Breast Cancer Events Research Articles

Abstract P617: Light to Moderate Alcohol Consumption is Not Associated With Breast Cancer Incidence in Italian Adult Women: Results From the Moli-Sani Study

Introduction: Epidemiologic studies suggest that heavy alcohol drinking is associated with unhealthy profile, whereas its light to moderate intake is associated with reduced hazard of total mortality as compared with lifetime abstention, a result largely driven by a reduction in cardiovascular mortality. Up to date, there is no agreement on a possible safe threshold for alcohol consumption in relation with cancer risk, especially breast cancer (BC) in women. Hypothesis: We assessed the hypothesis that the association of alcohol consumption with development of BC is mostly dependent on the average daily volume consumed. Methods: A prospective investigation was conducted on 11,394 women (age ≥35y) from the Moli-sani study (apparently free from any cancer at baseline; 2005-2010). The alcohol volume consumed in the year before enrolment was classified as: lifetime or former or occasional drinkers and current drinkers who drank 1-12, 12.1-24, and > 24 g/d. Incident cases of BC were validated through medical and histological records. Multivariable hazard ratio (HR) and 95% confidence interval (CI) for BC were estimated using Cox proportional hazard models and multiple imputation for missing data on covariates. Results: During a median follow-up of 13.2 years, 296 BC events occurred. In comparison with lifetime abstention, intake of alcohol up to 12 g/d was not associated with BC, while consumption >12 g/d had higher hazard of BC (Table). These findings remained consistent after the exclusion of BC events occurred during the first 12 months of follow-up or stratifying by BC subtypes (Table). Conclusions: Drinking up to one unit of alcohol (12 g) per day was not associated with either a protection or an increased BC risk in women. In contrast, drinking more than 12 g/d of alcohol had hazardous impact on BC incidence. These findings contribute to the current literature debate, suggesting that there is indeed an alcohol threshold below which alcohol drinking would not affect breast cancer risk.

Justifying Ribociclib Dose in Patients with Advanced Breast Cancer with Renal Impairment Based on PK, Safety, and Efficacy Data: An Innovative Approach Integrating Data from a Dedicated Renal Impairment Study and Oncology Clinical Trials.

Renal impairment is common in patients with cancer and can alter the PK and thus the safety and efficacy of drugs. We assessed the impact of renal impairment during treatment with ribociclib, a cyclin-dependent kinase 4/6 inhibitor, and determined dose recommendations for patients with advanced breast cancer with renal impairment. A comprehensive assessment integrating pharmacokinetic, safety, and efficacy data from a phase I dedicated renal impairment study in non-cancer subjects and six phase I-III trials in patients with cancer was performed. Ribociclib showed higher pharmacokinetic exposure in subjects with renal impairment than those with normal renal function following a single 400-mg dose in the dedicated renal impairment study. However, in patient trials, both single-dose and steady‑state ribociclib exposure was comparable between patients with cancer with mild/moderate renal impairment and those with normal renal function following the recommended starting dose of 600 mg. Model-predicted steady‑state exposure in patients with advanced breast cancer was also similar across the renal function groups. Progression-free survival was similar and safety profiles were generally consistent across the renal cohorts (normal/mild/moderate) in patients with advanced breast cancer, with low-grade and manageable adverse events, demonstrating a positive benefit-risk profile. From the collective evidence and considering a real-world clinical setting, no dose adjustment is recommended for patients with mild/moderate renal impairment, whereas a reduced dose is recommended for patients with severe renal impairment. This report presented a holistic and innovative strategy to determine dose in patients with renal impairment and demonstrated the effectiveness of integrating the data of both a clinical pharmacology study and patient trials to justify doses in patients with renal impairment. Clinicaltrials.gov identifiers: NCT02431481, NCT01958021, NCT02422615, NCT02278120, NCT01237236, NCT01898845, NCT01872260.

Variation in second breast cancer risk after primary invasive cancer by time since primary cancer diagnosis and estrogen receptor status.

In women with previously treated breast cancer, occurrence and timing of second breast cancers have implications for surveillance. The authors examined the timing of second breast cancers by primary cancer estrogen receptor (ER) status in the Breast Cancer Surveillance Consortium. Women who were diagnosed with American Joint Commission on Cancer stage I-III breast cancer were identified within six Breast Cancer Surveillance Consortium registries from 2000 to 2017. Characteristics collected at primary breast cancer diagnosis included demographics, ER status, and treatment. Second breast cancer events included subsequent ipsilateral or contralateral breast cancers diagnosed >6months after primary diagnosis. The authors examined cumulative incidence and second breast cancer rates by primary cancer ER status during 1-5 versus 6-10years after diagnosis. At 10years, the cumulative second breast cancer incidence was 11.8% (95% confidence interval [CI], 10.7%-13.1%) for women with ER-negative disease and 7.5% (95% CI, 7.0%-8.0%) for those with ER-positive disease. Women with ER-negative cancer had higher second breast cancer rates than those with ER-positive cancer during the first 5 years of follow-up (16.0 per 1000 person-years [PY]; 95% CI, 14.2-17.9 per 1000 PY; vs. 7.8 per 1000 PY; 95% CI, 7.3-8.4 per 1000 PY, respectively). After 5 years, second breast cancer rates were similar for women with ER-negative versus ER-positive breast cancer (12.1 per 1000 PY; 95% CI, 9.9-14.7; vs. 9.3 per 1000 PY; 95% CI, 8.4-10.3 per 1000 PY, respectively). ER-negative primary breast cancers are associated with a higher risk of second breast cancers than ER-positive cancers during the first 5 years after diagnosis. Further study is needed to examine the potential benefit of more intensive surveillance targeting these women in the early postdiagnosis period.

Contralateral lymph node metastasis in recurrent ipsilateral breast cancer with Lynch syndrome: a locoregional event

IntroductionContralateral axillary lymph node metastasis (CALNM) in breast cancer (BC) is considered a distant metastasis, marking stage 4cancer. Therefore, it is generally treated as an incurable disease. However, in clinical practice, staging and treatment remain controversial due to a paucity of data, and the St. Gallen 2021 consensus panel recommended a curative approach in patients with oligometastatic disease. Aberrant lymph node (LN) drainage following previous surgery or radiotherapy is common. Therefore, CALNM may be considered a regional event rather than systemic disease, and a re-sentinel procedure aided by lymphoscintigraphy permits adequate regional staging.Case reportHere, we report a 37-year-old patient with Lynch syndrome who presented with CALNM in an ipsilateral relapse of a moderately differentiated invasive ductal BC (ER 90%, PR 30%, HER2 negative, Ki-67 25%, microsatellite stable), 3 years after the initial diagnosis. Lymphoscintigraphy detected a positive sentinel LN in the contralateral axilla despite no sign of LN involvement or distant metastases on FDG PET/CT or MRI. The patient underwent bilateral mastectomy with sentinel node dissection, surgical reconstruction with histological confirmation of the CALNM, left axillary dissection, adjuvant chemotherapy, and anti-hormone therapy. In addition to her regular BC follow-up visits, the patient will undergo annual colonoscopy, gastroscopy, abdominal, and vaginal ultrasound screening. In January 2023, the patient was free of progression for 23 months after initiation of treatment for recurrent BC and CALNM.ConclusionThis case highlights the value of delayed lymphoscintigraphy and the contribution of sentinel procedure for local control in the setting of recurrent BC. Aberrant lymph node drainage following previous surgery may be the underlying cause of CALNM. We propose that CALNM without evidence of systemic metastasis should be considered a regional event in recurrent BC, and thus, a curative approach can be pursued. The next AJCC BC staging should clarify the role of CALNM in recurrent BC to allow for the development of specific treatment guidelines.

Prognostic role of immune environment in luminal B early breast cancer.

The importance of the immune microenvironment in triple negative and HER2-amplified breast cancer (BC) is well-established; less is known about the immune environment in luminal breast cancers. We aimed to assess for the impact of immune biomarkers on BC outcome in a group of luminal B patients with archived tissue and annotated clinical information. Patients with early breast cancer (EBC) treated in a single institution over a 14-year period, with prospectively collected data were included. Luminal B EBC patients were identified and defined into three cohorts: A: grade 2 or 3, ER & PR positive, HER2-negative; B: Any grade, ER positive, PR and HER2-negative (Ki67 ≥ 14% in cohorts A & B); and C: Any grade, ER or PR positive, HER2-positive. Within each cohort, patients with a relapsed BC event (R) were compared on a 1:1 basis with a control patient (C) who remained disease-free, balanced for key characteristics in an effort to balance the contribution of each clinical group to outcome. Archival breast, involved and uninvolved axillary nodes were assessed by immunohistochemistry for biomarkers identifying effector and suppressor immune cells, and compared between R and C. In total, 120 patients were included (80, 22, and 18 patients in cohorts A, B, and C, respectively). R were 1.5 years older (p=0.016), with all other characteristics being balanced. Overall, there were no statistically significant differences in immune biomarkers in breast or nodal tissue of R and C. However, there was a trend toward higher levels of TILs in breast tumors of C, while GAL-9 was consistently expressed on lymphocytes and tumor cells in all breast and nodes of C and was absent from all tissues of R. These trends in checkpoint molecule expression deserve further research.

Development and validation of genome-wide polygenic risk scores for predicting breast cancer incidence in Japanese females: a population-based case-cohort study.

This study aimed to develop an ancestry-specific polygenic risk scores (PRSs) for the prediction of breast cancer events in Japanese females and validate it in a longitudinal cohort study. Using publicly available summary statistics of female breast cancer genome-wide association study (GWAS) of Japanese and European ancestries, we, respectively, developed 31 candidate genome-wide PRSs using pruning and thresholding (P + T) and LDpred methods with varying parameters. Among the candidate PRS models, the best model was selected using a case-cohort dataset (63 breast cancer cases and 2213 sub-cohorts of Japanese females during a median follow-up of 11.9years) according to the maximal predictive ability by Harrell's C-statistics. The best-performing PRS for each derivation GWAS was evaluated in another independent case-cohort dataset (260 breast cancer cases and 7845 sub-cohorts of Japanese females during a median follow-up of 16.9years). For the best PRS model involving 46,861 single nucleotide polymorphisms (SNPs; P + T method with PT = 0.05 and R2 = 0.2) derived from Japanese-ancestry GWAS, the Harrell's C-statistic was 0.598 ± 0.018 in the evaluation dataset. The age-adjusted hazard ratio for breast cancer in females with the highest PRS quintile compared with those in the lowest PRS quintile was 2.47 (95% confidence intervals, 1.64-3.70). The PRS constructed using Japanese-ancestry GWAS demonstrated better predictive performance for breast cancer in Japanese females than that using European-ancestry GWAS (Harrell's C-statistics 0.598 versus 0.586). This study developed a breast cancer PRS for Japanese females and demonstrated the usefulness of the PRS for breast cancer risk stratification.

Determinants Of Breast Self-Exam (BSE) Behavior As Early Detection Of Breast Cancer In Students At Poltekkes Kemenkes Jakarta II

Self breast care is one of the early detection methods to find early-stage breast cancer that will be more effective if done as early as possible when women reach reproductive age. Data on Cancer Sub Directorate of the Directorate of Non-Communicable Disease in Indonesia Control at the Ministry of Health there are around 36,761,000 women throughout who have breast cancer.. This study aims to study and explain the determinants of breast self-examination (BSE) behavior as early detection of breast cancer in female students at Poltekkes Kemenkes Jakarta II. The research design used is Cross Sectional. The sample in this study were 295 respondents. Univariate data analysis, bivariate using chi square and multivariate multiple logistic regression with (a <0.05). Variables related to BSE behavior as early detection of breast cancer events were knowledge(p = 0,008), attitudes (p = 0,000), parental support (p = 0,000) role of health personnel (p = 0,000),information media(p=0,000) and age (0,022. Confounding variables are information media (p = 0.191), knowledge (p = 0.136), parental support (p = 0.095). The dominant variable related to breast self-examination (BSE) behavior female student is the role of health workes with Odds Ratio (OR) 6,875.

Estrogen receptor α K303R mutation reorganizes its binding to forkhead box protein A1 regions and induces chromatin opening

BackgroundEstrogen receptor alpha (ERα) is a frequently mutated gene in breast cancer (BC). While many studies have investigated molecular dysregulation by hotspot mutations at Y537 and D538, which exhibit an estrogen-independent constitutively active phenotype, the functional abnormalities of other mutations remain obscure. The K303R mutation in primary invasive BC has been implicated with endocrine resistance, tumor size, and lymph node positivity. However, the impact of the K303R mutation on the cell epigenome is yet unknown.Methods and resultsWe introduced the K303R ERα mutant in ERα-negative MDA-MB-453 cells to monitor ERα-dependent transactivation and to perform epigenomic analyses. ATAC-seq and ChIP-Seq analyses indicated that both wild-type (WT) and the K303R mutant associated with Forkhead box (Fox) protein family motif regions at similar rates, even without an ERα-binding sequence, but only the K303R mutant induced chromatin opening at those regions. Biochemical analyses demonstrated that the WT and the K303R mutant can be tethered on DNA by FoxA1 indirectly, but only the K303R/FoxA1/DNA complex can induce associations with the nuclear receptor cofactor 2 (NCOA2).ConclusionsThese findings suggest that the K303R mutant induces chromatin opening at the Fox binding region through the FoxA1-dependent associations of the K303R mutant to NCOA2 and then probably disrupts the regulation of Fox-target genes, resulting in K303R-related BC events.

Second Conservative Treatment for Ipsilateral Breast Cancer Recurrence: First 10-Year Oncological Outcome Report

<h3>Purpose/Objective(s)</h3> To analyze long-term oncological outcome after 2^nd conservative treatment (2^ndCT) for patients with ipsilateral 2^nd breast cancer event (2^ndBCE). <h3>Materials/Methods</h3> In this retrospective observational single institution study (Health-data-hub N°F20210402152843), patients with 2^ndBCE underwent 2^ndCT based on lumpectomy plus re-irradiation of the tumor bed with multicatheter interstitial brachytherapy (MIB). Oncological outcome was investigated based on 3^rd breast cancer event (3^rdBCE-FS) and metastatic disease (MD-FS) -free survivals as well as disease-free (DFS), cause-specific (CSS) and overall (OS) survival. Prognostic factors were analyzed. Late toxicity was reported. <h3>Results</h3> From 09/2000 to 05/2013, 113 pts presented a 2^ndBCE managed by 2^ndCT. Median relapse age was 64.8 years [31 - 85]. Median time interval between 1^st and 2^ndBCE was 162 months [24 - 420]. 2^ndIBE occurred in or close to the primary tumor bed in 47.8% and 31% respectively. Median 2^ndBCE size was 11.3 mm [1 - 40] while histological type was invasive ductal or lobular carcinoma in 77% and 13.3% respectively. Regarding APBI classification, patients were low, intermediate and high-risk in 37.2%, 44.4% and 18.6% respectively. Regarding molecular classification, patients were HR+/Her2-, Her2+ and triple negative in 88.8%, 5.1% and 6.1% respectively. New axillary lymph node dissection was performed in 5 pts (4.4%). Low and high-dose rate MIB were used for 27 (24%) and 86 pts (76%) respectively. Median HDR dose was 32 Gy [32 - 34]. Systemic treatments were hormonal (83.2%) and chemo- (13.3%) therapies. With a MFU of 121.5 months [48 – 129.6], 10-y 3^rdBCE-FS, MDFS, DFS, CSS and OS were 89% [83 - 96], 89% [83 - 96], 78% [70 - 87], 95% [91 - 100] and 94% [90 – 99] respectively. In univariate analysis, APBI classification was prognostic factor for 3^rdBCE (LR: 4.8%, IR: 12% and HR: 23.8%; p = 0.02) with a trend for DFS (LR: 19%, IR: 24% and HR: 42.9%; p = 0.055). Ninety-seven complications occurred in 73 pts (G1: 55.7%; G2: 38.1%; G3: 5.2%; G4: 1%) with cutaneous (36.1%) and sub-cutaneous (27.8%) fibrosis, telangiectasia (13.4%) and hyperpigmentation (4.1%). Cosmetic outcome was excellent, good, fair and poor in 70 pts (61.9%), 33 pts (29.2%), fair 9 pts (8%) and 1 pt (0.9%) respectively. <h3>Conclusion</h3> With long-term follow-up, 2^ndBCE managed with lumpectomy and tumor bed re-irradiation (MIB) allows the patient to avoid salvage mastectomy without compromise in oncological outcome. With about 5% of G≥3 late toxicity, final cosmetic outcome remains acceptable. Larger patient cohorts are needed to refine eligibility criteria for 2^ndCT while the place of systemic therapy remains under debate.

Breast cancer and cardiovascular outcomes after breast cancer in survivors of Hodgkin lymphoma.

Hodgkin lymphoma (HL) survivors treated with chest radiotherapy have an increased risk of breast cancer (BC). Prior HL treatment and associated cardiovascular disease (CVD) risk may limit BC treatment options. It is unknown how treatment adaptations affect BC and CVD outcomes. The authors compared 195 BC patients treated with chest/axillary radiotherapy for HL (BC-HL) with 5988 age- and calendar year-matched patients with first primary BC (BC-1). Analyses included cumulative incidence functions and Cox regression models, accounting for tumor characteristics and BC treatment. Compared to BC-1 patients, BC-HL patients received anthracycline-containing chemotherapy (23.7% vs. 43.8%, p < .001) and breast-conserving surgery followed by radiotherapy (7.1% vs. 57.7%, p < .001) less often. BC treatment considerations were reported for 71% of BC-HL patients. BC-HL patients had a significantly higher risk of 15-year overall mortality than BC-1 patients (61% vs. 23%). Furthermore, risks of BC-specific mortality and nonfatal BC events were significantly increased among BC-HL patients, also when accounting for tumor and treatment characteristics (2.2- to 4.5-fold). BC-HL patients with a screen-detected BC had a significantly reduced (61%) BC-specific mortality. One-third of BC-HL patients had CVD at BC-diagnosis, compared to <0.1% of BC-1 patients. Fifteen-year CVD-specific mortality and CVD incidence were significantly higher in BC-HL patients than in BC-1 patients (15.2% vs. 0.4% and 40.4% vs. 6.8%, respectively), which was due to HL treatment rather than BC treatment. BC-HL patients experience a higher burden of CVD and worse BC outcomes than BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors. Patients with breast cancer after Hodgkin lymphoma (BC-HL) may have limited options for BC treatment, due to earlier HL treatment and an associated increased risk of cardiovascular disease (CVD). BC treatment considerations were reported for 71% of BC-HL patients. We examined whether BC-HL patients have a higher risk of CVD or BC events (recurrences/metastases) compared to patients with breast cancer that had no earlier tumors (BC-1). We observed a higher burden of CVD and worse BC outcomes in HL patients compared to BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors.

Association of Longitudinal Mammographic Breast Density Changes with Subsequent Breast Cancer Risk.

Background Although Breast Imaging Reporting and Data System (BI-RADS) density classification has been used to assess future breast cancer risk, its reliability and validity are still debated in literature. Purpose To determine the association between overall longitudinal changes in mammographic breast density and breast cancer risk stratified by menopausal status. Materials and Methods In a retrospective cohort study using the Korean National Health Insurance Service database, women aged at least 40 years without a history of cancer who underwent three consecutive biennial mammographic screenings in 2009-2014 were followed up through December 2020. Participants were divided according to baseline breast density: fatty (BI-RADS categories a, b) versus dense (BI-RADS categories c, d) and then into subgroups on the basis of changes from the first to second and from second to third screenings. Women without change in breast density were used as the reference group. Main outcomes were incident breast cancer events, both invasive breast cancer and ductal carcinoma in situ. Cox proportion hazard regression was used to calculate the hazard ratio (HR) with adjustment for other covariables. Results Among 2 253 963 women (mean age, 59 years ± 9) there were 22 439 detected breast cancers. Premenopausal women with fatty breasts at the first screening had a higher risk of breast cancer as density increased in the second and third screenings (fatty-to-dense HR, 1.45 [95% CI: 1.27, 1.65]; dense-to-fatty HR, 1.53 [95% CI: 1.34, 1.74]; dense-to-dense HR, 1.93 [95% CI: 1.75, 2.13]). In premenopausal women with dense breasts at baseline, those in whom density continuously decreased had a 0.62-fold lower risk (95% CI: 0.56, 0.69). Similar results were observed in postmenopausal women, remaining significant after adjustment for baseline breast density or changes in body mass index (fatty-to-dense HR, 1.50 [95% CI: 1.39, 1.62]; dense-to-fatty HR, 1.42 [95% CI: 1.31, 1.53]; dense-to-dense HR, 1.62 [95% CI: 1.51, 1.75]). Conclusion In both premenopausal and postmenopausal women undergoing three consecutive biennial mammographic screenings, a consecutive increase in breast density augmented the future breast cancer risk whereas a continuous decrease was associated with a lower risk. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kataoka et al in this issue.

Integrative Bioinformatics Analysis Reveals That miR-524-5p/MEF2C Regulates Bone Metastasis in Prostate Cancer and Breast Cancer.

Bone metastases are highly prevalent in patients with advanced prostate cancer and breast cancer and have a serious impact on the survival time and quality of life of these patients. It has been reported that microRNAs (miRNAs) are expressed abnormally in different types of cancer and metastases. However, it remains unknown whether the underlying miRNAs are associated with prostate and breast cancer bone metastasis. Differentially expressed miRNAs (DE-miRNAs) and their potential targets in the metastatic process were identified by bioinformatics analysis. Additionally, qPCR confirmed that the miR-524-5p expression was downregulated in prostate and breast cancer cells. The overexpression of miR-524-5p restrained cell proliferation, invasion, and metastasis in prostate and breast cancer cells. Meanwhile, miR-524-5p could target and inhibit the expression of MEF2C, which was verified by a luciferase assay. In conclusion, our data strongly suggest that downregulation of miR-524-5p appears to be a precocious event in prostate and breast cancer, and the miR-524-5p/MEF2C axis plays a novel role in bone metastases from prostate and breast cancers.

NBN, RAD51 and XRCC3 Polymorphisms as Potential Predictive Biomarkers of Adjuvant Radiotherapy Toxicity in Early HER2-Positive Breast Cancer.

Simple SummaryAdjuvant radiotherapy for breast cancer patients significantly improves survival and causes side effects. It is known that the response to radiotherapy is individual, but we are not yet able to predict patients with high risk for acute or late radiotherapy adverse events. This study aimed to investigate the association between homologous recombination repair (HRR) polymorphisms and radiotherapy toxicity and thus contribute to the knowledge on potential predictive biomarkers of radiotherapy toxicity in early HER2-positive breast cancer. This study was among the first to evaluate the role of HRR genetic variability with cardiac toxicity. RAD51 polymorphisms were associated with cardiac adverse events, while XRCC3 polymorphisms were associated with skin adverse events. Our results suggest that polymorphisms in key HRR genes might be used as potential biomarkers of late treatment-related adverse events in early HER2-positive breast cancer treated with radiotherapy.Radiotherapy (RT) for breast cancer significantly impacts patient survival and causes adverse events. Double-strand breaks are the most harmful type of DNA damage associated with RT, which is repaired through homologous recombination (HRR). As genetic variability of DNA repair genes could affect response to RT, we aimed to evaluate the association of polymorphisms in HRR genes with tumor characteristics and the occurrence of RT adverse events in early HER2-positive breast cancer. Our study included 101 breast cancer patients treated with adjuvant RT and trastuzumab. All patients were genotyped for eight single nucleotide polymorphisms in NBN, RAD51 and XRCC3 using competitive allele-specific PCR. Carriers of XRCC3 rs1799794 GG genotype were less likely to have higher tumor differentiation grade (OR = 0.05, 95% CI = 0.01–0.44, p = 0.007). Carriers of RAD51 rs1801321 TT genotype were more likely to have higher NYHA class in univariable (OR = 10.0; 95% CI = 1.63–61.33; p = 0.013) and multivariable (OR = 9.27; 95% CI = 1.28–67.02; p = 0.027) analysis. Carriers of RAD51 rs12593359 GG genotype were less likely to have higher NYHA class in univariable (OR = 0.09; 95% CI = 0.01–0.79; p = 0.030) and multivariable (OR = 0.07; 95% CI = 0.01–0.81; p = 0.034) analysis. Carriers of XRCC3 rs1799794 GG genotypes experienced more skin adverse events based on LENT-SOMA scale in univariable (OR = 5.83; 95% CI = 1.22–28.00; p = 0.028) and multivariable (OR = 10.90; 95% CI = 1.61–73.72; p = 0.014) analysis. In conclusion, XRCC3 and RAD51 polymorphisms might contribute to RT adverse events in early HER2-positive breast cancer patients.

Effects Of A Tai Chi App On Mental Health Among Breast Cancer Survivors

PURPOSE: To our best knowledge, few studies have integrated Tai Chi (TC) and social media apps to facilitate disease prevention and management in breast cancer survivors (BCS). In response, this study investigated the effects of a mobile TC app and Facebook (FB) program on stress and quality of life (QoL) among BCS. METHODS: This study was a remote, 12-week 2-arm parallel randomized controlled trial (RCT). Participants were randomly assigned into either the intervention condition (practicing TC app exercise three times a day, at least five days/week and receiving FB health tips) or the comparison condition (receiving FB health tips). The final sample comprised 35 female BCS ( = 56.17). The Perceived Stress Scale was used to measure stress and the Patient Reported Outcome Measurement Information System was used to assess QoL - mental health (anxiety and depression) and physical health. RESULTS: There were no significant time*group interaction effects for stress and mental health (Wilk’s lambda =0.96, F (2, 32) = 0.74, p = 0.48, η2 = 0.04) and physical health (Wilk’s lambda =1.00, F (1,33) = 0.14, p = 0.71, η2 = 0.00). However, a significant time effect was observed for mental health, F (1,33) = 5.51, p = 0.02, η2 = 0.14; and physical health, F (1,33) = 5.59, p = 0.05, η2 = 0.14; but not for stress, F (1,33) = 1.70, p = 0.20, η2 = 0.05. Specifically, participants’ physical health (1.57 vs. 1.42) and mental health (1.80 vs. 1.63) significantly improved over time across both groups. Also, a group effect for mental health approached the significant level, F (1,33) = 4.06, p = 0.05, η2 = 0.11. In detail, the intervention participants had significantly better mental health at post-test (1.43 vs. 1.90) compared to the comparison participants (p 0.05, 95%CI: -0.91 to -0.40). CONCLUSION: The study findings suggested that the implementation of the Tai Chi app combined FB health tips program had positive effects on BCS’s mental health. Also, offering a health education program could be beneficial to BCS’s physical health as well. The present findings are meaningful given that physical activity plays an important role in promoting health and reducing cancer-related death and breast cancer events (e.g., recurrence, new breast cancer primaries) in BCS.

Dose-dependent relation between metformin and the risk of hormone receptor-positive, her2-negative breast cancer among postmenopausal women with type-2 diabetes.

Metformin has demonstrated a chemoprotective effect in breast cancer but there is limited evidence on the effect of cumulative exposure to metformin and the risk of hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR + /HER2-) breast cancer. This study assessed this risk with dose and intensity of metformin in postmenopausal women with type-2 diabetes mellitus (T2DM). This nested case-control study used the Surveillance, Epidemiology, and End Results-Medicare data (2008-2015). Cohort entry was the date of incident T2DM diagnosis. Cases were those diagnosed with HR + /HER2- breast cancer (event date) as their first/only cancer. Non-cancer T2DM controls were matched using variable-ratio-matching. Cumulative dose and average intensity of metformin were measured during the 1-year lookback period. Dose(mg) was categorized as: (1)0, (2)0-30,000, (3)30,001-136,000, (4)136,001-293,000, and (5) > 293,000, and intensity(mg/day) as: 0, 1-500, and > 500. Covariates were conceptualized using the Andersen Behavioral Model. Conditional logistic regression was used to assess the risk of HR + /HER2- breast cancer with metformin-use. There were 690 cases and 2747 controls. The median duration of T2DM was 1178days in controls and 1180days in cases. Higher cumulative dose categories: 4 (adjusted odds ratio(aOR) = 0.72, 95% CI 0.55-0.95,p = 0.02), and 5 (OR = 0.60, 95% CI 0.42-0.85,p < 0.01) had significantly lower odds of HR + /HER2- breast cancer compared to category 0. The highest intensity category of metformin had 39% lower odds of HR + /HER2- breast cancer (OR = 0.61, 95% CI 0.46-0.82,p < 0.01) compared to the 0mg/day group. Higher metformin exposure was associated with reduced risk of HR + /HER2- breast cancer, adding to the evidence supporting metformin's chemoprotective effect.

Tumor Infiltrating Lymphocytes in Multi-National Cohorts of Ductal Carcinoma In Situ (DCIS) of Breast.

Simple SummaryTumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. We used different scoring methods for TILs in multi-national cohorts from Asian and European women. Stromal TILs, touching TILs, circumferential TILs, and hotspots were quantified on H&E-stained slides and correlated with the development of second breast cancer events (BCE) and other clinico-pathological variables. Older women, hormone receptor positivity, and the presence of circumferential TILs were weakly associated with the absence of BCE at 5-year follow-up in all cohorts. In multivariable analysis, older women with circumferential TILs were less likely to develop BCEs (Wald test p = 0.01). Asian patients were younger with larger, higher grade, HR negative DCIS lesions, and higher TIL variables. The spatial arrangement of TILs may serve as a better prognostic indicator in DCIS cases than stromal TILs alone.Tumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. To investigate the prognostic role of TILs in DCIS outcome, we used different scoring methods for TILs in multi-national cohorts from Asian and European women. Self-described race was genetically confirmed using QC Infinium array combined with radmixture software. Stromal TILs, touching TILs, circumferential TILs, and hotspots were quantified on H&E-stained slides and correlated with the development of second breast cancer events (BCE) and other clinico-pathological variables. In univariate survival analysis, age older than 50 years, hormone receptor positivity and the presence of circumferential TILs were weakly associated with the absence of BCE at the 5-year follow-up in all cohorts (p < 0.03; p < 0.02; and p < 0.02, respectively, adjusted p = 0.11). In the multivariable analysis, circumferential TILs were an independent predictor of a better outcome (Wald test p = 0.01), whereas younger age was associated with BCE. Asian patients were younger with larger, higher grade, HR negative DCIS lesions, and higher TIL variables. The spatial arrangement of TILs may serve as a better prognostic indicator in DCIS cases than stromal TILs alone and may be added in guidelines for TILs evaluation in DCIS.

Loss of genes in chromosome arms 5q and 16q in breast cancer.

Losses of genetic material from chromosomes 5q and 16q commonly occur in sub-sets of breast cancer. Their significance from a pathophysiologic point of view is not well-defined. This study uses publicly available genomic data from extensive breast cancer datasets to define the landscape of losses in chromosomal arms 5q and 16q in the two sub-types of breast cancer they most commonly occur, basal-like and luminal A cancers, respectively. It is shown that dozens of genes from these chromosomal arms are putatively hemi-deleted in few samples each. No individual gene from either 5q or 16q shows an incidence of deep deletion above 10% in the cohorts with basal-like and luminal A cancers or in the whole cohorts. A few tumor suppressor genes are deleted in a small number of samples, less than 5% in each cohort. Losses of 5q or 16q confer no survival advantage in either the basal-like or the luminal A cohorts from TCGA that harbor them. Results suggest that there are no individual genes in chromosomes 5q and 16q whose loss can be implicated in a dominant pathophysiologic sequence of events in breast cancer or its sub-sets.

Identifying Breast Cancer Recurrence in Administrative Data: Algorithm Development and Validation.

Breast cancer recurrence is an important outcome for patients and healthcare systems, but it is not routinely reported in cancer registries. We developed an algorithm to identify patients who experienced recurrence or a second case of primary breast cancer (combined as a “second breast cancer event”) using administrative data from the population of Ontario, Canada. A retrospective cohort study design was used including patients diagnosed with stage 0-III breast cancer in the Ontario Cancer Registry between 1 January 2009 and 31 December 2012 and alive six months post-diagnosis. We applied the algorithm to healthcare utilization data from six months post-diagnosis until death or 31 December 2013, whichever came first. We validated the algorithm’s diagnostic accuracy against a manual patient record review (n = 2245 patients). The algorithm had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 67%, a negative predictive value of 98%, an accuracy of 93%, a kappa value of 71%, and a prevalence-adjusted bias-adjusted kappa value of 85%. The second breast cancer event rate was 16.5% according to the algorithm and 13.0% according to manual review. Our algorithm’s performance was comparable to previously published algorithms and is sufficient for healthcare system monitoring. Administrative data from a population can, therefore, be interpreted using new methods to identify new outcome measures.

Hormonal and Genetic Regulatory Events in Breast Cancer and Its Therapeutics: Importance of the Steroidogenic Acute Regulatory Protein.

Estrogen promotes the development and survival of the majority of breast cancers (BCs). Aromatase is the rate-limiting enzyme in estrogen biosynthesis, and it is immensely expressed in both cancerous and non-cancerous breast tissues. Endocrine therapy based on estrogen blockade, by aromatase inhibitors, has been the mainstay of BC treatment in post-menopausal women; however, resistance to hormone therapy is the leading cause of cancer death. An improved understanding of the molecular underpinnings is the key to develop therapeutic strategies for countering the most prevalent hormone receptor positive BCs. Of note, cholesterol is the precursor of all steroid hormones that are synthesized in a variety of tissues and play crucial roles in diverse processes, ranging from organogenesis to homeostasis to carcinogenesis. The rate-limiting step in steroid biosynthesis is the transport of cholesterol from the outer to the inner mitochondrial membrane, a process that is primarily mediated by the steroidogenic acute regulatory (StAR) protein. Advances in genomic and proteomic technologies have revealed a dynamic link between histone deacetylases (HDACs) and StAR, aromatase, and estrogen regulation. We were the first to report that StAR is abundantly expressed, along with large amounts of 17β-estradiol (E2), in hormone-dependent, but not hormone-independent, BCs, in which StAR was also identified as a novel acetylated protein. Our in-silico analyses of The Cancer Genome Atlas (TCGA) datasets, for StAR and steroidogenic enzyme genes, revealed an inverse correlation between the amplification of the StAR gene and the poor survival of BC patients. Additionally, we reported that a number of HDAC inhibitors, by altering StAR acetylation patterns, repress E2 synthesis in hormone-sensitive BC cells. This review highlights the current understanding of molecular pathogenesis of BCs, especially for luminal subtypes, and their therapeutics, underlining that StAR could serve not only as a prognostic marker, but also as a therapeutic candidate, in the prevention and treatment of this life-threatening disease.

Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study.

BackgroundBone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients.MethodsWe retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model.ResultsThe median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268–5.841, P = 0.010).ConclusionAlcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.