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Breast cancer in young women (ages 18–40 years) is rare, yet remains a leading cause of cancer-related death. Time to treatment (TTT) is an increasingly important factor in breast cancer outcomes, specifically time to systemic therapy. Our objective was to review patterns of care for young women presenting with invasive breast cancer and compare TTT for surgery first versus neoadjuvant chemotherapy (NAC). A retrospective chart review of young women with non-metastatic, non-inflammatory invasive breast cancer between 2012 and 2018 at a single institution was completed. The primary outcome was time to first treatment (surgery or NAC). One hundred forty-two young women were treated for invasive breast cancer during the study period. The majority of patients underwent surgery first (57.7%) compared with NAC (42.3%). Women who underwent NAC were more likely to have abnormal lymph nodes on imaging (p = 0.002) and clinical exam (p

BACKGROUND: Ki-67 immunohistochemistry (IHC) staining is a widely used cancer proliferation assay; however, its limitations could be improved with automated scoring. The OncotypeDXTM Recurrence Score (ORS), which primarily evaluates cancer proliferation genes, is a prognostic indicator for breast cancer chemotherapy response; however, it is more expensive and slower than Ki-67. OBJECTIVE: To compare manual Ki-67 (mKi-67) with automated Ki-67 (aKi-67) algorithm results based on manually selected Ki-67 “hot spots” in breast cancer, and correlate both with ORS. METHODS: 105 invasive breast carcinoma cases from 100 patients at our institution (2011–2013) with available ORS were evaluated. Concordance was assessed via Cohen’s Kappa (κ). RESULTS: 57/105 cases showed agreement between mKi-67 and aKi-67 (κ 0.31, 95% CI 0.18–0.45), with 41 cases overestimated by aKi-67. Concordance was higher when estimated on the same image (κ 0.53, 95% CI 0.37–0.69). Concordance between mKi-67 score and ORS was fair (κ 0.27, 95% CI 0.11–0.42), and concordance between aKi-67 and ORS was poor (κ 0.10, 95% CI −0.03–0.23). CONCLUSIONS: These results highlight the limits of Ki-67 algorithms that use manual “hot spot” selection. Due to suboptimal concordance, Ki-67 is likely most useful as a complement to, rather than a surrogate for ORS, regardless of scoring method.

(1) Background: Wait times to chemotherapy are associated with morbidity and mortality in breast cancer patients, however, it is unclear how primary care physician (PCP) continuity impacts these wait times, or whether this association is different in immigrants, who experience cancer care inequities. We assessed the association between PCP continuity and the contact-to-chemotherapy interval (wait time from when a patient first presents to healthcare to the first day of receiving breast cancer chemotherapy), with a specific look at the immigrant population. (2) Methods: Population-based, retrospective cohort study of women who were diagnosed with stage I–III breast cancer in Ontario who received surgery and adjuvant chemotherapy. We used quantile regression at the median and 90th percentile to quantify the effect of PCP continuity on the contact-to-chemotherapy interval, performing a separate analysis on the immigrant population. (3) Results: Among 12,781 breast cancer patients, including 1706 immigrants, the median contact-to-chemotherapy interval (126 days) was 3.21 days shorter (95% confidence interval (CI) 0.47–5.96) in symptom-detected patients with low PCP continuity, 10.68 days shorter (95% CI 5.36–16.00) in symptom-detected patients with no baseline PCP visits and 17.43 days longer (95% CI 0.90–34.76) in screen-detected immigrants with low PCP continuity compared to the same groups with high PCP continuity. (4) Conclusions: Higher PCP continuity was not associated with a change in the contact-to-chemotherapy interval for most of our study population, but was associated with a marginally longer interval in our symptom-detected population and a shorter contact-to-chemotherapy interval in screen-detected immigrants. This highlights the importance of PCP continuity among immigrants with positive screening results. Additionally, having no PCP visits at baseline was associated with a shorter contact-to-chemotherapy interval in symptom-detected patients.

Biomarkers are considered as an innovative tool in the diagnosis and follow-up of breast cancer. The aim of the study was to assess the profile of circulating tumour markers CA 15-3 and CEA in patients under chemotherapy for breast cancer in Ouagadougou. This is a prospective cross-sectional study with a descriptive and analytical aims which was done from July to November 2020. Patients with histologically confirmed malignant breast tumour and under chemotherapy were included. Results revealed that the study was on thirty (30) female patients whose average age was 47.47 ± 2.10 years with a mean BMI of 27.29 ± 1.09 kg/m2. It was a non-specific type of infiltrating carcinoma with SBRm II grade in 90% of the patients. The mean CA 15-3 was 212.98 U/mL before chemotherapy and 165.75 U/mL after it. The CEA mean value was 3.13 ng/L before chemotherapy and 16.14 ng/L after it. Serum CA 15-3 was significantly associated with tumour site, SBRm grade, chemotherapy line and treatment response. Serum CEA level was significantly associated with tumour site and SBRm grade. Despite their lack of sensitivity, tumour markers, particularly CA 15-3 enabled assessment of the response to treatment in patients in this study. Key words: Tumour markers, CA 15-3, CEA, breast cancer, chemotherapy.

Objective. To investigate the changes in cognitive function and its influencing factors in patients with breast cancer after chemotherapy, to provide a scientific basis for further cognitive correction therapy. Methods. In this study, general information on age, marital status, and chemotherapy regimen was collected from 172 breast cancer chemotherapy patients. 172 patients with breast cancer undergoing chemotherapy were investigated by convenience sampling method, and the subjects were tested one-on-one using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) computer system. Results. The mean value of standardized t-value of cognitive function and its abnormal dimensions in breast cancer patients undergoing chemotherapy were MCCB total cognition (66.3%, 36.99 ± 13.06, abnormal), working memory (73.3%, 36.84 ± 10.25), attention and alertness (70.3%, 37.20 ± 12.50), social cognition (65.1%, 39.54 ± 10.17), and visual memory (61.6%, 42.19 ± 9.38). A comparison of cognitive function among breast cancer chemotherapy patients with different demographic characteristics showed that differences in place of residence, educational level, monthly income, timing of chemotherapy, chemotherapy regimen, and chemotherapy times may be associated with abnormal cognitive function. Further multiple linear regression analysis was performed and the results showed that there was a linear regression between literacy, number of chemotherapy sessions, monthly personal income, and cognitive function. Conclusion. Cognitive impairment is common in patients with breast cancer after chemotherapy. Nurses should pay attention to the cognitive function changes and intervention of patients with breast cancer after chemotherapy, to prevent the changes of cognitive function and promote the rehabilitation of patients.

Cisplatin (CDDP) is widely prescribed for the treatment of various cancers including bladder cancers, whereas its clinical use for breast cancer chemotherapy is restricted owing to easy acquisition of the chemoresistance. Here, we established a highly CDDP-resistant variant of human breast cancer MCF7 cells and found that procuring the resistance aberrantly elevates the expression of aldo-keto reductase (AKR) 1C3. Additionally, MCF7 cell sensitivity to CDDP was decreased and increased by overexpression and knockdown, respectively, of AKR1C3, clearly inferring that the enzyme plays a crucial role in acquiring the CDDP resistance. The CDDP-resistant cells suppressed the formation of cytotoxic reactive aldehydes by CDDP treatment, and the suppressive effects were almost completely abolished by pretreating with AKR1C3 inhibitor. The resistant cells also exhibited the elevated glutathione amount and 26S proteasomal proteolytic activities, and their CDDP sensitivity was significantly augmented by pretreatment with an inhibitor of glutathione synthesis or proteasomal proteolysis. Moreover, the combined treatment with inhibitors of AKR1C3, glutathione synthesis and/or proteasomal proteolysis potently overcame the CDDP resistance and docetaxel cross-resistance. Taken together, our results suggest that the combination of inhibitors of AKR1C3, glutathione synthesis and/or proteasomal proteolysis is effective as an adjuvant therapy to enhance CDDP sensitivity of breast cancer cells.

Breast cancer is the most common causing death in women. Tamoxifen, 1-[4-(2-dimethyl-aminoethoxy) phenyl]-1,2-diphenyl-1-butene), is a nonsteroidal antiestrogen breast cancer prevention drug causing liver toxicity. This study was carried out to elucidate the efficacy of Moringa oleifera aqueous extract against carcinogenic effect of Tamoxifen in male rats. 50 male albino rats were divided equally into five groups: control group (I); Moringa oleifera aqueous group (II) of dose (300mg/Kg/day for 6 weeks); group (III) received Tamoxifen (3mg/Kg/3 days for 6 weeks); rats received orally Tamoxifen and Moringa oleifera aqueous extract together for 6 weeks group (IV) and rats pretreated with Moringa oleifera aqueous extract then Tamoxifen with the same dose and period group (V). In group (III) there were elevate in serum activities of ALT, AST, LDH, and serum levels of TNF-α, IL-1β, Il-10, cholesterol, TG, LDL, HDL, Urea, Creatinine also liver MDA; NO; ATPase. There were decrease in serum Total protein, Albumin and liver antioxidants markers (TAC and GSH) compared to control. In conclusion, oral administration of Moringa oleifera aqueous extract improved the biochemical markers and provided antioxidant activity against the toxicity of Tamoxifen in liver tissues.

Mitochondrial unfolded protein response plays an important role in the occurrence and development of breast cancer. However, the role of mitochondrial unfolded protein response (UPRmt) in the sensitivity of breast cancer to cisplatin chemotherapy has not yet been cleared. The purpose of this study is to explore the role of mitochondrial unfolded protein response in breast cancer sensitivity to cisplatin. In this study, qRT-PCR, Western blotting, Immunofluorescence, CCK-8, Colony formation, Transwell assay and TUNEL staining assay were used to confirm the role of UPRmt in breast cancer cells treated with cisplatin. Cisplatin increased the levels of UPRmt including CLPP, HSP60, LONP1 in MCF7 and MDA-MB-231 cells. UPRmt inducer Nicotinamide ribose (NR) could promote the proliferation and invasion of breast cancer cells treated with cisplatin. Importantly, SIRT3 was discovered to increase UPRmt in breast cancer cells and silencing of SIRT3 could inhibit the effect of NR in breast cancer. UPRmt regulated by SIRT3 could protect breast cancer cell from cisplatin. Controlling SIRT3-induced UPR may be a potential therapeutic target to increase the sensitivity of breast cancer chemotherapy.

Signal Transducer and Activator of Transcription 3 (STAT3) phosphorylation plays a key role in the transformation and proliferation of breast cancer cells. According to previous studies, STAT3 phosphorylation can be inhibited by curcumin in various cancer cells. Even so, its use is restricted due to low oral bioavailability. This study aimed to enhance curcumin solubility and bioavailability by loading it on Folic Acid-Selenium nanoparticles and determine their effect on STAT3 activation in breast cancer cell line. The synthesized nanoparticles were characterized by Fourier-transform infrared spectroscopy, Dynamic light scattering, and transmission electron microscope. MTT and western blotting methods were applied to determine the viability and protein level of MCF cell line. The size and zeta potential of nanoparticles were found to be about 130 nm and − 45 mV, respectively. The results indicated a reduction of 49.62 ± 1.85% (p

Breast cancer is one of the most common malignant tumors in women. The existence of multiple breast cancer subtypes often leads to chemotherapy failure or the development of drug resistance. In recent years, photodynamic therapy has been proven to enhance the sensitivity of tumors to chemotherapeutic drugs. Porphyrin-based metal-organic framework (MOF) materials could simultaneously be used as carriers for chemotherapy and photosensitizers in photodynamic therapy. In this paper, doxorubicin hydrochloride (DOX) was loaded in porphyrin MOFs, and the mechanism of the synergistic effect of the DOX carriers and photodynamic therapy on breast cancer was investigated. In vitro and in vivo experiments have shown that MOFs could prolong the residence time of DOX in tumor tissues and promote the endocytosis of DOX by tumor cells. In addition, adjuvant treatment with photodynamic therapy can promote breast cancer tumors to resensitize to DOX and synergistically enhance the chemotherapy effect of DOX. Therefore, this study can provide effective development ideas for reversing drug resistance during breast cancer chemotherapy and improving the therapeutic effect of chemotherapy on breast cancer.

Bing-Xin Lin, Chun-Sen Xu Department of Breast Surgery, Union Hospital of Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Chun-Sen XuDepartment of Breast Surgery, Union Hospital of Fujian Medical University, No. 29 of Xinquan Road, Gulou District, Fuzhou, 350001, People’s Republic of ChinaTel/Fax +86 591 83357896Email chunsenxuparis@163.comBackground: To analyze the risk factors of a peripherally inserted central catheter (PICC)-related venous thrombosis in patients with breast cancer undergoing chemotherapy and explore its preventive measures.Methods: Data of 780 patients with breast cancer who underwent PICC chemotherapy in our hospital from January 2014 to June 2015 were retrospectively analyzed. The incidence of catheter-related thrombosis was observed, and related factors of venous thrombosis were analyzed.Results: Among the 780 patients with breast cancer, 36 developed PICC-related venous thrombosis. The incidence of which was 4.62% (36/780). The PICC retention time ranged between 60 and 136 days, and the median time was 92 days. Thrombosis was found to occur within seven days after catheterization in three patients (8.33%), between 7 and 30 days in 18 patients (50%), between 31 and 92 days in 12 patients (33.3%), and ≥ 92 days in three patients (8.33%). Basilic vein puncture-induced thrombosis occurred in 25 patients (3.68%), and median cubital vein and cephalic vein puncture-induced thrombosis occurred in 11 patients (10.78%). The difference was statistically significant (P = 0.001). Thrombosis was not associated with age, punctured limb, platelet count, or chemotherapy drugs (P > 0.05).Conclusion: Blood vessel puncture was the main factor that affected PICC-related thrombosis in breast cancer chemotherapy. The basilic vein should be the primary choice for blood vessel puncture. Prolonged catheter retention does not increase the risk of thrombosis.Keywords: breast cancer, peripherally inserted central catheter, thrombosis

Aim This research aimed to explore the level of hope and symptom burden of breast cancer women undergoing chemotherapy, and predictive factors of hope were also investigated. Background Chemotherapy brings physical and psychological stress to breast cancer patients. As an effective coping strategy, hope gives them the courage to overcome difficulties and improve prognosis and survival. Therefore, efforts are needed to raise hope. Design/methods A total of 450 women who were undergoing breast cancer chemotherapy participated in this cross-sectional study. Sociodemographic data, disease characteristics, and measures of hope and symptom burden were collected using questionnaires. Hope was assessed using the validated Herth Hope Index, and the previously validated Memorial Symptom Assessment Scale was used to assess symptom burden. This paper adhered to the STROBE guidelines. Results Chinese breast cancer chemotherapy women hope average scores of 30.15 ± 4.82 were in the medium range of the Hearth Hope Index as specified by Herth to be 24-35. Patients with age ≤45, religious beliefs and lighter symptom burden have a higher level of hope. These variables explained a total of 22.9% of the variation in hope. Conclusions The level of hope for women undergoing breast cancer chemotherapy still needs to be further improved. Symptom burden can negatively predict hope. Relevance to clinical practice If nurses can decrease breast cancer chemotherapy women symptom burden, there is an impact on increasing levels of hope.

Objective:To analyze the occurrence of tinnitus and peripheral sensory neuropathy in women during breast cancer chemotherapy. Methods:This is a retrospective analytical study with a quantitative approach, performed in medical records of an oncology outpatient service between February 2014 and February 2015, using the toxicitiesscores of Common Terminology Criteria for Adverse Events (CTCAE). Results: Considering 181 patients with breast cancer who met the inclusion criteria, 49.2% reported tinnitus at some point of the treatment, while 65.1% peripheral sensory neuropathy. In both conditions, the predominant severity score was grade 1, with frequencies of 23.8% and 33.1%, respectively. A significant, positive and weak correlation was observed between the severity of tinnitus and peripheral sensory neuropathy (ρ = 0.325 andp = 0.001), as well as very weak between the number of complete cycles of chemotherapy and tinnitus (ρ = 0.195 andp = 0.009) and neuropathy peripheral sensory (ρ = 0.237 and p = 0.002).Conclusions:Tinnitus and peripheral sensory neuropathy were frequent toxicities during chemotherapy treatment of breast cancer, and both manifested with low severity/functional impact in most participants. Objetivo: Analisar a ocorrência de zumbido e neuropatia sensorial periférica em mulheres durante quimioterapia para câncer de mama. Métodos: Trata-se de um estudo analítico e retrospectivo com abordagem quantitativa, realizado em prontuários de um serviço ambulatorial de oncologia entre fevereiro de 2014 e fevereiro de 2015, utilizando os escores de toxicidades do Common Terminology Criteria for Adverse Events (CTCAE). Resultados: Das 181 pacientes com câncer de mama que atenderam aos critérios de inclusão, 49.2% relataram zumbido e 65.1% neuropatia sensorial periférica em algum momento do tratamento. Em ambas as condições, o escore de gravidade predominante foi grau 1, com frequências de 23.8% e 33.1%, respectivamente. Foi observada uma correlação significativa, positiva e fraca entre a severidade do zumbido e da neuropatia sensorial periférica (ρ = 0,325 e p = 0,001), bem como muito fraca entre a quantidade de ciclos completos de quimioterapia e zumbido (ρ = 0,195 e p = 0,009) e neuropatia sensorial periférica (ρ = 0,237 e p = 0,002). Conclusões: Zumbido e neuropatia sensorial periférica foram toxicidades frequentes durante o tratamento quimioterápico do câncer de mama e ambos se manifestaram com baixa gravidade/impacto funcional na maioria das participantes.

Background Adjuvant systemic breast cancer treatment improves disease specific outcomes, but also presents with cardiac toxicity. In this post-hoc exploratory analysis of the OptiTrain trial, the effects of exercise on cardiotoxicity were monitored by assessing fitness and biomarkers over the intervention and into survivorship. Methods; Women starting 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). Outcome measures included plasma troponin-T (cTnT), Nt-pro-BNP and peak oxygen uptake (VO2peak), assessed at baseline, post-intervention, and at 1- and 2-years. Results For this per-protocol analysis, 88 women met criteria for inclusion. Plasma cTnT increased in all groups post-intervention. At the 1-year follow-up, Nt-pro-BNP was lower in the exercise groups compared to UC. At 2-years there was a drop in VO2peak for patients with high cTnT and Nt-pro-BNP. Fewer patients in the RT-HIIT group fulfilled biomarker risk criteria compared to UC (OR 0.200; 95% CI = 0.055–0.734). Conclusions In this cohort, high-intensity exercise was associated with lower levels of NT-proBNP 1-year post-baseline, but not with cTnT directly after treatment completion. This may, together with the preserved VO2peak in patients with low levels of biomarkers, indicate a long-term cardioprotective effect of exercise. Trial registration Clinicaltrials.govNCT02522260, Registered 13th of august 2015 – Retrospectively Registered Graphical abstract

The article presents a review, systematizing the state and directions of development in the fabrication of targeted drug delivery systems in relation to the treatment of breast cancer. Drug delivery systems constructed on the basis of natural and artificial liposomes, nanoparticles of various nature, polymers, and dendrimer structures are consistently considered. For each class of platforms, information is provided on the features of the structure and functional properties of carriers, on successful examples of their use for the treatment of breast cancer at various stages of preclinical and clinical trials. The most probable directions to achieve a progress in the development of new systems for targeted delivery of antitumor drugs are shown.

Different tumor-related factors have been proposed to assess the risk of disease progression and death in women undergoing neoadjuvant breast cancer chemotherapy. Recently, besides the classical pre-treatment clinical stage (CS) and post-treatment pathologic stage (PS), estrogen receptor status and histologic grade (CPS + EG score) and HER2 results (Neo-Bioscore) have also been added to this suite of staging systems, generating new scores. The present study aims to compare the performance of these four staging systems, namely CS, PS, CPS + EG and Neo-Bioscore, in the prognosis of breast cancer in women undergoing neoadjuvant chemotherapy. This study comprises a retrospective cohort study of female breast cancer patients diagnosed at the Brazilian National Cancer Institute, Brazil from January 2013 to December 2015. A descriptive analysis of patient characteristics was conducted, and Kaplan–Meier curves, a Cox proportional hazard analysis and Receiver Operating Characteristic (ROC) curves were developed according to the assessed staging system scores. A total of 803 patients were eligible for this study. Most were under 65 years old (88.0%), presented advanced tumors (clinical stage ≥ IIB 77.1%), with positive estrogen receptor (71.2%) and negative HER2 (75.7%) results. During the follow-up, 172 patients (21.4%) evolved to death. A statistical difference (p

Background: Estrogens are essential for the growth of breast cancer in the case of premenopausal as well as in postmenopausal women. However, most of the breast cancer incidences are reported in postmenopausal women and the concurrent risk surges with an increase in age. Since the enzyme aromatase catalyses essential steps in estrogen biosynthesis, Aromatase Inhibitors (AIs) are effective targeted therapy in patients with Estrogen Receptor positive (ER+) breast cancer. AIs are more effective than Selective Estrogen Receptor Modulators (SERMs) because they block both the genomic and nongenomic activities of ER. Till date, first, second and third-generation AIs have been approved by the FDA. The third-generation AIs, viz. Letrozole, Anastrozole, Exemestane, are currently used in the standard treatment for postmenopausal breast cancer. Methods: Data were collected from Medline, PubMed, Google Scholar, Science Direct through searching of keywords: ‘aromatase’, ‘aromatase inhibitors’, ‘breast cancer’, ‘steroidal aromatase inhibitors’, ‘non-steroidal inhibitors’ and ‘generations of aromatase inhibitors’. Results: In the current scenario of breast cancer chemotherapy, AIs are the most widely used agents which reveal optimum efficacy along with the least side effects. Keeping in view the prominence of AIs in breast cancer therapy, this review covered the detailed description of aromatase including its role in the biosynthesis of estrogen, biochemistry, gene expression, 3D-structure, and information of reported AIs along with their role in breast cancer treatment. Conclusion: AIs are the mainstream solution of the ER+ breast cancer treatment regimen with the continuous improvement of human understanding of the importance of a healthy life of women suffering from breast cancer.

Many young women diagnosed with breast cancer will be confronted with premature ovarian insufficiency and infertility as a consequence of systemic therapies used to treat their cancer. This is a concern for nearly half of young women diagnosed with breast cancer. We will review the impact of breast cancer chemotherapy, endocrine therapy, and immunotherapy on fertility and surrogate markers of fertility. Modern breast cancer treatments continue to have an impact on a woman’s fertility potential. This risk is reduced as more patients are able to safely eliminate chemotherapy as part of their treatment plan without compromising cancer-related outcomes. Research is being done to assess whether patient outcomes are affected from pausing endocrine therapy to allow for pregnancy. With varying extent, most breast cancer treatments have some impact on fertility although more data is necessary. Individualized fertility counseling is an important aspect of comprehensive cancer care. This review highlights the special population of premenopausal breast cancer patients and the challenge in their care should they desire children.

Background Multidrug resistance (MDR) limits the beneficial outcomes of conventional breast cancer chemotherapy. Ras-related nuclear protein (Ran-GTP) plays a key role in these resistance mechanisms, assisting cancer cells to repair damage to DNA. Herein, we investigate the co-delivery of Ran-RCC1 inhibitory peptide (RAN-IP) and doxorubicin (DOX) to breast cancer cells using liposomal nanocarriers. Research design A liposomal delivery system, co-encapsulating DOX, and RAN-IP, was prepared using a thin-film rehydration technique. Dual-loaded liposomes were optimized by systematic modification of formulation variables. Real-Time-Polymerase Chain Reaction was used to determine Ran-GTP mRNA expression. In vitro cell lines were used to evaluate the effect of loaded liposomes on the viability of breast and lung cancer cell lines. In vivo testing was performed on a murine Solid Ehrlich Carcinoma model. Results RAN-IP reversed the Ran-expression-mediated MDR by inhibiting the Ran DNA damage repair function. Co-administration of RAN-IP enhanced sensitivity of DOX in breast cancer cell lines. Finally, liposome-mediated co-delivery with RAN-IP improved the anti-tumor effect of DOX in tumor-bearing mice when compared to single therapy. Conclusions This study is the first to show the simultaneous delivery of RAN-IP and DOX using liposomes can be synergistic with DOX and lead to tumor regression in vitro and in vivo.

Progress in oncology has allowed to improve outcomes in many breast cancer patients. The core stone of breast cancer chemotherapy is anthracycline-based chemotherapy. Unfortunately, anthracyclines cause cardiotoxicity which is a limiting factor of its use and lifetime cumulative dose of anthracyclines is the major risk factor for cardiotoxicity. With evolution of echocardiography subclinical damage is identified, and more sensitive evaluation can be performed. This leads to understanding the heart damage beyond cumulative dose in early phase and importance of other risk factors. There are many risk factors for anthracycline-based chemotherapy cardiotoxicity (ABCC) like arterial hypertension, obesity, diabetes, genetic predisposition, etc. One of possible pathophysiological pathways is iron metabolism, especially HFE gene-regulated iron metabolism pathway. Pre-existing genetic iron metabolism dysregulation increases risk for ABCC. Clinical studies and experimental models in mice have shown potential impact of HFE gene SNP on ABCC. The main objective of our study was to identify the impact of HFE C282Y and H63D SNP on the development of subclinical heart damage during and/or after doxorubicin-based chemotherapy in breast cancer patients. Data of 81 women with breast cancer treated with doxorubicin-based chemotherapy in the outpatient clinic were analyzed and SNP RT-PCR tests were performed. Statistically significant association between H63D and ABCC after completion of chemotherapy was observed (p

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become the best comprehensive treatment choice for breast cancer. Epirubicin is a crucial drug widely used in breast cancer chemotherapy, but it is often used with a reduced dosage in NAC for Chinese patients for its notable cardiotoxicity and frequent adverse events. This study aimed to investigate the efficacy and safety of standard-dose epirubicin in NAC for Chinese breast cancer patients retrospectively. METHODS: We retrospectively collected clinicopathological parameters of breast cancer patients who underwent epirubicin-based NAC and a later surgery from three separate medical centers. Patients were divided into standard-dose and low-dose groups according to the epirubicin dose. The pathological complete response (pCR) rate, as the main therapeutic outcomes, and the incidence of adverse events were recorded and compared. RESULTS: The pCR rate of the standard-dose group was 41.2%, while the low-dose group was 10.1% (P

PURPOSE The use of growth factors adds considerable expense and some toxicity to adjuvant breast cancer chemotherapy. We tested the feasibility and safety of omitting routine peg-filgrastim use during the paclitaxel portion of the dose-dense doxorubicin-cyclophosphamide–paclitaxel regimen. PATIENTS AND METHODS This was a prospective, single-arm study in which patients 18 to 65 years of age who completed 4 cycles of dose-dense doxorubicin-cyclophosphamide for stage I-III breast cancer received paclitaxel 175 mg/m2 every 2 weeks. Peg-filgrastim was administered after paclitaxel only if patients had had febrile neutropenia in a prior cycle or at investigator discretion if patients had infections or treatment delays of > 1 week. Once a patient received peg-filgrastim, it was administered in all future cycles. The primary end point was the rate of paclitaxel completion within 7 weeks from cycle 1 day 1 to cycle 4 day 1. If ≥ 100 out of 125 patients completed 4 cycles of paclitaxel without dose delay, the regimen would be considered feasible. RESULTS The enrollment goal of 125 patients was met. Median age was 46 years (range, 21-65 years), and 112 patients (90% [95% CI, 83% to 94%]) completed dose-dense paclitaxel within 7 weeks. Omission of peg-filgrastim was not causally related to noncompletion of paclitaxel in any patients. The most common reasons for dose reduction or delays were nonhematologic. One patient experienced febrile neutropenia but was able to complete paclitaxel on time. Eight patients (6.4%) received peg-filgrastim during the trial. Overall, peg-filgrastim was administered in only 4.3% of paclitaxel cycles. CONCLUSION Omission of routine peg-filgrastim during dose-dense paclitaxel according to a prespecified algorithm seems to be safe and feasible and was associated with a 95.7% reduction in the use of peg-filgrastim relative to the current standard of care.

Background Breast cancer patients may experience an increased chance of survival with adjuvant chemotherapy. However dermatologic adverse effects can cause major discomfort due to physical or cosmetic problems. This study aims to describe dermatologic complications in breast cancer patients during chemotherapy. Methods This longitudinal prospective observational study included data on women with non-metastatic breast cancer whom were treated with AC-T protocol (anthracycline, cyclophosphamide, and taxane) adjuvant chemotherapy and consecutively enrolled during two years. The study was performed in an educational and tertiary referral center. The patients' information including age, body mass index (BMI), past medical history, and different dermatologic complications were collected for all participants. Results Of 190 enrolled women, all patients experienced alopecia, which occurred in 131 patients (68.9%) after the first cycle. Skin, mucosal, and nail involvement were respectively seen in 46 (24.2%), 51 (26.8%), and 86 (45.2%) cases. Cutaneous complications were observed mainly between the third and sixth chemotherapy cycles. Palmoplantar erythema and palmoplantar dysesthesia were the most common cutaneous complications. Dermatologic adverse effects were significantly more frequent in the patients with an underlying disease. Conclusion These findings suggest that dermatologic adverse effects of adjuvant chemotherapy are common and could be induced by all components of AC-T regimen. These complications should be skillfully managed to increase patients' comfort.

Objective: Evidence is scant regarding symptom clusters and quality of life (QOL) over 1 year in women who receive adjuvant breast cancer chemotherapy (CTX). Our purpose was to identify the prevalence and severity of individual symptoms, symptom clusters, and QOL in women receiving adjuvant breast cancer CTX from baseline over 1 year. Methods: Symptoms were identified in a sample (n = 219) at three times: baseline (prior to the first adjuvant CTX treatment), 1 month after the last CTX (approximately 6 months after baseline), and 1 year after baseline. The Hospital Anxiety and Depression Scale and Symptom Experience Scale measured symptoms. The Medical Outcomes Study, Short-Form Survey, measured QOL. Exploratory factor analysis identified symptom clusters at each time and core symptoms in clusters over time. Results: The prevalence and severity of 10 symptoms decreased over time (P < 0.05). Fatigue, sleep disturbance, and pain were most prevalent; all were of mild severity. Two symptom clusters were identified at baseline and one met internal consistency reliability criteria at the later times. Core symptoms were identified. Both the physical and mental component scores of QOL improved over time (P < 0.01), but physical was below the general population norms 1 year after baseline. Conclusions: The symptom experience was dynamic, and symptom clusters changed over 1 year. Despite mild severity, core symptoms and clusters persisted over 1 year, and physical health was below the general population norms. Breast cancer survivors with persistent single and co-occurring symptoms need to be taught to manage the patterns of symptoms over time because they may not resolve by 1 year.

Introduction Granulocyte colony-stimulating factor (G-CSF) is widely used as a neutrophil supportive therapy in breast cancer chemotherapy. Common adverse events of G-CSF include bone pain, headache, and fatigue; however, reports of G-CSF-associated vasculitis are few. Case report A 66-year-old woman who had undergone surgery for breast cancer received adjuvant chemotherapy with prophylactic use of pegfilgrastim (peg-G). She developed peg-G-associated vasculitis 11 days after initially receiving peg-G. Management and outcome: Although various blood and culture tests were required to rule out other vasculitis syndromes and infections, her symptoms spontaneously disappeared without any treatment other than discontinuation of the causal drug. Discussion G-CSF-associated vasculitis is occasionally accompanied by severe complications such as aortic dissection and aneurysm formation. This case report is important to draw attention towards this rare and difficult-to-diagnosis adverse event of peg-G.

AIM: The goal of this study was to determine whether a delay in starting treatment via surgery or neoadjuvant chemotherapy is related to a decrease in cancer-specific survival (CSS) in women with operable breast cancer (BrCr). BACKGROUND: Limited medical infrastructure and a lack of cancer prevention awareness in low- and middle-income countries have caused high BrCr incidence and mortality rates. METHODS: We analyzed a retrospective cohort of 720 women treated at a single center from 2005 to 2012. CSS estimates were obtained by the Kaplan-Meier method. A Cox model of proportional risks was performed to obtain the risk of dying from BrCr. We also obtained the risk according to the category of treatment initiation. RESULTS: Women with locally advanced stages and without hormone receptor expression were more likely to initiate treatment after 45 days. Patients in Stage IIIA had a 78.1% survival if treatment was initiated before 45 days (95% CI, 0.70–0.84) and 63.6% survival if treatment was started after 45 days (95% CI, 0.44–0.78; p

Background. The breast cancer chemotherapy leads to diverse aspects of noxious or unintended adverse drug reactions (ADRs) that cause the relative dose intensity (RDI) reduced to below optimal (i.e., if the percentage of actual dose received per unit time divided by planned dose per unit time is less than 85%). Hence, this prospective observational study was conducted to evaluate chemotherapy-induced ADRs and their impact on relative dose intensity among women with breast cancer in Ethiopia. Methods. The study was conducted with a cohort of 146 patients from January 1 to September 30, 2017, Gregorian Calendar (GC) at the only nationwide oncology center, Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia. The ADRs of the chemotherapy were collected using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.03). The patients were personally interviewed for subjective toxicities, and laboratory results and supportive measures were recorded at each cycle. SPSS version 22 was used for analysis. Results. Grade 3 neutropenia (23 (15.8%)) was the most frequently reported ADR among grade 3 hematological toxicity on cycle 4. However, overall grade fatigue (136 (93.2%)) and grade 3 nausea (31 (21.2%)) were the most frequently reported nonhematological toxicities on cycle 1. The majority of ADRs were reported during the first four cycles except for peripheral neuropathy. Oral antibiotics and G-CSF use (17 (11.6%)) and treatment delay (31 (21.2%)) were frequently reported on cycle 3. Overall, 61 (41.8%) and 42 (28.8%) of study participants experienced dose delay and used G-CSF, respectively, at least once during their enrollment. Of the 933 interventions observed, 95 (10%) cycles were delayed due to toxicities in which neutropenia attributed to the delay of 89 cycles. Forty-four (30.1%) of the patients received overall RDI P<0.05) for the incidence of first cycle hematological toxicities such as neutropenia, anemia, and leukopenia and nonhematological toxicities like vomiting. Conclusion. Ethiopian women with breast cancer on anthracycline-based AC and AC-T chemotherapy predominantly experienced grade 1 to 3 hematological and nonhematological ADRs, particularly during the first four cycles. Neutropenia was the only toxicity that led to RDI

Background It has been shown that exercise may improve NK cell immune response.In the past decades, several investigations also showed that physical activity training(PAT) during breast cancer treatment was able to maintain cardiorespiratory function and quality of life. This study is aimed to investigate effect of simple PAT on Immune cells changes, cardiorespiratory function and quality of life during breast cancer chemotherapy (CT).Trial designation Breast cancer patients, aged from 20 to 80 years old with stage I, II, III disease, who receive adjuvant or neoadjuvant chemotherapy are candidates for the study. Sixty patients will be recruited, and divided randomly into two arms, exercise interventional arm (n=30) and control arm (n=30). For PAT interventional participants Aerobic and muscular exercises are instructed by a sport trainer to the participants, and the participants are asked to do it at home, including 150 minutes moderate or 75 vigorous physical activity a week, 30 minutes each time. For control participantsOnly PAT manual is distributed to the control participants. Measurement and Data collection In this study, the following measurements are selected including: 1. Immune cells: lymphocyte subsets(CD3+, CD4+, CD8+, CD56+ T cells, and CD4+/CD8+ ratio) will be measured. Peripheral blood immune cells is analyzed before and 10-14 days after each cycle of adjuvant or neoadjuvant CT(usually 6-8 cycles of CT). 2. Cardiorespiratory function measurement including 6-minute walk test and echocardiography, before the 1st CT and at the end of whole CT courses. 3. Body weight, BMI, waist circumference and body composition assessment (body fat, muscle mass, and basal metabolic rate), WHOQOL are measured before the 1st CT and at end of the whole CT courses. Outcomes The primary outcome is the change of immune cell member per cycle of CT, and the secondary outcomes are chemotherapy completion rate, on schedule chemotherapy rate, improvement of cardiorespiratory function and quality of life. Statistical analysis In this study, to achieve a 95% power with 0.05 significance level, 18 subjects are required for each arm and this sample size calculation is based on effect size 0.25 and correlation between repeated measurements of immune cells using repeated measure analysis of variance (ANOVA). As a result, the changes of immune cell number over time will be examined by repeated measure ANOVA.To examine the difference of improvement of cardiorespiratory function and quality of life between 2 arms, 2-sample t-test or the Wilcoxon rank sum test will be used. To compare the chemotherapy completion rate and on-schedule chemotherapy rate, the Chi-square test or Fisher’s exact test will be employed. All statistical analyses will be performed using SPSS 22.0 software. A P value of 0.05 is considered to be significant in all tests Discussion The study will be started after approval of IRB(The institutional Review Board) in our hospital. Citation Format: Chia-Ming Hsieh, Kuan-Der Lee, Meng-Hsiu Wu, Ning-Chiang Yang, Hsin-Yi Chen, I-Shiang Tzeng. Effect of physical activity training on cardiovascular function, immune cells, quality of life during breast cancer chemotherapy in Taiwan [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-12-02.

Background Understanding the longer-term exercise behavior of patients with breast cancer after chemotherapy is important to promote sustained exercise. The purpose of the current study was to report the longer-term patterns and predictors of exercise behavior in patients with breast cancer who exercised during chemotherapy. Methods In the Combined Aerobic and Resistance Exercise (CARE) Trial, 301 patients with breast cancer were randomized to three different exercise prescriptions during chemotherapy. Exercise behaviors after chemotherapy were self-reported at 6-, 12-, and 24-month follow-up. Exercise patterns were identified by categorizing patients according to which exercise guideline they were meeting (neither, aerobic only, resistance only, or combined) at each of the three follow-up timepoints (64 possible patterns). Predictors of longer-term exercise behavior included physical fitness, patient-reported outcomes, and motivational variables from the theory of planned behavior assessed at postintervention (postchemotherapy). Univariate and multivariate stepwise multinomial logistic regression and linear regression were used for statistical analyses. Results A total of 264 (88%) participants completed all three follow-up exercise behavior assessments and exhibited 50 different exercise patterns. Postintervention aerobic fitness was the most consistent predictor of longer-term exercise behavior at all three timepoints. For example, higher aerobic fitness (per 1 ml/kg/min) predicted better adherence to the “aerobic only” (OR = 1.09; p = 0.005) and “combined” (OR = 1.12; p p = 0.025) and “combined” (OR = 1.08; p p = 0.010) and “aerobic only” (OR = 0.58; p = 0.002) guideline compared to the “neither” guideline at the 24-month follow-up. Conclusions Our study is the first to show that the longer-term exercise patterns of patients with breast cancer who exercised during chemotherapy are diverse and predicted by physical fitness and motivational variables after chemotherapy. Our novel implications are that improving physical fitness during chemotherapy and applying motivational counseling after chemotherapy may improve longer-term exercise behavior in patients with breast cancer. Trial registration (NCT00249015).

Chemotherapy is an important method for treating breast cancer. However, multidrug resistance is one of the major challenges in breast cancer chemotherapy. There is an urgent need to develop novel, effective antitumor strategies that will perfect existing therapeutic regimens. In this study, the double-targeted nanocarrier, Quercetin-3’3-dithiodipropionic acid-Astragalus polysaccharides-Folic acid (QDAF), was successfully synthesized and self-assembled into a neoteric nano-targeted delivery strategy, named nano-pomegranates, and which were utilized to effectively inhibit multidrug resistance in estrogen receptor α (ERα)-positive breast tumor. The outstanding abilities of nano-pomegranates to release the drug in a reducing environment was determined by in vitro release assay. The cellular studies in MCF-7 cells were examined that nano-pomegranates have remarkable efficiencies of enhancing cellular uptake, inhibition and necrosis and apoptosis. In vivo antitumor experiments showed that nano-pomegranates have better anti-tumor effects and lower systemic toxicity than free Cur. In conclusion, nano-pomegranates have great potential in anti-breast cancer treatment.

Background MicroRNAs (miRNAs) are a class of non-coding RNAs that have been linked with breast cancer chemoresistance, which is a major clinical problem causing disease relapse and poor prognosis. miR-7 exerts several tumor suppressive activities. Purpose This study was designed to clarify whether and how miR-7 regulates breast cancer chemoresistance. Methods miR-7 level in breast cancer was determined by qRT-PCR analysis. Cell viability was assessed by MTS assay to quantify the IC50 value of paclitaxel and carboplatin. The targets of miR-7 were confirmed by luciferase reporter assay. Results Higher miR-7 expression predicts better pathological complete response (pCR) of breast cancer patients receiving paclitaxel/carboplatin chemotherapy. In vitro, miR-7 sensitizes breast cancer cell lines (MCF-7 and MDA-MB-231) to paclitaxel and carboplatin, alone and in combination. In addition, we reveal that both the multidrug resistance-associated protein 1 (MRP1) and anti-apoptotic B cell lymphoma 2 (BCL2) are targets of miR-7 in breast cancer cells. Furthermore, miR-7-induced sensitization of breast cancer to paclitaxel/carboplatin is markedly reversed by restoration of MRP1 and BCL2. Conclusion These findings show that miR-7 reverses breast cancer chemoresistance through suppressing MRP1 and BCL2, and also suggest that miR-7 may possess a predictive value and represent a therapeutic target in breast cancer chemotherapy.

Breast cancer causes the most cancer fatalities in women worldwide. Approximately one‐third of breast cancers metastasize, or spread from primary tumors to other tissues, and have a 70% 5‐year mortality rate. Current breast cancer treatments like doxorubicin and paclitaxel become ineffective when breast cancer cells develop multi‐drug resistance and overexpress ATP‐binding cassette transporters, as the transporters cause a substantial efflux of the chemotherapies. Jadomycins, a group of molecules isolated from Streptomyces venezuelae ISP5230, are shown to be cytotoxic against a variety of cancers, especially breast cancer. Furthermore, jadomycins retain their cytotoxic properties in multi‐drug resistant breast cancer cells, as they are not expelled through ATP‐binding cassette transporters. Here, we describe the research that supports the potential use of jadomycins as a novel chemotherapy in the treatment of multi‐drug resistant, metastatic breast cancer. We present the supportive findings, as well as the mechanisms of action investigated thus far. These include copper‐mediated reactive oxygen species generation, aurora B kinase inhibition, and topoisomerase IIα and IIβ inhibition. We also suggest future directions of jadomycin research, which will help to determine if jadomycins can be used as a breast cancer chemotherapy in clinical practice., Jadomcyins are isolated from the soil bacterium Streptomyces venezuelae and are cytotoxic against a variety of human cancer cells, including those that express multi‐drug resistance transporters. Here we describe the research that supports the potential use of jadomycins, especially against human breast cancer cells, and the mechanisms of action investigated so far. We also suggest novel future directions to develop jadomycin and breast cancer research.

No study has examined myocardial work in subjects with cancer therapy-related cardiac dysfunction (CTRCD). Myocardial work, as a new ultrasonic indicator, reflects the metabolism and oxygen consumption of the left ventricle. The aim of this study was to test the relative value of new indices of myocardial work and global longitudinal strain (GLS) in detecting changes in myocardial function during the treatment of breast cancer by two-dimensional and three-dimensional echocardiography. We enrolled 79 breast cancer patients undergoing different tumor treatment regimens. Follow-up observation was conducted before and after chemotherapy. The effects of breast cancer chemotherapy and targeted therapy on the development of CTRCD [defined as an absolute reduction in left ventricular ejection fraction (LVEF) of >5% to p < 0.05). The three-dimensional strain changes after T6 and T8 had no advantages compared with GLS. Body mass index (BMI), the GLS change rate after the second cycle of chemotherapy (G2v) and the 3D-GCS change rate after the second cycle of chemotherapy (C2v) were independent factors that could predict the occurrence of CTRCD during follow-up, among which BMI was the best predictor (area under the curve, 0.922). In conclusion, the current study determined that GLS was superior to GWI in predicting cardiac function in patients with tumors with little variation in blood pressure. BMI, G2v and C2v can be used to predict the occurrence of CTRCD.

Breast cancer is the most common malignancy diagnosed in women. Traditionally, radical surgical resection was the cornerstone of breast cancer management, with limited exceptions. In recent times, our enhanced appreciation of the biomolecular characteristics of breast cancer has transformed the treatment paradigm to include prescription of chemotherapeutical agents, radiotherapies, targeted therapies, as well as more refined surgical approaches. While treatments with such modalities have enhanced clinico-oncological outcomes for breast cancer patients, the efforts of oncological and translational research have concentrated on the identification of novel biomarkers which may successfully inform prognosis and response to therapies, improve current therapeutic strategies, and enhance prognostication. Mi(cro)RNAs are small, non-coding molecules which are known to play regulatory roles in governing gene expression and cellular activity. Measurement of miRNA expression profiles have been illustrated to inform the response to therapies, such as conventional chemotherapy, and are currently undergoing assessment as means of enhancing treatment strategies with these cytotoxic agents. Herein, this review outlines how chemotherapy prescription has revolutionised breast cancer treatment and illustrates the novel role of miRNAs as biomarkers capable of enhancing current therapeutic strategies using chemotherapy in patients being treated with curative intent for breast cancer.

We explore the association of hope and quality of life in breast cancer chemotherapy women. Their quality of life is related to treatment effects and disease outcomes. This cross-sectional study was conducted in City, China, in 2017. In a convenience sampling, 450 women who underwent breast cancer chemotherapy were selected from two hospitals. Descriptive statistics, single-factor analysis, Spearman correlation, linear regression, and structural equation modeling were used to analyze data. The mean quality of life score was 65.65. In linear regression analysis, we found patients’ quality of life was significantly related to age, marital status, education level, chemotherapy cycle, and hope. Structural equation results showed the “temporality and future” and “interconnectedness” subscales of the HHI explained 43% of the variance in quality of life. We found hope is an important aspect in quality of life, and further research is needed to determine if nurses can influence this aspect of care.

Individual treatment with either the standard chemotherapeutic drug tamoxifen (Tam), the natural product hesperidin (Hes), or camel milk exosomes (Exo) has been shown to inhibit breast cancer MCF7 cells proliferation. However, little is known regarding their combined effect on MCF7 both in vitro and in vivo. This study aimed to investigate whether the combined therapy of Tam, Hes, and Exo could synergistically inhibit the proliferation of MCF7 both in vitro and in vivo and could decrease Tam side effects. Combined treatment with Tam, Hes, and Exo significantly inhibited MCF7 proliferation as compared to the individual treatment. This cotreatment also had higher apoptotic, anti-migratory, and anti-invasive effects against MCF7 than individual treatment as revealed by; (1) Bax and caspase3 upregulation and Bcl2 downregulation; (2) downregulation of breast cancer-related genes (EGFR and ERα); (3) downregulation of MMP9 and upregulation of TIMP1; and (4) decreased number of migratory cells (transwell assay). This therapeutic potential was confirmed by the results of the in vivo study (mouse model of breast cancer induced by MCF7 xenograft). Cotreated mice had the smallest tumor size, highest Bax and caspase3, lowest Bcl2 and VEGF expression in the xenograft. This cotreatment was safer and reduced Tam side effects as revealed by; (1) lower serum levels of AST, ALT, creatinine, and urea; (2) lower levels of the lipid peroxide MDA; and (3) higher activities of the antioxidant enzymes CAT and GPx. Cotreatment with tamoxifen, hesperidin, and camel milk exosomes synergistically inhibited MCF7 proliferation, migration and minimized tamoxifen adverse effects. Therefore, exosomes and hesperidin could be utilized as safe adjuvants/vehicles to tamoxifen during breast cancer chemotherapy.

A growing amount of evidence has indicated immune genes perform a crucial position in the development and progression of breast cancer microenvironment. The purpose of our study was to identify immunogenic prognostic marker and explore potential regulatory mechanisms for breast cancer. We identified the genes related to ImmuneScore using ESTIMATE algorithm and WGCNA analysis, and we identified the differentially expressed gene (DEGs). Then, Glia maturation factor γ (GMFG) was determined as a predictive factor by intersecting immune-related genes with DEGs and survival analysis. We found the expression of GMFG was lower in breast cancer tissues compared with normal breast tissues, which was further verified by immunohistochemical (IHC). Moreover, the decreased expression of GMFG was significantly related to the poor prognosis. Besides, the expression of GMFG was related to the age, ER status, PR status, HER2 status and tumor size, which further suggested that the expression of GMFG was correlated with the subtype and the growth of tumor. The univariate and multivariate Cox regression analyses revealed that age, stage, the expression level of GMFG and radiotherapy were independent factors for predicting the prognosis of breast cancer patients. Subsequently, a prognostic model to predict the 3-year, 5-year and 10-year overall survival rate was developed based on the above four variables, and visualized as a nomogram. The values of area under the curve of the nomogram at 3-year, 5-year and 10-year were 0.897, 0.873 and 0.922, respectively, which was higher than stage in prognostic accuracy. In addition, we also found that GMFG expression level was correlated with sensitivity of some breast cancer chemotherapy drugs. Furthermore, the results of GSEA indicated immune-related pathways were mainly enriched in GMFG-high-expression group. CIBERSORT analysis for the proportion of tumor-infiltrating immune cells (TIICs) suggested that expression of GMFG was positively association with multiple kinds T-cell in BC. Among them, CD8+ T cells had the strongest correlation with GMFG expression, which revealed that GMFG might has an antitumor effect by increasing the infiltration of CD8+ T cells in breast cancer. Accordingly, GMFG has the potential to become a novel immune biomarker for the diagnosis and treatment of breast cancer.

Objective. Comparison of the cardioprotective efficacy of valsartan/sacubitril and candesartan in women with heart failure (HF) and an initially reduced left ventricular ejection fraction receiving breast cancer chemotherapy.Material and methods. A prospective study included 112 women aged 53 to 65 years with systolic heart failure, who received surgical treatment for breast cancer followed by adjuvant polychemotherapy according to the FAC scheme (fluorouracil + doxorubicin + cyclophosphamide) - 6 cycles with intervals between 21 days of administration. After randomization, HF therapy with nebivolol, eplerenone, and valsartan/sacubitril (n = 55) or candesartan (n = 57) was performed. A general clinical laboratory study, electrocardiography, daily Holter monitoring of an electrocardiogram, echocardiography, a 6-minute walk test, quality of life assessment were performed initially and repeatedly after 1, 3, and 6 chemotherapy courses.Results. Both groups showed a tendency to troponin I level increase and a significant decrease in the concentration of N-terminal prohormone of brain natriuretic peptide. Only the valsartan/sacubitril group showed a statistically significant increase in the 6-minute walk distance, suppression of ventricular cardiac arrhythmias, improved indicators of systolic function of the left ventricle and quality of life when the Minnesota questionnaire was used.Conclusion. The first randomized trial of valsartan/sacubitril showed superiority compared to candesartan in the treatment of heart failure in women with breast cancer, who received adjuvant chemotherapy, which included anthracycline antibiotic, doxorubicin.

Tamoxifen (TAM) is used in breast cancer chemotherapy since its approval by the Food and Drug Administration in 1977. However, TAM therapy is accompanied with hepatotoxicity - a source of worry to clinicians. Oxidative stress and inflammation are the major implicated mechanisms contributing to TAM hepatotoxicity. In this study, we explored whether zinc (Zn) supplementation could prevent TAM-induced hepatotoxicity in female Wistar rats. Rats were subjected to oral pretreatment of Zn (100 mg/kg body weight (b.w.)/day) for 14 days against hepatic toxicity induced by single intraperitoneal administration of TAM (50 mg/kg b.w.) on day 13. TAM markedly elevated serum liver enzymes, whereas total protein and albumin considerably reduced. TAM caused prominent depletion of hepatic-reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity. Also, TAM significantly increased malondialdehyde (MDA) level. Further, it raised liver levels of tumor necrosis factor-α (TNF-α), interleukin-1β, (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by the liver histopathological alterations. The mechanistic inflammatory expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-ĸB), and expression of caspase-3 protein prominently increased. Zinc supplementation significantly modulated serum liver function markers, antioxidant enzymes, and GSH and MDA levels. Zinc downregulated the expression of cytokines, NO, iNOS, NF-ĸB and caspase-3, and ameliorated histopathological changes. Zinc protects against TAM-induced hepatotoxicity; it may serve as an adjuvant supplement for female patients undergoing TAM chemotherapy.

Purpose Discrepancies exist between healthcare provider and patient perceptions surrounding breast cancer treatment. Significant treatment changes in the last 10 years have made re-evaluation of these perceptions necessary. Methods Physicians and nurses involved in breast cancer treatment, and patients who had received breast cancer chemotherapy (past 5 years), were questioned using an Internet survey. Participants ranked physical concerns (treatment side effects), psychological concerns, priorities for treatment selection, and side effects to be avoided during treatment. Patients were asked about desired treatment information/information sources. Rankings were calculated using the mean value of scores. Spearman’s rank correlation was used to determine the concordance of rankings among groups. Results Survey respondents included 207 patients, 185 physicians, and 150 nurses. Patients and nurses similarly ranked distressing physical concerns; physician rankings differed. Quality of life (QoL) and treatment response ranked high with physicians and patients when considering future treatment; nurses prioritized QoL. All three groups generally agreed on ranking of psychological concerns experienced during chemotherapy, explanation of treatment options, and how treatment decisions were made, although more patients thought treatment decisions should be made independently. Healthcare providers reported providing explanations of treatment side effects and information on physical/psychological support options while patients felt both were lacking. Concordance was calculated as 0.47 (patient–physician), 0.83 (patient–nurse), and 0.76 (physician–nurse). Patients desired additional information, preferring healthcare providers as the source. Conclusions Specific areas for improvement in breast cancer patient care were identified; programs should be implemented to address unmet needs and improve treatment in these areas. Electronic supplementary material The online version of this article (10.1007/s00520-019-05029-z) contains supplementary material, which is available to authorized users.

Background Drug resistance is one of the prime reasons of chemotherapy failure in breast cancer and is also an important factor affecting prognosis. Purpose In this study, we constructed a functional magnetic mesoporous silica-based nanocomposite (MMSN) for breast cancer chemotherapy/photodynamic therapy. Methods MMSN was characterized by scanning electron microscopy and transmission electron microscopy to observe the morphology. The size distribution and zeta potential of the MSNs were determined using Malvern Particle Size Analyzer. Anti-tumor activity in vitro was investigated by CCK-8 assay, flow cytometry and transwell experiment, and the anti-tumor activity in vivo was probed into by magnetic targeting, toxicity, and antitumor effects in breast cancer-bearing BABL/c nude mice. Results The results showed that the release of doxorubicin in the nanocomposites was pH sensitive, and the cumulative release rate reached 80.53% at 60 h under acidic conditions. The nanocomposites had a high cellular uptake ability in MCF-7/ADR cells, and the IC50 value of the nanocomposites on MCF-7/ADR cells was 4.23 μg/mL, much smaller than that of free DOX (363.2 μg/mL). The nanocomposites could effectively reverse resistance and induce apoptosis of MCF-7/ADR cells. The blood biochemistry parameters and H&E staining results showed no serious adverse effects after treatment with the nanocomposites. Prussian blue staining showed that the nanocomposites were able to target tumor tissues in tumor-bearing mice under a magnetic field. The combined chemical/photodynamic therapy significantly inhibited tumor growth in vivo. Conclusion Nanocomposites with magnetic and pH dual-responsive performance has shown a promising platform for enhanced drug-resistant breast cancer treatment.

Women who inherit a BRCA1 or BRCA2 mutation have an increased risk of breast cancer. Preliminary evidence suggests they may also have defects in bone marrow function. To test this hypothesis, we conducted a multicenter, retrospective, matched cohort study, comparing women with localized breast cancer requiring cytotoxic chemotherapy who carried an inherited BRCA1 or BRCA2 mutation to similar wild‐type patients treated between 1995 and 2017 and matched based on age, race, site, and chemotherapy regimen. The proportion who developed specific hematologic toxicities, timing of these toxicities, and patterns of blood count fluctuations over time were compared among BRCA1 carriers vs matched wild‐type patients and among BRCA2 carriers vs matched wild‐type patients. 88 BRCA1 carriers and 75 BRCA2 carriers were matched to 226 and 242 wild‐type patients, respectively. The proportions and timing of experiencing any grade or grade 3/4 cytopenias during chemotherapy were not significantly different for BRCA1 carriers or BRCA2 carriers vs matched wild‐type patients. Proportions requiring treatment modifications and time to first modification were also similar. Patterns of blood count fluctuations over time in mutation carriers mirrored those in wild‐type patients overall and by the most common regimens. Women with an inherited mutation in BRCA1 or BRCA2 experience similar frequency, severity, and timing of hematologic toxicities during curative intent breast cancer chemotherapy as matched wild‐type patients. Our findings suggest that BRCA1 or BRCA2 haploinsufficiency is sufficient for adequate bone marrow reserve in the face of short‐term repetitive hematopoietic stressors., In this multicenter, retrospective, matched cohort study, we investigated whether women with an inherited mutation in BRCA1 or BRCA2 experience more severe hematologic toxicities during curative intent chemotherapy for breast cancer than similar women without a mutation. We found that the frequency, severity, and timing of toxicities were similar in these two groups. This study is reassuring that women with an inherited mutation are able to tolerate the repetitive bone marrow stress of modern chemotherapy regimens with usual supportive care measures as well as those without a mutation.

Objective To investigate the effects of the Chinese herbal medicine Xiaoaiping to treat chemotherapy-induced side effects in breast cancer patients. Methods Ninety-three adult patients who attended our hospital and met the entry criteria from January 2016 to December 2017 were included. Patients were randomly divided into the control group (routine chemotherapy only) and the combined group (routine chemotherapy and Xiaoaiping). Demographic data and clinical variables were collected, and side effects including alopecia, nausea and vomiting, diarrhea, white blood cell (WBC) count, aspartate aminotransferase (AST) levels, and the quality of life were evaluated. Results Basic clinical characteristics were not different between the groups. There were significantly fewer patients with alopecia grade 3–4, but significantly more patients with alopecia grade 1–2, in the combined group compared with the control group. Disease-free time for alopecia was longer in the combined compared with the control group. Overall, the side effects were significantly more serious in the control compared with the combined group. Patients in the combined group had better quality of life than the control patients. Conclusion Xiaoaiping can improve alopecia, nausea and vomiting, and diarrhea symptoms, WBC count, AST levels, and the quality of life in breast cancer patients.

Background Nicotinamide N-methyltransferase (NNMT) is overexpressed in various human tumors and involved in the development and progression of several carcinomas. In breast cancer, NNMT was found to be overexpressed in several cell lines. However, the clinical relevance of NNMT in breast cancer is not yet clear. Methods NNMT expression in breast carcinoma was examined by immunohistochemistry, and then, its relationship with patient clinicopathological characteristics was analyzed. The effects of NNMT on chemoresistance in breast cancer cells were assessed by cell viability, colony formation, and apoptosis assay. The NNMT, SIRT1, p53, and acetyl-p53 proteins, which are involved in NNMT-related chemoresistance, were examined by Western blotting. The SIRT1 mRNA was examined by real-time PCR, and its activity was measured by using the SIRT1 deacetylase fluorometric reagent kit. Results NNMT expression was significantly higher (53.9%) in breast carcinoma than in paracancerous tissues (10.0%) and breast hyperplasia (13.3%). A high level of NNMT expression correlated with poor survival and chemotherapy response in breast cancer patients who received chemotherapy. Ectopic overexpression of NNMT significantly inhibited the apoptotic cell death and suppression of colony formation induced by adriamycin and paclitaxel. Mechanistic studies revealed that NNMT overexpression increased SIRT1 expression and promoted its activity. Either inhibition of SIRT1 by EX527 or knockdown of SIRT1 by siRNA could reverse NNMT-mediated resistance to adriamycin and paclitaxel, which suggests that SIRT1 plays a critical role in NNMT-related chemoresistance in breast cancer. Conclusions The results of this study demonstrate a novel correlation between the NNMT expression level and patient survival, suggesting that NNMT has the potential to become a new prognostic biomarker to predict the treatment outcomes of the clinical chemotherapy in breast cancer. Moreover, targeting NNMT or downstream SIRT1 may represent a new therapeutic approach to improve the efficacy of breast cancer chemotherapy. Electronic supplementary material The online version of this article (10.1186/s13058-019-1150-z) contains supplementary material, which is available to authorized users.

Doxorubicin (Dox) is a first-line drug for breast cancer chemotherapy. However, with the prolongation of chemotherapy cycle, breast cancer cells are increasingly tempt to resist Dox, and meanwhile, high cumulative dose of Dox brings enhancing toxic side effects, and these effects may lead to chemotherapy failure. Hence, it is necessary to search an agent in combination medication with Dox, which can not only enhance the chemosensitivity of Dox but also reduce the toxic side effects. Tanshinone IIA (Tan IIA) is reported to have antitumor activity in addition to its cardiovascular protective effects. We employed human breast cancer MCF-7 and MCF-7/dox cells in order to assess whether Tan IIA might perform such function. Our in vitro studies showed that Tan IIA could enhance the sensitivity of breast cancer cells to Dox through inhibiting the PTEN/AKT pathway and downregulating the expression of efflux ABC transporters including P-gp, BCRP, and MRP1. In addition, our in vivo studies showed Tan IIA enhanced the chemotherapeutic effect of Dox against breast cancer while reducing its toxic side effects including weight loss, myelosuppression, cardiotoxicity, and nephrotoxicity. Therefore, Tan IIA could be used as a novel agent combined with Dox in breast cancer therapy.

The organoantimony(V) derivative of salicylic acid (SalH2), {[Ph3Sb(SalH)]2O} (SalOSbi) was synthesized and tested for its anti-proliferative activity. SalOSbi was characterized by melting point and FT-IR, 1H NMR, Uv–Vis spectroscopic techniques. Its crystal and molecular structure is also determined by single-crystal X-ray diffraction crystallography. The antiproliferative activity of SalOSbi against human breast cancer cells: MCF-7 (Hormone Dependent (HD)) and MDA-MB-231 (Hormon Independent (HI) is congener or better than that of cisplatin. However SalOSbi is less toxic (by 7-fold) against human lung embryonic fibroblast cells (MRC-5), than cisplatin. Micronucleus assay shows that SalOSbi demonstrates similar in vitro genotoxicity with cisplatin against MRC-5 cells. The apoptotic type of cells death, caused by SalOSbi, was studied by cell cycle arrest and permeabilization of the mitochondrial membrane test. Electronic spectroscopic data confirm strong covalent binding of SalOSbi with DNA, through N(purine or pyrimidine)-M bonds in a similar manner to cisplatin. No inhibitory interaction with lipoxygenase (LOX) has been detected suggesting the non-involvement of the mitochondrial apoptotic pathway.

Background: Obesity is an established risk factor for developing breast cancer and is also a negative prognostic indicator for higher recurrence risk.1 Adjuvant chemotherapy reduces the likelihood of metastatic recurrence and improves disease-free and overall survival.2 However, the practice of optimal dosing of adjuvant breast cancer chemotherapy amongst obese patients remains contentious with concerns regarding excessive toxicity if obese patients are dosed based on actual body weight (ABW).2-4 A 2014 study reported that obese patients were five times more likely to have dose reductions in cycle 1 than non-obese patients.5 Inadequate dosing amongst obese breast cancer patients may have deleterious implications on ultimate prognosis.2-4 This study aimed to investigate whether chemotherapy dosing using ABW in obese breast cancer patients is associated with comparable incidences of toxicity. Methods: A retrospective cross-sectional study was conducted amongst 257 patients (aged ≥18) treated in the adjuvant setting with doxorubicin-cyclophosphamide-paclitaxel (AC-P) or docetaxel-cyclophosphamide (TC) with/without trastuzumab between 2014 and 2017. Obesity was classified as a body mass index (BMI) of ≥30, with morbid obesity defined as a BMI≥35. Chemotherapy dosing based on body surface area calculated using ABW was considered the standard protocol with any variations from this dosing method for cycle 1 being recorded. Subsequent dose adjustments were also noted. The primary outcome was tolerability of chemotherapy regimens dosed using ABW with outcome measures of toxicity defined as the incidence of febrile neutropaenia, the incidence of grade 3 or 4 non-haematological toxicities and the number of hospitalisations during the treatment course. Results: 257 patients were eligible (1 male, 256 females). Median age was 55 (range, 31-78). AC-P was the most commonly used regimen (48.6%), followed by TC (40.1%). Obesity and morbid obesity were noted amongst 17.9% and 15.6% of patients respectively; with 63.8% with a BMI≥25. Chemotherapy dosing was largely based on ABW, with only 4.3% of patients dosed based on ABW or had their dosing body surface area capped at 2.0m2. In patients with a BMI≥25, 25% had febrile neutropaenia compared to 21.8% in those with normal BMI (p=0.58). Incidence of febrile neutropaenia during treatment by BMI – underweight: 33.3% (p=0.61); normal: 24.1%; overweight: 24.4% (p=0.97); obese: 17.4% (p=0.37); morbidly obese: 25%(p=0.92). Grade 3-4 non-haematological toxicities had comparable incidences between the normal BMI group as opposed to the overweight/obese group (23.0% vs 18.9% respectively, p=0.44). Hospitalisations by BMI - underweight: 50% (p=0.85); normal BMI: 46%; overweight: 42.3% (p=0.64); obese: 54.3%(p=0.36); morbidly obese: 57.5%(p=0.23). Conclusion: This study demonstrates that obese breast cancer patients do not experience higher toxicities when their adjuvant chemotherapy is dosed based on ABW. This supports current guidelines for dosing amongst obese patients. Citation Format: Tam LL, Mcguigan B, Connor A, Allan S, Sanmugarajah J. Exploring the real-life incidence of toxicities amongst obese breast cancer patients receiving adjuvant chemotherapy dosed based on absolute body weight [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-06.

Most women in reproductive age diagnosed with breast cancer receive (neo)adjuvant chemotherapy. Fertility preservation is part of the standard of care for these young women. Patients and methods We report preliminary results of a prospective multicentric cohort evaluating ovarian reserve during and after chemotherapy and fertility preservation in young (≤ 38 years old) in women aged ≤ 38 years, treated for a breast cancer with (neo)adjuvant anthracyclins and taxanes based chemotherapy, between July 2011 and December 2016. Fertility preservation was offered in patients (pts) who received adjuvant chemotherapy. The median duration of follow up was 2,6 years (4 months-5,3 years). The aim of this study was to evaluate the ovarian reserve assessed by antimullerian hormone and antral follicular count. The incidence of amenorrhea (defined by absence of menses ≥ 3 months), ovarian failure (absence of menses ≥ 12 months), chemotherapy induced menopause (absence of menses ≥ 24 months) was collected. Results One hundred and thirty-two pts were included in 10 centers. Data are available for 127 pts. For 4 pts, the scheduled chemotherapy was not received. One pt withdrew her consent. Chemotherapy was neoadjuvant for 43 pts and adjuvant for the 84 others. Fifty-eight asked for fertility preservation and received ovarian stimulation (all in adjuvant setting). Median age was 32 years (23-37). Eighty pts had a previous pregnancy. Three of them remained nulliparous. Among the 77 others, 36 had 1 child, 31 had 2 children and 10 pts 3 or more children respectively. At the time of diagnosis, 90% had regular menses and 75% had a contraception. The median initial antral follicular count was 21.5 (Min 1- Max 100). The AMH level significantly decreased during chemotherapy with no secondary return to baseline value over the first 9 months after end of treatment: median of 20.9 pmol/l (0.5-223) before chemotherapy, 12,8 (0,5-120) at the second cycle of chemotherapy (C2), 3 (0,5-20) at C4, 0,5 (0,5-4,4) at C6, 0,5 (0,5-25,1) 3 months after the end of chemotherapy (M3), 0,6 (0,5-29) at M6, and 3 (0,5-29,8) at M9. At last follow-up, 46% of pts experienced amenorrhea, 7% an ovarian failure and 3% a chemo-induced menopause. The highest incidence of amenorrhea (61%) was at M3. At M12, 7% of pts remained amenorrhoeic. The AMH initial level was not significantly lower in pts who experienced amenorrhea compared to those who did not (25.5 versus 35.1, p = 0,087). Ovarian stimulation and BRCA status did not impact risk of amenorrhea. At 2 years, overall survival rate was 96% and progression free survival rate was 90% (6 deaths and 18 progression events). Conclusion (Neo)adjuvant sequential breast cancer chemotherapy is associated with a decrease of AMH level and amenorrhea. Our results suggest a significant risk of premature ovarian failure. Fertility preservation has to be proposed to these young patients. Citation Format: Mailliez A, Pigny P, Bogart E, Diomande S, Jeazet Tiotsia H, Bonneterre J, Le Deley MC, Decanter C. Systematic evaluation of ovarian reserve in young breast cancer patients treated by sequential chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-06.

Breast cancer has developed to become the leading type of cancer in females. For this study, 80 women were examined after chemotherapy for breast cancer and compared to 80 healthy age-matched women. This cross-sectional study comprised a dental examination with number of teeth, caries frequency (DMFT) and the presence of periodontal diseases (PSI). With the help of X-rays (OPG), the number of root canal fillings and apical lesions (LEO/LPO) were recorded. Furthermore, the education level, body mass index (BMI), smoking habits and general health conditions were recorded. All women completed questionnaires on oral health-related quality of life (OHIP-G14) and general well-being (HADS-D). To assess the influence of cancer therapy on oral health parameters, appropriate generalized linear models were fitted with disease status as main explanatory variable, adjusting for age and education. For OHIP and HADS, we additionally adjusted for number of missing teeth. The examined 160 women showed a comparable mean age (60.4 years) and an average BMI of 24.6. Cancer patients showed a higher risk for missing teeth (p