Breast Cancer : Basic and Clinical Research最新文献

Background: Breast cancer is the most prominent cancer type to affect women. Surgical treatment of invasive breast cancers involves mastectomy. Due to mastectomy, women are subjected to social, emotional, and cultural problems which need to be addressed.

Objective: The objective of the study is to understand how women cope with body image-related issues, trauma, anxiety, and depression post-mastectomy.

Design: A systematic literature review was conducted for understanding the coping in post-mastectomy patients. The methods for identifying the studies were based on Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines.

Databases: Medline/PubMed, PsycInfo, and Cochrane databases were used for searching relevant articles. A final of 19 studies were analyzed for the work.

Methods: Search strings such as "coping strategies and post mastectomy," "body image coping and post mastectomy" and "anxiety coping and post mastectomy" were used for identification of references from databases. Eligibility criteria were used for finalizing the references.

Results: Analysis of the 19 studies has clearly shown that women who undergo mastectomy suffer from anxiety, stress, and trauma. This study has observed that women have problems with their body image post-mastectomy along with bouts of depression. Self-coping has been observed in relatively few studies. Psychological interventions before surgery have been observed to be a better coping strategy. In most of the studies, women opted for breast reconstruction to overcome the trauma associated with mastectomy.

Conclusion: Mastectomy has a severe impact on women's appearance and psychology. Breast reconstruction and acceptance have played an important role in coping among these women. However, breast reconstruction is not accepted by many women due to a multitude of factors. Thus, it is essential to have proper intervention programs in place to ensure women can cope with this situation and can lead healthy lives.

Registration: Systematic literature review (SLR) is submitted to PROSPERO. The application confirmation number is 449135.Registration awaited from the database.

Background: Breast cancer (BC) screening with mammography reduces mortality but considers currently only age as a risk factor. Personalized risk-based screening has been proposed as a more efficient alternative. For that, risk prediction tools are necessary. Genome-wide association studies have identified numerous genetic variants (single-nucleotide polymorphisms [SNPs]) associated with BC. The effects of SNPs are combined into a polygenic risk score (PRS) as a risk prediction tool.

Objectives: We aimed to develop a clinical-grade PRS test suitable for BC risk-stratified screening with clinical recommendations and implementation in clinical practice.

Design and methods: In the first phase of our study, we gathered previously published PRS models for predicting BC risk from the literature and validated them using the Estonian Biobank and UK Biobank data sets. We selected the best performing model based on prevalent data and independently validated it in both incident data sets. We then conducted absolute risk simulations, developed risk-based recommendations, and implemented the PRS test in clinical practice. In the second phase, we carried out a retrospective analysis of the PRS test's performance results in clinical practice.

Results: The best performing PRS included 2803 SNPs. The C-index of the Cox regression model associating BC status with PRS was 0.656 (SE = 0.05) with a hazard ratio of 1.66. The PRS can stratify individuals with more than a 3-fold risk increase. A total of 2637 BC PRS tests have been performed for women between the ages 30 and 83. Results in clinical use overlap well with expected PRS performance with 5.7% of women with more than 2-fold and 1.4% with more than 3-fold higher risk than the population average.

Conclusion: The PRS test separates different BC risk levels and is feasible to implement in clinical practice.

Background: Metastatic triple-negative breast cancer (mTNBC) is an aggressive subtype of breast cancer with poor survival. Currently, the literature lacks comprehensive real-world evidence on locally recurrent and mTNBC patients. To validate the optimal treatment for patients with mTNBC, real-world evidence in combination with data from clinical trials must be evaluated as complementary.

Objectives: The objective of the study is to examine outcomes and treatment patterns of patients with advanced triple-negative breast cancer (TNBC) utilizing real-world data of patients from all oncology sites across Denmark.

Design: This is a retrospective, non-interventional, multi-site, population-based observational study conducted across all oncology departments in Denmark.

Methods: We included all women diagnosed with metastatic or locally recurrent TNBC from January 1, 2017, to December 31, 2019, using the national Danish Breast Cancer Group database. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in the first to third treatment line.

Results: The study included 243 women diagnosed with metastatic or recurrent TNBC. The median OS (mOS) was 11.6 months after the first line of treatment, 6.5 months after the second line, and 6.5 months after the third line. De novo mTNBC was associated with shorter OS (mOS: 8.3 vs 14.2 months), and those with a relapse within 18 months of primary diagnosis had shorter OS than those with a relapse after 18 months (mOS: 10.0 vs 18.2). In the first line, taxane was the preferred choice of treatment for patients with de novo mTNBC, whereas capecitabine was preferred for patients with recurrent TNBC.

Conclusions: This real-world, nationwide study demonstrated poor OS among patients with metastatic or recurrent TNBC, with a mOS of 11.6 months (95% CI, 9.9-17.3). Patients who presented with de novo mTNBC or who had a relapse of their breast cancer within 18 months of primary diagnosis had shorter OS.

Registration: The study was registered and approved by the Danish Capital Regions research overview (P-2021-605).

Background: Homologous recombination deficiency (HRD) is the hallmark of breast cancer gene 1/2 (BRCA1/2)-mutated tumors and the unique biomarker for predicting response to double-strand break (DSB)-inducing drugs. The demonstration of HRD in tumors with mutations in genes other than BRCA1/2 is considered the best biomarker of potential response to these DSB-inducer drugs.

Objectives: We explored the potential of developing a practical approach to predict in any tumor the presence of HRD that is similar to that seen in tumors with BRCA1/2 mutations using next-generation sequencing (NGS) along with machine learning (ML).

Design: We use copy number alteration (CNA) generated from routine-targeted NGS data along with a modified naïve Bayesian model for the prediction of the presence of HRD.

Methods: The CNA from NGS of 434 targeted genes was analyzed using CNVkit software to calculate the log2 of CNA changes. The log2 values of various sequencing reads (bins) were used in ML to train the system on predicting tumors with BRCA1/2 mutations and tumors with abnormalities similar to those detected in BRCA1/2 mutations.

Results: Using 31 breast or ovarian cancers with BRCA1/2 mutations and 84 tumors without mutations in any of 12 homologous recombination repair (HRR) genes, the ML demonstrated high sensitivity (90%, 95% confidence interval [CI] = 73%-97.5%) and specificity (98%, 95% CI = 90%-100%). Testing of 114 tumors with mutations in HRR genes other than BRCA1/2 showed 39% positivity for HRD similar to that seen in BRCA1/2. Testing 213 additional wild-type (WT) cancers showed HRD positivity similar to BRCA1/2 in 32% of cases. Correlation with proportional loss of heterozygosity (LOH) as determined using whole exome sequencing of 51 samples showed 90% (95% CI = 72%-97%) concordance. The approach was also validated in an independent set of 1312 consecutive tumor samples.

Conclusions: These data demonstrate that CNA when combined with ML can reliably predict the presence of BRCA1/2 level HRD with high specificity. Using BRCA1/2 mutant cases as gold standard, this ML can be used to predict HRD in cancers with mutations in other HRR genes as well as in WT tumors.

Background: Breast cancer is the most common non-cutaneous malignancy and the second leading cause of cancer mortality in the United States. Breast cancer is a heterogeneous disease; diagnosis at an early stage renders it potentially curable, whereas advanced metastatic disease carries a worse prognosis.

Objectives: To investigate whether hepatic steatosis (HS) is associated with liver metastases in patients with newly diagnosed stage IV female breast cancer patients (either de novo metastatic breast cancer or recurrent metastatic breast cancer) using non-contrast computed tomography (CT) as a marker of HS.

Design: Retrospective analysis.

Methods: We retrospectively identified 168 patients with stage IV breast cancer with suitable imaging from a prospectively maintained oncologic database. Three radiologists manually defined hepatic regions of interest on non-contrast CT images, and attenuation data were extracted. HS was defined as a mean attenuation <48 Hounsfield units. The frequency of hepatic metastatic disease was calculated for patient with and without HS. Relationships between HS and various patient (age, body mass index, race) and tumor (hormone receptor status, HER2 status, tumor grade) characteristics were also analyzed.

Results: There were 4 patients with liver metastasis in the HS group (41 patients) versus 20 patients with liver metastases in the non-HS group (127 patients). The difference in frequencies of liver metastases among patients with (9.8%) versus without (15.7%) hepatic steatosis (odds ratio = 1.72 [0.53-7.39]) was not statistically significant (P = .45). Body mass index was significantly higher (P = .01) among patients with hepatic steatosis (32.2 ± 7.3 vs 28.8 ± 7.1 kg/m²). Otherwise, there were no significant differences between patients with versus without HS with respect to regarding age, race, hormone receptor status, HER2 status, or tumor grade.

Conclusion: The frequency of hepatic metastatic disease in patients with stage IV breast cancer is similar for steatotic and non-steatotic livers.

Purpose: Breast cancer is the most diagnosed cancer and the leading cause of cancer death in women globally, and mesenchymal stem cells have been widely implicated in tumour progression. This systematic review and meta-analysis seeks to identify and summarise existing literature on the effects of human mesenchymal stem cells (hMSCs) on the migration of breast cancer cells (BCCs) in vitro, to determine the direction of this relationship according to existing research and to identify the directions for future research.

Methods: A systematic literature search was conducting using a collection of databases, using the following search terms: in vitro AND mesenchymal stem cells AND breast cancer. Only studies that investigated the effects of human, unmodified MSCs on the migration of human, unmodified BCCs in vitro were included. Standardised mean differences (SMDs) were calculated to determine pooled effect sizes.

Results: This meta-analysis demonstrates that hMSCs (different sources combined) increase the migration of both MDA-MB-231 and MCF-7 cell lines in vitro (SMD = 1.84, P = .03 and SMD = 2.69, P < .00001, respectively). Importantly, the individual effects of hMSCs from different sources were also analysed and demonstrated that MSCs derived from human adipose tissue increase BCC migration (SMD = 1.34, P = .0002) and those derived from umbilical cord increased both MDA-MB-231 and MCF-7 migration (SMD = 3.93, P < .00001 and SMD = 3.01, P < .00001, respectively).

Conclusions: To our knowledge, this is the first systematic review and meta-analysis investigating and summarising the effects of hMSCs from different sources on the migration of BCCs, in vitro.

Prognostic and predictive factors for early and late distant distance recurrence risk in estrogen-receptor positive and HER2-receptor negative early breast cancer are well known, but not all these variables work equally for the prediction. The following are the most widely accepted variables for categorizing risk levels: clinic-pathologic features (tumor size, lymph node involvement, histological grade, age, menopausal status, Ki-67 expression, estrogen, and progesterone expression), primary systemic treatment response (pathologic response and/or Ki-67 downstaging), and gene expression signatures stratification. Treatment guidelines from cancer societies and collaborative groups, online predict-tools, real-world data and experts' opinion recommends different adjuvant strategies (chemotherapy, endocrine therapy, ovarian suppression, olaparib, or abemaciclib) depending on the low (< 10%), intermediate (10%-20%) or high-risk of distance recurrence at least in the first 5 years. Multiple randomized prospective trials were updated in 2022, that evidence allow us to perform a stratification of risk in pre- and postmenopausal women with estrogen-receptor positive and HER2-receptor negative early breast cancer based on a combination of clinic-pathologic features and genomic assays and guide the adjuvant systemic treatment recommendation for those with high risk.

Background: The TP53 signature that predicts the mutation status of TP53 has been shown to be a prognostic factor and predictor of neoadjuvant chemotherapy (NAC) response.

Objectives: The current study sought to investigate the utility of the TP53 signature for predicting pathological complete response (pCR) and its prognostic significance among patients with residual disease (RD).

Design: The study followed a retrospective cohort study design.

Methods: Patients with T1-3/N0-1 from a cohort of those with HER2-negative breast cancer who received NAC were selected. Ability to predict pCR was evaluated using odds ratio, positive and negative predictive values, sensitivity, and specificity. Prognostic factors in the RD group were explored using the Cox proportional hazards model with distant recurrence-free survival (DRFS). Four independent cohorts were used for validation.

Results: A total of 333 eligible patients were classified into the TP53 mutant signature (n = 154) and wild-type signature (n = 179). Among the molecular and pathological factors, the TP53 signature had the highest predictive power for pCR. In 4 independent cohorts (n = 151, 85, 104, and 67, respectively), pCR rate in TP53 mutant signature group was significantly higher than that in the wild-type group. Univariate and multivariate analyses on DRFS in the RD group identified the TP53 signature and nodal status as independent prognostic factors, with the former having a better hazard ratio than the latter. After comparing DRFS between 3 groups (pCR, RD/TP53 wild-type signature, and RD/TP53 mutant signature groups), the RD/TP53 mutant signature group showed significantly worse prognosis compared with others. The RD/TP53 wild-type signature group did not exhibit inferior DRFS compared with the pCR group.

Conclusion: Our results showed that the TP53 mutant signature can predict pCR and that combining pathological response and TP53 mutant signature allows for the identification of subgroups with truly poor prognosis.

Background: Contrast-enhanced mammography (CEM) is an emerging breast imaging modality. Clinical data is scarce.

Objectives: To summarize clinical evidence on the use of iopromide in CEM for the detection or by systematically analyzing the available literature on efficacy and safety.

Design: Systematic review and meta-analysis.

Data sources and methods: Iopromide-specific publications reporting its use in CEM were identified by a systematic search within Bayer's Product Literature Information (PLI) database and by levering a recent review publication. The literature search in PLI was performed up to January 2023. The confirmatory-supporting review publication was based on a MEDLINE/EMBASE + full text search for publications issued between September 2003 and January 2019. Relevant literature was selected based on pre-defined criteria by 2 reviewers. The comparison of CEM vs traditional mammography (XRM) was performed on published results of sensitivity and specificity. Differences in diagnostic parameters were assessed within a meta-analysis.

Results: Literature search: A total of 31 studies were identified reporting data on 5194 patients. Thereof, 19 studies on efficacy and 3 studies on safety. Efficacy: in 11 studies comparing iopromide CEM vs XRM, sensitivity was up to 43% higher (range 1%-43%) for CEM. Differences in specificity were found to be in a range of -4% to 46% for CEM compared with XRM. The overall gain in sensitivity for CEM vs XRM was 7% (95% CI [4%, 11%]) with no statistically significant loss in specificity in any study assessed. In most studies, accuracy, positive predictive value, and negative predictive value were found to be in favor of CEM. In 2 studies comparing CEM with breast magnetic resonance imaging (bMRI), both imaging modalities performed either equally well or CEM tended to show better results with respect to sensitivity and specificity. Safety: eight cases of iopromide-related adverse drug reactions were reported in 1022 patients (0.8%).

Conclusions: Pertinent literature provides evidence for clinical utility of iopromide in CEM for the detection or confirmation of breast cancer. The overall gain in sensitivity for iopromide CEM vs XRM was 7% with no statistically significant loss in specificity.

Background: Breast self-examination (BSE) is an important part of health care for all women in every stage of life. This study aimed to investigate the effect of theory of planned behavior (TPB) on doing BSE in a sample of Iranian women.

Methods: A cross-sectional study was carried out to examine the factors affecting the BSE in 400 women. Then, a quasi-experimental study was conducted on 200 subjects (100 in experimental group and 100 in control group). The educational intervention for the experimental group consisted of 8 training sessions. A questionnaire including demographic characteristics, knowledge, and constructs of TPB was used to measure BSE performance before and 6 months after the intervention. Constructs of attitude, subjective norms, and perceived behavioral control predicted the intention to do the BSE.

Results: The mean age of the subjects was 31.65 ± 7.59 years. The studied variables predicted 38.7% of behavioral intention (P < .001, odds ratio = 0.387). Six months after the intervention, the experimental group showed a significant increase in the knowledge, attitude, perceived behavioral control, subjective norms, intention, and BSE performance compared with the control group (P < .001).

Conclusions: This study showed that educational intervention based on the TPB was effective in promoting breast cancer screening behavior such as BSE. Therefore, it is suggested that health educators and health care planners use educational texts based on these constructs of TPB to increase their influence on individuals via screening behavior for breast cancer.