Activation of the YY1-UGT2B7 Axis Promotes Mammary Estrogen Homeostasis Dysregulation and Exacerbates Breast Tumor Metastasis.

Metastasis is the most common pathway of cancer death. The lack of effective predictors of breast cancer metastasis is a pressing issue in clinical practice. Therefore, exploring the mechanism of breast cancer metastasis to uncover reliable predictors is very important for the clinical treatment of breast cancer patients. In this study, tandem mass tag quantitative proteomics technology was used to detect protein content in primary breast tumor tissue samples from patients with metastatic and nonmetastatic breast cancer at diagnosis. We found that the high expression of yin-yang 1(YY1) is strongly associated with poor prognosis in high-grade breast cancer. YY1 expression was detected in both clinical tumor tissue samples and tumor tissue samples from mammary-specific polyomavirus middle T antigen overexpression mouse model mice. We demonstrated that upregulation of YY1 expression was closely associated with breast cancer metastasis and that high YY1 expression could promote the migratory invasive ability of breast cancer cells. Mechanistically, YY1 directly binds to the UGT2B7 mRNA initiation sequence ATTCAT, thereby transcriptionally regulating the inhibition of UGT2B7 expression. UGT2B7 can regulate the development of breast cancer by regulating estrogen homeostasis in the breast, and the abnormal accumulation of estrogen, especially 4-OHE2, promotes the migration and invasion of breast cancer cells, ultimately causing the development of breast cancer metastasis. In conclusion, YY1 can regulate the UGT2B7-estrogen metabolic axis and induce disturbances in estrogen metabolism in breast tumors, ultimately leading to breast cancer metastasis. Disturbances in estrogen metabolism in the breast tissue may be an important risk factor for breast tumor progression and metastasis SIGNIFICANCE STATEMENT: In this study, we propose for the first time a regulatory relationship between YY1 and the UGT2B7/estrogen metabolism axis and explore the molecular mechanism. Our study shows that the YY1/UGT2B7/estrogen axis plays an important role in the development and metastasis of breast cancer. This study further elucidates the potential mechanisms of YY1-mediated breast cancer metastasis and the possibility and promise of YY1 as a predictor of cancer metastasis.

Pre- and Postoperative Antioxidant Use, Aryl Hydrocarbon Receptor (AhR) Activation and Clinical Outcome in Different Treatment Groups of Breast Cancer Patients.

BACKGROUND: Cancer patients often use antioxidants that may interact with adjuvant treatments. The purpose was to investigate pre- and postoperative antioxidant use in relation to clinicopathological characteristics and prognosis in different breast cancer treatment groups. METHODS AND PATIENTS: Pre- and postoperative antioxidant (vitamin A, C, E, carotenoids, or Q10) or multivitamin use was self-reported by patients from Lund (n = 1855) and Helsingborg (n=478), Sweden. Patients were followed for up to 15 years. Clinical data were obtained from patient charts. The aryl hydrocarbon receptor (AhR) was evaluated in tumor tissue arrays from 915 patients from Lund and with Western blot in MCF-7 and MDA-MB-231 cells. RESULTS: About 10% of patients used antioxidants. Nuclear AhR (AhRnuc) positivity was twice as common in preoperative antioxidant users compared to non-users. In mechanistic studies vitamin C increased AhR levels and its downstream target CYP1B1, indicating AhR activation. There were significant interactions between tumor AhRnuc status and preoperative antioxidant use in relation to clinical outcome. In all patients, antioxidant use (other than multivitamins) at both visits was associated with poorer prognosis, while use only at the follow-up visit was associated with better prognosis, compared with no use at either visit. CONCLUSION: The clinical impact of antioxidants depended on antioxidant type, timing of use, and tumor AhR activation. Antioxidants may influence clinical outcome by activation of the master regulator AhR in addition to interference with free radicals. Further studies are needed to identify breast patients that might improve or worsen their prognosis when using antioxidants postoperatively.

Surgical management of a giant fibroadenoma during lactation.

Fibroadenomas are the most common breast lesion in women of reproductive age. During pregnancy and lactation, fibroadenomas can undergo rapid growth in response to hormonal stimulus. These changes may prompt further investigation and/or intervention due to the risk of an underlying phyllodes tumour. We present a case of a female patient who underwent surgical excision of a giant fibroepithelial lesion at 4 months post partum while continuing to breastfeed. The lesion was successfully excised while maintaining lactation. A postoperative milk fistula resolved with non-operative management. There is limited literature on the surgical management of breast lesions in lactating women. This case illuminates the surgical management of breast lesions in an often well informed group of patients who may choose to have surgery while lactating in spite of the increased risk of complications. This case also highlights the need for a holistic approach to maintain the overall health of mother and child.

Neoadjuvant chemotherapy for breast cancer: Pathologic response rates but not tumor size, has an independent prognostic impact on survival.

AIM: We investigated the pathologic complete response rates (pCR) and survival outcomes of early breast cancer patients who underwent neoadjuvant chemotherapy (NAC) over 14 years at a French comprehensive cancer center and reported pCR and survival outcomes by tumor subtypes and size. METHODS: From January 2005 to December 2018, 1150 patients receiving NAC were identified. Correlations between cT stage, breast tumor response, axillary lymph node response, pCR, surgery, and outcomes were assessed. pCR was defined as (ypT0/ypTis) and (ypN0/pN0sn). RESULTS: A pCR was reached in 31.7% (365/1150) of patients and was strongly associated with tumor subtypes, but not with tumor size (pretreatment cT category). Luminal-B Her2-negative and triple-negative (TN) subtypes, cN1 status, older age, and no-pCR had an independent negative prognostic value. Overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS) were not significantly different for cT0-1 compared to cT2 stages. In Cox-model adjusted on in-breast pCR and pN status, ypN1 had a strong negative impact (OS, RFS, and MFS: HR = 3.153, 4.677, and 6.133, respectively), higher than no in-breast pCR (HR = 2.369, 2.252, and 2.323). A negative impact of no pCR on OS was observed for cN0 patients and TN tumors (HR = 4.972) or HER2-positive tumors (HR = 11.706), as well as in Luminal-B Her2-negative tumors on MFS (HR = 2.223) and for Luminal-A on RFS (HR = 4.465) and MFS (HR = 4.185). CONCLUSION: Achievement of pCR, but not tumor size (pretreatment cT category), has an independent prognostic impact on survival. These results suggest potential NAC benefits in patients with small tumors (<2 cm), even in absence of clinically suspicious lymph nodes. Residual lymph node disease after NAC is the most powerful adverse prognostic factor.

[Whole-cycle management norms of bone health in breast cancer].

Bone health management of breast cancer runs through the whole cycle of patient treatment. During the process of adjuvant treatment for early breast cancer, clinicians should be pay attention to the prevention of bone loss caused by treatment. Adjuvant use of bone-modifying agents can help improve the prognosis of some patients, and patients with bone metastases should be given multidisciplinary comprehensive treatment and use bone-modifying agents to prevent the occurrence bone related adverse events. Therefore, no matter for the treatment of early or advanced breast cancer, it is necessary to manage bone health, formulate appropriate treatment strategies, and deal with adverse events of drugs. Good bone health management will help improve the quality of life and survival of patients. The breast cancer expert committee of the National Cancer Quality Control Center organized relevant experts to deeply explore the full cycle management of bone health in breast cancer based on Evidence-based medicine evidence. The risk classification and treatment strategy of cancer treatment-induced bone loss in early breast cancer, the applicable population and benefits of adjuvant treatment of bone modifying drugs, the diagnosis and treatment of bone metastasis in advanced breast cancer, and the treatment of adverse reactions of bone modifying drugs were elaborated in detail. We hope to guide clinicians to better deal with bone health problems in clinical practice by putting forward reasonable suggestions for patients with breast cancer.

Effect of yoga on cancer-related fatigue in patients with breast cancer: A systematic review and meta-analysis.

BACKGROUND: Breast cancer is a common malignant tumor in women and most patients with breast cancer experience fatigue. Numerous studies have investigated the relationship between yoga and cancer-related fatigue (CRF) in patients with breast cancer. However, these studies drew their conclusions from small sample sizes and lacked sufficient evidence to demonstrate that yoga can effectively alleviate CRF. Therefore, this meta-analysis aims to systematically examine the effects of yoga on cancer fatigue in patients with breast cancer and establish a scientific basis for enhancing their quality of life. OBJECTIVE: To assess the effect of yoga on CRF in patients with breast cancer. METHODS: Computer searches were conducted on PubMed, Embase, Web of Science, CKNI, and Wanfang databases to retrieve articles related to yoga and CRF in patients with breast cancer from the hospital establishment date to July 2023. The literature was independently screened, and the information was extracted by the researchers. A meta-analysis was conducted using Review Manager Software (version 5.3). RESULTS: The findings from the meta-analysis of 18 studies indicate that yoga can effectively enhance CFR (standardized mean difference (SMD) = -0.51, 95% confidence interval [CI] = -0.92 to -0.10), improve sleep quality (MD = -3.86, 95%CI = -4.03 to -3.70) in patients with breast cancer, alleviate anxiety and depression (SMD = -0.93, 95%CI = -1.68, -0.18, SMD = -1.23, 95%CI = -2.02 to -0.44), and enhance quality of life (MD = -11.20, 95%CI = -14.16 to -8.24). CONCLUSION: Our study offers evidence for the subsequent reduction of CFR in patients with breast cancer. Yoga can alleviate fatigue, improve sleep quality and negative emotions, and improve the quality of life of patients with breast cancer.

Implementation of Virtual Integrative Oncology Shared Medical Appointment Series (VIOSMAS) Within Mixed Diagnosis Population.

BACKGROUND: Integrative oncology [IO] is sought-after by patients, endorsed by clinical guidelines, and valued within National Cancer Institute Centers. Shared Medical Appointments [SMA] leverage health education and social connection to deliver enhanced patient experience, population health, cost-reduction, and clinician well-being. Integrative Oncology Shared Medical Appointments increase access to integrative medicine but delivering these services via telehealth have not been evaluated. OBJECTIVE: We created, and pilot tested a Virtual Integrative Oncology Shared Medical Appointment Series (VIOSMAS) to assess its feasibility, acceptability, and efficacy at an urban academic teaching hospital. METHODS: The 7-session hour-long Living Well with and after Cancer series included didactics, multi-disciplinary experiential sessions, and group discussion. Topics included (1) Introduction, (2) Herbs/Botanicals/Fungi, (3) Mindful Movement, (4) Acupuncture, (5) Narratives and Nature, (6) Diet and Culinary Medicine, and (7) Vitamins/Supplements. Virtual visits via telehealth were offered to enhance patient participation during the pandemic. Outcome measures included recruitment, retention, pre/post-series patient survey and qualitative clinician feedback. RESULTS: Between 9/2021 and 4/2023, 72 unique patients were recruited to 5 cohorts and had a total of 332 VIOSMAS visits. A total of 50 patients (69%) attended 4 or more of the 7-session series; 60 (83% were women); patients ranged in age from 28 to 93 years (median 66); 36 (50%) lived outside the city center; the most common cancer diagnoses were breast, lymphoma, and lung cancer. Patients were from diverse demographics. Pre-program, patients reported desiring assistance in addressing diverse symptoms including fatigue, insomnia, pain, gastrointestinal (GI) symptoms, anxiety, and depression. Post-series, patients reported that the VIOSMAS addressed their goals and symptoms; they also reported incorporating recommended lifestyle changes in diet, exercise, sleep, and stress management; they were satisfied with the number of sessions and telehealth format. The participating clinicians reported high levels of satisfaction with VIOSMAS. Revenue to the institution from VIOSMAS exceeded the revenue potential of equivalent time spent for individual visits while supporting extended physician-patient contact. CONCLUSION: VIOSMAS is feasible for patients and clinicians, addresses patients' symptoms and questions about lifestyle and complementary therapies, and generates more revenue than individual visits. Larger implementation trials with appropriate comparison groups are recommended.

Ozone Therapy for Breast Cancer: An Integrative Literature Review.

Breast cancer is the most prevalent form of cancer in women. Despite significant advances in conventional treatment, additional safer complementary treatment options are needed. Recently, ozone therapy has been considered as a type of medical adjunctive treatment that could inhibit cancer cell survival and reduce chemoresistance. However, only a few studies have been conducted on its use in breast cancer, and the optimal dosage and time of administration are unknown. Currently, preclinical studies suggest that ozone alone or in combination with chemotherapy is an effective method for inhibiting breast cancer cell growth. However, rather than investigating the effects of ozone as an antitumor therapy, current clinical trials have generally assessed its effect as an adjunctive therapy for reducing chemotherapy-induced side effects, increasing oxygen tension, normalizing blood flow, restoring blood lymphocytes more rapidly, and reducing fatigue symptoms. In this article, the use of ozone as a medical adjunctive treatment for breast cancer and its role in integrative therapy are summarized and discussed.

[Extensive transfixing skin necrosis after breast biopsy under local anesthesia: About four cases]. / Nécrose cutanée étendue transfixiante après biopsie mammaire sous anesthésie locale : rapport de quatre cas.

INTRODUCTION: Local anesthetics with adrenaline are widely used in routine practice and have long proven their benefits and safety. The rare complications due to their use mainly concern immuno-allergic and vascular mechanisms. DESCRIPTION: In this article, we present four similar cases of early transfixing skin necrosis occurring after radioguided breast biopsy under local anesthesia using epinephrine local anesthetics in the context of a diagnostic approach to breast cancer. DISCUSSION: Although the literature is comforting about the use of local anesthetics, even on the extremities, severe skin complications continue to be reported sporadically. The analysis and understanding of these phenomena would allow, in the long run, to avoid them and to reduce their importance. CONCLUSION: The occurrence of skin necrosis after breast biopsy under radiographic control is rare and seems to be related to the local anesthetic procedure. Although similar cases have been reported in the literature, it does not seem possible today to conclude on the exact physiopathology of these complications. A better knowledge of the pathophysiology of these complications would help to avoid their occurrence in the future.

Intraoperative Radiation Therapy as a Safe Alternative to Whole Breast Radiation for Treatment of Minimally Invasive Breast Cancers: A Retrospective Cohort Study.

BACKGROUND: Intraoperative radiation therapy (IORT) in select populations is a viable alternative to whole breast radiation therapy (WBRT) in the treatment of biopsy-proven localized invasive and non-invasive breast cancer. We aim to assess recurrence and complication rates following IORT in lumpectomy patients at a community hospital in Baltimore City. METHODS: An IRB-approved retrospective cohort study was conducted on consecutive cases of lumpectomy with IORT from 2013 through 2020 by a single surgeon. Patient demographics, tumor and operative characteristics, and complications were retrieved from electronic medical records. Primary outcomes were postoperative complications and local recurrence rates. RESULTS: The final cohort included 117 patients with mean follow-up time of 2.60 + 1.78 years. Mean age was 69.84 + 8.77 years. Thirty-three (28.21%) of patients developed a seroma. Odds of seroma formation were mildly significant for skin spacing [OR: 1.18, 95% CI: (1.02-1.37)] and balloon fill volume [1.04 (1.00-1.08)], but not for age, BMI, diabetes, former or current smoking status, history of WBRT, tumor size, or balloon size. Three (2.6%) patients had local recurrence. Odds of local recurrence were mildly significant for increased tumor size [1.14 (1.04-1.24)] and not significant for any other covariates. CONCLUSIONS: IORT exposure did not confer higher rates of complications and the local recurrence rate mirrored that of the general population undergoing lumpectomy and WBRT. This study demonstrates the need for equitable treatment options based on individual needs: IORT is a safe alternative to WBRT in certain subpopulations, especially those with physical, social, or personal limitations preventing participation in a 3- to 7-week time commitment of WBRT.

Decrease of radiation-induced skin reactions in breast cancer patients by preventive application of film dressings-a systematic review.

PURPOSE: Radiation-induced skin reactions remain one of the most frequent side effects of adjuvant radiotherapy for breast cancer, which is the most common global malignancy. In individual cases, we observed a decrease in radiation dermatitis under film dressings used for skin marking purposes. Therefore, we decided to revise the available evidence regarding the prophylactic use of film dressings to reduce radiation dermatitis in breast cancer patients. METHODS: On 20 March 2023, we conducted a systematic review of literature for randomized controlled trials published in the English, German, French, or Spanish language, available in the PubMed database. RESULTS: Of 82 publications, 9 full texts were assessed and 6 randomized controlled trials were included in the final synthesis. Two trials analyzed the application of polyurethane film (Hydrofilm, Paul Hartmann AG, Heidenheim, Germany), the other four of silicone-based polyurethane film (Mepitel film, Molnlycke Health Care Limited, Milton Keynes, United Kingdom). The evaluation scales Common Terminology Criteria for Adverse Events (CTCAE), Radiation Therapy Oncology Group (RTOG), and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) were used for assessment. All six trials, with a total of 788 patients yielding data for analysis, demonstrate a significant decrease in radiation-induced skin reactions by use of the film (mainly p < 0.001). CONCLUSION: Our analysis demonstrates a significant decrease in radiation-induced skin reactions by prophylactically applied film dressings in breast cancer patients. Consequent preventive use of film dressings might systematically reduce acute radiation-induced skin reactions in these patients.

Advances in the care of breast cancer survivors.

Breast cancer survivors may experience significant after effects from diagnoses of breast cancer and cancer directed therapies. This review synthesizes the evidence about optimal management of the sequelae of a diagnosis of breast cancer. It describes the side effects of chemotherapy and endocrine therapy and evidence based strategies for management of such effects, with particular attention to effects of therapies with curative intent. It includes strategies to promote health and wellness among breast cancer survivors, along with data to support the use of integrative oncology strategies. In addition, this review examines models of survivorship care and ways in which digital tools may facilitate communication between clinicians and patients. The strategies outlined in this review are paramount to supporting breast cancer survivors' quality of life.

FBXW7 in breast cancer: mechanism of action and therapeutic potential.

Breast cancer is one of the frequent tumors that seriously endanger the physical and mental well-being in women. F-box and WD repeat domain-containing 7 (FBXW7) is a neoplastic repressor. Serving as a substrate recognition element for ubiquitin ligase, FBXW7 participates in the ubiquitin-proteasome system and is typically in charge of the ubiquitination and destruction of crucial oncogenic proteins, further performing a paramount role in cell differentiation, apoptosis and metabolic processes. Low levels of FBXW7 cause abnormal stability of pertinent substrates, mutations and/or deletions in the FBXW7 gene have been reported to correlate with breast cancer malignant progression and chemoresistance. Given the lack of an effective solution to breast cancer's clinical drug resistance dilemma, elucidating FBXW7's mechanism of action could provide a theoretical basis for targeted drug exploration. Therefore, in this review, we focused on FBXW7's role in a range of breast cancer malignant behaviors and summarized the pertinent cellular targets, signaling pathways, as well as the mechanisms regulating FBXW7 expression. We also proposed novel perspectives for the exploitation of alternative therapies and specific tumor markers for breast cancer by therapeutic strategies aiming at FBXW7.

LC/MS-based untargeted lipidomics reveals lipid signatures of nonpuerperal mastitis.

BACKGROUND: Nonpuerperal mastitis (NPM) is a disease that presents with redness, swelling, heat, and pain during nonlactation and can often be confused with breast cancer. The etiology of NPM remains elusive; however, emerging clinical evidence suggests a potential involvement of lipid metabolism. METHOD: Liquid chromatography‒mass spectrometry (LC/MS)-based untargeted lipidomics analysis combined with multivariate statistics was performed to investigate the NPM lipid change in breast tissue. Twenty patients with NPM and 10 controls were enrolled in this study. RESULTS: The results revealed significant differences in lipidomics profiles, and a total of 16 subclasses with 14,012 different lipids were identified in positive and negative ion modes. Among these lipids, triglycerides (TGs), phosphatidylethanolamines (PEs) and cardiolipins (CLs) were the top three lipid components between the NPM and control groups. Subsequently, a total of 35 lipids were subjected to screening as potential biomarkers, and the chosen lipid biomarkers exhibited enhanced discriminatory capability between the two groups. Furthermore, pathway analysis elucidated that the aforementioned alterations in lipids were primarily associated with the arachidonic acid metabolic pathway. The correlation between distinct lipid populations and clinical phenotypes was assessed through weighted gene coexpression network analysis (WGCNA). CONCLUSIONS: This study demonstrates that untargeted lipidomics assays conducted on breast tissue samples from patients with NPM exhibit noteworthy alterations in lipidomes. The findings of this study highlight the substantial involvement of arachidonic acid metabolism in lipid metabolism within the context of NPM. Consequently, this study offers valuable insights that can contribute to a more comprehensive comprehension of NPM in subsequent investigations. TRIAL REGISTRATION: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Number: 2019-702-57; Date: July 2019).

The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left-Right Functional Differences.

Breast cancer is a complex and heterogeneous disease that displays diverse molecular subtypes and clinical outcomes. Although it is known that the location of tumors can affect their biological behavior, the underlying mechanisms are not fully understood. In our previous study, we found a differential methylation profile and membrane potential between left (L)- and right (R)-sided breast tumors. In this current study, we aimed to identify the ion channels responsible for this phenomenon and determine any associated phenotypic features. To achieve this, experiments were conducted in mammary tumors in mice, human patient samples, and with data from public datasets. The results revealed that L-sided tumors have a more depolarized state than R-sided. We identified a 6-ion channel-gene signature (CACNA1C, CACNA2D2, CACNB2, KCNJ11, SCN3A, and SCN3B) associated with the side: L-tumors exhibit lower expression levels than R-tumors. Additionally, in silico analyses show that the signature correlates inversely with DNA methylation writers and with key biological processes involved in cancer progression, such as proliferation and stemness. The signature also correlates inversely with patient survival rates. In an in vivo mouse model, we confirmed that KI67 and CD44 markers were increased in L-sided tumors and a similar tendency for KI67 was found in patient L-tumors. Overall, this study provides new insights into the potential impact of anatomical location on breast cancer biology and highlights the need for further investigation into possible differential treatment options.

Extensive review on breast cancer its etiology, progression, prognostic markers, and treatment.

As the most frequent and vulnerable malignancy among women, breast cancer universally manifests a formidable healthcare challenge. From a biological and molecular perspective, it is a heterogenous disease and is stratified based on the etiological factors driving breast carcinogenesis. Notably, genetic predispositions and epigenetic impacts often constitute the heterogeneity of this disease. Typically, breast cancer is classified intrinsically into histological subtypes in clinical landscapes. These stratifications empower physicians to tailor precise treatments among the spectrum of breast cancer therapeutics. In this pursuit, numerous prognostic algorithms are extensively characterized, drastically changing how breast cancer is portrayed. Therefore, it is a basic requisite to comprehend the multidisciplinary rationales of breast cancer to assist the evolution of novel therapeutic strategies. This review aims at highlighting the molecular and genetic grounds of cancer additionally with therapeutic and phytotherapeutic context. Substantially, it also renders researchers with an insight into the breast cancer cell lines as a model paradigm for breast cancer research interventions.

The Potential Role of Epigallocatechin-3-Gallate (EGCG) in Breast Cancer Treatment.

Breast cancer is one of the most diagnosed cancers worldwide, with an incidence of 47.8%. Its treatment includes surgery, radiotherapy, chemotherapy, and antibodies giving a mortality of 13.6%. Breast tumor development is driven by a variety of signaling pathways with high heterogeneity of surface receptors, which makes treatment difficult. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol isolated as the main component in green tea; it has shown multiple beneficial effects in breast cancer, controlling proliferation, invasion, apoptosis, inflammation, and demethylation of DNA. These properties were proved in vitro and in vivo together with synergistic effects in combination with traditional chemotherapy, increasing the effectiveness of the treatment. This review focuses on the effects of EGCG on the functional capabilities acquired by breast tumor cells during its multistep development, the molecular and signal pathways involved, the synergistic effects in combination with current drugs, and how nanomaterials can improve its bioavailability on breast cancer treatment.

Outcomes in breast cancer-does ethnicity matter?

Ethnic or racial differences in breast cancer (BC) survival outcomes have been reported, but current data are largely restricted to comparisons between African Americans and non-Hispanic whites. Most analyses have traditionally been based on self-reported race which may not always be accurate, or are oversimplified in their classification. With increasing globalization, quantification of the genetic ancestry from genomic data may offer a solution to infer the complex makeup from admixture of races. Focusing on the larger and the latest studies, we will discuss recent findings on the differing host and tumor biology that may be driving these disparities, in addition to the extrinsic environmental or lifestyle factors. Socioeconomic disparities with lower cancer literacy may lead to late presentation, poorer adherence to treatment, and other lifestyle factors such as unhealthy diet, obesity, and inadequate physical activity. These hardships may also result in greater allostatic load, which is in turn associated with aggressive BC features in disadvantaged populations. Epigenetic reprogramming may mediate the effects of the environment or lifestyle factors on gene expression, with ensuing differences in BC characteristics and outcome. There is increasing evidence that germline genetics can influence somatic gene alterations or expression, as well as modulate the tumor or immune microenvironment. Although the precise mechanisms remain elusive, this may account for the varying distribution of different BC subtypes across ethnicities. These gaps in our knowledge highlight the need to interrogate the multiomics landscape of BC in diverse populations, ideally in large-scale collaborative settings with standardized methodology for the comparisons to be statistically robust. Together with improving BC awareness and access to good quality health care, a holistic approach with insights of the biological underpinnings is much needed to eradicate ethnic disparities in BC outcomes.