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.

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.

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.

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.

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.

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.

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.

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.

Insulin-like growth factor-1, metabolic abnormalities, and pathological complete remission rate in HER2-positive breast cancer patients receiving neoadjuvant therapy.

Purpose: HER2-positive breast cancer (BC) achieving pathological complete remission (pCR) after neoadjuvant therapy (NAT) had a superior disease outcome. Dysmetabolism and stimulation of insulin-like growth factor 1 (IGF-1)-axis would increase BC risk, but we are lacking data for their association with pCR in HER2-positive+ BC. We aim to evaluate the pCR predictive value of above factors in HER2-positive BC patients receiving NAT. Patients and methods: HER2-positive BC patients receiving NAT ± trastuzumab were retrospectively included between January 2013 and December 2016. Data were compared between baseline at biopsy and surgery. Median value of IGF-1 expression was used as cutoff value to classify patients into low or high group. pCR was defined as no residual invasive carcinoma in breast and axilla. Results: Overall, 101 patients were included. Metabolic syndrome was diagnosed in 29 (28.71%) with an average of 1.71±1.51 metabolic disorders at baseline, significantly increased after NAT (2.12±1.54, P<0.001). Lipid metabolism factors, including triglycerides, TC, HDL-C and LDL-C significantly worsened after NAT (all P<0.05). Average post-NAT IGF-1 was 196.14±86.03 ng/mL (vs preNAT 186.41±75.03 ng/mL, P=0.182). pCR was achieved in 29 (28.71%) patients. pCR rate was 40.00% and 17.65% for those with low or high preIGF-1 level (P=0.013). Multivariate analysis found that low IGF-1 expression, but not any other metabolic variable, was significantly associated with higher pCR rate in whole population (OR: 3.83, 95%CI: 1.32-11.11, P=0.014) or in patients receiving NAT + trastuzumab (OR: 3.93, 95%CI: 1.13-13.63, P=0.031). With a median follow-up of 29.03 (range: 10.42-56.98) months, IGF-1 level was not associated with overall survival (P=0.328) or disease-free survival (P=0.288). Conclusion: Low IGF-1 level was related with higher pCR rate in HER2-positive BC patients receiving NAT, which deserves further clinical evaluation.

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.

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.

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.

Neutrophil-to-lymphocyte ratio, obesity, and breast cancer risk in Chinese population.

Breast cancer (BC), obesity, and metabolic syndrome (MetS) shared a common mechanism of dysregulated metabolism and inflammatory response in disease initiation. Neutrophil-to-lymphocyte ratio (NLR) is associated with adverse survival of BC patients. The aim of this study is to identify risk effect between NLR and BC in Chinese population with or without obesity and MetS. BC and age-matched breast benign disease (BBD) patients were retrospectively analyzed from Comprehensive Breast Health Center, Shanghai Ruijin Hospital. MetS was defined using AHA/NHLBI criteria. Individuals were classified into very low (0-1.30), low (1.31-1.67), intermediate (1.68-2.20), and high (>2.20) NLR subsets by each NLR quartile. In all, 1540 BC and 1540 BBD patients were included. Univariate and multivariate analysis found that NLR (OR: 1.27, 95% CI: 1.16-1.39, P < .001) and obesity (OR: 1.19, 95% CI: 1.00-1.42, P = .046) but not MetS (P = .060) were significantly associated with increased BC risk. Intermediate or high NLR substantially increased BC risk compared to very low NLR group (OR: 1.57, 95% CI: 1.29-1.92, P < .001; OR: 1.84, 95% CI: 1.50-2.25, P < .001; respectively) in whole population. Subgroup analysis found that the impact of higher NLR on BC risk was more obvious in patients without obesity (intermediate NLR, OR: 1.72, 95% CI: 1.37-2.16, P < .001; high NLR, OR: 1.92, 95% CI: 1.53-2.41, P < .001) or without MetS (intermediate NLR, OR: 1.70, 95% CI: 1.35-2.14, P < .001; high NLR, OR: 1.98, 95% CI: 1.57-2.51, P < .001). Higher preoperative NLR was found in BC patients compared with BBD patients. Intermediate to high NLR level substantially increased BC risk, which was more relevant for those without obesity or MetS.

Prognostic factors of survival in pathologic incomplete response patients with locally advanced breast cancer after neoadjuvant chemotherapy.

The study aims to identify clinical and pathological factors predictive of disease-free survival (DFS) and overall survival (OS) in locally advanced breast cancer (LABC) patients who do not have a pathologic complete response (no-pCR) of primary tumor after neoadjuvant chemotherapy (NC) with vinorelbine/epirubicin (VE) intravenous combination regimen. Retrospectively reviewed data of LABC patients in our Hospital. 97 patients who had no-pCR after NC were identified and enrolled in the study. All patients were treated with three cycles of VE intravenous administration before operation. Local-regional radiotherapy was offered to patients after the completion of chemotherapy followed by hormone therapy according to hormone receptor status. Neoadjuvant chemotherapy consisting of intravenous vinorelbine 25 mg/m on day 1 and 8 plus epirubicin 60 mg/m on day 1 was administered every 3 weeks. The relationship of survival with clinical and pathological factors was evaluated. Univariate analysis (log-rank tests) and multivariate analysis (Cox regression analysis) were performed to identify independent predictors for DFS and OS. Study was analyzed with a median follow-up of 65 months. The 5-year rates for DFS and OS were 58.0 and 68.5 %, respectively. Multivariate analysis revealed that three factors such as the estrogen receptor expression before NC (pre-ER), Ki-67 expression after NC (post-Ki-67), and pathological response of primary tumor (pRT) were independent prognostic factors of LABC patients (pre-ER and pRT for DFS, all three for OS). The DFS at 5 years was 73.8 % for patients without both factors, 51.5 % for patients with any one of both factors, and 10.3 % for patients with both factors. The OS at 5 years was 90.5 % for patients without these three factors, 64.3 % for patients with any one of these three factors, and 30.8 % for patients with any two of these three factors. Patients with all three factors died within 3 years. In LABC patients with no-pCR, three factors independently predicted of survival and, without those three high-risk factors, patients had the promising outcome.

Outcomes of adjuvant endocrine therapy and hormone receptor status change following neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: This retrospective study investigated the therapeutic benefit of adjuvant endocrine therapy (ET) in breast cancer patients with hormone receptor (HR) status change from positive to negative after neoadjuvant chemotherapy (NAC). METHODS: From December 2000 to November 2010, 97 eligible patients with a positive-to-negative switch of HR status after NAC were identified. All patients were categorized into 2 groups on the basis of the administration of ET: 57 ET-administered patients and 40 ET-naïve patients. Survival analyses were performed to examine the prognostic value of ET administration as well as other clinical and pathologic variables. RESULTS: The administration of ET was significantly associated with improved disease-free survival (p=0.018) in patients with a positive-to-negative switch of HR status. The 5-year disease-free survival rates were 77.0% and 55.5%, respectively, in ET-administered patients and ET-naïve patients. The 5-year overall survival rate for ET-administered patients was also higher than that of ET-naïve patients (81.3% vs. 72.7%, p=0.053), albeit this was statistically insignificant. CONCLUSIONS: This study revealed that patients with HR altered from positive to negative after NAC still benefit from ET. The HR status should be evaluated not only in specimens obtained during post-NAC surgery but also in specimens biopsied before NAC.

Long-term outcomes following adjuvant endocrine therapy in breast cancer patients with a positive-to-negative change of hormone receptor status following neoadjuvant chemotherapy.

The aim of the present study was to investigate whether breast cancer patients with changes from positive to negative in the hormone receptor following neoadjuvant chemotherapy (NAC) could benefit from adjuvant endocrine therapy (ET). Between December 2000 and November 2010, 97 eligible patients with a positive-to-negative switch of the hormone receptor status following NAC were identified. All the patients were categorized into two groups on the basis of the administration of ET: 57 ET-administered and 40 ET-naïve patients. Survival analyses were performed to examine the prognostic value of ET administration, as well as other clinical and pathological variables. The administration of ET was associated with a significantly improved disease-free survival (DFS) (P=0.018) in patients with a positive-to-negative switch of the hormone receptor status. The 5-year DFS rates were 77.0 and 55.5% in ET-administered and ET-naïve patients, respectively. The 5-year overall survival (OS) rate for ET-administered was also higher than that of the ET-naïve patients (81.3 vs. 72.7%, P=0.053), but the difference between the two groups did not reach a statistical significance. The present study revealed that patients with the hormone receptor that was altered from positive to negative following NAC benefit from ET, and the hormone receptor status should be evaluated not only in specimens obtained during post-NAC surgery, but also in specimens biopsied prior to NAC.

Both carboplatin and bevacizumab improve pathological complete remission rate in neoadjuvant treatment of triple negative breast cancer: a meta-analysis.

Triple negative breast cancer (TNBC) is associated with high pathological complete remission (pCR) rate in neoadjuvant treatment (NAT). TNBC patients who achieve pCR have superior outcome than those without pCR. A meta-analysis was done to evaluate whether integrating novel approaches into NAT can improve the pCR rate in TNBC. Medical subject heading terms (Breast Neoplasm) and key words (triple negative OR estrogen receptor (ER) negative OR HER2 negative) AND (primary systemic OR neoadjuvant OR preoperative) were used to select eligible studies. Experimental arm in each study was considered as the testing regimen, and control arm was defined as the standard regimen in this meta-analysis. A total of 11 studies with 14 paired regimens were included in the final analysis. Aggregate pCR rate was 37.3% and 44.6% in the standard and testing group, respectively. Novel approaches in the testing regimen significantly improved the pCR rate in NAT of TNBC patients compared with the standard regimen, with an odds ratio (OR) of 1.34 (95% confidence interval (CI) 1.11-1.62, P = 0.002). Considering specific regimens, we demonstrated the pCR rate to be much higher in the carboplatin-containing (OR = 1.80, 95% CI 1.39-2.32, P<0.001) or bevacizumab-containing regimens (OR = 1.36, 95% CI 1.11-1.66, P = 0.003) than in the control regimens. The addition of carboplatin in NAT had a pCR rate as high as 51.2% in TNBC patients, with an absolute pCR difference of 13.8% as compared with control regimens. No significant heterogeneity was identified among studies evaluating the addition of carboplatin or bevacizumab efficacy in NAT. This meta-analysis indicates that these novel NAT regimens have achieved a significant pCR improvement in TNBC patients, especially among patients treated with carboplatin-containing or bevacizumab-containing regimen. This can help us design appropriate trials in the adjuvant setting and guide clinical practice.

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.