ResearchPad - breast-cancer https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[<i>In silico</i> analyses identify lncRNAs: WDFY3-AS2, BDNF-AS and AFAP1-AS1 as potential prognostic factors for patients with triple-negative breast tumors]]> https://www.researchpad.co/article/elastic_article_13870 Long non-coding RNAs (lncRNAs) are characterized as having 200 nucleotides or more and not coding any protein, and several been identified as differentially expressed in several human malignancies, including breast cancer.MethodsHere, we evaluated lncRNAs differentially expressed in triple-negative breast cancer (TNBC) from a cDNA microarray data set obtained in a previous study from our group. Using in silico analyses in combination with a review of the current literature, we identify three lncRNAs as potential prognostic factors for TNBC patients.ResultsWe found that the expression of WDFY3-AS2, BDNF-AS, and AFAP1-AS1 was associated with poor survival in patients with TNBCs. WDFY3-AS2 and BDNF-AS are lncRNAs known to play an important role in tumor suppression of different types of cancer, while AFAP1-AS1 exerts oncogenic activity.ConclusionOur findings provided evidence that WDFY3-AS2, BDNF-AS, and AFAP1-AS1 may be potential prognostic factors in TNBC development. ]]> <![CDATA[Early budget impact analysis on magnetic seed localization for non-palpable breast cancer surgery]]> https://www.researchpad.co/article/elastic_article_13866 Current localization techniques used in breast conserving surgery for non-palpable tumors show several disadvantages. Magnetic Seed Localization (MSL) is an innovative localization technique aiming to overcome these disadvantages. This study evaluated the expected budget impact of adopting MSL compared to standard of care.MethodsStandard of care with Wire-Guided Localization (WGL) and Radioactive Seed Localization (RSL) use was compared with a future situation gradually adopting MSL next to RSL or WGL from a Dutch national perspective over 5 years (2017–2022). The intervention costs for WGL, RSL and MSL and the implementation costs for RSL and MSL were evaluated using activity-based costing in eight Dutch hospitals. Based on available list prices the price of the magnetic seed was ranged €100-€500.ResultsThe intervention costs for WGL, RSL and MSL were respectively: €2,617, €2,834 and €2,662 per patient and implementation costs were €2,974 and €26,826 for MSL and RSL respectively. For standard of care the budget impact increased from €14.7m to €16.9m. Inclusion of MSL with a seed price of €100 showed a budget impact of €16.7m. Above a price of €178 the budget impact increased for adoption of MSL, rising to €17.6m when priced at €500.ConclusionMSL could be a cost-efficient localization technique in resecting non-palpable tumors in the Netherlands. The online calculation model can inform adoption decisions internationally. When determining retail price of the magnetic seed, cost-effectiveness should be considered. ]]> <![CDATA[Regulation of cell growth and migration by miR-96 and miR-183 in a breast cancer model of epithelial-mesenchymal transition]]> https://www.researchpad.co/article/elastic_article_7836 Breast cancer is the most commonly diagnosed malignancy in women, and has the second highest mortality rate. Over 90% of all cancer-related deaths are due to metastasis, which is the spread of malignant cells from the primary tumor to a secondary site in the body. It is hypothesized that one cause of metastasis involves epithelial-mesenchymal transition (EMT). When epithelial cells undergo EMT and transition into mesenchymal cells, they display increased levels of cell proliferation and invasion, resulting in a more aggressive phenotype. While many factors regulate EMT, microRNAs have been implicated in driving this process. MicroRNAs are short noncoding RNAs that suppress protein production, therefore loss of microRNAs may promote the overexpression of specific target proteins important for EMT. The goal of this study was to investigate the role of miR-96 and miR-183 in EMT in breast cancer. Both miR-96 and miR-183 were found to be downregulated in post-EMT breast cancer cells. When microRNA mimics were transfected into these cells, there was a significant decrease in cell viability and migration, and a shift from a mesenchymal to an epithelial morphology (mesenchymal-epithelial transition or MET). These MET-related changes may be facilitated in part by the regulation of ZEB1 and vimentin, as both of these proteins were downregulated when miR-96 and miR-183 were overexpressed in post-EMT cells. These findings indicate that the loss of miR-96 and miR-183 may help facilitate EMT and contribute to the maintenance of a mesenchymal phenotype. Understanding the role of microRNAs in regulating EMT is significant in order to not only further elucidate the pathways that facilitate metastasis, but also identify potential therapeutic options for preventing or reversing this process.

]]>
<![CDATA[OR05-04 Steroid Receptor Co-Activators Complexes Cooperate with Progesterone Receptors (PR) to Reprogram Metabolic Pathways that Drive Therapy Resistant Populations in ER+ Breast Cancer]]> https://www.researchpad.co/article/elastic_article_6041 Late recurrence of metastatic disease stemming from acquired therapy resistance remains a significant health burden for women with ER+ breast cancer. Disseminated ER+ tumor cell populations can remain quiescent for years to decades, and contributing factors include breast cancer stem cells (CSCs), which are non-proliferative and frequently exist as a minority population in recurrent therapy-resistant tumors. Progesterone receptors (PR) are known drivers of normal stem and breast CSCs. Our objective was to define novel signaling pathways governing cell fate transitions involved in driving therapy resistance in ER+ breast cancer. We reported that cytoplasmic complexes composed of steroid receptor (SR) co-activators, PELP1 and SRC-3, drive breast CSC outgrowth. SRC-3 knockdown abrogated PELP1-induced CSC expansion and target genes required for cell survival, suggesting an essential role for PELP1/SRC-3 complexes. PELP1 also forms a signaling and transcriptional complex with ER and PR-B. Phospho-PR species are key mediators of stemness in ER+ breast cancer models. Accordingly, PR knockdown and antiprogestins disrupted PELP1/SRC-3 complexes and blocked PELP1-induced breast CSC outgrowth. Mammary stem cell (MaSC) populations were increased in vivo in MMTV-tTA;TRE-cyto-PELP1 transgenic mice as well as in MMTV-tTA;TRE-hPR-B mice. To better understand PELP1-mediated pathways, we performed RNA-seq on MCF-7 PELP1+ models grown in tumorsphere conditions to enrich for CSC populations (ALDH+, CD44+/CD24-). Cytoplasmic PELP1-expressing cells had a different global gene profile relative to WT PELP1 (i.e. nuclear). Gene sets associated with stem cell biology, hypoxic stress, and cancer metabolism were differentially regulated, including members of the glycolytic bi-functional kinase/phosphatase PFKFB family. Seahorse metabolic phenotyping demonstrated cytoplasmic PELP1 influences metabolism by increasing both glycolysis and mitochondrial respiration. Cytoplasmic PELP1 interacted strongly with PFKFB3 and PFKFB4, and inhibition of PFKFB3 or PFKFB4 kinase activity blocked PELP1-induced tumorspheres and protein-protein interactions with SRC-3. Additionally, antiprogestin and PFKFB inhibitors were synergistic when combined with ER+ targeted therapies. These aspects of PELP1/SRC-3 biology were phenocopied in therapy resistant models (tamoxifen resistant [TamR], paclitaxel resistant [TaxR]). Together, our data suggest that PELP1, SRC-3, PR, and PFKFBs form complexes that reprogram cellular metabolism to drive breast CSC expansion. Identifying the mechanisms that regulate recurrent ER+ tumor cell populations will enable specific targeting within heterogeneous breast tumors and may lead to the development of non-ER targets that can be used in combination with endocrine treatments to overcome therapy resistance.

]]>
<![CDATA[OR05-01 Small Heterodimer Partner Modulates Antigen Presenting Myeloid Cells to Impair Regulatory T Cell Expansion, Promoting Anti-Tumor Immunity in Models of Breast Cancer]]> https://www.researchpad.co/article/elastic_article_5967 Immune checkpoint blockade has had underwhelming responses in breast cancer, in part due to the highly immune suppressive microenvironment. As a result, breast cancer continues to be the second most common cancer-related mortality amongst women, providing strong rationale for the development of new therapeutic approaches. Elevated circulating cholesterol is a poor prognostic, while breast cancer patients taking cholesterol-lowering drugs display increased time to recurrence. We and others have previously demonstrated that cholesterol metabolites mediate these effects by promoting breast cancer growth and metastasis, in part by suppressing the immune system. Therefore, given the demonstrated importance of cholesterol and its metabolites in breast cancer pathophysiology and immunology, we hypothesized that proteins involved in the regulation of cholesterol homeostasis would influence cancer progression. Through informatics analysis of breast tumors, we found that elevated expression of Small Heterodimer Partner (SHP; NR0B2) was a favorable prognostic. Antigen presenting cells such as macrophages and dendritic cells were found to express SHP, and manipulation of SHP altered the expression of genes involved in cross-talk with T cells. Intriguingly, when activated T cells were co-cultured with macrophages overexpressing SHP, there was a decrease in the expansion of regulatory T cells (Tregs) and vice versa in the absence of SHP. Adoptive transfer studies confirmed that loss of SHP resulted in immune suppressive Tregs. We hypothesized that myeloid cell-expressed SHP would promote immune surveillance and tumor clearance. In support of this hypothesis, tumors in the MMTV-PyMT model of mammary cancer grew at an accelerated rate in SHP-knockout mice. Tumors from these mice had significantly more Tregs and fewer effector T cells. Furthermore, orthotopic mammary tumor grafts grew at an increased rate in mice lacking SHP expression in myeloid cells (SHPfl/fl;LysMCre), compared to controls. A small molecule agonist of SHP impaired primary and metastatic tumor growth, and significantly enhanced the efficacy of immune checkpoint blockade in murine models of mammary cancer. Therefore, SHP represents a potential target to decrease suppressive Tregs, thereby allowing for immune-clearance of tumors.

]]>
<![CDATA[Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer]]> https://www.researchpad.co/article/N711332f9-c9cf-4b1c-add5-d871710ae8b7

The molecular phenotype of circulating tumor cells is associated with clinical outcome of patients with breast cancer. The aim of this study was to enhance the prognostic accuracy of the circulating tumor cell phenotype in metastatic breast cancer by incorporating miRNA into a combined prediction model.

]]>
<![CDATA["Clicks, likes, shares and comments" a systematic review of breast cancer screening discourse in social media]]> https://www.researchpad.co/article/N8d8d3073-6769-4a60-aed8-e2beb958c228

Background

Unsatisfactory participation rate at population based organised breast cancer screening is a long standing problem. Social media, with 3.2 billion users in 2019, is potentially an important site of breast cancer related discourse. Determining whether these platforms might be used as channels by screening providers to reach under-screened women may have considerable public health significance.

Objectives

By systematically reviewing original research studies on breast cancer related social media discourse, we had two aims: first, to assess the volume, participants and content of breast screening social media communication and second, to find out whether social media can be used by screening organisers as a channel of patient education.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After searching PubMed, ScienceDirect, Web of Science, Springer and Ebsco, 17 studies were found that met our criteria. A systematic narrative framework was used for data synthesis. Owing to the high degree of heterogeneity in social media channels, outcomes and measurement included in this study, a meta-analytic approach was not appropriate.

Results

The volume of breast cancer related social media discourse is considerable. The majority of participants are lay individuals as opposed to healthcare professionals or advocacy groups. The lay misunderstandings surrounding the harms and benefits of mammography is well mirrored in the content of social media discourse. Although there is criticism, breast cancer screening sentiment on the social media ranges from the neutral to the positive. Social media is suitable for offering peer emotional support for potential participants.

Conclusion

Dedicated breast screening websites operated by screening organisers would ensure much needed quality controlled information and also provide space for reliable question and answer forums, the sharing of personal experience and the provision of peer and professional support.

]]>
<![CDATA[Deep learning assessment of breast terminal duct lobular unit involution: Towards automated prediction of breast cancer risk]]> https://www.researchpad.co/article/N8ae86a5e-90c1-41b1-ba31-58a5a939e3bc

Terminal duct lobular unit (TDLU) involution is the regression of milk-producing structures in the breast. Women with less TDLU involution are more likely to develop breast cancer. A major bottleneck in studying TDLU involution in large cohort studies is the need for labor-intensive manual assessment of TDLUs. We developed a computational pathology solution to automatically capture TDLU involution measures. Whole slide images (WSIs) of benign breast biopsies were obtained from the Nurses’ Health Study. A set of 92 WSIs was annotated for acini, TDLUs and adipose tissue to train deep convolutional neural network (CNN) models for detection of acini, and segmentation of TDLUs and adipose tissue. These networks were integrated into a single computational method to capture TDLU involution measures including number of TDLUs per tissue area, median TDLU span and median number of acini per TDLU. We validated our method on 40 additional WSIs by comparing with manually acquired measures. Our CNN models detected acini with an F1 score of 0.73±0.07, and segmented TDLUs and adipose tissue with Dice scores of 0.84±0.13 and 0.87±0.04, respectively. The inter-observer ICC scores for manual assessments on 40 WSIs of number of TDLUs per tissue area, median TDLU span, and median acini count per TDLU were 0.71, 0.81 and 0.73, respectively. Intra-observer reliability was evaluated on 10/40 WSIs with ICC scores of >0.8. Inter-observer ICC scores between automated results and the mean of the two observers were: 0.80 for number of TDLUs per tissue area, 0.57 for median TDLU span, and 0.80 for median acini count per TDLU. TDLU involution measures evaluated by manual and automated assessment were inversely associated with age and menopausal status. We developed a computational pathology method to measure TDLU involution. This technology eliminates the labor-intensiveness and subjectivity of manual TDLU assessment, and can be applied to future breast cancer risk studies.

]]>
<![CDATA[Plasma membrane expression of G protein-coupled estrogen receptor (GPER)/G protein-coupled receptor 30 (GPR30) is associated with worse outcome in metachronous contralateral breast cancer]]> https://www.researchpad.co/article/Naf611639-dea0-4cb3-8951-2157f0424339

Background

G protein-coupled estrogen receptor (GPER), or G protein-coupled receptor 30 (GPR30), is reported to mediate non-genomic estrogen signaling. GPR30 associates with breast cancer (BC) outcome and may contribute to tamoxifen resistance. We investigated the expression and prognostic significance of GPR30 in metachronous contralateral breast cancer (CBC) as a model of tamoxifen resistance.

Methods

Total GPR30 expression (GPR30TOT) and plasma membrane-localized GPR30 expression (GPR30PM) were analyzed by immunohistochemistry in primary (BC1; nBC1 = 559) and contralateral BC (BC2; nBC2 = 595), and in lymph node metastases (LGL; nLGL1 = 213; nLGL2 = 196). Death from BC (BCD), including BC death or death after documented distant metastasis, was used as primary end-point.

Results

GPR30PM in BC2 and LGL2 were associated with increased risk of BCD (HRBC2 = 1.7, p = 0.03; HRLGL2 = 2.0; p = 0.02). In BC1 and BC2, GPR30PM associated with estrogen receptor (ER)-negativity (pBC1<0.0001; pBC2<0.0001) and progesterone receptor (PR)-negativity (pBC1 = 0.0007; pBC2<0.0001). The highest GPR30TOT and GPR30PM were observed in triple-negative BC. GPR30PM associated with high Ki67 staining in BC1 (p<0.0001) and BC2 (p<0.0001). GPR30TOT in BC2 did not associate with tamoxifen treatment for BC1. However, BC2 that were diagnosed during tamoxifen treatment were more likely to express GPR30PM than BC2 diagnosed after treatment completion (p = 0.01). Furthermore, a trend was observed that patients with GPR30PM in an ER-positive BC2 had greater benefit from tamoxifen treatment.

Conclusion

PM-localized GPR30 staining is associated with increased risk of BC death when expressed in BC2 and LGL2. Additionally, PM-localized GPR30 correlates with prognostic markers of worse outcome, such as high Ki67 and a triple-negative subtype. Therefore, PM-localized GPR30 may be an interesting new target for therapeutic exploitation. We found no clear evidence that total GPR30 expression is affected by tamoxifen exposure during development of metachronous CBC, or that GPR30 contributes to tamoxifen resistance.

]]>
<![CDATA[Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial]]> https://www.researchpad.co/article/Nf52b3d22-02a5-4e7e-bb1d-9e73ca6c7e6b

This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment. We evaluated the effects of melatonin on cognition, depressive symptoms and sleep quality, and whether these effects were related to serum levels of Brain Derived Neurotrophic Factor (BDNF) and its receptor, tropomyosin kinase B (TrkB). Thirty-six women were randomly assigned to receive melatonin or placebo for 10 days. To evaluate cognitive performance, we used the Trail-Making-Test Parts A and B (A-B), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and an inhibitory task type Go / No-Go. Our results revealed that melatonin improved executive function on TMT scores, enhanced episodic memory (immediate and delayed) and recognition on RAVLT, and increased verbal fluency in the orthographic COWAT. The TMT-A-B(A-B) were negatively correlated with baseline levels of TrkB and BDNF, respectively. At the end of treatment, changes in TrkB and BDNF were inversely associated with depressive symptoms and sleep quality, but not with the TMT scores. These results suggest a neuroprotective effect of melatonin to counteract the adverse effects of ACBC on cognitive function, sleep quality and depressive symptoms.

]]>
<![CDATA[Talazoparib in Patients with a Germline BRCA‐Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial]]> https://www.researchpad.co/article/N6ecc4bdf-e429-404f-8dcc-def44777f426

Abstract

Background

In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression‐free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2‐mutated HER2‐negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail.

Materials and Methods

Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126). Adverse events (AEs) were evaluated, including timing, duration, and potential overlap of selected AEs. The relationship between talazoparib plasma exposure and grade ≥3 anemia was analyzed. Time‐varying Cox proportional hazard models assessed the impact of dose reductions on PFS. Patient‐reported outcomes (PROs) in patients with common AEs and health resource utilization (HRU) were assessed in both treatment arms.

Results

The most common AEs with talazoparib were hematologic (195 [68.2%] patients) and typically occurred within the first 3–4 months of receiving talazoparib. Grade 3‐4 anemia lasted approximately 7 days for both arms. Overlapping grade 3‐4 hematologic AEs were infrequent with talazoparib. Higher talazoparib exposure was associated with grade ≥3 anemia. Permanent discontinuation of talazoparib due to hematologic AEs was low (<2%). A total of 150 (52.4%) patients receiving talazoparib had AEs associated with dose reduction. Hematologic toxicities were managed by supportive care medication (including transfusion) and dose modifications. Among patients with anemia or nausea and/or vomiting AEs, PROs favored talazoparib. After accounting for the treatment‐emergent period, talazoparib was generally associated with a lower rate of hospitalization and supportive care medication use compared with chemotherapy.

Conclusion

Talazoparib was associated with superior efficacy, favorable PROs, and lower HRU rate versus chemotherapy in gBRCA‐mutated ABC. Toxicities were manageable with talazoparib dose modification and supportive care.

Implications for Practice

Talazoparib was generally well tolerated in patients with germline BRCA‐mutated HER2‐negative advanced breast cancer in the EMBRACA trial. Common toxicities with talazoparib were primarily hematologic and infrequently resulted in permanent drug discontinuation (<2% of patients discontinued talazoparib due to hematologic toxicity). Hematologic toxicities typically occurred during the first 3–4 months of treatment and were managed by dose modifications and supportive care measures. A significant efficacy benefit, improved patient‐reported outcomes, lower rate of health resource utilization and a tolerable safety profile support incorporating talazoparib into routine management of germline BRCA‐mutated locally advanced/metastatic breast cancer.

]]>
<![CDATA[Young Women With Breast Cancer in Mexico: Results of the Pilot Phase of the Joven & Fuerte Prospective Cohort]]> https://www.researchpad.co/article/N78f19ec6-edde-4f4e-8e12-2c2e842ae043

PURPOSE

The pilot-phase report of the Joven & Fuerte prospective cohort broadly characterizes and assesses the needs of Mexican young women with breast cancer (YWBC).

PATIENTS AND METHODS

Women age ≤ 40 years with nonmetastatic primary breast cancer were consecutively accrued from 2 hospitals. Data were collected at the first/baseline oncology visit and 2 years later using a sociodemographic survey, European Organisation for Research and Treatment of Cancer Quality-of-Life (QOL) Questionnaire Core 30 (QLQ-C30) and Breast Cancer–Specific QOL Questionnaire (QLQ-BR23), Hospital Anxiety and Depression Scale (HADS), Female Sexual Functioning Index (FSFI), Sexual Satisfaction Inventory, and patients’ medical records. Pearson χ2 and 2-sided t tests were used for statistical analysis. An unadjusted P value < .05 was considered significant.

RESULTS

Ninety patients were included, all with government health care coverage. Most had low monthly household incomes (98%) and at least a high school education (59%). There was a considerable prevalence of unpartnered patients (36%) and unmet parity (25%). Patients’ most common initial symptom was a palpable mass (84%), and they were most frequently diagnosed with stage III disease (48%), with 51% having had a physician visit ≤ 3 months since detection but 39% receiving diagnosis > 12 months later. At baseline, 66% of patients were overweight/obese, and this proportion had significantly increased by 2 years (P < .001). Compared with baseline, global QLQ-C30 had improved significantly by 2 years (P = .004), as had HADS-Anxiety (P < .001). However, both at baseline and at 2 years, nearly half of patients exhibited FSFI sexual dysfunction.

CONCLUSION

These preliminary findings demonstrate that YWBC in Mexico have particular sociodemographic and clinicopathologic characteristics, reinforcing the necessity to further describe and explore the needs of these young patients, because they may better represent the understudied and economically vulnerable population of YWBC in limited-resource settings.

]]>
<![CDATA[Abstracts]]> https://www.researchpad.co/article/N16e1628c-c3f5-44f1-8bc3-198ec647b8c3 ]]> <![CDATA[Oral Care Evaluation to Prevent Oral Mucositis in Estrogen Receptor‐Positive Metastatic Breast Cancer Patients Treated with Everolimus (Oral Care‐BC): A Randomized Controlled Phase III Trial]]> https://www.researchpad.co/article/N55d95938-a9e1-4de7-b0f8-3e004139eb3c

Abstract

Background

The incidence of oral mucositis (any grade) after everolimus treatment is 58% in the general population and 81% in Asian patients. This study hypothesized that professional oral care (POC) before everolimus treatment could reduce the incidence of everolimus‐induced oral mucositis.

Materials and Methods

This randomized, multicenter, open‐label, phase III study evaluated the efficacy of POC in preventing everolimus‐induced mucositis. Patients were randomized into POC and control groups (1:1 ratio) and received everolimus with exemestane. Patients in the POC group underwent teeth surface cleaning, scaling, and tongue cleaning before everolimus initiation and continued to receive weekly POC throughout the 8‐week treatment period. Patients in the control group brushed their own teeth and gargled with 0.9% sodium chloride solution or water. The primary endpoint was the incidence of all grades of oral mucositis. We targeted acquisition of 200 patients with a 2‐sided type I error rate of 5% and 80% power to detect 25% risk reduction.

Results

Between March 2015 and December 2017, we enrolled 175 women from 31 institutions, of which five did not receive the protocol treatment and were excluded. Over the 8 weeks, the incidence of grade 1 oral mucositis was significantly different between the POC group (76.5%, 62 of 82 patients) and control group (89.7%, 78 of 87 patients; p = .034). The incidence of grade 2 (severe) oral mucositis was also significantly different between the POC group (34.6%, 28 of 82 patients) and control group (54%, 47 of 87 patients; p = .015). As a result of oral mucositis, 18 (22.0%) patients in the POC group and 28 (32.2%) in the control group had to undergo everolimus dose reduction.

Conclusion

POC reduced the incidence and severity of oral mucositis in patients receiving everolimus and exemestane. This might be considered as a treatment option of oral care for patients undergoing this treatment. Clinical trial identification number: NCT 02069093.

Implications for Practice

The Oral Care‐BC trial that prophylactically used professional oral care (POC), available worldwide, did not show a greater than 25% difference in mucositis. The 12% difference in grade 1 or higher mucositis and especially the ∼20% difference in grade 2 mucositis are likely clinically meaningful to patients. POC before treatment should be considered as a treatment option of oral care for postmenopausal patients who are receiving everolimus and exemestane for treatment of hormone receptor‐positive, HER2‐negative advanced breast cancer and metastatic breast cancer. However, POC was not adequate for prophylactic oral mucositis in these patients, and dexamethasone mouthwash prophylaxis is standard treatment before everolimus.

]]>
<![CDATA[Mortality of Pregnancy Following Breast Cancer Diagnoses in Taiwanese Women]]> https://www.researchpad.co/article/N097b1eff-3ab4-4755-820a-ce9eb14cfbd2

Abstract

Background

This work examined the association between pregnancy after breast cancer (BC) diagnosis and total mortality in Taiwanese patients with BC.

Materials and Methods

The Taiwan Cancer Registry, National Health Insurance database, and Taiwan National Death Certificate database were reviewed. Patients who became pregnant after being diagnosed with BC were selected (n = 249). Four nonpregnant patients with BC were selected and matched to every pregnant patient with BC by age at diagnosis, year at diagnosis, and propensity score based on disease stage, tumor size, node involvement, and histological grade. The disease‐free time interval for the selected control needed to have been longer than the time interval between the cancer diagnosis and pregnancy for the index case. Follow‐up was calculated from the pregnancy date of the index case to the date of death or December 31, 2014, whichever came first. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

After adjusting for age, year at BC diagnosis, stage, positive nodes, and hormone therapy, patients with BC who became pregnant after their cancer diagnosis had lower total mortality than did the comparison group (HR = 0.44, 95% CI = 0.23–0.84), including that of estrogen receptor‐positive patients (HR = 0.23, 95% CI = 0.07–0.77). The inverse association was more pronounced for those who became pregnant more than 3 years after diagnosis (HR = 0.19, 95% CI = 0.05–0.78).

Conclusion

Our nationwide retrospective analysis revealed that pregnancy after BC diagnosis was associated with lower mortality than that of nonpregnant patients with BC at a similar age, year at diagnosis, and clinical characteristics.

Implications for Practice

This article provides high‐level evidence based on an Asian population for pregnancy counseling after a breast cancer diagnosis, including for patients with estrogen receptor‐positive cancers. The study also revealed the optimal time for patients who would like to become pregnant after breast cancer.

]]>
<![CDATA[Lymph Node Imaging in Patients with Primary Breast Cancer: Concurrent Diagnostic Tools]]> https://www.researchpad.co/article/Nb602c4c4-063d-42c6-a392-9bd95fb8407e

Abstract

The detection of lymph node metastasis affects the management of patients with primary breast cancer significantly in terms of staging, treatment, and prognosis. The main goal for the radiologist is to determine and detect the presence of metastatic disease in nonpalpable axillary lymph nodes with a positive predictive value that is high enough to initially select patients for upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with different imaging modalities, but ultrasound is the method of choice for evaluating axillary lymph nodes and for performing image‐guided lymph node interventions. This review aims to provide a comprehensive overview of the available imaging modalities for lymph node assessment in patients diagnosed with primary breast cancer.

Implications for Practice

The detection of lymph node metastasis affects the management of patients with primary breast cancer. The main goal for the radiologist is to detect lymph node metastasis in patients to allow for the selection of patients who should undergo upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with mammography, computed tomography, and magnetic resonance imaging, but ultrasonography is the imaging modality of choice for evaluating axillary lymph nodes. A normal axillary lymph node is characterized by a reniform shape, a maximal cortical thickness of 3 mm without focal bulging, smooth margins, and, depending on size, a discernable central fatty hilum.

]]>
<![CDATA[Effects of Exercise on Chemotherapy Completion and Hospitalization Rates: The OptiTrain Breast Cancer Trial]]> https://www.researchpad.co/article/N0e48e854-4bd6-4aca-b15f-ec06145bbab2

Abstract

Background

Exercise during chemotherapy is suggested to provide clinical benefits, including improved chemotherapy completion. Despite this, few randomized controlled exercise trials have reported on such clinical endpoints. From the OptiTrain trial we previously showed positive effects on physiological and health‐related outcomes after 16 weeks of supervised exercise in patients with breast cancer undergoing chemotherapy. Here, we examined the effects of exercise on rates of chemotherapy completion and hospitalization, as well as on blood cell concentrations during chemotherapy.

Patients and Methods

Two hundred forty women scheduled for chemotherapy were randomized to 16 weeks of resistance and high‐intensity interval training (RT‐HIIT), moderate‐intensity aerobic and high‐intensity interval training (AT‐HIIT), or usual care (UC). Outcomes included chemotherapy completion, hospitalization, hemoglobin, lymphocyte, thrombocyte, and neutrophil concentrations during chemotherapy.

Results

No significant between‐groups differences were found in the proportion of participants who required dose reductions (RT‐HIIT vs. UC: odds ratio [OR], 1.08; AT‐HIIT vs. UC: OR, 1.39), or average relative dose intensity of chemotherapy between groups (RT‐HIIT vs. UC: effect size [ES], 0.08; AT‐HIIT vs. UC: ES, −0.07). A significantly lower proportion of participants in the RT‐HIIT group (3%) were hospitalized during chemotherapy compared with UC (15%; OR, 0.20). A significantly lower incidence of thrombocytopenia was found for both RT‐HIIT (11%) and AT‐HIIT (10%) versus UC (30%; OR, 0.27; OR, 0.27).

Conclusion

No beneficial effects of either RT‐HIIT or AT‐HIIT on chemotherapy completion rates were found. However, combined resistance training and high‐intensity interval training were effective to reduce hospitalization rates, and both exercise groups had a positive effect on thrombocytopenia. These are important findings with potential positive implications for the health of women with breast cancer and costs associated with treatment‐related complications.

Implications for Practice

Completing the prescribed chemotherapy regimen is strongly associated with a good prognosis for patients with primary breast cancer. Despite this, treatment‐induced side effects make it necessary to reduce or alter the treatment regimen and can also lead to hospitalization. Exercise during chemotherapy is suggested to provide clinical benefits, including improved chemotherapy completion. This study showed that combined resistance and high‐intensity interval training during chemotherapy resulted in lower hospitalization rates and a lower incidence of thrombocytopenia in women with breast cancer undergoing chemotherapy. However, no beneficial effects of either exercise program on chemotherapy completion rates were found, which is in contrast to previous findings in this population. The findings reported in the current article have positive implications for the health of women with breast cancer and costs associated with treatment‐related complications.

]]>
<![CDATA[Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value]]> https://www.researchpad.co/article/Nb043f4fb-483e-4ba4-815b-8ab0ed813667

This article presents a comprehensive review of the current evidence related to PD‐L1 testing in breast cancer and its use as a biomarker in prediction of response to immunotherapies.

]]>
<![CDATA[Integrated structural variation and point mutation signatures in cancer genomes using correlated topic models]]> https://www.researchpad.co/article/5c99020ad5eed0c484b97533

Mutation signatures in cancer genomes reflect endogenous and exogenous mutational processes, offering insights into tumour etiology, features for prognostic and biologic stratification and vulnerabilities to be exploited therapeutically. We present a novel machine learning formalism for improved signature inference, based on multi-modal correlated topic models (MMCTM) which can at once infer signatures from both single nucleotide and structural variation counts derived from cancer genome sequencing data. We exemplify the utility of our approach on two hormone driven, DNA repair deficient cancers: breast and ovary (n = 755 samples total). We show how introducing correlated structure both within and between modes of mutation can increase accuracy of signature discovery, particularly in the context of sparse data. Our study emphasizes the importance of integrating multiple mutation modes for signature discovery and patient stratification, and provides a statistical modeling framework to incorporate additional features of interest for future studies.

]]>
<![CDATA[Tailored NEOadjuvant epirubicin, cyclophosphamide and Nanoparticle Albumin-Bound paclitaxel for breast cancer: The phase II NEONAB trial—Clinical outcomes and molecular determinants of response]]> https://www.researchpad.co/article/5c6f152dd5eed0c48467ae8b

Background

This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored.

Patients and outcome measures

Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25. Patients were treated with epirubicin and cyclophosphamide, followed by nab-paclitaxel, with the addition of trastuzumab if HER2-amplified. The primary endpoint was pathological complete response (pCR) in the breast. Pre- and post-treatment tumour samples underwent variant burden, gene and gene pathway, mutational signature profile and clonal evolution analyses.

Results

The pCR rates were: overall 55% (n = 22), HER2-amplified 80% (n = 12), triple-negative 46% (n = 7) and HR-positive, HER2-non-amplified 30% (n = 3). Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (18%), sensory neuropathy (5%), deranged transaminases (5%), fatigue (2%), diarrhoea (2%), and pneumothorax (2%). Molecular analyses demonstrated strong similarities between residual disease and matched primary tumour. ATM signalling pathway alterations and the presence of a COSMIC Signature 3 implied the majority of tumours contained some form of homologous repair deficiency. ATM pathway alterations were identified in the subset of TNBC patients who did not achieve pCR; Signature 3 was present in both pCR and non-pCR subgroups. Clonal evolution analyses demonstrated both persistence and emergence of chemoresistant clones.

Conclusions

This treatment regime resulted in a high rate of pCR, demonstrating that tailored neoadjuvant therapy using a genomic recurrence score is feasible and warrants further investigation. Molecular analysis revealed few commonalities between patients. For TNBC future clinical gains will require precision medicine, potentially using DNA sequencing to identify specific targets for individuals with resistant disease.

Trial registration

Clinicaltrials.gov NCT01830244

]]>