The latest medical research on Breast Cancer

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about breast cancer gathered by our medical AI research bot.

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Long-term prospective outcome data using EndoPredict as risk stratification and chemotherapy decision biomarker in hormone receptor-positive, HER2-negative early breast cancer.

Breast Cancer

To report the prospective long-term outcome data of patients whose chemotherapy decision was guided by the EndoPredict test.

Patients with hormone receptor-positive HER2-negative early breast cancer with 0-3 positive lymph nodes were enrolled. The EndoPredict test was carried out on all tumor samples. Treatment compliance, local recurrence, distant metastases, and survival were evaluated. Associations of EPclin risk stratification with 5-year disease-free survival and distant metastasis-free survival were evaluated by time-to-event analysis.

368 consecutive patients were included in the analysis. Median follow-up was 8.2 years. EndoPredict allocated 238 (65%) in the low-risk and 130 (35%) patients in the high-risk group. Risk for disease recurrence or death in EPclin high-risk patients was twofold higher than in EPclin low-risk patients (hazard ratio [HR] 2.08; 95% CI 1.26-3.44; p = 0.004). EPclin low-risk patients had a 5-year disease-free survival of 95.3% (95% CI 92.6-98.0%). EPclin high-risk patients were at higher risk of developing distant metastases or death (HR 2.21; 95% CI 1.27-3.88; p = 0.005). EPclin high-risk patients who underwent chemotherapy had a 5-year DFS of 89.1% (95% CI 82.7-96.1%) in contrast to high-risk patients without chemotherapy (68.9%; 95% CI 56.2-84.5%; HR 0.46; 95% CI 0.23-0.95; p = 0.036). EPclin high-risk patients were at higher risk of experiencing distant metastases or death than EPclin low-risk patients regardless of menopausal status (premenopausal: HR 3.55; 95% CI 1.17-12.32; p = 0.025; postmenopausal: HR 1.92; 95% CI 0.99-3.7; p = 0.054).

EndoPredict can guide decisions on adjuvant chemotherapy in early luminal breast cancer. EndoPredict risk stratification is also applicable in premenopausal women.

SLC34A2 promotes cell proliferation by activating STX17-mediated autophagy in esophageal squamous cell carcinoma.

Thoracic Cancer

Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive.

Western blotting, quantitative real-time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan-Meier curves were employed for survival analysis. CCK-8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA-sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP-GFP-LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2-interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability.

The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki-67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy-related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17.

These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.

KIAA1429 regulates lung adenocarcinoma proliferation and metastasis through the PI3K/AKT pathway by modulating ARHGAP30 expression.

Thoracic Cancer

Alterations in epigenetic factors are recognized as key contributors to the emergence of human cancer. The active and reversible alteration of N6-methyladenosine (m6A) RNA is crucial for controlling gene activity and determining cellular destiny. Even with these insights, the triggering of KIAA1429 (also called VIRMA) and its role in lung adenocarcinoma (LUAD) is mostly unclear. As a result, the objective of this study was to elucidate how KIAA1429 contributes to cancer development in LUAD.

This study utilized multiple methods for investigation, encompassing the in vitro functional examination of KIAA1429 in lung adenocarcinoma cells, transcriptome sequencing, methylation RNA immunoprecipitation sequencing (MeRIP-seq), as well as RNA stability tests to ascertain the half-life and stability of the target genes.

The results indicated that modifying the expression of KIAA1429 regulated the proliferation and metastasis of LUAD. By employing transcriptome sequencing alongside MeRIP-seq analysis, the research pinpointed genes affected by m6A alterations triggered by KIAA1429. In a more detailed manner, it was discovered that KIAA1429 plays a regulatory role in the expression of ARHGAP30. Suppressing KIAA1429 results in reduced m6A levels in the mRNA of the target gene ARHGAP30, boosting its stability and expression, thus inhibiting tumor proliferation and metastasis.

This study revealed the activation mechanism and pivotal function of KIAA1429 in LUAD tumor development, paving the way for molecular-based interventions for LUAD.

Left ventricular global longitudinal strain is worse in BRCA mutation positive breast cancer patients prior to cancer treatment and premature menopause.

Breast Cancer

Breast cancer patients with mutations in human tumor suppressor genes BRCA1 and BRCA2 are at higher risk of cardiovascular disease (CVD) than the general population, as they are frequently exposed to cardiotoxic chemotherapy, anti-estrogen therapy, radiation, and/or oophorectomy for cancer-related treatment and prophylaxis. Animal and cell culture models suggest that BRCA mutations may play an independent role in heart failure. We sought to evaluate cardiac structure and function in female BRCA1 and BRCA2 mutation carriers with breast cancer compared to BRCA wildtype women with breast cancer.

We performed a 1:2 age- and hypertension-matched retrospective cohort study comparing BRCA1 and BRCA2 mutation carriers (n = 38) versus BRCA wildtype controls (n = 76) with a new diagnosis of breast cancer. Echocardiographic data were obtained within 6 months of breast cancer diagnosis and prior to chemotherapy, anti-estrogen therapy, radiation, or oophorectomy. Left ventricular global longitudinal strain (LV-GLS), a highly sensitive marker of LV function, was measured using QLab 15 (Philips Healthcare).

In the total cohort of 114 patients with a new diagnosis of breast cancer, the median age was 45 ± 11 years and the prevalence of hypertension was 8%. There were no differences in traditional cardiovascular disease risk factors between cases and controls. BRCA carriers had lower LV-GLS (- 18.1% ± 4.7% vs. - 20.1% ± 3.8%, p = 0.02) and greater right atrial area (12.9 cm2 ± 2.7 cm2 vs. 11.8 cm2 ± 2.0 cm2, p = 0.04) compared to controls; however, both LV-GLS and right atrial area were within the normal range. Compared to controls, BRCA carriers had a trend toward worse LV posterior wall thickness (0.89 cm ± 0.15 cm vs. 0.83 cm ± 0.16 cm, p = 0.06) although not statistically significant.

In women with newly diagnosed breast cancer and prior to treatment, LV-GLS was worse in BRCA1 and BRCA2 mutation carriers compared to those with BRCA wildtype. These findings suggest that BRCA mutations may be associated with subtle changes in cardiac function. Whether differences in GLS translate to increased cardiovascular risk in women with BRCA mutations needs to be further characterized.

Residual cancer burden in two-stage nipple sparing mastectomy after first stage lumpectomy and devascularization of the nipple areolar complex.

Breast Cancer

Ischemic complications after nipple-sparing mastectomy (NSM) can be ameliorated by 2-stage procedures wherein devascularization of the nipple-areolar complex (NAC) and lumpectomy with or without nodal staging surgery is performed first (1S), weeks prior to a completion NSM (2S). We report the time interval between procedures in relation to the presence of residual carcinoma at 2S NSM.

Women with breast cancer who received 2S NSM from 2015 to 2022 were identified. Both patient level and breast level analyses were conducted. Clinical staging at presentation, pathologic staging at 1S and residual disease at 2S pathology are noted. Residual disease was classified as microscopic (1-2 mm), minimal (3-10 mm), and moderate (> 10 mm).

59 patients (108 breasts) underwent 2S NSM. The median time interval between 1 and 2S for all patients was 34 days: 31 days for upfront surgery invasive cancer, 41 days for upfront DCIS surgery and 31 days for those receiving neoadjuvant therapy. Completion NSM was performed within 6 weeks for 72% of the breasts analyzed. Of the 53 breasts with invasive cancer on 1S pathology, 35% (19/53) had no residual invasive disease and 24.5% (13/53) had neither residual invasive nor in situ carcinoma on final 2S. Among the 50 women who had upfront surgery, 16 (32%) had residual invasive cancer found at 2S NSM, 9 of which had less than or equal to 1 cm disease.

Invasive cancers were completely resected during 1S procedure in 65% of breasts. Residual disease was minimal and there was only one case of upstaging at 2S. Added time of two-stage surgery is offset by a reduction in ischemic mastectomy flap complications.

Impact of exercise on chemotherapy-induced peripheral neuropathy in survivors with post-treatment primary breast cancer.

Breast Cancer

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of neurotoxic chemotherapy. Exercise activates neuromuscular function and may improve CIPN. We examined the association between exercise and CIPN symptoms in breast cancer survivors.

In a retrospective cross-sectional study, we included patients completing a survey assessing exercise exposure and neuropathy symptoms in a tertiary cancer center survivorship clinic. We evaluated exercise duration and intensity using a standardized questionnaire quantified in metabolic equivalent tasks (MET-h/wk). We defined exercisers as patients meeting the National Physical Activity Guidelines' criteria. We used multivariable logistic regressions to examine the relationship between exercise and CIPN and if this differed as a function of chemotherapy regimen adjusting for age, gender, and race.

We identified 5444 breast cancer survivors post-chemotherapy (median age 62 years (interquartile range [IQR]: 55, 71); median 4.7 years post-chemotherapy (IQR: 3.3, 7.6)) from 2017 to 2022. CIPN overall prevalence was 34% (95% confidence interval [CI]: 33%, 36%), 33% for non-taxane, and 37% for taxane-based chemotherapy. CIPN prevalence was 28% (95% CI: 26%, 30%) among exercisers and 38% (95% CI: 37%, 40%) among non-exercisers (difference 11%; 95% CI: 8%, 13%; p < 0.001). Compared to patients with low (<6 MET-h/wk) levels of exercise (42%), 11% fewer patients with moderate (6-20.24 MET-h/wk) to high (>20.25 MET-h/wk) levels of exercise reported CIPN. Exercise was associated with reduced prevalence of all CIPN symptoms regardless of chemotherapy type.

CIPN may persist several years following chemotherapy among patients with breast cancer but is significantly reduced by exercise in a dose-dependent manner.

Berberine inhibits the progression of breast cancer by regulating METTL3-mediated m6A modification of FGF7 mRNA.

Thoracic Cancer

Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood.

Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase-like 3 (METTL3), and insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)-qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay.

BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR-treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A-IGF2BP3-dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo.

BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3-mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment.

Clinical and molecular predictors of very late recurrence in oestrogen receptor-positive breast cancer patients.

Breast Cancer

Risk of recurrence from primary ER+ breast cancer continues for at least 20 years. We aimed to identify clinical and molecular features associated with risk of recurrence after 10 years.

ER+ breast cancers from patients with and without recurrence were analysed with the BC360 NanoString Panel and an 87 gene targeted-exome panel. Frequency of clinical, pathologic and molecular characteristics was compared between cases (recurred between 10 and 20 years) and controls (no recurrence by 20 years) in the Very Late Recurrence (VLR) cohort. Analogous data from METABRIC were examined to confirm or refute findings.

VLR cases had larger tumours and higher node positivity. Both VLR and METABRIC cases had higher clinical treatment score at 5 years (CTS5). There was a trend for fewer GATA3 mutations in cases in both VLR and METABRIC but no statistically significant differences in mutation frequency. Cell cycle and proliferation genes were strongly expressed in VLR cases. Immune-related genes and cell cycle inhibitors were highly expressed in controls. Neither of these changes were significant after correction for multiple testing.

Clinicopathologic features are prognostic beyond 10 years. Conversely, molecular features, such as copy number alterations, TP53 mutations and intrinsic subtype which have early prognostic significance, have little prognostic value after 10 years.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

Breast Cancer

This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed.

Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison.

Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018].

Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

Simultaneous integrated boost intensity-modulated radiotherapy post breast-conserving surgery: clinical efficacy, adverse effects, and cosmetic outcomes in breast cancer patients.

Breast Cancer

Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) is an innovative technique delivering a higher dose to the tumor bed while irradiating the entire breast. This study aims to assess the clinical outcomes, adverse effects, and cosmetic results of SIB-IMRT following breast-conserving surgery in breast cancer patients.

We conducted a retrospective analysis of 308 patients with stage 0-III breast cancer who underwent breast-conserving surgery and SIB-IMRT from January 2016 to December 2020. The prescribed doses included 1.85 Gy/27 fractions to the whole breast and 2.22 Gy/27 fractions or 2.20 Gy/27 fractions to the tumor bed. Primary endpoints included overall survival (OS), local-regional control (LRC), distant metastasis-free survival (DMFS), acute and late toxicities, and cosmetic outcomes.

The median follow-up time was 36 months. The 3-year OS, LRC, and DMFS rates were 100%, 99.6%, and 99.2%, respectively. Five patients (1.8%) experienced local recurrence or distant metastasis, and one patient succumbed to distant metastasis. The most common acute toxicity was grade 1-2 skin reactions (91.6%). The most common late toxicity was grade 0-1 skin and subcutaneous tissue reactions (96.7%). Five patients (1.8%) developed grade 1-2 upper limb lymphedema, and three patients (1.1%) had grade 1 radiation pneumonitis. Among the 262 patients evaluated for cosmetic outcomes at least 2 years post-radiotherapy, 96.9% achieved excellent or good results, while 3.1% had fair or poor outcomes.

SIB-IMRT after breast-conserving surgery in breast cancer patients demonstrated excellent clinical efficacy, mild acute and late toxicities, and satisfactory cosmetic outcomes in our study. SIB-IMRT appears to be a feasible and effective option for breast cancer patients suitable for breast-conserving surgery.

Treatment patterns and clinical outcomes in patients with metastatic triple-negative breast cancer: a large-scale data analysis using the Japanese claims database.

Breast Cancer

This study evaluated treatment patterns and clinical outcomes among patients with metastatic triple-negative breast cancer (mTNBC) in real-world clinical settings in Japan.

The treatment patterns, time to next treatment or death (TTNTD), time to treatment discontinuation, adverse events of interest, and medical costs of treating patients with mTNBC in first-, second-, and third-line settings were investigated using data of patients meeting the inclusion criteria between January 2017 and March 2022 in a Japanese medical claims database. The treatment regimens for mTNBC were defined according to the Japanese Breast Cancer Society Clinical Practice Guidelines.

In this study, 2236 patients with mTNBC (median age 66.0 years; 99.8% female) were included in the first-line cohort. Of these, 46.6% and 20.8% were included in the second- and third-line cohorts, respectively. The two most frequently used treatments were capecitabine (19.1%) and S-1 (tegafur-gimeracil-oteracil) (14.5%) in the first-line cohort, eribulin (18.3%) and bevacizumab/paclitaxel (14.4%) in the second-line cohort, and eribulin (19.4%) and bevacizumab/paclitaxel (17.5%) in the third-line cohort. The TTNTD shortened as the line of therapy progressed (median 8.0, 6.5, and 5.2 months for the first-, second-, and third-line treatments, respectively). Nausea/vomiting and neutropenia/leukopenia occurred in 62.8% and 18.3% of all patients, respectively. The medical total costs per day were 6.7, 10.2, and 12.9 thousand yen during the first-/second-/third-line treatments, respectively.

This study provides insight into current treatment patterns for mTNBC in Japan. The cost-benefit balance worsens with later-line treatment and a high unmet need for mTNBC drug treatment remains.

Multi-omics portrait of ductal carcinoma in situ in young women.

Breast Cancer

Young patients with breast ductal carcinoma in situ (DCIS) often face a poorer prognosis. The genomic intricacies in young-onset DCIS, however, remain underexplored.

To address this gap, we undertook a comprehensive study encompassing exome, transcriptome, and vmethylome analyses. Our investigation included 20 DCIS samples (including 15 young-onset DCIS) and paired samples of normal breast tissue and blood.

Through RNA sequencing, we identified two distinct DCIS subgroups: "immune hot" and "immune cold". The "immune hot" subgroup was characterized by increased infiltration of lymphocytes and macrophages, elevated expression of PDCD1 and CTLA4, and reduced GATA3 expression. This group also exhibited active immunerelated transcriptional regulators. Mutational analysis revealed alterations in TP53 (38%), GATA3 (25%), and TTN (19%), with two cases showing mutations in APC, ERBB2, and SMARCC1. Common genomic alterations, irrespective of immune status, included gains in copy numbers at 1q, 8q, 17q, and 20q, and losses at 11q, 17p, and 22q. Signature analysis highlighted the predominance of signatures 2 and 1, with "immune cold" samples showing a significant presence of signature 8. Our methylome study on 13 DCIS samples identified 328 hyperdifferentially methylated regions (DMRs) and 521 hypo-DMRs, with "immune cold" cases generally showing lower levels of methylation.

In summary, the molecular characteristics of young-onset DCIS share similarities with invasive breast cancer (IBC), potentially indicating a poor prognosis. Understanding these characteristics, especially the immune microenvironment of DCIS, could be pivotal in identifying new therapeutic targets and preventive strategies for breast cancer.