Breast Cancer : Basic and Clinical Research最新文献

Juvenile fibroadenoma typically is seen in the adolescent patient and has distinctive clinical and histopathological features that are related to the early onset of the benign tumor. Only rarely can juvenile fibroadenoma occur as a prepubertal lesion or may be detected earlier in childhood, raising questions about differential diagnosis and management of the lesion. We present a case of very early first manifestation of juvenile fibroadenoma in a 2-year-old patient. Under clinical observation and conservative management over a 7-year period, there was no progression. At the age of 9 years, rapid growth of the lesion occurred causing clinical symptoms. Complete surgical excision resulted in a good clinical outcome. Histologically, the diagnosis of juvenile fibroadenoma was made. In summary, juvenile fibroadenoma is the most common breast neoplasia in adolescents and may cause excessive unilateral growth resulting in gross asymmetry and pain. However, it can be detectable in early childhood and after a dormant period of several years, as in this case, lead to sudden massive growth at the onset of puberty. The clinical management should include an interdisciplinary treatment approach with gynecology, pediatrics, and pediatric surgery to balance the risks and benefits of conservative management. Surgical removal can be safely postponed until it becomes necessary due to clinical symptoms.

Introduction: The purpose of this study was to determine the prognostic utility of vitamin D concentrations and BMI (body mass index) values and the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI) and the pan-immune-inflammation value (PIV) to predict the achievement of a complete response to neoadjuvant treatment (NAT) in patients with breast cancer. The correlations between systemic inflammatory response indices and vitamin D concentrations and BMI values were also analysed.

Material and methods: The study included 96 patients with breast cancer, prior to the start of NAT, of which 51 patients were diagnosed with triple-negative breast cancer (TNBC) and 45 patients with human epidermal growth factor receptor type 2 (HER2)-positive type.

Results: The SIRI and PIV indices were shown to be significantly higher in patients with TNBC (P = .001; P = .001) than in patients with HER2. There were no statistical differences in SII, SIRI, PIV, BMI, and vitamin D, according to the response to NAT treatment (pCR vs non-pCR). In the HER2+ group without pCR after NAT, there was a positive correlation of the SII coefficient with BMI values (R = .41; P = .045). Furthermore, in the entire HER2+ group (irrespective of the NAT response), SII values were negatively correlated with vitamin D levels (R = -0.39; P = .008).

Conclusions: In patients with breast cancer, high SIRI and PIV values may indicate the biological subtype of TNBC. In the HER2+ group, higher SII values were associated with low vitamin D concentrations and elevated BMI.

Background: Breast cancers (BRCs) can be classified into 6 molecular subtypes based on gene expression profiles. Previous research suggests that tumor-infiltrating lymphocytes are associated with metastasis-free survival (MFS) in triple-negative and HER2-overexpressing BRC.

Objectives: Our study aims to investigate further how the immune response (IR) may impact MFS in different molecular subtypes of BRC.

Design: A single hospital-based retrospective cohort study.

Methods: A training series of 327 BRCs was used to identify 297 IR transcripts that were correlated with the T cell-associated CD3D transcript or the B cell-associated CD19 transcript. Using these IR transcripts, each of the 6 molecular subtypes was hierarchically clustered into high and low immune responders. An IR score based on the average of the 297 IR transcripts was determined for each BRC. Correlations between the IR score and 3 signatures for IR or response to immune checkpoint inhibition therapy (ICIT) were investigated. A series of 884 BRCs from public datasets was used for confirmation, and the other independent series of 988 BRCs was used for validation.

Results: For subtype I, high immune responders had a statistically significantly better MFS than low immune responders in all the training, confirmation, and validation series by Kaplan-Meier survival analysis (P = .0039, .049, .039, log-rank test). The same trend was observed for subtype II (P = .16, .052, .015) and subtype IV (P = .0078, .0002, .12). Our IR scores were linearly correlated with the Teschendorff, the T-effector and IFNg, and the T-cell inflamed signatures for IR or ICIT. The IR scores were also linearly correlated with the expression of 6 different immune checkpoint genes.

Conclusions: Tumor IR is a biomarker for MFS for BRCs of I, II, and IV subtypes. Our study supports the potential use of the IR score for identifying patients responsive to ICIT.

Background: Breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) has emerged as a new category benefiting from anti-HER2 therapies. This study evaluated the prevalence of HER2-low expression and concordance of HER2 scoring among pathologists at King Hussein Cancer Center (KHCC) in Jordan.

Objectives: To determine the prevalence of HER2-low breast cancer tumors and evaluate the interpathologist concordance in HER2 scoring using the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.

Design: This is a retrospective observational study.

Methods: In total, 116 breast cancer samples were randomly selected from routine practice at KHCC. Each tumor was scored for HER2 expression by 3 pathologists independently using the 2018 ASCO/CAP guidelines. Concordance among pathologists was evaluated using Fleiss' kappa and Cohen's weighted kappa statistics.

Results: The original HER2 scoring revealed 7 tumors (6%) as HER2-negative (0 immunohistochemistry [IHC] score), 84 (72.4%) as HER2-low (including tumors with 1+ IHC score or 2+ IHC score with negative fluorescence in situ hybridization [FISH]), 21 (18.1%) as HER2-positive (including tumors with 3+ IHC score or 2+ IHC score with positive FISH), and 4 (3.4%) as equivocal (2+ IHC score with no FISH). Consensus scoring showed 1+ as the most frequent HER2 score. Complete agreement among all 3 pathologists occurred in 78 tumors (67.2%), while high agreement (agreement among 2 pathologists) occurred in 38 tumors (32.8%). Cohen's weighted kappa ranged from 0.691 to 0.849, indicating substantial agreement. The Fleiss kappa of overall agreement on HER2 scoring was 0.645.

Conclusion: This study highlights a significant prevalence of HER2-low tumors among the randomly selected sample of Jordanian breast cancer patients and demonstrates substantial interpathologist agreement in HER2 scoring. These findings underscore the importance of standardized HER2 scoring and the potential impact of emerging therapies on a large patient population in Jordan.

Breast cancer (BC) is the most prevalent malignancy in women. The emergence of targeted therapies and advancements in comprehensive treatment protocols have significantly improved survival outcomes for patients with early-stage BC. However, individuals with refractory BC, particularly those who have received multiple lines of therapy or presented with distant metastases at diagnosis, continue to face challenges due to the limitations of conventional antibodies and cytotoxic agents in meeting therapeutic needs. Thus, the development of novel and effective treatments for BC, along with strategies to prevent recurrence, remains an urgent priority. Research has shown that nanodrug delivery systems can modify the pharmacokinetic profiles of traditional chemotherapeutic agents, thereby markedly reducing adverse drug reactions. Furthermore, studies have demonstrated that innovative approaches, such as hyaluronic acid-based systems, ultrasound-mediated microbubbles, and antibody-drug conjugates (ADCs), enable targeted and controlled drug release, offering advantages including high drug efficacy, reduced toxicity, and significant antitumor effects. Among these, ADCs have gained increasing attention in BC therapy over recent years. This article provides a comprehensive review of the development and progress of various drug delivery systems in BC treatment, offering an in-depth analysis of their potential applications in clinical practice.

Background: While sentinel lymph node biopsy (SLNB) in breast cancer patients with limited axillary disease undergoing upfront surgery is well-accepted, there are insufficient data supporting its safety with residual nodal disease (RND) following neoadjuvant chemotherapy (NAC). Objectives: To evaluate axillary management and oncologic outcomes of patients with RND. Design: A retrospective review comparing patients receiving SLNB to those receiving axillary lymph node dissection (ALND). Methods: Patients treated for breast cancer at our institution between 2015 and 2023, who received NAC and had RND, were identified. Patient and tumor characteristics, treatments, and outcomes information were collected. The relationship between axillary management and oncologic outcomes was examined. Results: Of 155 patients, median age was 55 years (interquartile range [IQR] 46-64) and follow-up 56 months (IQR 34-73). Most patients were pathologic tumor stage 1-2 (105, 67.7%) and nodal stage 1 (106, 68.4%), with ductal histology (127, 81.9%). The most common receptor pattern was estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative. A total of 107 (69.0%) underwent mastectomy, 47 (30.3%) lumpectomy, and 138 (89.0%) received adjuvant radiation. Regarding axillary management, 121 (78.1%) underwent ALND and 34 (21.9%) SLNB. Univariate analysis found no differences in overall survival (68.6% vs 70.6%; P = 1), any recurrence (local, axillary, or distant; 36.4% vs 35.3%; P = 1), or specifically axillary recurrence (9.9% vs 8.8%; P = 1), between ALND and SLNB groups, respectively. This was also demonstrated on multivariate analysis. Conversely, there was a significantly increased rate of lymphedema in the ALND, 57.9%, vs the SLNB group, 35.3% (P = 0.03). Conclusions: ALND was not associated with improved survival or recurrence risk compared with SLNB in patients with RND following NAC, but was found to have a higher rate of lymphedema. This study is limited due to its retrospective nature. Further data, such as from the ALLIANCE A011202 trial, will help to further clarify the optimal oncologic management for this group of patients.

Breast cancer remains the most prevalent malignant tumor and a leading cause of cancer-related mortality among women worldwide. The disease comprises distinct molecular subtypes that influence tumor behavior, metastatic potential, and therapeutic response. This review presents recent advances in breast cancer research, with a particular emphasis on molecular and epigenetic mechanisms that contribute to tumor development, progression, and treatment resistance. Key signaling pathways-including estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), Notch, fibroblast growth factor receptor (FGFR), Wnt, and Hedgehog-play essential roles in the regulation of mammary stem cells and oncogenesis. Increasing evidence highlights the significance of epigenetic alterations such as DNA methylation, histone modifications, and microRNA expression in modulating gene activity relevant to tumor initiation and therapy resistance. Epigenetic molecular targets, including DNA methyltransferases (DNMTs), histone deacetylases (HDACs), EZH2, and non-coding RNAs, are gaining attention for their potential use in diagnosis, prognosis, and targeted therapy. Integration of multigene panel testing with epigenetic biomarkers has facilitated improved risk assessment and the development of individualized treatment strategies. Moreover, novel therapeutic approaches-such as CAR-T cell therapy, nanoparticle-mediated drug delivery systems, and the involvement of circular RNAs (circRNAs) in immune modulation-offer promising directions for precision medicine. This review consolidates current insights into the molecular and epigenetic landscape of breast cancer to provide a comprehensive understanding of disease complexity and to inform the development of more effective, personalized treatment options.

Background: Screening for breast cancer via mammography is underutilised in Ghana, with fear of the disease influencing women's participation. However, little is known about the role fear of breast cancer plays in screening decisions, partly due to the lack of a Ghana-specific measure to assess this fear. There is a need for a valid and reliable measure to assess breast cancer-related fear among Ghanaian women.

Objectives: To evaluate the construct validity and internal consistency reliability of the Champion Breast Cancer Fear Scale among Ghanaian women.

Design: Cross-sectional research design.

Methods: The participants were women (aged 18-78 years) recruited in the general population through convenience sampling. The total sample was randomly split into 2 equivalent subsamples to perform the construct validity analysis via exploratory factor analysis (n = 428) and confirmatory factor analysis (n = 427), along with internal consistency reliability testing using McDonald omega (ω) and Cronbach alpha (α).

Results: The original one-factor structure of the Champion Breast Cancer Fear Scale was supported by both exploratory factor analysis and confirmatory factor analysis in the present study. Omega and alpha coefficients for the total sample (ω = .877; α = .876), subsample 1 (ω = .877; α = .875), and subsample 2 (ω = .879; α = .877), were found to be good. Overall, the confirmatory factor analysis found sound validity evidence, χ²(19) = 62.84, P < .001, comparative fit index = .971, root mean square error of approximation = .074, 90% confidence interval = [.05, .09], standardised root mean square residual = .031, for the use of the Champion Breast Cancer Fear Scale for assessing fear of breast cancer among Ghanaian women in the general population. Other results revealed that most of the participants reported a high fear of breast cancer, whereas a substantial number reported a moderate fear of breast cancer.

Conclusion: The study confirms the Champion Breast Cancer Fear Scale as a valid and reliable measure for identifying women with a fear of breast cancer.

Background: Estrogen-receptor (ER), progesterone-receptor (PR), and human epidermal growth factor-2 (HER2) are performed on pre-neoadjuvant chemotherapy (NAC) biopsies of invasive breast carcinoma (IBC). However, they are not done routinely on post-NAC IBC with residual tumor.

Objectives: This study helps in understanding the effect of alteration in expression of ER, PR, and HER2 in pre and post NAC IBC with residual tumors in terms of disease outcome, such as disease-free survival (DFS) and overall survival (OS).

Design: This was a Cohort study (Prospective and Retrospective Cohort).

Methods: All newly diagnosed cases of IBC who had undergone surgery after NAC with pre-NAC biopsies available with residual tumors in the breast, from January 2017 to January 2020 were enrolled in the study (n = 174) and were followed up till July 2022.

Results: There were 174 cases included in this study. Of the 174 cases, 77 (44%) ER+ cases turned -ve, 10 ER +ve cases remained +ve and 87(50%) cases which were ER-ve remained the same. 48(27%) of PR +ve cases turned -ve, 10 PR +ve cases remained +ve and 116 (67%) cases remained -ve. 64(36%) of HER2 +ve cases turned -ve, 4 (2%) of HER2 +ve cases remained +ve; whereas 103(59%) cases remained -ve. The cases with changes in ER and HER2 status from positive to negative showed a longer DFS and OS which was statistically significant.

Conclusion: There is a change in the HR and HER2 status in cases of IBC with residual tumor post NAC and patients with changes in the receptor status post-NAC have a better OS and DFS than those whose receptor status do not show a change.

Background: Advanced breast cancer (ABC) is an incurable disease, with a median overall survival (OS) of 3 years, even in high-income countries. Oncological treatment has improved survival rates, particularly for hormone receptor-positive and HER2-positive subtypes; however, access to new therapies in Latin American (LATAM) countries is limited.

Objectives: The impact of sequencing 2 lines of therapy in Peruvian patients with HER2-positive ABC in a single public institution was evaluated. First-line (1L) treatment consisted of trastuzumab and chemotherapy (CT, with taxanes), followed by second-line (2L) treatment with lapatinib plus capecitabine.

Design: In this retrospective study, we analyze clínico-pathological features (including blood biomarkers) collected from medical records of patients with HER2-positive ABC treated in a public Peruvian oncologic institution and its association with survival between 2020 and 2022.

Methods: Efficacy was measured using OS and progression-free survival (PFS). A discussion was added on the impact of OS based on clinicopathological characteristics, including outcomes in 2L "long-term responder" patients (who achieved response to 2L therapy ⩾6 months) and the evaluation of blood biomarkers.

Results: Treatment sequencing has been demonstrated to enhance OS in patients with HER2-positive ABC, with a median OS of 34 months. This effect is more pronounced among long-term responders (37 months), particularly those without central nervous system (CNS) involvement, as compared with those with CNS metastases (51 vs 34 months). Blood biomarkers were not found to be prognostic indicators for either PFS or OS.

Conclusions: Treatment sequencing has been demonstrated to enhance OS in LATAM patients with HER2-positive ABC. This study did not identify any prognostic blood biomarkers. These outcomes could influence the selection criteria for patients to receive treatment sequencing in countries without full access to innovative oncological therapies.