Stage Breast Cancer Research Articles

Lessons from the SOUND trial and future perspectives on axillary staging in breast cancer.

Lessons from the SOUND trial and future perspectives on axillary staging in breast cancer.

HER2-Targeted Therapy-From Pathophysiology to Clinical Manifestation: A Narrative Review.

Trastuzumab is the primary treatment for all stages of HER2-overexpressing breast cancer in patients. Though discovered over 20 years ago, trastuzumab-induced cardiotoxicity (TIC) remains a research topic in cardio-oncology. This review explores the pathophysiological basis of TIC and its clinical manifestations. Their understanding is paramount for early detection and cardioprotective treatment. Trastuzumab renders cardiomyocytes susceptible by inhibiting the cardioprotective NRG-1/HER2/HER4 signaling pathway. The drug acts on HER2-receptor-expressing cardiomyocytes, endothelium, and cardiac progenitor cells (see the Graphical Abstract). The activation of immune cells, fibroblasts, inflammation, and neurohormonal systems all contribute to the evolution of TIC. A substantial amount of research demonstrates that trastuzumab induces overt and subclinical left ventricular (LV) systolic failure. Data suggest the development of right ventricular damage, LV diastolic dysfunction, and heart failure with preserved ejection fraction. Further research is needed to define a chronological sequence of cardiac impairments to guide the proper timing of cardioprotection implementation.

An integrative evaluation of circadian gene TIMELESS as a pan-cancer immunological and predictive biomarker

BackgroundThe gene TIMELESS, which is involved in the circadian clock and the cell cycle, has recently been linked to various human cancers. Nevertheless, the association between TIMELESS expression and the prognosis of individuals afflicted with pan-cancer remains largely unknown.ObjectivesThe present study aims to exhaustively scrutinize the expression patterns, functional attributes, prognostic implications, and immunological contributions of TIMELESS across diverse types of human cancer.MethodsThe expression of TIMELESS in normal and malignant tissues was examined, as well as their clinicopathologic and survival data. The characteristics of genetic alteration and molecular subtypes of cancers were also investigated. In addition, the relationship of TIMELESS with immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity was illustrated. Immunohistochemistry (IHC) was used to validate the expression of TIMELESS in clinical patients with several types of cancer.ResultsIn contrast to the matching normal controls, most tumor types were found to often overexpress TIMELESS. Abnormal expression of TIMELESS was significantly related to more advanced tumor stage and poorer prognosis of breast cancer, as well as infiltrating immune cells such as cancer-associated fibroblast infiltration in various tumors. Multiple cancer types exhibited abnormal expression of TIMELESS, which was also highly correlated with MSI and TMB. More crucially, TIMELESS showed promise in predicting the effectiveness of immunotherapy and medication sensitivity in cancer therapy. Moreover, cell cycle, DNA replication, circadian rhythm, and mismatch repair were involved in the functional mechanisms of TIMELESS on carcinogenesis. Furthermore, immunohistochemical results manifested that the TIMELESS expression was abnormal in some cancers.ConclusionsThis study provides new insights into the link between the circadian gene TIMELESS and the development of various malignant tumors. The findings suggest that TIMELESS could be a prospective prognostic and immunological biomarker for pan-cancer.

Abstract B045: Effect of the COVID-19 pandemic on disparities in stage of breast cancer diagnosis

Abstract Background Black women historically present with more advanced stages of breast cancer (BC). The 2019 novel Coronavirus (COVID-19) led to stressors on healthcare systems resulting in reduction of resources for non-urgent care needs including screening. Limiting screening access may further exacerbate already existing delays in cancer screening and potentially widen racial differences in stage of BC at diagnosis. We examined our institutional data to evaluate differences in the stage of BC at presentation between Black and White women before and during the COVID-19 pandemic. Methods This was a retrospective cohort study of self-identified Black and White women aged 18 and over with invasive BC at The Ohio State University Stefanie Spielman Comprehensive Breast Center between 2018 and 2021. Demographic and clinicopathological characteristics were obtained from medical records with geocoding based on census tract level used to generate a Yost index of neighborhood socioeconomic composition. Study variables included socio-demographic factors (race, age, education) and breast tumor information such as receptor status and clinical stage group early (Stages I and II) vs. late stage (III and IV). Categorical variables were analyzed by chi-square test or Fisher’s Exact test. Continuous variables were analyzed by Wilcoxon Two Sample tests. Logistic regression was used to assess associations between time (pre-COVID (2018-2019) vs. COVID era (2020-2021)) and sociodemographic factors, socioeconomic composition categorized by Yost index (categorized as low (1-33), medium (34-66), and high (67-100)), tumor status, and clinical stage group. Results The total sample included 3162 women (321 Black and 2831 White). More White women (35.2%) had a higher Yost index compared to Black women (16.7%) (P<0.001, indicating higher socioeconomic composition). Pre-pandemic, 81.8% of Black women vs. 86.4% of White women were diagnosed with early stage BC (P=0.489) and 18.2% of Black women vs. 13.6% of White women with late stage BC (P=0.489). During the pandemic, 86.4% of Black vs. 86.7% of White women presented with early stage BC and 13.6% of Black (P=0.489) vs. 13.3% of White women with late stage BC (P=0.489). Results of the multivariate analysis show participants with a medium Yost index had a higher probability of a late-stage diagnosis compared to those with a high Yost index (P=0.0410). Significant predictors of the probability of a late-stage diagnosis included higher age at diagnosis (P=0.0002) and positive estrogen (P=0.0013), progesterone (P<0.0001) and HER2 receptors (P=0.0032). Race and time (pre vs mid-COVID) were not significant predictors of late stage diagnosis. Conclusion Given the novel nature of the coronavirus pandemic, the clinical implications and effects on healthcare delivery will continue to be observed. It is reassuring that we found no significant change in the differences in the stage of BC diagnosis between Black and White women at our institution. On a national scale, how the pandemic will impact existing BC inequalities requires exploration. Citation Format: Ruvarashe P. Rumano, Nicci Owusu-Brackett, Akia Clarke, Robert Tamer, Elizabeth Ghias, Jesse Plascak, Electra D. Paskett, Bridgett A. Oppong. Effect of the COVID-19 pandemic on disparities in stage of breast cancer diagnosis [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B045.

A case of ductal carcinoma in situ (DCIS) with markedly elevated CA15-3 levels requiring 2 years of diagnosis

BackgroundCA15-3 is often elevated in breast cancer recurrence and rarely in ductal carcinoma in situ (DCIS). We report a case of DCIS with elevated CA15-3 levels, which was diagnosed after over 2 years of follow-up.Case presentationA 74-year-old woman presented with a left-sided breast mass and pain. Redness, swelling, and induration were observed in the left breast. Ultrasonography revealed a non-mass lesion in the left 3 o'clock position, skin thickening, and axillary lymphadenopathy. Serum CA15-3 levels were markedly high at 640 U/mL, suggesting inflammatory breast cancer. However, biopsies showed no malignancy. We diagnosed chronic mastitis with elevated CA15-3 levels and followed up with magnetic resonance imaging and a biopsy, as needed. Finally, DCIS was diagnosed 27 months after the first visit. She underwent a left mastectomy and a sentinel lymph node biopsy; DCIS had spread 6.5 cm and was immunohistochemically positive for CA15-3. No metastasis was found in the lymph nodes, but incidental Hodgkin lymphoma was observed. Postoperative normalization of CA15-3 levels indicated that she had DCIS with elevated CA15-3 levels. The patient underwent chemotherapy for Hodgkin lymphoma postoperatively, and there was no evidence of recurrence 1 year after surgery.ConclusionHigh CA15-3 levels can also be observed in DCIS, indicating that CA15-3 should not be used solely in breast cancer staging.

Utility of positron emission tomography for determination of axillary metastasis of breast cancer.

The involvement of axillary lymph nodes plays a key role in breast cancer staging. Positron emission tomography is a promising modality for detecting axillary lymph node metastasis. In addition, nomograms are used to predict the status of axillary lymph nodes. In this study, the role of positron emission tomography in determining axillary metastasis and its correlation with the nomogram was evaluated. The axillary maximum standard uptake value (SUVmax) values of the patients in the preoperative period, the features in the perioperative and postoperative specimen and Memorial Sloan Kettering Cancer Center nomogram data were evaluated. As axillary SUVmax detected by Positron emission tomography in the preoperative period increased, so did the likelihood of lymph node involvement. Axillary SUVmax value were compared with Memorial Sloan Kettering Cancer Center nomogram data but no correlation was found. Age, lymph node number, histopathology results, mass diameter, presence or absence of lymphovascular invasion and/or perineural invasion, tumor type, estrogen receptor status, Ki67 and Cerb-B2 statuses were not correlated. However, axillary SUVmax was inversely correlated with grade and progesterone receptor status. Results from positron emission tomography of axillary lymph nodes in breasts cancer patients showed that SUVmax was only inversely related to cancer grade and progesterone receptor status while not correlating with other accepted parameters for tumor assessment. Thus there is insufficient reliability for the use of axillary SUVmax alone for accurate assessment of tumor characteristics at present.

Diagnostic Accuracy of Contrast-Enhanced Thoracic Photon-Counting Computed Tomography for Opportunistic Locoregional Staging of Breast Cancer Compared With Digital Mammography: A Prospective Trial.

Accurate locoregional staging is crucial for effective breast cancer treatment. Photon-counting computed tomography (PC-CT) is an emerging technology with high spatial resolution and the ability to depict uptake of contrast agents in tissues, making it a promising tool for breast cancer imaging. The aim of this study was to establish the feasibility of locoregional staging of breast cancer through contrast-enhanced thoracic PC-CT, assess its diagnostic performance, and compare it with that of digital mammography (DM). Patients with newly diagnosed breast cancer, DM, and indication of thoracic CT staging were prospectively enrolled in this clinical cohort study over a period of 6 months. Participants underwent contrast-enhanced thoracic PC-CT and breast magnetic resonance imaging in prone position. After blinding to patient data, 2 radiologists independently rated PC-CT and DM regarding the following 6 characteristics: (1) diameter of the largest mass lesion, (2) infiltration of cutis/pectoral muscle/thoracic wall, (3) number of mass lesions, (4) presence/absence of adjacent ductal carcinoma in situ (DCIS), (5) tumor conspicuity, and (6) diagnostic confidence. Reference standard was generated from consensus reading of magnetic resonance imaging combined with all histopathological/clinical data by an independent adjudication committee applying TNM eighth edition. Among 32 enrolled female subjects (mean ± SD age, 59 ± 13.0 years), diagnostic accuracy for T-classification was higher for PC-CT compared with DM (0.94 vs 0.50, P < 0.01). Moreover, the correlation of the number of detected tumor masses with the reference standard was stronger for PC-CT than for DM (0.72 vs 0.50, P < 0.01). We observed that PC-CT significantly ( P < 0.04) outperformed DM regarding not only sensitivity (0.83 and 0.25, respectively) but also specificity (0.99 and 0.80, respectively) for adjacent DCIS. The κ values for interreader reliability were higher for PC-CT compared with DM (mean 0.88 vs 0.54, respectively; P = 0.01). Photon-counting computed tomography outperformed DM in T-classification and provided higher diagnostic accuracy for the detection of adjacent DCIS. Therefore, opportunistic locoregional staging of breast cancer in contrast-enhanced thoracic PC-CT is feasible and could overcome limitations of DM with the potential to improve patient management.

Polyacrylic Acid-Modified Superparamagnetic Iron Oxide Nanoparticles Differentiate Between Hyperplastic and Metastatic Breast Cancer Lymph Nodes

The recognition of lymph node (LN) metastasis is critical for breast cancer staging. Axillary lymph node (ALN) puncture or resection followed by biopsy, to determine whether the presence of metastasis is the diagnostic ‘gold standard’ for axillary lymph node metastasis. This procedure is an invasive procedure that triggers a series of complications. To solve this problem, we developed an ultrasmall superparamagnetic polyacrylic acid-modified iron oxide nanoparticles (PAA@IONs), which exhibit excellent physicochemical characteristics and are extremely stable in the aqueous state. They had an average hydrated particle size of 37.81±0.80 nm, average zeta potential of −38.7±3.8 mV, relaxivity R1 of 25.53±1.58 s−1mM−1, and R2 of 43.10±3.43 s−1mM−1. Animal magnetic resonance imaging (MRI) of the inflammatory hyperplasia model and tumor metastasis model of lymph nodes showed that the samples could effectively detect the metastasized tumors in lymph nodes (n =8). The inflammatory lymphadenopathy did not affect lymph node diagnosis, and this property helped overcome the challenge of current lymph node diagnosis, showing high sensitivity (100%) and specificity (83%). Body weight, hematology, coagulation parameters, serum biochemistry, gross anatomy, and histopathological examination of all Sprague-Dawley (SD) rats after intravenous administration of single or multiple doses of PAA@IONs showed no abnormal findings. Therefore, the ultrasmall superparamagnetic iron oxide nanoparticles constructed herein are a promising contrast agent for nodal tumor staging.

SYNCHRONOUS BILATERAL BREAST CANCER RIGHT HER 2 POSITIVE AND LEFT HER 2 NEGETIVE- A CASE REPORT

Bilateral breast cancers (BBCs) represent 2–11% of breast cancers. The diagnosis of breast cancer at the same time or up to 6 months in both breasts is known as Synchronous bilateral breast cancer (s-BBC).[1,2]In about 15% to 20% of breast cancers, the cancer cells make too much of a growth-promoting protein known as HER2. These cancers, known as HER2-positive breast cancers, tend to grow and spread more aggressively than HER2-negative breast cancers. Targeted drug therapy uses medicines that are directed at (target) proteins on breast cancer cells that help them grow, spread, and live longer. Anti-HER2 therapies (also called as HER2 inhibitors or HER2 targeted therapies) are a class of medicines used to treat all stages of HER2-positive breast cancer and certain HER2-low breast cancers.Trastuzumab is currently used sequentially after completion of anthracycline-based chemotherapy as a single agent or in combination with taxanes. In this case report we present a female 51 year old patient with synchronous bilateral breast cancer Left breast wasHER2 negative cT2N0M0, stage I and Right breast was HER2 positive cT2N2M0 stage Ia, both breast cancers were hormone receptor positive. The patient was administered six cycles of Inj. genexol-PM, Inj. carboplatin, Inj. pertuzumab, Inj. trastuzumab, Inj. Pegasta as NAC, Followed by bilateral radical mastectomy, patient showed a complete tumor reduction with residual node in right breast contrary to left breast which showed partial response. (Left breast ypT1N0 (sn)M0 and right breast ypT0N1aM0).

Circulating levels of biomarkers and risk of ductal carcinoma in situ of the breast in the UK Biobank study.

Observational studies have shown associations between circulating levels of various biomarkers (eg, total cholesterol [TC], low-density lipoprotein cholesterol [LDL], insulin-like growth factor-1 [IGF-1], C-reactive protein [CRP] and glycated hemoglobin-1c [HbA1c]) and the risk of invasive breast cancer (IBC). Ductal carcinoma in situ of the breast (DCIS) is a nonobligate precursor of IBC and shares several risk factors with it. However, the relationship between these biomarkers and DCIS risk remains unexplored. We studied the association between circulating levels of TC, LDL-C, high-density lipoprotein cholesterol (HDL-C), Lipoprotein (a) (Lp-(a)), IGF-1, CRP and HbA1c, with the risk of DCIS in 156801women aged 40 to 69 years and breast cancer-free at enrolment when blood samples and information on demographic and health-related factors were collected. Incident cases of DCIS were ascertained during the follow-up via linkage to the UK cancer registries Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of interest. In all, 969 DCIS incident cases were diagnosed during 11.4 years of follow-up. Total cholesterol was inversely associated with the risk of DCIS (HRquintile(Q)5vsQ1 = 0.47, 95% CI: 0.27-0.82, Ptrend = .008). Conversely, LDL-C was positively associated with DCIS risk (HRQ3vsQ1 = 1.43, 95% CI: 1.01-2.04, HRQ4vsQ1 = 1.60, 95% CI: 1.04-2.47, HRQ5vsQ1 = 2.29, 95% CI: 1.36-3.88, Ptrend = .004). In postmenopausal women, CRP had a weak positive association with DCIS risk, while HbA1c showed a nonlinear association with the risk. These results, in conjunction with those from previous studies on IBC, provide support for the association of several biomarkers with the risk of an early stage of breast cancer.

Exercise during chemotherapy to prevent breast cancer-related cognitive decline: protocol for a pilot randomized controlled trial

BackgroundCancer-related cognitive decline (CRCD) is one of the most reported and debilitating symptoms associated with breast cancer treatment with no currently accepted treatment. Physical activity has emerged as a promising solution for maintaining cognitive health after cancer, with research suggesting that earlier intervention may be important for preventing or mitigating CRCD. There is a clear need to pilot the feasibility and efficacy of pragmatic physical activity interventions to promote cognitive health during active breast cancer treatment. The purpose of this study is to pilot test a home-based prehabilitation physical activity intervention aimed at preventing cognitive decline during chemotherapy, as well as assess the feasibility, acceptability and appropriateness of the intervention among patients.MethodsThis study is a two-arm, pilot randomized controlled trial in 40 adult patients newly diagnosed with breast cancer stages I-III who are scheduled to receive curative intent neo-adjuvant chemotherapy. Participants will be randomized 1:1 to a usual care waitlist control group or a home-based prehabilitation physical activity intervention delivered by a licensed physical therapist. The exercise group will receive an individualized, tapered exercise program comprised of home exercise sessions and virtual coaching calls. Both groups will receive activity monitors and be encouraged to maintain a healthy lifestyle during treatment. Participant adherence and adverse events will be assessed throughout the study.ResultsThis research was supported by the Alvin J. Siteman Cancer Center through The Foundation for Barnes-Jewish Hospital (award No. 6257). The protocol was approved by Washington University's Protocol Review and Monitoring Committee and Institutional Review Board. Enrollment began in May 2023 and is anticipated to continue through July 2024.ConclusionsThis study will provide the necessary preliminary data to support larger trials investigating if and how physical activity can be incorporated into early rehabilitation strategies to prevent chemotherapy-related sequelae.Trial registrationClinicalTrials.gov, NCT05716542.

Ultrasound Pretreatment Lymph Node Evaluation in Early-Stage Breast Cancer: Should We Biopsy High Suspicion Nodes?

With the growing incidence of breast cancer, efficient and correct staging is essential for further treatment decisions. Axillary ultrasound (US) remains the most common method for regional nodal involvement assessment. The aim of this study was to evaluate whether high-risk US features can accurately predict axillary lymph node metastasis. A total of 150 early-stage breast cancer patients (T1 or T2) were prospectively included in the study. Based on axillary US, patients were classified as normal, low-risk, or high-risk, with all patients in the low-risk and high-risk groups undergoing fine-needle aspiration (FNAB) and core-needle biopsies. For the low-risk US group, a lower prediction rate of axillary nodal metastasis was achieved than for the group with high-risk features, recording a sensitivity of 66.6% vs. 89.2%, a specificity of 57.1% vs. 100%, a positive predictive value (PPV) of 26.6% vs. 100%, a negative predictive value (NPV) of 88% for both groups, and an accuracy of 58.9% vs. 94%, respectively. FNAB resulted in more false-negative results compared to core-needle biopsy in both low-risk and high-risk US groups. Our findings suggest that high-risk US features can predict axillary lymph node metastasis with high accuracy.

The practice of breast self-examination and associated factors among female healthcare professionals working in selected hospitals in Kigali, Rwanda: a cross sectional study

BackgroundBreast self-examination (BSE) is considered one of the main screening methods in detecting earlier stages of breast cancer. It is a useful technique if practiced every month by women above 20 years considering that breast cancer among women globally contributed to 685,000 deaths in 2020. However, the practice of breast self-examination among healthcare professionals is low in many developing countries and it is not well known in Rwanda. Therefore, this research was intended to measure the level of breast self-examination practice and its associated factors among female healthcare professionals working in selected hospitals in Kigali, Rwanda.MethodsA cross-sectional study was conducted among 221 randomly selected female healthcare professionals in four district hospitals in Kigali, Rwanda. A self-administered structured questionnaire was used as data collection instrument. The predictor variables were socio-demographic and obstetrics variables, knowledge on breast cancer and breast self-examination as well as attitude towards breast cancer and breast self-examination. Sample statistics such as frequencies, proportions and mean were used to recapitulate the findings in univariate analysis. Multiple logistic regression analysis was employed to identify statistically significant variables that predict breast self-examination practice. Adjusted odds ratio with 95% confidence level were reported. P-value < 0.05 was used to declare statistical significance.ResultsBreast self-examination was practiced by 43.5% of female healthcare professionals. This prevalence is low compared to other studies. Attitude towards breast self-examination and breast cancer was the only predictor variable that was significantly associated with breast self-examination practice [AOR = 1.032; 95% CI (1.001, 1.065), p-value = 0.042]. However, number of pregnancy and number of children were not significantly associated with BSE practice in the multi-variate analysis. In addition, there was a positive linear link between knowledge and attitude, with a correlation coefficient (r) of 0.186 (p = 0.005).ConclusionsThe breast self-examination practice among healthcare professionals was found to be low. Attitude towards breast cancer and breast self-examination was positively associated with BSE practice. Moreover, attitude and knowledge were positively correlated. This suggests the need for continuous medical education on breast self-examination and breast cancer to increase the knowledge & BSE practice level of female healthcare professionals.

ASIC1a contributes to the epithelial-mesenchymal transformation of breast cancer by activating the Ca2+ /β-catenin pathway.

Breast cancer is the most common cancer in the world, with metastasis being one of the leading causes of death among patients. The acidic environment of breast cancer tissue promotes tumor cell invasion and migration by inducing epithelial-mesenchymal transformation (EMT) in tumor cells, but the exact mechanisms are not yet fully understood. This study investigated the expression of acid-sensitive ion channel 1a (ASIC1a) in breast cancer tissue samples and explored the mechanisms by which ASIC1a mediates the promotion of EMT in breast cancer cells in an acidic microenvironment through in vivo and in vitro experiments. The results showed that first, the expression of ASIC1a was significantly upregulated in breast cancer tissue and was correlated with the TNM (tumor node metastasis) staging of breast cancer. Furthermore, ASIC1a expression was higher in tumors with lymph node metastasis than in those without. Second, the acidic microenvironment promoted [Ca2+ ]i influx via ASIC1a activation and regulated the expression of β-catenin, Vimentin, and E-cadherin, thus promoting EMT in breast cancer cells. Inhibition of ASIC1a activation with PcTx-1 could suppress EMT in breast cancer cells. Finally, in vivo studies also showed that inhibition of ASIC1a could reduce breast cancer metastasis, invasion, and EMT. This study suggests that ASIC1a expression is associated with breast cancer staging and metastasis. Therefore, ASIC1a may become a new breast cancer biomarker, and the elucidation of the mechanism by which ASIC1a promotes EMT in breast cancer under acidic microenvironments provides evidence for the use of ASIC1a as a molecular target for breast cancer treatment.

Cumulative environmental quality is associated with breast cancer incidence differentially by summary stage and urbanicity

Individual environmental contaminants have been associated with breast cancer; however, evaluations of multiple exposures simultaneously are limited. Herein, we evaluated associations between breast cancer summary stages and the Environmental Quality Index (EQI), which includes a range of environmental factors across five domains. The EQI (2000–2005) was linked to county-level age-standardized incidence rates (SIRs) obtained from the North Carolina Central Cancer Registry (2010–2014). Incidence rates and SIRs of total, in situ, localized, regional, and distant breast cancers were evaluated stratified by rural–urban status. In counties with poor environmental quality compared to those with good environmental quality, total breast cancer incidence was higher by 10.82 cases per 100,000 persons (95% CI 2.04, 19.60, p = 0.02). This association was most pronounced for localized breast cancer (β = 5.59, 95% CI 0.59, 10.58, p = 0.03). Higher incidence of early-stage disease (carcinoma in situ β = 5.25, 95% CI 2.34, 8.16, p = 0.00 and localized breast cancer β = 6.98, 95% CI 2.24, 11.73, p = 0.00) and total breast cancer (β = 11.44, 95% CI 3.01, 19.87, p = 0.01) occurred in counties with poor land quality, especially urban counties. Our analyses indicate significant associations between environmental quality and breast cancer incidence, which differ by breast cancer stage and urbanicity, identifying a critical need to assess cumulative environmental exposures in the context of cancer stage.

Medical care costs according to the stage and subtype of breast cancer in a municipal setting: a case study of Hachioji City, Japan

BackgroundIt is important to assess whether the early detection of breast cancer affects medical care costs. However, research remains scant on the actual medical care costs associated with breast cancer treatment in Japan. This study aimed to determine the medical care costs of breast cancer treatment based on its stage using national health insurance claims data.MethodsThis was an observational study including patients with breast cancer who had undergone breast cancer treatment, as defined by the disease name and related treatment codes. Between August 2013 and June 2016, patients who underwent surgical treatment without axillary lymph node dissection and other radical treatment were classified as the curable group, while those who underwent palliative treatment were classified as the non-curable group. Patients were further stratified by subtype. The total and treatment-specific medical care costs for the five years were calculated using the national health insurance claims data of Hachioji City between August 2013 and May 2021.ResultsThe mean total medical care costs for the curable and non-curable groups for the 5 years were JPY 3958 thousand (standard deviation 2664) and JPY 8289 thousand (8482), respectively. The mean medical care costs for specific breast cancer treatment for the curable and non-curable groups were JPY 1142 (728) thousand and JPY 3651 thousand (5337), respectively. Further, human epidermal growth factor receptor 2 + , Hormone + patients had the highest mean cost over the 5 years.ConclusionsThe results suggest that the early detection of breast cancer may reduce medical care costs at the patient level.

Inhibition of Pard3 promotes breast cancer metastasis via the USP28 mediated deubiquitination of Snail1

Pard3 is a core component of the Par complex and is a critical regulator of cell polarity. However, the biological role of Pard3 in breast cancer (BC) remains unclear. In this study we found that Pard3 levels were down-regulated in BC cells and tissues. Pard3 down-regulation was associated with the TNM stage of BC. Further, Pard3 knockdown enhanced colony formation and metastasis in vitro and in vivo. Interestingly, Pard3 knockdown also enhanced Snail1 deubiquitination and promoted BC invasion and migration via Snail1. Moreover, Pard3 silencing led to activation of the NFκB pathway, promoting the expression of USP28. Subsequently, USP28 interacted with and deubiquitinated Snail1; these effects were dependent on GSK-3β-mediated phosphorylation. Together, the findings indicated that Pard3 knockdown facilitated the migration and invasion of BC cells by enhancing USP28-mediated Snail1 deubiquitination. Collectively, targeting the Pard3/NFκB/USP28/Snail1 signaling pathway might be a promising treatment option for breast cancer.

Detección de la infiltración de la cadena mamaria interna en pacientes con cáncer de mama mediante PET/RM con 18F-FDG y sus implicaciones terapéuticas

ObjectiveTo evaluate the detection rate and therapeutic implication of the infiltration of the internal mammary chain (IMCI) by [18F]FDG PET/MRI for staging of patients with breast cancer. MethodsProspective study including 41 women with breast cancer (stage ≥IIB) staged by [18F]FDG PET/MR. Two-phase exam: breast imaging (prone), whole-body (supine). TNM stage assessed by peer consensus with Nuclear Medicine and Radiology specialists. Study of the afferent vessel (AV) to IMC by breast MRI. IMCI was correlated with age, AV-IMC, T stage, breast quadrants, axillary and distant infiltration. Therapeutic re-evaluation by a multidisciplinary committee. ResultsIMCI detection rate of 34% (14/41), with 8/14 patients under 55 years of age. All 14 patients with IMCI showed AV-IMC, 6 of them (43.9%) without VA-axillary. Of 27/41 patients without IMCI, in 13 (48.1%) only AV-axillary was found, in the remaining 14 (51.9%), AV-axillary and AV-IMC was found. In 57% (8/14) tumours were multicentric and 42% (6/14) focal, in inner quadrants in 4/6 (66.7%). In 1/14 patient (7.1%) only IMCI was found, in 9/14 (64.3%) axillary and IMC, in 4/14 patients (28.6%) distant lesions were detected. Committee re-evaluation: no further treatment in 27/41 patients (65.8%), thoracic radiotherapy in 10/41 patients (24.4%), systemic therapy in 4/41 patients (9.7%). ConclusionOur detection rate of IMCI in breast cancer staging by [18F]FDG PET/MR was 34%. Related factors were age, multicentric tumours, inner quadrants, detection of AV-IMC, NM staging.The evidence of IMCI allowed tailored therapy, with thoracic radiotherapy implementation in 24.4% of patients.

Radiomics to Differentiate Malignant and Benign Breast Lesions: A Systematic Review and Diagnostic Test Accuracy Meta-Analysis.

Breast cancer is a prevalent global health concern, necessitating accurate diagnostic tools for effective management. Diagnostic imaging plays a pivotal role in breast cancer diagnosis, staging, treatment planning, and outcome evaluation. Radiomics is an emerging field of study in medical imaging that contains a broad set of computational methods to extract quantitative features from radiographic images. This can be utilized to guide diagnosis, treatment response, and prognosis in clinical settings. A systematic review was performed in concordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. Quality was assessed using the radiomics quality score. Diagnostic sensitivity and specificity of radiomics analysis, with 95% confidence intervals (CIs), were included for meta-analysis. The area under the curve analysis was recorded. An extensive statistical analysis was performed following the Cochrane guidelines. Statistical significance was determined if p-values were less than 0.05. Statistical analyses were conducted using Review Manager (RevMan), Version 5.4.1. A total of 31 manuscripts involving 8,773 patients were included, with 17 contributing to the meta-analysis. The cohort comprised 56.2% malignant breast cancers and 43.8% benign breast lesions. MRI demonstrated a sensitivity of 0.91 (95% CI: 0.89-0.92) and a specificity of 0.84 (95% CI: 0.82-0.86) in differentiating between benign and malignant breast cancers. Mammography-based radiomic features predicted breast cancer subtype with a sensitivity of 0.79 (95% CI: 0.76-0.82) and a specificity of 0.81 (95% CI: 0.79-0.84). Ultrasound-based analysis yielded a sensitivity of 0.92 (95% CI: 0.90-0.94) and a specificity of 0.85 (95% CI: 0.83-0.88). Only one study reported the results of radiomic evaluation from CT, which had a sensitivity of 0.95 (95% CI: 0.88-0.99) and a specificity of 0.56 (95% CI: 0.45-0.67). Across different imaging modalities, radiomics exhibited robust diagnostic accuracy in differentiating benign and malignant breast lesions. The results underscore the potential of radiomic assessment as a minimally invasive alternative or adjunctive diagnostic tool for breast cancer. This is pioneering data that reports on a novel diagnostic approach that is understudied and underreported. However, due to study limitations, the complexity of this technology, and the need for future development, biopsy still remains the current gold standard method of determining breast cancer type.

Physiological Uptake Characteristics of Breast on 68Ga-FAPI-04 PET/CT.

Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET/CT is sensitive on breast cancer staging, but its clinical utility may be limited by the high physiological 68Ga-FAPI-04 uptake in normal breast tissue that can obscure primary tumors. The aim of this study was to elucidate the characteristics of physiological 68Ga-FAPI-04 uptake in normal breast. A total of 143 consecutive women with 68Ga-FAPI-04 PET/CT data were reviewed retrospectively. SUVmax, density and thickness of breast, as well as SUVmax of nipple, were measured. Univariate and multivariate regression analyses were used to identify factors related to the breast and nipple SUVs. Twenty-eight premenopausal, 62 menopausal and 10 post-operative (after bilateral adnexectomy) women with 103 examinations were included. All had a diffuse, symmetrical uptake in breast. There was no difference in 68Ga-FAPI-04 uptake between bilateral breasts (right: median, 1.14[IQR, 0.85-1.54] vs. left: median, 1.09[IQR, 0.86-1.54]; P = 0.253). Patients in menstrual status with expected high estrogen level (late follicular, ovulatory and mid luteal phases) had higher breast SUVs (median SUV, 3.91 [IQR, 2.85-4.35]) than those with expected moderate (early follicular, early luteal and late luteal phases; median SUV, 1.57 [IQR, 1.39-2.08]; P < 0.001) or low level (menopause and post-operation; median SUV, 0.98 [IQR, 0.83-1.21]; P < 0.001). Menstrual status was an independent predictors of breast SUV (r2 = 0.689, P < 0.001). All the patients had a focal, symmetrical uptake in nipples. Nipple SUV did not correlate with menstrual status (P = 0.913).