ signaling on the immune microenvironment. Our findings reveal that the activity of the Hippo pathway is associated with worse disease outcomes in TNBC and could increase TAM infiltration through the TAZ/IL-34 axis, leading to an immunosuppressive microenvironment and impairing the treatment efficacy of anti-PD-L1. Thus, the TAZ/IL-34 axis may serve as a novel target for TNBC patients.

Influence of Adjuvant Radiotherapy Timing on Survival Outcomes in High-Risk Patients Receiving Neoadjuvant Treatments.

Purpose: To determine the relationship between time to radiotherapy (TTR) and survival outcomes in breast cancer (BC) patients treated with neoadjuvant treatments (NATs). Methods: Continuous non-metastatic BC patients receiving NAT and adjuvant radiotherapy (RT) from 2009 to 2016 were retrospectively reviewed. A multivariable Cox model with restricted cubic splines (RCSs) was used to determine the panoramic relationship between TTR and survival outcomes. Multivariable analysis was used to control for confounding factors between the groups of TTR. Results: A total of 315 patients were included. The RCS modeling demonstrated a non-linear relationship between TTR and survival outcomes. The lowest risk for distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) was observed at the TTR of 12 weeks, and the lowest risk of BC-specific survival (BCSS) at 10 weeks. TTR was accordingly transformed into categorical variables as ≤10, 11-20, and >20 weeks. Multivariable analysis revealed that the TTR of ≤10 weeks was an independent prognostic factor for worse DMFS (HR = 2.294, 95% CI 1.079-4.881) and RFS (HR = 2.126, 95% CI 1.038-4.356) compared with the TTR of 10-20 weeks, while the is no difference in DMFS, RFS, and BCSS between TTR >20 weeks and TTR of 10-20 weeks. Conclusion: There exists a non-linear relationship between TTR after surgery and survival outcomes in patients treated with NAT. Early initiation of RT following surgery does not seem to be associated with a better therapeutic outcome. A relatively flexible recommendation of TTR could be adopted in clinical practice.

Postoperative Radiotherapy Contributes to the Survival Benefit of Breast-Conserving Therapy over Mastectomy.

Purpose: A survival benefit of breast-conserving therapy (BCT) over mastectomy has been shown in recent studies. This study aimed to explore differences in recurrence patterns between BCT and mastectomy and clarify the contribution of radiotherapy (RT) to the survival benefit of BCT. Methods: Consecutive patients with pT1-2/pN0-1/M0 breast cancer between 2009 and 2015 in our institution were retrospectively reviewed and compared in matched cohorts using 1 : 1 propensity score matching (PSM). Results: A total of 2370 patients were enrolled with a median follow-up of 75 (3-148) months. In the cohort without regional nodal irradiation (RNI), WBI was associated with significantly increased 10-year relapse-free survival (RFS), distant metastasis-free survival (DMFS), and regional recurrence-free survival (RRFS) compared with mastectomy alone. There were 419 pairs in the cohort without RNI and 87 pairs in the cohort with RNI after PSM. In the PSM cohort, improved 10-year RFS (95.4% vs. 82.7%, p < 0.05), DMFS (97.4% vs. 84.1%, p < 0.05), and RRFS (99.1% vs. 95.5%, p < 0.05) were observed in WBI compared with mastectomy alone. Regarding the first recurrence event, WBI demonstrated a significantly lower cumulative rate of distant metastases than mastectomy alone. There was no significant difference in survival outcomes between WBI plus RNI and PMRT before and after the PSM. In patients without RNI, mastectomy alone was significantly associated with unfavorable RFS (HR = 2.3, 95% CI 1.2-4.5, p < 0.05) and DMFS (HR = 2.5, 95% CI 1.1-5.8, p < 0.05). Conclusion: This study found the benefit of RFS and DMFS in BCT patients compared with those treated with mastectomy without RNI but not in those treated with RNI. We hypothesized that RT played an important role in reducing the risk of regional recurrence and distant metastases.

Hypofractionated versus conventional intensity-modulated radiation irradiation (HARVEST-adjuvant): study protocol for a randomised non-inferior multicentre phase III trial.

INTRODUCTION: Short course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40-42.5 Gy in 15-16 fractions has been established as a preferred option for whole breast irradiation. However, few evidences of hypofractionated regional nodal irradiation (RNI), especially involving internal mammary nodes (IMNs), could be available during the era of intensity-modulated radiation therapy (IMRT). Against this background, we design this trial to explore the hypothesis that HF-RT regimen involving RNI (including infraclavicular, supraclavicular nodes and IMNs) will be non-inferior to a standard schedule by using IMRT technique. METHODS AND ANALYSIS: This is an open-label randomised, non-inferior, multicentre phase III trial. Patients with breast cancer with an indication for RNI after breast conserving surgery or mastectomy are randomised at a ratio of 1:1 into the following two groups: hypofractionated regimen of 2.67 Gy for 16 fractions or conventional regimen of 2 Gy for 25 fractions. The dose was prescribed to ipsilateral chest wall or whole breast and RNI (including infraclavicular, supraclavicular nodes and IMNs, lower axilla if indicated). The trial plans to enrol a total of 801 patients and all patients will be treated using IMRT technique. The primary endpoint is 5-year locoregional recurrence. The secondary endpoints include 5-year distant metastasis free survival, invasive recurrence-free survival, overall survival, accumulative acute radiation-induced toxicity and accumulative late radiation-induced toxicity, cosmetic outcomes and quality of life. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine (version 2018-95-3) and approvals from ethical committee of each participating centre have also been obtained. Research findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03829553.

Accuracy of MRI in prediction of pathologic complete remission in breast cancer after preoperative therapy: a meta-analysis.

OBJECTIVE: Prediction of pathologic complete remission in breast cancer after preoperative therapy presents difficulties. We performed a meta-analysis to determine the ability of MRI to predict pathologic complete remission in patients with breast cancer after preoperative therapy. MATERIALS AND METHODS: Medical subject heading terms ("MRI" and "Breast Neoplasm") and key words ("neoadjuvant" or "primary systemic" or "preoperative" or "presurgery") were used for a literature search in the MEDLINE database. A meta-analysis of pooled data from eligible studies was performed to estimate the accuracy of MRI in predicting pathologic complete remission after preoperative therapy in patients with breast cancer. RESULTS: Twenty-five studies were included in this meta-analysis. Pooled weighted estimates of sensitivity and specificity were 0.63 (range, 0.56-0.70) and 0.91 (range, 90.89-0.92), respectively. Heterogeneity between studies was highly influenced by the pathologic complete remission rate, with a regression coefficient of -6.160 (p = 0.020). Subgroup analysis showed that the specificity of MRI in studies with a pathologic complete remission rate of > or = 20% was lower than that in studies with a pathologic complete remission rate of < 20% (p = 0.0003). CONCLUSION: This meta-analysis indicates that MRI has high specificity and relatively lower sensitivity in predicting pathologic complete remission after preoperative therapy in patients with breast cancer. The pathologic complete remission rate may influence the performance of MRI accuracy in this setting, which deserves further investigation.

Molecular subtype approximated by quantitative estrogen receptor, progesterone receptor and Her2 can predict the prognosis of breast cancer.

AIMS AND BACKGROUND: To investigate the clinicopathological characteristics and prognosis of breast cancer subtypes classified by quantitative estrogen receptor (ER), progesterone receptor (PR), and Her2. METHODS AND STUDY DESIGN: 923 patients with primary breast cancer having a median age of 53 years who were treated at the Cancer Hospital of Fudan University in Shanghai between January 2002 and June 2004 were retrospectively analyzed. Four molecular subtypes were constructed from the immunohistochemical results of quantitative hormone receptor (HR) and Her2 status. HR+ was defined as ER+ and PR+, HR+/- as ER/PR+ at lower levels or lacking either ER or PR, and HR- as both ER- and PR-. The four subtypes were HR+/Her2-, HR+/-/Her2-, HR-/Her2- (triple-negative), and Her2+. Clinical and pathological parameters, disease-free survival (DFS), and overall survival (OS) measurements were compared between patients with different molecular subtypes. RESULTS: The proportions of HR+/Her2-, HR+/-/Her2-, triple-negative, and Her2+ breast cancer were 36.6% (338/923), 22.9% (211/923), 20.6% (190/923), and 19.9% (194/923). The median follow-up was 49.0 months (4-77 months). In 145 cases disease recurrence or death occurred. In multivariate analysis with the HR+/Her2- subtype taken as the reference category, triple-negative and Her2+ subtypes were associated with increased recurrence and death with a hazard ratio (HR) of 2.05 (95% CI 1.31-3.20; P = 0.002) and 1.89 (95% CI 1.20-2.97, P = 0.006) for DFS and 2.84 (95% CI 1.45-5.55; P = 0.002) and 2.95 (95% CI 1.51-5.77, P = 0.002) for OS, respectively; the HR+/-/Her2- subtype was marginally associated with poor prognosis with HR 1.51 (95% CI 0.94-2.43; P = 0.088) and 1.90 (95% CI 0.92-3.94; P = 0.084) for DFS and OS, respectively. CONCLUSIONS: Breast cancer subtypes based on quantitative ER, PR, and Her2 may be predictive of prognosis. Patients whose tumors were not HR+/Her2- had a worse outcome in our study.

miR-106b-5p contributes to the lung metastasis of breast cancer via targeting CNN1 and regulating Rho/ROCK1 pathway.

OBJECTIVES: Breast cancer has been the second most prevalent and fatal malignancy due to its frequent metastasis to other organs. We aim to study the effects of a key miRNA-mRNA signaling in breast cancer. RESULTS: CNN1 was identified as the key gene in breast cancer by the bioinformatics analysis, and the downregulation of CNN1 in breast cancer tissues and cell lines was observed. Upregulating CNN1 inhibited cell survival, migration, invasion, and adhesion, but enhanced cell apoptosis. miR-106b-5p not only bound to CNN1 mRNA 3'UTR, but also promoted lung metastasis in vivo. Besides, the miR-106b-5p mimic enhanced breast cancer canceration by targeting CNN1 and activating Rho/ROCK1 signaling pathway. CONCLUSION: Overall, our results proved that miR-106b-5p promoted the metastasis of breast cancer by suppressing CNN1 and activating Rho/ROCK1 pathway. METHODS: Bioinformatics analysis was performed to select the key gene in breast cancer. The overexpression and knockdown of Calponin 1 (CNN1) in breast cancer cell lines were performed to conduct cell viability, migrating, invasion, proliferation, adhesion, and apoptosis experiments. To identify the role of miR-106b-5p and Rho/ROCK1 in CNN1-induced breast cancer, a dual-luciferase assay, tumor lung metastasis assay, transcript half-life assay, and Rho/ROCK1 inhibition assay were performed.

Pattern of distant metastases in inflammatory breast cancer - A large-cohort retrospective study.

Inflammatory breast cancer (IBC) is a fatal form of breast cancer. IBC patients present with unfavorable prognosis mainly attributable to high risk of distant metastasis. Thus, in this cohort study, we aimed to explore metastatic profiles of different molecular subtypes of IBC and elucidate the clinical and prognostic characteristics among different metastatic sites. Patients diagnosed as IBC between 2010 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Chi-square tests were performed to compare metastatic distribution among different molecular subtypes. We further used odds ratio calculation to analyze the combined metastatic patterns. Kaplan-Meier methods and multivariate Cox regression models were applied to analyze survival data among different metastatic organs. In total, we enrolled 635 IBC patients between 2010 and 2014 as the training cohort and 242 IBC patients between 2015 and 2016 as the validation cohort, All the included patients were recorded with known metastatic status, follow-up data and molecular subtype. In the present study, we elaborated the following three points: (1) Elucidating the distribution of single-organ metastases in IBC. Bone and brain were the most and least common metastatic lesions for all subtypes of IBC, separately. (2) Clarifying the combined metastatic patterns and tendency of co-metastases. Bi-organ metastasis occurred most frequently among all combined metastases. Several combinations, such as liver and bone, lung and brain, were preferential for bi-organ metastasis. (3) Analyzing prognostic values of single-organ and bi-organ metastases. All single-organ distal metastases were independent risk factors indicating an unfavorable prognosis. In conclusion, our results would provide more information for clinical decision and future studies.

A Risk Stratification Model for Predicting Overall Survival and Surgical Benefit in Triple-Negative Breast Cancer Patients With de novo Distant Metastasis.

Background and Aims: This research aimed to construct a novel model for predicting overall survival (OS) and surgical benefit in triple-negative breast cancer (TNBC) patients with de novo distant metastasis. Methods: We collected data from the Surveillance, Epidemiology, and End Results (SEER) database for TNBC patients with distant metastasis between 2010 and 2016. Patients were excluded if the data regarding metastatic status, follow-up time, or clinicopathological information were incomplete. Univariate and multivariate analyses were applied to identify significant prognostic parameters. By integrating these variables, a predictive nomogram and risk stratification model were constructed and assessed with C-indexes and calibration curves. Results: A total of 1,737 patients were finally identified. Patients enrolled from 2010 to 2014 were randomly assigned to two cohorts, 918 patients in the training cohort and 306 patients in the validation cohort I, and 513 patients enrolled from 2015 to 2016 were assigned to validation cohort II. Seven clinicopathological factors were included as prognostic variables in the nomogram: age, marital status, T stage, bone metastasis, brain metastasis, liver metastasis, and lung metastasis. The C-indexes were 0.72 [95% confidence interval [CI] 0.68-0.76] in the training cohort, 0.71 (95% CI 0.68-0.74) in validation cohort I and 0.71 (95% CI 0.67-0.75) in validation cohort II. Calibration plots indicated that the nomogram-based predictive outcome had good consistency with the recoded prognosis. A risk stratification model was further generated to accurately differentiate patients into three prognostic groups. In all cohorts, the median overall survival time in the low-, intermediate- and high-risk groups was 17.0 months (95% CI 15.6-18.4), 11.0 months (95% CI 10.0-12.0), and 6.0 months (95% CI 4.7-7.3), respectively. Locoregional surgery improved prognosis in both the low-risk [hazard ratio [HR] 0.49, 95% CI 0.41-0.60, P < 0.0001] and intermediate-risk groups (HR 0.55, 95% CI 0.46-0.67, P < 0.0001), but not in high-risk group (HR 0.73, 95% CI 0.52-1.03, P = 0.068). All stratified groups could prognostically benefit from chemotherapy (low-risk group: HR 0.50, 95% CI 0.35-0.69, P < 0.0001; intermediate-risk group: HR 0.34, 95% CI 0.26-0.44, P < 0.0001; and high-risk group: HR 0.16, 95% CI 0.10-0.25, P < 0.0001). Conclusion: A predictive nomogram and risk stratification model were constructed to assess prognosis in TNBC patients with de novo distant metastasis; these methods may provide additional introspection, integration and improvement for therapeutic decisions and further studies.

Clinicopathological features of the triple-negative tumors in Chinese breast cancer patients.

In order to analyze the clinicopathological features of Chinese triple negative tumors, we performed a retrospective study of 1993 female unilateral breast cancer patients undergoing surgery in Cancer Hospital of Fudan University, Shanghai, China. Survival curves were performed with Kaplan-Meier method and annual recurrence hazard was estimated by hazard function. We observed that the rate of larger tumors in triple negative patients was higher than that in HR+/ERBB2- women, but lower than that in ERBB2+ subgroup (P = 0.0001). In addition, 21.83% of triple negative patients had four or more axillary lymph nodes involved as compared to 27.40% of ERBB2+ women and 22.75% of HR+/ERBB2- subgroup (P = 0.0056). In the survival analysis, we found a statistical significance for recurrence-free survival (RFS) among the three subgroups (P = 0.0037), with the rate of 72.89% for ERBB2+ patients, 78.40% for HR+/ERBB2- ones and 75.76% for triple negative ones at the 11th year respectively. When it came to hazard peaks, discrepancies existed in different subgroups. Similar to HR+/ERBB2- patients, triple negative subgroup showed an early major recurrence surge peaking at approximately year 2.5 as opposed to ERBB2+ counterparts with a tapering sharp at the 1st year. Furthermore, the first peak of triple negative tumors was higher than that of HR+/ERBB2- patients, but lower than that of ERBB2+ ones. Therefore, our findings suggested biological characteristics and prognostic outlook of Chinese triple negative breast cancers might be more favorable and somewhat different from those in Western populations.

Breast cancer in a transitional society over 18 years: trends and present status in Shanghai, China.

As a metropolis with rapid social and economic development over the past three decades, Shanghai has a breast cancer incidence that surpasses all other cancer registries in China. In order to estimate the regular changing patterns of female breast cancer in urban Shanghai, population-based incidence data from 1975 to 2004 were studied. In addition, a one-hospital-based in-patient database of 7,443 female breast cancer patients treated surgically between January-1990 and July-2007 were reviewed, retrospectively. We observed that breast cancer incidence increased dramatically over the past 30 years and documented a peak incidence represented by the middle-age group (45-59 years), which emerged in the last 20 years. The incidence peak moved from the 40-44 year group in the previous two decades to the 50-54 year group in the most recent decade. Median age at diagnosis was earlier in Shanghai than in the western countries, although it increased from 47.5-year in 1990 to 50-year in 2007. Considerably higher exposure to reproductive risk factors and relatively fewer hormone-dependent cases were observed. The proportion of asymptomatic cases detected by screening gradually increased, as well as that of early-stage cases (from 78.6% in 1990 to 93.3% in 2007) and carcinoma in situ (14.7% in 2007). Analysis of surgical treatment patterns suggested a trend of less-invasive options. Both age of peak incidence and median age at diagnosis increase with time, which suggests that increased incidence trending along with increasing age, will be observed in the future. Consequently, specific screening protocol should be refined to consider birth cohorts.

The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives.

PALB2 has been recently identified as breast cancer susceptibility gene in western populations. To investigate the contribution of PALB2 mutations to Chinese non-BRCA1/BRCA2 hereditary breast cancer, we screened all coding exons and intron-exon boundaries of PALB2 in 360 Chinese women with early-onset breast cancer or affected relatives from five breast disease clinical centers in China by utilizing PCR-DHPLC and DNA sequencing analysis. Some genetic variants identified in the cases were then studied in 864 normal controls with no personal or family history of breast cancer. Two protein-truncating PALB2 mutations, 751C>T and 1050_1051delAAinsTCT, were identified in three separate families, and 751C>T was a recurrent mutation. Neither of them, however, were present in the controls (P=0.025). All the truncating mutations occurred in exon 4 of PALB2, and there were still three unclassified variants were detected in the same fragment. We found that exon 4 accounted for 44.1% (15/34) of the person-times carrying with any variant in our study. PALB2 mutations were responsible for approximately 1% of Chinese women with early-onset breast cancer and affected relatives. Our results suggested that a detection of exon 4 before the assay of the whole PALB2 gene might be a cost-effective approach to the screening of Chinese population.