Dynamic changes in tumor profiling reveal intra- and inter-tumoral heterogeneity focused on an uncharacterized HER2 mutation: a case report of a young breast cancer patient.

Despite multiple recent advances in systemic therapy for metastatic breast cancer, cases which display suboptimal response to guideline-driven treatment are frequently seen in the clinic. Effective options for such patients are limited, particularly in later line of therapy, and selection of optimal treatment options is essentially empirical and based largely on considerations of previous regimens received. Comprehensive cancer profiling includes detection of genetic alterations in tissue and circulating tumor DNA (ctDNA), immunohistochemistry (IHC) from re-biopsied metastatic disease, circulating tumor cells (CTCs), gene expression analysis and pharmacogenomics. The advent of this methodology and application to metastatic breast cancer, facilitates a more scientifically informed approach to identification of optimal systemic therapy approaches independent of the restrictions implied by clinical guidelines. Here we describe a case of metastatic breast cancer where consecutive comprehensive tumor profiling reveals ongoing tumor evolution, guiding the identification of novel effective therapeutic strategies.

Evaluating Magnetic Seed Localization in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy: A Comprehensive Review and Pooled Analysis.

Background/Objectives: De-escalation of axillary surgery is made possible by advancements in both neoadjuvant systemic therapy (NST) and in localisation technology for breast lesions. Magseed®, developed in 2013 by Dr. Michael Douk of Cambridge, United Kingdom, is a wire-free localisation technology that facilitates the localisation and retrieval of lymph nodes for staging. Targeted axillary dissection (TAD), which entails marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), has emerged as the preferred method to assess residual disease in post-NST node-positive patients. This systematic review and pooled analysis evaluate the performance of Magseed® in TAD. Methods: The search was carried out in PubMed and Google Scholar. An assessment of localisation, retrieval rates, concordance between MLNB and SLNB, and pathological complete response (pCR) in clinically node-positive patients post NST was undertaken. Results: Nine studies spanning 494 patients and 497 procedures were identified, with a 100% successful deployment rate, a 94.2% (468/497) [95% confidence interval (CI), 93.7-94.7] localisation rate, a 98.8% (491/497) retrieval rate, and a 68.8% (247/359) [95% CI 65.6-72.0] concordance rate. pCR was observed in 47.9% (220/459) ) [95% CI 43.3-52.6] of cases. Subgroup analysis of studies reporting the pathological status of MLNB and SLNB separately revealed an FNR of 4.2% for MLNB and 17.6% for SLNB (p = 0.0013). Mean duration of implantation was 37 days (range: 0-188). Conclusions: These findings highlight magnetic seed localisation's efficacy in TAD for NST-treated node-positive patients, aiding in accurate axillary pCR identification and safe de-escalation of axillary surgery in excellent responders.

Harnessing Micronutrient Power: Vitamins, Antioxidants and Probiotics in Breast Cancer Prevention.

Breast cancer remains a global health challenge, prompting a search for preventive strategies beyond conventional approaches. This review explores the potential of specific micronutrients, including antioxidants, vitamins, and probiotics, in breast cancer prevention. Through an extensive literature search encompassing PubMed up to March 2024, 14 micronutrients emerged with promising roles in breast cancer prevention. These include five vitamins: folate, vitamin D, vitamin B6, beta carotene, and vitamin C and nine other micronutrients: curcumin, piperine, epigallocatechin-3-gallate, quercetin, sulforaphane, indole-3-carbinol, lactobacillus, n-3 polyunsaturated fatty acids and lycopene. Understanding the efficacy of these micronutrients could pave the way for personalized preventive interventions, offering new avenues for reducing breast cancer incidence and improving public health outcomes.

Evaluating Radar Reflector Localisation in Targeted Axillary Dissection in Patients Undergoing Neoadjuvant Systemic Therapy for Node-Positive Early Breast Cancer: A Systematic Review and Pooled Analysis.

SAVI SCOUT® or radar reflector localisation (RRL) has proven accurate in localising non-palpable breast and axillary lesions, with minimal interference with MRI. Targeted axillary dissection (TAD), combining marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), is becoming a standard post-neoadjuvant systemic therapy (NST) for node-positive early breast cancer. Compared to SLNB alone, TAD reduces the false negative rate (FNR) to below 6%, enabling safer axillary surgery de-escalation. This systematic review evaluates RRL's performance during TAD, assessing localisation and retrieval rates, the concordance between MLNB and SLNB, and the pathological complete response (pCR) in clinically node-positive patients post-NST. Four studies (252 TAD procedures) met the inclusion criteria, with a 99.6% (95% confidence [CI]: 98.9-100) successful localisation rate, 100% retrieval rate, and 81% (95% CI: 76-86) concordance rate between SLNB and MLNB. The average duration from RRL deployment to surgery was 52 days (range:1-202). pCR was observed in 42% (95% CI: 36-48) of cases, with no significant migration or complications reported. Omitting MLNB or SLNB would have under-staged the axilla in 9.7% or 3.4% (p = 0.03) of cases, respectively, underscoring the importance of incorporating MLNB in axillary staging post-NST in initially node-positive patients in line with the updated National Comprehensive Cancer Network (NCCN) guidelines. These findings underscore the excellent efficacy of RRL in TAD for NST-treated patients with positive nodes, aiding in accurate axillary pCR identification and the safe omission of axillary dissection in strong responders.

Breath of Danger: Unveiling PM2.5's Stealthy Impact on Cancer Risks.

This article explores the intricate relationship between airborne particulate matter (PM), specifically PM2.5, and its profound impact on human health, emphasising the heightened risks of cancer. Examining the composition and characteristics of PM2.5, such as particle size and surface area, reveals its ability to induce inflammatory injury and oxidative damage. The carcinogenic potential extends beyond respiratory implications, affecting various organs, including the digestive tract, breast, and prostate. In addition to the genotoxic effects of PM2.5, attached polycyclic aromatic hydrocarbons are recognized to be endocrine-disrupting chemicals with specific implications for breast and prostate cancer. Long-term exposure to PM2.5 is associated with increased cancer mortality, with specific risks identified for different cancer types. The linear correlation between cancer risk and PM2.5 concentration calls for a re-evaluation of permissible emission levels. The article concludes by proposing specific mitigating strategies for individuals exposed to elevated PM2.5. It suggests antioxidant-rich diets and supplements, and exploring inhalation-based antioxidant administration as potential protective measures.

Reevaluating Axillary Lymph Node Dissection in Total Mastectomy for Low Axillary Burden Breast Cancer: Insights from a Meta-Analysis including the SINODAR-ONE Trial.

Complete axillary lymph node dissection (cALND) was previously the standard of care for breast cancer (BC) patients with axillary node disease or macro-metastases found via sentinel lymph node biopsy (SLNB). However, due to significant morbidity, contemporary management now considers a more selective approach, influenced by studies like ACOSOG Z0011. This trial showed that cALND could be omitted without compromising local control or survival in patients with low axillary nodal disease burden undergoing breast-conserving therapy, radiotherapy, and systemic therapy. The relevance of this approach for women with low axillary nodal burden undergoing total mastectomy (TM) remained unclear. A PubMed search up to September 2023 identified 147 relevant studies, with 6 meeting the inclusion criteria, involving 4184 patients with BC and low-volume axillary disease (1-3 positive lymph nodes) undergoing TM. Postmastectomy radiotherapy receipt was similar in both groups. After a mean 7.2-year follow-up, both the pooled results and the meta-analysis revealed no significant differences in overall survival. The combined analysis of the published studies, including the subgroup analysis of the SINODAR-One trial, indicates no survival advantage for cALND over SLNB in T1-T2 breast cancer patients with 1-3 positive sentinel lymph nodes (pN1) undergoing mastectomy. This suggests that, following a multidisciplinary evaluation, cALND can be safely omitted. However, the impact of other patient, tumor, and treatment factors on survival requires consideration and therefore further prospective trials are needed for conclusive validation.

Elucidating Axillary Soft Tissue Involvement in Breast Cancer: Unveiling Metastatic Mechanisms and Therapeutic Perspectives.

This perspective focuses on axillary soft tissue (AXT) involvement in breast cancer, revealing diverse pathological entities beyond traditional axillary lymph node metastasis. AXT involvement is linked to increased risks of distant metastasis and locoregional failure, emphasizing its significance in predicting breast cancer outcomes. We posit that AXT involvement could signify a retrograde metastatic event stemming from reactivated circulating tumor cells navigating towards the axillary soft tissue guided by chemokines. Therefore, AXT disease warrants aggressive systemic therapy. Axillary radiation therapy could be a potentially preferable alternative to axillary lymph node dissection. Routine reporting of axillary soft tissue involvement is crucial for accurate treatment planning.

Unlocking the Power of the Homing Phenomenon: Why Breast Conserving Surgery Outshines Mastectomy in Overall Survival.

Breast cancer stands as the most frequently diagnosed malignancy in women, holding a prominent position among the leading causes of cancer-related fatalities on a global scale. Despite significant advances in treatment modalities, approximately 20% of patients experience relapses after the first 5 years of postdiagnosis surveillance. While initial investigations from the 1970s indicated comparable survival rates between breast-conserving surgery (BCS) coupled with radiation therapy and mastectomy, recent research suggests that, within the context of modern systemic and radiation therapy, BCS followed by radiation may offer an improved overall survival benefit. Nevertheless, extended follow-up studies have unveiled a notable increase in the risk of locoregional recurrence associated with breast conserving therapy in contrast to mastectomy. This article introduces a novel hypothesis rooted in the biological phenomenon of homing to elucidate this intriguing clinical observation. We postulate that a breast homing mechanism of reactivated circulating and disseminated tumor cells mediated by chemotaxis involving at least the CXCR4-SDF-1 axis may provide a biological rationale for this clinical phenomenon.

Cryogenic Media in Biomedical Applications: Current Advances, Challenges, and Future Perspectives.

This paper explores the crucial role of cryogenic mediums in driving breakthroughs within the biomedical sector. The objective was to investigate, critically discuss, and present the current knowledge and state-of-the-art practices, along with the challenges and perspectives of the most common applications. Through an extensive literature review, this work aims to supplement existing research, offering a comprehensive and up-to-date understanding of the subject. Biomedical research involving cryogenic mediums is advancing on multiple fronts, including the development of advanced medical technologies, clinical treatments for life-threatening conditions, high-quality biospecimen preservation, and antimicrobial interventions in industrial food processing. These advances open new horizons and present cutting-edge opportunities for research and the medical community. While the current body of evidence showcases the impressive impact of cryogenic mediums, such as nitrogen, helium, argon, and oxygen, on revolutionary developments, reaching definitive conclusions on their efficiency and safety remains challenging due to process complexity and research scarcity with a moderate certainty of evidence. Knowledge gaps further underline the need for additional studies to facilitate cryogenic research in developing innovative technological processes in biomedicine. These advancements have the potential to reshape the modern world and significantly enhance the quality of life for people worldwide.

The Evolving Role of Cryosurgery in Breast Cancer Management: A Comprehensive Review.

Breast cancer is the most commonly diagnosed type of cancer, accounting for approximately one in eight cancer diagnoses worldwide. In 2020, there were approximately 2.3 million new cases of breast cancer globally, resulting in around 685,000 deaths. Consequently, there is an ongoing need to develop innovative therapeutic approaches that can improve both clinical outcomes and patient quality of life. The use of ultra-low cryogenic temperatures, facilitated by cryogenic media such as liquid nitrogen, has revolutionized the biomedical field and opened up new possibilities for advanced clinical treatments, including cryosurgery. Cryosurgery has demonstrated its feasibility as a minimally invasive technique for destroying breast tumors and eliciting a significant antitumor immune response in the host. This feature sets cryosurgery apart from other ablative techniques. It has been shown to be well tolerated and effective, offering several advantages such as simplicity, the avoidance of general anesthesia, minimal pain, low morbidity, short recovery time, cost-effectiveness, and notably, improved aesthetic outcomes. The reviewed studies indicate that cryosurgery holds promise in the management of early-stage breast cancer and metastatic disease, especially in triple-negative and Her2-positive molecular subtypes in conjunction with checkpoint inhibitors and anti-Her2 antibodies, respectively. Furthermore, the effectiveness of cryosurgery in the management of ductal carcinoma in situ should be investigated as an alternative modality to surgery or surveillance. The minimally invasive nature of cryosurgery has the potential to significantly enhance the quality of life for patients.

Omitting Sentinel Lymph Node Biopsy after Neoadjuvant Systemic Therapy for Clinically Node Negative HER2 Positive and Triple Negative Breast Cancer: A Pooled Analysis.

Recent advances in systemic treatment for breast cancer have been underpinned by recognising and exploiting subtype-specific vulnerabilities to achieve higher rates of pathologic complete response (pCR) after neo-adjuvant systemic therapy (NAST). This down-staging of disease has permitted safe surgical de-escalation in patients who respond well. Triple-negative (TNBC) or HER2-positive breast cancer is most likely to achieve complete radiological response (rCR) and pCR after NAST. Hence, for selected patients, particularly those who are clinically node-negative (cN0) at diagnosis, the probability of disease in the sentinel node after NAST could be low enough to justify omitting axillary surgery. The aim of this pooled analysis was to determine the rate of sentinel node positivity (ypN+) in patients with TNBC or HER2-positive breast cancer who were initially cN0, achieving rCR and/or pCR in the breast after NAST. MedLine was searched using appropriate search terms. Five studies (N = 3834) were included in the pooled analysis, yielding a pooled ypN+ rate of 2.16% (95% CI: 1.70-2.63). This is significantly lower than the acceptable false negative rate of sentinel lymph node biopsy (SLNB) and supports consideration of omission of SLNB in this subset of patients.

Simultaneous Salvage Auto-augmentation: Contemporary Strategy for Management of the Breast Explantation Patient.

The treatment of patients requiring explantation of breast prostheses is a complicated clinical issue, for which a consensus regarding the best way forward is still evolving. We believe that simultaneous salvage auto-augmentation (SSAA) is a viable option for the treatment of patients with explantation. Methods: Sixteen cases (32 breasts) were reviewed over a 19-year period. The management of the capsule is based on intraoperative findings and not on preoperative evaluation because of the poor interobserver correlation of Baker grades. Results: The mean age and clinical follow-up duration were 48 years (range: 41-65) and 9 months, respectively. We observed no complications, and only one patient underwent unilateral surgical revision of the periareolar scar, under local anaesthesia. Conclusions: This study suggests that SSAA with or without autologous fat injection is a safe option for women undergoing explantation, with potential aesthetic and cost-saving benefits. In the current climate of public anxiety regarding breast implant illness, breast implant-associated atypical large cell lymphoma, and asymptomatic textured implants, it is anticipated that the number of patients desiring explantation and SSAA will continue to increase.

ACBD3 Bioinformatic Analysis and Protein Expression in Breast Cancer Cells.

ACBD3 overexpression has previously been found to correlate with worse prognosis for breast cancer patients and, as an incredibly diverse protein in both function and cellular localisation, ACBD3 may have a larger role in breast cancer than previously thought. This study further investigated ACBD3's role in breast cancer. Bioinformatic databases were queried to characterise ACBD3 expression and mutation in breast cancer and to investigate how overexpression affects breast cancer patient outcomes. Immunohistochemistry was carried out to examine ACBD3 location within cells and tissue structures. ACBD3 was more highly expressed in breast cancer than in any other cancer or matched normal tissue, and expression over the median level resulted in reduced relapse-free, overall, and distant metastasis-free survival for breast cancer patients as a whole, with some differences observed between subtypes. IHC analysis found that ACBD3 levels varied based on hormone receptor status, indicating that ACBD3 could be a candidate biomarker for poor patient prognosis in breast cancer and may possibly be a biomarker for ER signal reprogramming of precancerous breast tissue.

Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells.

BACKGROUND: The early detection of breast cancer (BrC) is associated with improved survival. We describe a blood-based breast cancer detection test based on functional enrichment of breast-adenocarcinoma-associated circulating tumor cells (BrAD-CTCs) and their identification via multiplexed fluorescence immunocytochemistry (ICC) profiling for GCDFP15, GATA3, EpCAM, PanCK, and CD45 status. METHODS: The ability of the test to differentiate BrC cases (N = 548) from healthy women (N = 9632) was evaluated in a case-control clinical study. The ability of the test to differentiate BrC cases from those with benign breast conditions was evaluated in a prospective clinical study of women (N = 141) suspected of BrC. RESULTS: The test accurately detects BrAD-CTCs in breast cancers, irrespective of age, ethnicity, disease stage, grade, or hormone receptor status. Analytical validation established the high accuracy and reliability of the test under intended use conditions. The test detects and differentiates BrC cases from healthy women with 100% specificity and 92.07% overall sensitivity in a case-control study. In a prospective clinical study, the test shows 93.1% specificity and 94.64% overall sensitivity in differentiating breast cancer cases (N = 112) from benign breast conditions (N = 29). CONCLUSION: The findings reported in this manuscript support the clinical potential of this test for blood-based BrC detection.