Search

Proton radiotherapy may be a compelling technical option for the treatment of breast cancer due to its unique physical property known as the "Bragg peak." This feature offers distinct advantages, promising superior dose conformity within the tumor area and reduced radiation exposure to surrounding healthy tissues, enhancing the potential for better treatment outcomes. However, proton therapy is accompanied by inherent challenges, primarily higher costs and limited accessibility when compared to well-developed photon irradiation. Thus, in clinical practice, it is important for radiation oncologists to carefully select patients before recommendation of proton therapy to ensure the transformation of dosimetric benefits into tangible clinical benefits. Yet, the optimal indications for proton therapy in breast cancer patients remain uncertain. While there is no widely recognized methodology for patient selection, numerous attempts have been made in this direction. In this review, we intended to present an inspiring summarization and discussion about the current practices and exploration on the approaches of this treatment decision-making process in terms of treatment-related side-effects, tumor control, and cost-efficiency, including the normal tissue complication probability (NTCP) model, the tumor control probability (TCP) model, genomic biomarkers, cost-effectiveness analyses (CEAs), and so on. Additionally, we conducted an evaluation of the eligibility criteria in ongoing randomized controlled trials and analyzed their reference value in patient selection. We evaluated the pros and cons of various potential patient selection approaches and proposed possible directions for further optimization and exploration. In summary, while proton therapy holds significant promise in breast cancer treatment, its integration into clinical practice calls for a thoughtful, evidence-driven strategy. By continuously refining the patient selection criteria, we can harness the full potential of proton radiotherapy while ensuring maximum benefit for breast cancer patients. [ABSTRACT FROM AUTHOR]

Deep-learning-based breast cancer image diagnosis is currently a prominent and growingly popular area of research. Existing convolutional-neural-network-related methods mainly capture breast cancer image features based on spatial domain characteristics for classification. However, according to digital signal processing theory, texture images usually contain repeated patterns and structures, which appear as intense energy at specific frequencies in the frequency domain. Motivated by this, we make an attempt to explore a breast cancer histopathology classification application in the frequency domain and further propose a novel multi-branch spectral channel attention network, i.e., the MbsCANet. It expands the interaction of frequency domain attention mechanisms from a multi-branch perspective via combining the lowest frequency features with selected high frequency information from two-dimensional discrete cosine transform, thus preventing the loss of phase information and gaining richer context information for classification. We thoroughly evaluate and analyze the MbsCANet on the publicly accessible BreakHis breast cancer histopathology dataset. It respectively achieves the optimal image-level and patient-level classification results of 99.01% and 98.87%, averagely outperforming the spatial-domain-dominated models by a large margin, and visualization results also demonstrate the effectiveness of the MbsCANet for this medical image application. [ABSTRACT FROM AUTHOR]

Background: Recently, there has been a growing focus on the prognostic significance of nutrition-related biomarkers. We attempted to explore the association between a novel albumin-related nutrition marker called "lymphocyte × albumin (LA)" and disease-free survival (DFS) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Methods: In total, 711 non-metastatic breast cancer patients who underwent NAC at two medical centers were retrospectively analyzed. We performed least absolute shrinkage and selection operator (LASSO) Cox regression analysis as well as multivariate Cox regression analyses to identify the variables associated with DFS and to establish a predictive nomogram. Results: The nomogram incorporated four variables based on the multivariate analysis of DFS in the training cohort: LA, ypN stage, ypT stage, and hormone receptor status. In comparison with the traditional TNM staging system, the nomogram demonstrated superior discrimination, calibration ability, and clinical usefulness in both the training set and internal and external validation sets. Furthermore, patients stratified into different risk groups resulted in significant differences in DFS. Conclusions: LA is an independent prognostic biomarker, and LA-based prognostic nomogram offers a more precise assessment of DFS for breast cancer patients treated with NAC, potentially serving as a valuable tool for personalized prognostic predictions. [ABSTRACT FROM AUTHOR]

To investigate the survival outcomes, patterns and risks of recurrence in cN3c breast cancer patients after multimodality therapy, as well as the predictors of candidates for ipsilateral supraclavicular (SCV) area boosting. Consecutive cN3c breast cancer patients from January 2009 to December 2020 were retrospectively reviewed. Based on nodal response to primary systemic therapy (PST), patients were categorized into three groups: clinical complete response (cCR) not achieved in SCV lymph nodal (SCLN, Group A), SCLN cCR but axillary node (ALN) did not achieve pathological complete response (pCR, Group B), cCR in SCLN and pCR in ALN (Group C). The median follow-up time was 32.7 months. The 5-year overall survival (OS) and recurrence-free survival (RFS) were 64.6% and 43.7% respectively. Multivariate analysis showed cumulative SCV dose and ypT stage, ALN response and SCV response to PST were significantly associated with OS and RFS respectively. Compared with Group A or B, Group C showed significantly improved 3 y-RFS (53.8% vs 73.6% vs 100%, p = 0.003), and the lowest rate of DM as first failure (37.9% vs 23.5% vs 0%, p = 0.010). In Group A, the 3 y-OS for patients receiving the cumulative SCV dose of ≥60 Gy versus <60 Gy was 78.0% versus 57.3% (p = 0.029). Nodal response to PST is an independent prognostic factor for survival and pattern of failure. A cumulative SCV dose of ≥60 Gy is positively associated with improved OS, especially in Group A. Our data supports the perspective of optimizing radiotherapeutic strategy based on nodal response. • CN3c breast cancer with SCLN cCR and ALN pCR after PST are potentially curable. • Nodal response to PST is an independent prognostic factor for cN3c breast cancer. • SCLN non-cCR, HR-negative, or HER2-positive patient may benefit from SCV boost. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Our study is one of the first studies focusing on BCRL and UED among Chinese early breast cancer patients. • Aggressive ALND remains the primary risk factor for BCRL and UED. • Our study confirmed the safety of replacing ALND with SLNB + RNI. [ABSTRACT FROM AUTHOR]

Purpose: The effect of adjuvant irradiation after mastectomy in early-stage breast cancer patients remains controversial. The present study aims to explore the clinical benefit obtained from adjuvant radiotherapy among post-mastectomy pT1-2N1 breast cancer patients who received adjuvant modern systemic therapy. Methods: Medical records of consecutive patients with pT1-2N1 breast cancer who received mastectomy in our institution between January 2009 and December 2016 were retrospectively reviewed. High-risk features consist of patient age, number of positive lymph nodes, T stage, and Ki67 index, which were developed previously at our institution using early-stage breast cancer patients after mastectomy without adjuvant radiotherapy. Differences of survival and local recurrence were compared between no-postmastectomy radiotherapy (PMRT) and PMRT group according to number of risk factors. The time-to-event curves were calculated by the Kaplan–Meier methods and compared by the log-rank test. Propensity score matching (PSM) was performed to reduce the imbalances in patient characteristics. Results: A total of 548 patients were enrolled (no-PMRT: 259 and PMRT: 289). After a median follow-up of 69 months, the 5-year rate of DFS, BCSS, and LRR in the overall cohort was 90.2%, 97.4%, and 3.6%, respectively. PMRT did not significantly improve DFS, BCSS, and LRRFS in the whole cohort. Patients were divided into low-risk (with no or one risk factor) and high-risk (with two or more risk factors) groups. According to the univariable and multivariable analysis, high-risk group (HR = 1.81, 95% CI 1.11–2.98, p = 0.02) was demonstrated as an independent risk factor for DFS. For the high-risk group, PMRT significantly improved DFS from 81.4% to 91.9% and BCSS from 95.5% to 98.6% and decreased the 5-year rate of LRR from 5.6% to 1.4%, respectively (p < 0.01, p = 0.05, and p = 0.06). However, no survival benefit from PMRT was observed in the low-risk group in terms of DFS, BCSS, and LRR (p = 0.45, p = 0.51, and p = 0.99, respectively). In multivariate analysis, PMRT remained an independent prognostic factor for DFS (HR = 0.50, 95% CI 0.24–1.00, p = 0.05) in the high-risk group. After PSM analysis, the survival benefit of PMRT was sustained in high-risk patients. Conclusion: PMRT significantly improved DFS in high-risk pT1-2N1 breast cancer patients, but not in low-risk patients. Independent validation of our scoring system is recommended. [ABSTRACT FROM AUTHOR]

Objective: The outbreak of COVID-19 pandemic has greatly impacted on radiotherapy (RT) strategy for breast cancer patients, which might lead to increased distressing psychological symptoms. We performed a multi-center cross-section survey to investigate prevalence of fear of cancer recurrence (FCR) and predictors for FCR in patients referred to RT during pandemic. Methods: 542 patients were consecutively enrolled from three regions in China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients' characteristics were collected using an information sheet, Fear of progression questionnaire-short form, Hospital Anxiety/Depression Scale and EORTC QLQ-C30. The hierarchical multiple regression models were performed. Results: 488 patients with complete data were eligible. The RT strategy was affected in 265 (54.3%) patients, including 143 with delayed RT initiation, 66 believing to have delayed RT initiation but actually not, 24 with RT interruptions, 19 shifting to local hospitals for RT and the remaining 13 influenced on both RT schedule and hospital level. The model explained 59.7% of observed variances in FCR (p<0.001) and showed that influence of RT strategy had significantly impacted on FCR (△R2 = 0.01, △F=2.966, p=0.019). Hospitals in Shanxi province (β=-0.117, p=0.001), emotional function (β=-0.19, p<0.001), social function (β=-0.111, p=0.006), anxiety (β=0.434, p<0.001) and RT interruption (β=0.071, p=0.035) were independent predictors. Conclusions: RT strategy for breast cancer patients was greatly influenced during pandemic. RT interruption is an independent predictor for high FCR. Our findings emphasize the necessity to ensure continuum of RT, and efforts should be taken to alleviate FCR through psychological interventions. [ABSTRACT FROM AUTHOR]

Aim: To establish and validate a nomogram for predicting prognosis of breast cancer patients with pN0-1 who were treated with mastectomy and without adjuvant radiotherapy. Material and Methods: The LASSO regression was performed to identify predictors of breast cancer-specific survival (BCSS), local regional recurrence (LRR) and distant metastasis (DM). Model performance was evaluated by the concordance index (C-index) and calibration plot. Results: The 5-year BCSS, LRR and DM rates for the entire cohort were 98%, 2% and 4%, respectively. LASSO regression analysis found that pathological T stage, number of positive LN, grade and Ki-67 were significant predictors for both BCSS and DM-free survival, while number of resected LN and PR status were predictors for DM-free survival. In addition, number of positive LN was the only significant predictor for developing LRR. The C-indexes for the 5-year BCSS and DM nomograms were 0.81 and 0.78 in the training data set, 0.65 and 0.70 in the testing set and 0.72 and 0.69 in the external validation set, respectively. Conclusion: Our prognostic nomograms accurately predict 5-year BCSS and DM-free survival in post-mastectomy breast cancer without adjuvant radiotherapy, which provides a useful tool to identify high-risk patients who could benefit from additional adjuvant therapy. [ABSTRACT FROM AUTHOR]

To determine whether the addition of regional nodal irradiation (RNI) to whole-breast irradiation (WBI) would improve outcomes over WBI alone in T1-2N1 breast cancer after breast-conserving surgery (BCS) and adjuvant systematic therapy. Data were obtained from two randomized controlled trials (NCT00174655 and NCT00312208). Univariate and multivariate Cox-regression analysis were performed to investigate predictors for overall survival and disease-free survival. A 1:1 propensity score matching (PSM) analysis was applied to eliminate selection bias. With median follow-up 80 months (range: 3–155 months), the 5-year local regional recurrence in the WBI group was 2% vs. 5% (p = 0.28) in the WBI + supraclavicular radiotherapy, and the rate of 5-year distant metastasis in the WBI group was 7% vs. 13% in the WBI + supraclavicular radiotherapy (p = 0.0748); In addition, the 5-year local regional recurrence in the WBI group was 3% vs. 9% (p = 0.19) in the WBI + internal mammary irradiation (IMI); However, the rate of 5-year distant metastasis in the in the WBI group was significantly lower than that in the WBI + IMI (8% vs. 24%, p = 0.036). After PSM, cox-regression analysis indicated that neither RNI nor IMI in combination with WBI in T1-2N1 breast cancer was associated with an improved overall survival and disease-free survival when compared to WBI alone. The addition of RNI to WBI in T1-2N1 breast cancer after BCS and adjuvant systematic therapy did not improve outcomes in comparison with WBI alone. Further studies are still needed to identify patients who would most benefit from RNI in this patient population. • The addition of RNI to WBI in unselected T1-2N1 breast cancer after BCS and adjuvant systematic therapy does not significantly improve outcomes in comparison with WBI alone. • Early stage (pT1-2N1) breast cancer after BCS represents a diverse population. • An individualized risk analysis based on clinical-genomic models is recommended to identify patients who would benefits or omit from RNI in further prospective studies. [ABSTRACT FROM AUTHOR]

Background: The progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC) is prevented by normal breast myoepithelial cells. Studies have suggested that EMT-associated genes were enriched in IDC in contrast to DCIS. This paper explored the relationship and potential mechanism between myoepithelial cells and EMT-associated genes in facilitating the transformation from DCIS to breast cancer. Methods: EMT markers and myoepithelial phenotypic markers in IDC, DCIS, and healthy breast tissue were characterized using immunohistochemical assay. Both in vivo and in vitro models were created to mimic the various cell–cell interactions in the development of invasive breast cancer. Results: We found that EMT markers were more abundant in invasive carcinomas than DCIS and adjacent normal breast tissue. Meanwhile, TGF-β1 regulated the morphology of MCF-7 (epithelial cells substitute) migration and EMT markers during the transformation from DCIS to invasive breast cancer. Additionally, TGF-β1 also regulated invasion, migration and cytokines secretion of MDA-MB-231 (myoepithelial cells substitute) and epithelial cells when co-cultured with MCF-7 both in vitro and in vivo. Conclusions: In conclusion, these findings demonstrated that both EMT phenotypes and cancer-associated myoepithelial cells may have an impact on the development of invasive breast cancer. [ABSTRACT FROM AUTHOR]

In this study, we attempted to assess the efficacy of upfront brain radiotherapy (RT) in breast cancer (BC) patients with brain metastases (BM). Medical records of 111 consecutive BC patients treated with WBRT or SRS between August 2009 and November 2017 in single center were retrospectively reviewed. Eighty patients received upfront brain RT after BM diagnosis and 31 had delayed RT. The median age at BM was 54 years (22‐77), with median KPS 80 (50‐90). The molecular BC subtypes of Luminal A, Luminal B, triple‐negative and HER2 overexpression were 16, 47, 27, and 19, respectively, with 2 unknown. Of them, 83 received WBRT after BM and 28 SRS. Median overall survival (OS) was significantly related to Breast‐GPA, as following: 6.5, 9.9, 14.4, and 24.5 months in 0‐1.0, 1.5‐2.0, 2.5‐3.0, and 3.5‐4.0 subgroups, respectively (P = 0.007). Univariate and multivariate analysis showed that KPS ≤70, infratentorial involvement, extracranial metastases, and no continuing systemic therapy were independent risk factors for OS. In the whole group, no significant difference in OS was found between upfront or delayed RT. For Breast‐GPA 0‐2.0 subgroup, upfront RT was associated with increased median OS (3.3 vs 9.8 months, P = 0.04). In GPA 2.5‐4.0 subgroup, the median OS for upfront and delayed RT was 13.8 and 16.5 months, respectively (P = 0.58). In conclusion, BCBM patients with better KPS, systemic therapy, without infratentorial involvement and extracranial metastases are associated with better OS. Patients with Breast‐GPA 0‐2.0 might benefit from upfront brain RT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: The mechanism of androgen receptor (AR) promoting tumour growth in oestrogen receptor‐negative (ER−) breast cancer (BC) is undetermined. Prostate‐derived ETS factor (PDEF) is highly restricted to the hormone‐regulated tissues of epithelial cells, such as those in the prostate, breast and other tissues. It has been demonstrated that PDEF expression is associated with AR in prostate cancer. In this research, we aimed to investigate the relationship between PDEF and AR in ER−BC. Methods and results: We immunohistochemically evaluated the correlation between PDEF and AR expression in 246 cases of ER− invasive BC, and investigated their relationship in ER−BC cell lines. The expression of PDEF was associated with the positive expression of AR (P < 0.001) and a worse survival rate (P = 0.006). PDEF+ tumours were significantly more often AR+ (P < 0.001). AR and PDEF were more often co‐expressed and the series of AR+PDEF+ (126 of 246, 51.2%) had a poor survival rate (P = 0.046). In Cox models, PDEF expression (P = 0.028) was an independent predictor for overall survival (OS). At the cellular protein and mRNA levels, our experiments also showed a statistically significant positive correlation between PDEF and AR, and that PDEF may be regulated by AR. Conclusions: PDEF is associated with markers of bad prognosis, supporting its role as a growth promoter in ER−BC. Our findings also provide evidence that PDEF is strongly correlated with AR expression in ER− breast cancer; it may be a downstream target gene of AR and a potential prognostic factor in ER−BC. [ABSTRACT FROM AUTHOR]

Radiotherapy is an indispensable unit of multidisciplinary treatment of breast cancer. Although the application of modern techniques has led to a significantly reduction in radiation-induced heart disease, it is still recognized as the leading causes of morbidity and mortality among breast cancer survivors. With the growing number of long-term survivors, it is important to understand the cardiovascular risks associated with radiotherapy. Questions exist regarding the existence or not of a safe radiation threshold dose that the heart (or its substructures) can receive and strategies to minimize risk of radiation. This paper aims to review the current understanding of radiation-induced cardiotoxicity and try to give answers to those unsettled issues based on current literatures. [ABSTRACT FROM AUTHOR]

Background: Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of celastrol has attracted much research attention.Methods and Results: Here, we report that celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol's miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in celastrol-treated cells. NF-κB inhibitor, like celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of celastrol or not.Conclusions: For the first time, we disclose that celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in celastrol-treated cancer cell lines. We thus provide a novel way to increase celastrol's anti-cancer effects. [ABSTRACT FROM AUTHOR]

Background. Left ventricular ejection fraction (LVEF) is used routinely to monitor cardiac dysfunction associated with breast cancer treatment. In this study the prevalence of early left ventricular diastolic dysfunction (LVDD) and its relationship to the dose-volume of the heart irradiated were evaluated in HER2-positive breast cancer patients undergoing concurrent trastuzumab and adjuvant radiotherapy (RT). Materials and Methods. Data from 40 breast cancer patients treated with concurrent trastuzumab and left-sided adjuvant RT between September 2011 and October 2012 were collected prospectively. For comparison, 32 patients treated with concurrent trastuzumab and right-sided adjuvant RT and 71 patients treated with left-sided RT alone were collected retrospectively. Echocardiography was obtained before RT, immediately following RT, and 3 and 6 months after RT. Doses to the heart and left ventricle (LV) were quantified. Results. Prior to RT with concurrent trastuzumab, 11 of 29 (left) and 8 of 25 (right) patients with normal baseline left ventricular diastolic function (LVDF) developed LVDD. In patients receiving left-sided RT alone, 12 of 61 patients with normal baseline LVDF developed LVDD. Dmean, D15-D40, D60-D70, and V3-V10 of the LV were significantly higher in patients who developed LVDD after concurrent trastuzumab and left-sided RT. In contrast, only two patients developed grade 1 LVEF decrease after both concurrent treatment and left-sided RT alone. Conclusion. Changes in LVDF compared with LVEF are more sensitive for early detection of cardiotoxicity. The dose-volume of the heart contributes significantly to the risk of LVDD in patients with left-sided breast cancer treated concurrently with trastuzumab. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy and toxicity of concurrent radiation therapy (RT) and paclitaxel in the treatment of unresectable locoregionally recurrent breast cancer (RBC) after mastectomy as primary treatment.Methods: This was a prospective monocentric study of 51 patients (pts) diagnosed with unresectable locoregionally RBC after mastectomy and treated between 2008 and 2012. Radiotherapy (RT) was delivered at 60 Gy in 30 treatment fractions to recurrent sites. Chemotherapy was weekly paclitaxel of 50 mg/m2 for 5 weeks. All pts. underwent clinical examination, CT or PET/CT every 3 months in first 2 years and then every 6 months. Tumor response was evaluated clinically and by CT using the RECIST criteria. Toxicity was assessed weekly during RT by the NCI common toxicity criteria (version 3.0).Results: Fifty-one pts. with 61 recurrent sites were studied. The median age was 49 years. Sites of RBC were chest wall in 20 patients (32.8%), supraclavicular in 19 (31.1%), axilla in 11 (18.0%), and internal mammary lymph nodes in the remaining 11 (18.0%). RBC presented as single in 25 pts., multiple in 20 pts. and diffuse growth in 6 pts. Clinical response was observed in 47 pts. (92.2%), with 36 (70.6%) complete and 11 (21.6%) partial responses. Two patients (3.9%) presented with stable disease and 2 progressive disease. The cumulative local progression-free survival rate was 62.8% at 2 year and 53.0% at 5 years after treatment. No grade 4 toxicity was observed. Grade 3 radiation dermatitis and leukocytopenia were observed in 10 (19.6%) and 12 (23.5%) pts., respectively. One patient experienced grade 2 pneumonitis.Conclusions: Concurrent RT and weekly paclitaxel could be an effective therapeutic option for unresectable locoregionally recurrent breast cancer after mastectomy with an acceptable toxicity profile. [ABSTRACT FROM AUTHOR]

Background: Adherent junction associated protein 1 (AJAP1), a typical molecule of adherent junctions, has been found to be a tumor suppressor in many cancer types. Aberrant activation of β-catenin has been demonstrated to be associated with malignant biological properties of tumors including breast cancer. This study aimed to investigate the function and mechanism of AJAP1-mediated β-catenin activity of breast cancer lines in vitro and in breast cancer patients. Methods: AJAP1 and β-catenin expressions in breast cancer tissues and cell lines were detected by immunohistochemistry, western blotting and qRT-PCR. The EGF/EGFR axis-mediated AJAP1 attenuated β-catenin nuclear location was measured by western blotting, immunofluorescence assay, co-immunoprecipitation, luciferase assay and ubiquitination assays. Furthermore, the function of AJAP1 and β-catenin regulated breast cancer progression was explored both in vivo and in vitro. Results: It was found that AJAP1 had a high negative correlation with β-catenin nuclear expression and was a novel tumor suppressor in breast cancer. AJAP1 loss can mediate β-catenin accumulated in cytoplasm and then transferred it to the nucleus, activating β-catenin transcriptional activity and downstream genes. Additionally, β-catenin can reverse the invasion, proliferation ability and tumorigenicity of the depletion of AJAP1 caused both in vivo and in vitro. Besides, EGF/EGFR also involved in the process of AJAP1-depiction induced β-catenin transactivation to the nucleus. More importantly, EGFR depletion/AJAP1 knocked down promoted the progression of breast cancer by regulating the activity of β-catenin nuclear transactivation. Conclusion: This study demonstrated that AJAP1 acted as a putative tumor suppressor while β-catenin nuclear localization positively fed back on EGF/EGFR-attenuated AJAP1 expression in breast cancer, which might be beneficial to develop new therapeutic targets for decreasing nuclear β-catenin-mediated malignancy in breast cancer. [ABSTRACT FROM AUTHOR]

Background: The most striking feature of molecular apocrine breast cancer (MABC) is the expression of androgen receptor (AR). We report here the mechanism of the AR in regulating the behavior of MABC. Methods: The MABC cell line, MDA-MB-453, and the nonMABC cell line, MCF7, were used in this study. The effect of dihydrotestosterone (DHT) and heat shock protein 27 (HSP27) on cell proliferation was quantified using the cell counter kit-8 (CCK8) and clonogenic assays in vitro and by a xenograft tumor model in vivo. The expression of the AR and HSP27 was analyzed using western blot, qPCR, and immunofluorescence assays. Complexes of the AR and HSP27 were detected by co-immunoprecipitation (Co-IP). Results: In MDA-MB-453 cells, DHT promoted cell proliferation and stimulated AR and HSP27 translocation from the cytoplasm to the nucleus, whereas, it inhibited MCF7 cell growth, and only the AR translocated into the nucleus. HSP27 knock-down decreased the proliferative ability of MDA-MB-453 cells, which could be rescued by DHT, while HSP27 and DHT had synergistic effects on MCF7 cells. HSP27 phosphorylation was a prerequisite for AR translocation into the nucleus, especially phosphorylation on serine 82. In addition, DHT stimulated the tumorigenic and metastatic capacities of MDA-MB-453 cells, while HSP27 knock-down decreased the rate of tumor formation and induced apoptosis in cells. Conclusions: The results suggest that HSP27 assists the AR in regulating the malignant behavior of MABC, and these findings might be helpful in the treatment of MABC. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignant tumor in women. With the development of genomics technology and medical frontier technology, the systemic treatment of breast cancer has gradually entered the era of personalized medicine. However, the decision-making of adjuvant radiotherapy for breast cancer still mainly relies on traditional clinicopathological factors, and there is a lack of scientific and reliable tools to guide precise radiotherapy in different populations. Hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer is the most common molecular subtype of breast cancer. The 21-Gene recurrence score (RS) test (Oncotype Dx™, Genomic Health, Redwood City, CA) is a commercially available genomic test for breast cancer. In this article, we reviewed the current research evidence on the use of 21-Gene RS test for radiotherapy decision-making in HR-positive HER2-negative early breast cancer. Current clinical studies support the predictive value of 21-Gene RS test for adjuvant radiotherapy, and several large-scale prospective clinical studies in this area are underway.