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Background: BRCA1 and BRCA2 play a central role in DNA repair. Therefore, patients harbouring germline (g) BRCA1/2 mutations (m) treated with chemotherapy might be at higher risk of haematological toxicities., Methods: Patients from German Breast Group (GBG) and Arbeitsgemeinschaft Gynäkologische Onkologie-breast group studies with early triple-negative breast cancer (TNBC) and known gBRCA1/2m status treated with anthracycline-taxane-based neoadjuvant chemotherapy were analysed. Primary objective was the rate of neutropenia grade (G)III-IV in cycle 1 (C1). Secondary objectives included effects on overall and other haematological toxicities GIII-IV in C1, cumulative haematological toxicity across all cycles, relative total dose intensity, and granulocyte-colony stimulating factor prophylaxis. Haematological toxicities under taxanes, carboplatin, and cyclophosphamide were explored., Results: Two hundred nine of 1171 (17.8%) evaluated patients had gBRCA1/2m. In C1, 37.4% gBRCA1/2m versus 35.7% wild-type patients had neutropenia GIII-IV (P = 0.683). For C1, gBRCA1/2m predicted neither for neutropenia GIII-IV (odds ratio [OR]: 1.26, 95% confidence intervals [CI]: 0.87-1.82, P = 0.226) nor for other haematological toxicities GIII-IV (OR: 0.91, 95% CI: 0.64-1.31, P = 0.625) in multivariable regression models. Analyses of cumulative toxicities across all cycles yielded similar results except thrombocytopaenia GIII-IV, which was increased in gBRCA1m patients. In patients treated with taxanes, the rate of haematological toxicities GIII-IV was higher in gBRCA1/2m compared with wild-type (59.5% versus 43.1%; p < 0.001). No difference was seen under cyclophosphamide or platinum-containing chemotherapies., Conclusions: gBRCA1/2m was not associated with higher risk of overall severe haematological toxicities in the first cycle or cumulatively across all cycles under standard chemotherapy for TNBC. Under taxane, patients with gBRCA1/2m might have a higher risk of haematological toxicities GIII-IV, requiring further research., Competing Interests: Conflict of interest statement The authors declare the following conflicts of interest: A.S. reports receiving grants from Celgene, Roche, AbbVie; personal fees from Roche, AstraZeneca, Celgene, Roche, Pfizer, Novartis, MSD, Tesaro, Lilly, and others from Roche, outside the submitted work; C.H. reports receiving personal fees from Roche, Novartis, Lilliy, MSD, Astra Zeneca, and Pfizer; C.J. reports personal fees from Roche, AsraZeneca, Celgene, Pfizer, Novartis, and Amgen; F.J.C. reports receiving personal fees from AstraZeneca; receiving grants from GRAIL, others from Qiagen and Ambry Genetics, outside the submitted work; H.T. reports receiving personal fees from Novartis, Pfizer, AstraZeneca, Roche, Eisai, and Lilly, outside the submitted work; J.H. reports receiving grants and personal fees from Novartis, personal fees from Lilly, Astra Zeneca, Eisai, MSD, and Abbvie, personal fees and other from Pfizer and Roche, other from Daichii; receiving grants, personal fees and other from Celgene; receiving grants and personal fees from Hexal, outside the submitted work; J.U.B. reports receiving personal fees from AMGEN, ASTRA Zeneca, Novartis, Pfizer, Roche, SonoScape, and Sysmex, outside the submitted work; K.L. reports personal fees and non-financial support from Roche, Lilly, personal fees from Novartis and Genomic Health, outside the submitted work; K.R. reports personal fees from AstraZeneca, Tesaro and Pfizer, outside the submitted work; M.U. reports personal fees and non-financial support from Abbvie, Amgen GmbH, Eisai GmbH, Daiji Sankyo, Celgene GmbH, MSD Merck, Mundipharma, Roche Pharma AG, Odonate, TEVA Pharmaceuticals Ind Ltd., Sanofi Aventis Deutschland GmbH, Pfizer GmbH, Astra Zeneca and Lilly Int., Novartis, Clovis Oncology, and Myriad Genetics; personal fees from BMS, Lilly Deutschland, PUMA Biotechnology, Pierre Fabre, outside the submitted work; P.A.F. reports receiving personal fees from Novartis, Lilly, Pierre Fabre, and Seattle Genetics, Roche, Pfizer, Daiichi-Sankyo, Astra Zeneca, Eisai, Merck Sharp & Dohme; grants from Biontech, Cepheid. R.S. reports receiving grants from Cologne Furtune; S.L. reports receiving grants and other from AstraZeneca, Daiichi-Sankyo, Roche, Pfizer, Novartis, Abbvie, Amgen and Celgene during the conduct of the study; grants and non-financial support from Immunomedics; other from Seattle Genetics, PriME/Medscape, Lilly, Samsung, Eirgenix, BMS, Puma, MSD; personal fees from Chugai; grants from Teva and Vifor; outside the submitted work; In addition, S.L. has a patent EP14153692.0 pending. T.L. reports non-financial support from Pharma Mar, Celgene and Daiichi-Sankyo; personal fees and non-financial support from MSD, Pfizer, Roche, Clovis; personal fees from Amgen, Novartis, Teva, Tesaro, outside the submitted work; V.M. reports speaker honoraria from Amgen, Astra Zeneca, Celgene, Roche, TEVA, and consultancy honoraria from Roche, Amgen, Tesaro and Myelo Therapeutic; No other potential conflict of interest relevant to this article was reported., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Whether a sequential or concurrent regimen of anthracyclines and taxanes is superior for breast cancer is controversial. We compared the efficacy of two regimens in patients with operable breast cancer based on all relevant published data of phase III randomized controlled trials., Methods: A comprehensive literature search on PubMed, Web of Science, Embase, ScienceDirect, Google Scholar, and ClinicalTrials.gov databases was performed up to May 2020. Meta-analysis was performed to evaluate the different efficacy on disease-free survival (DFS) and overall survival (OS) for the two chemotherapy regimens. Subgroup analyses were further carried out in terms of node status and anthracycline selection., Results: Compared to the concurrent regimen, the sequential regimen did not improve the DFS or OS in the population studied. Subgroup analysis showed that in node-positive patients, the sequential regimen had better DFS, but not OS, than the concurrent regimen. In sequential regimen, patients who received doxorubicin and taxanes had improved DFS and OS than patients who were administered epirubicin and taxanes. Furthermore, for patients who received doxorubicin and taxanes, compared to the sequential regimen, fewer cycles (4 cycles) of concurrent treatment resulted in a worse DFS and OS, which can be rescued by more cycles (6 cycles)., Conclusions: The sequential regimen of anthracyclines and taxanes for patients with operable breast cancer did not yield a significant benefit in DFS or OS over the concurrent regimen. The sequential regimen, however, provided a better DFS than concurrent regimen for node-positive patients. Interestingly, further subgroup analysis showed that for node-positive patients who were given doxorubicin and taxanes, more cycles (6 cycles) of the concurrent regimen may rescue the efficacy for fewer cycles (4 cycles).

Purpose: We conducted a double-randomised phase III trial to evaluate a concomitant taxane-anthracycline regimen in node-positive breast cancer and the efficacy of trastuzumab in the human epidermal growth factor receptor 2 (HER2)-positive subpopulation., Methods: A total of 3010 patients with node-positive breast cancer were randomly assigned to receive 6 cycles of 500 mg/m 2 of fluorouracil, 100 mg/m 2 of epirubicin and 500 mg/m 2 of cyclophosphamide (FEC) or 75 mg/m 2 of epirubicin and 75 mg/m 2 of docetaxel (ED). Patients with HER2-positive tumours were secondary randomly assigned to either trastuzumab or observation. The primary end-point was disease-free survival (DFS) in the two chemotherapy arms., Results: After a 115-month median follow-up, DFS was not significantly better in the ED arm (DFS: 70%, 95% confidence interval [CI]: 67-72) than in the FEC arm (DFS: 68%, 95% CI: 65-70; hazard ratio [HR] = 0.88, 95% CI: 0.77-1.01; p = 0.064). The OS was not different between FEC (OS: 80%, 95% CI: 78-83) and ED (OS: 81%, 95% CI: 79-83); HR = 0.97, 95% CI: 0.81-1.16; p = 0.729). ED appeared more toxic. In the 528 HER2-positive subset, there was trend for a higher DFS, in the intention-to-treat population, in the trastuzumab arm (DFS: 68%, 95% CI: 61-74) than in the observation arm (DFS: 60%, 95% CI: 54-66; HR = 0.77, 95% CI: 0.57-1.03; p = 0.079). In the per-protocol population, DFS was significantly higher in the trastuzumab arm (DFS: 70%, 95% CI: 63-76) than in the observation arm (DFS: 59%, 95% CI: 53-65; HR = 0.69, 95% CI: 0.51-0.94; p = 0.0156). The OS was not different between these 2 arms., Conclusion: This study did not show superiority of the concomitant anthracycline-taxane arm which was more toxic in high-risk node-positive breast cancer patients. Long-term results of the HER2-positive subpopulation are in line with those of the other adjuvant trastuzumab trials but quantitatively less pronounced mostly because of lack of power., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim To compare the effect of neoadjuvant chemotherapy based on taxane and/or anthracycline to the extent of an objective response in female patients with unresectable breast cancer with evaluation of the toxic profile of applied chemotherapy. Methods One hundred patients with histologically verified breast cancer, treated with neoadjuvant chemotherapy were divided into two groups: a study group A (50 patients), who had received 4 to 6 cycles of taxane-based chemotherapy, and control group B (50 patients), who had received 4 to 6 cycles of anthracyclines-based chemotherapy. Pathohistological response was evaluated after tumour excision and axillary resection at the end of chemotherapy and it was defined as pathologic complete (pCR), partial (pPR), or no response (pNR). Toxic effects were evaluated and quantified by the Common Terminology Criteria for Adverse Events v4.0. Results After neoadjuvant chemotherapy, 8% of patients in the group A achieved pCR, 54% achieved pPR, while 38% of patients had no tumour response to applied chemotherapy. In the group B pCR was achieved in 6%, pPR in 42% of patients, while 51% of patients were pNR to the administered chemotherapy. Significant reduction of tumour mass was achieved in the group of patients treated with taxanes: 20.00 (7.75-30.25) vs. 13.50 (6.00-25.00) mm (p=0.024). Toxicity of chemotherapy in group A and group B was within the limits of grade 2. Conclusion The addition of taxane to anthracycline-based neoadjuvant chemotherapy in patients with breast cancer resulted in a significant reduction in tumour mass compared to the group of patients treated with anthracyclines, but without increasing the overall side effects., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Opinion Statement: Anthracycline-based regimens have been an important treatment component for patients with breast cancer. As demonstrated in the last Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis, anthracycline-based regimens decrease breast cancer mortality by 20-30%. Anthracycline toxicities include the rare-but potential morbid-cardiotoxicity or leukemogenic effect, and the almost universal-but very distressing-alopecia. Due to potential toxicities, and large number of patients being exposed, several worldwide trials have re-examined the role of anthracycline-based regimens in the management of breast cancer. Current literature supports that anthracyclines are not required for all patients with breast cancer and should be avoided in those with high cardiac risk. Recent results from the ABC trials suggest that anthracyclines should not be spared for patients with triple negative breast cancer (regardless of axillary node involvement) or HER2-/ER+ with significant node involvement. Based on current literature, for HER2-negative patients with low-risk breast cancer, anthracyclines could be spared with regimens such as cyclophosphamide, methotrexate, and fluorouracil (CMF) or docetaxel and cyclophosphamide (TC). Patients with intermediate or high-risk breast cancer should be considered for anthracycline-based regimens based on other factors such as age, comorbidities, tumor grade, lymphovascular invasion, and genomic profiling. Patients with HER2-positive breast cancer with low risk could be treated with paclitaxel and trastuzumab. For the remaining patients with HER2 overexpression, while docetaxel, carboplatin, and trastuzumab (TCH) has demonstrated to improve disease-free survival (DFS), anthracycline-containing regimens should be discussed, especially for those with very high-risk breast cancer. Although several biomarkers, such as topoisomerase II (TOP2A) and chromosome 17 centromeric duplication (Ch17CEP) have been proposed to predict benefit from anthracycline regimens, further research is required to delineate their proper utility in the clinical setting.

Background: Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC). Hence, autophagy-related gene 5 (ATG5), an essential molecule involved in autophagy regulation, is presumably associated with recurrence of TNBC. This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival (DFS) of early-stage TNBC patients treated with anthracycline- and/or taxane-based chemotherapy., Methods: We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline- and/or taxane-based chemotherapy using the sequenom's MassARRAY system. Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients., Results: Three genotypes, AA, GA, and GG, were detected in the rs473543 of ATG5 gene. The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence (P = 0.024). Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543 (P = 0.034). In addition, after adjusting for clinical factors, multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS (hazard risk [HR], 1.73; 95% confidence interval [CI], 1.04-2.87; P = 0.034). In addition, DFS was shorter in node-negative patients with the presence of A allele (AA/GA) than in those with the absence of A allele (P = 0.027)., Conclusion: ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.

Background: Taxanes and anthracyclines are considered as fundamental drugs for the treatment of a broad range of cancers. They have several side effects, which may limit their usage. Drug-induced nail pigmentation (DHNP) has been reported as one of the most striking dermatological side effect of both taxanes and doxorubicin., Objective: This study aimed to evaluate and compare pigmentary side effects of taxanes and doxorubicin with the help of onychoscopy., Methods: Forty-one consecutive patients (30 women, 11 men) with a diagnosis of cancer (16 gastric cancer, 25 breast cancer) were prospectively enrolled in a period of six months. Patients were categorized according to the chemotherapy regimens they had been administered: docetaxel received group [docetaxel (60 mg/m 2 , day 1), cisplatin (60 mg/m 2 , day 1) and fluorouracil (500 mg/m 2 , days 1-5) every 3 weeks], paclitaxel received group [paclitaxel (80-175 mg/m 2 ) every 21 days with or without trastuzumab/zoledronic acid] and doxorubicin received group [doxorubicin 50-60 mg/m 2 and cyclophosphamide 600-750 mg/m 2 every 21 days]. All the patients were asked whether they had diabetes mellitus (DM) and peripheral neuropathy. At the 16 weeks of chemotherapy, for each patient, all fingernails and toenails were evaluated in clinical and dermoscopic examinations for nail pigmentation. Dermoscopic examination was performed using a videodermatoscope. Descriptive statistics were computed for means, standard deviations, and frequencies. Chi-square test or Fisher's exact tests were used for the statistical analysis, with a significance threshold of p < 0.05., Results: 34.1% of the patients (14/41) demonstrated clinical signs of nail pigmentation. Nail pigmentation was observed in 4 of 13 patients (30.8%), who had received doxorubicin; 10 of 28 patients (35.7%), who had received taxanes (docetaxel and paclitaxel). There was no statistically significant relationship between the nail pigmentation and the type of the chemotherapeutic regimen administered (Fisher's exact test, p = 1.000). In addition, no statistically significant results were observed between nail pigmentation and DM (Fisher's exact test, p = 0.393), and nail pigmentation and peripheral neuropathy (Fisher's exact test, p = 1.000)., Conclusions: DHNP may cause considerable distress to patients. Dermoscopy is a noninvasive imaging method that increases diagnostic accuracy of both pigmented and nonpigmented lesions. Typical dermoscopic features of DHNP consist of a homogeneous brownish-gray coloration of the background with thin, longitudinal, gray lines, which allow the examiner to clearly make the correct diagnosis. Further studies are needed to assess both clinical and dermoscopical findings of DHNP.

Along with anthracyclines, taxanes are the most active cytotoxics in breast cancer (BC). Balancing efficacy against toxicity in older patients with reduced physiological reserves and significant comorbidities is both important and difficult. This is especially so given the under-representation of elderly patients in major trials and a consequent lack of evidence for drug, dose and schedule. However, BC is frequent in elderly women, who are a growing proportion of the population. Careful consideration of their care is therefore imperative. Treatment that can cure or extend the duration and quality of life should not be restricted by age, but needs to be tailored to the circumstances of elderly patients. In adjuvant use, taxane toxicity in older women is greater than in their younger counterparts, limiting its sequential combination with anthracyclines for high-risk disease unless patients are in very good health. More frequently taxanes are used alone (weekly paclitaxel, three-weekly docetaxel) or combined with cytotoxics other than anthracyclines (e.g. docetaxel plus cyclophosphamide) to reduce cardiac risk, especially in HER-2-positive patients who may develop additional trastuzumab-related cardiac events. In elderly patients with metastases, weekly paclitaxel and three-weekly docetaxel are among the cornerstones of treatment, with generally acceptable toxicity. Three-weekly docetaxel at the approved dose of 100mg/m(2) is not appropriate for the elderly. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication but has been little studied in older BC patients. A head-to-head comparison with weekly paclitaxel favoured the solvent-free formulation for pathologic response, but those studied were a general adult population. Compared with early stage disease, choice of taxane and regimen in the metastatic setting relies even more on availability and preferences with regard to schedule, toxicity profile and cost, especially for recently developed formulations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Despite the advances that have taken place in the past decade, including the development of novel molecular targeted agents, cytotoxic chemotherapy remains the mainstay of cancer treatment. In breast cancer, anthracyclines and taxanes are the two main chemotherapeutic options used on a routine basis. Although effective, their usefulness is limited by the inevitable development of resistance, a lack of response to drug-induced cancer cell death. A large body of research has resulted in the characterization of a plethora of mechanisms involved in resistance; ATP-binding cassette transporter proteins, through their function in xenobiotic clearance, play an important role in resistance. We review here the current evidence for drug transporters as biomarkers and the benefit of adding drug transporter modulators to conventional chemotherapy.

Introduction. This study aims to investigate the efficacy and tolerability of the vinorelbine-based combination chemotherapy with either cisplatin or capecitabine in metastatic triple-negative breast cancer (mTNBC) pretreated with anthracycline and taxane. Material and methods. This is an open-labeled randomized prospective single-institute study, that included all patients who received chemotherapy for mTNBC in the period between 1st of July 2016 and 30th of June 2017 and were pretreated with anthracycline and taxane. Patients were randomized to either vinorelbine 25 mg/m² i.v. on days 1 and 8 plus oral capecitabine 1000 mg/m² twice daily, on days 1-14 (NX); or vinorelbine 25 mg/m² i.v. on days 1 and 8 plus cisplatin 75 mg/m² (NP), every 21 days. The primary endpoint was time to progression (TTP), whereas the secondary endpoints were objective response rate (ORR), safety, and overall survival (OS). Results. Median TTP was 9.9 months with NP vs. 8 months with NX, (p = 0.22). ORR was 40% with NP vs. 36% with NX, (p = 0.77). Median OS was 13 months with NP vs. 13.2 months with NX (p = 0.599). Both regimens demonstrated similar rates of grade = 3 vomiting and neutropenia. A higher incidence of thrombocytopenia, tinnitus, and kidney function alteration were reported with NP. A higher incidence of anorexia, diarrhea, mucositis, and hand-foot syndrome were reported with NX. Conclusions. Vinorelbine-based combination chemotherapy regimens with either cisplatin or capecitabine are active in the treatment of mTNBC pretreated with anthracycline and taxane with manageable toxicity profiles. Both regimens have comparable TTP, ORR, OS, and safety profiles. [ABSTRACT FROM AUTHOR]

Polychemotherapy combined with trastuzumab (T) or trastuzumab with pertuzumab (TP) is a standard preoperative systemic treatment in patients with HER2-positive breast cancer. In Poland T is reimbursed according to the Drug Prescription Program of Ministry of Health (MoH) for patients with primary breast tumors bigger than 1cm independently from nodal status, whereas TP is reimbursed for patients with tumors bigger than 2 cm with positive lymph node(s) or lack of hormonal receptors expression. The Drug Prescription Program does not indicate which polychemotherapy should be combined with anti-HER2 therapy. Therefore, one can choose between classical sequential treatment based on anthracycline and taxane combined with T or dual HER2 blockade (usually 4 × AC - 12 × paclitaxel/4 × docetaxel + T/TP), or docetaxel with carboplatin combined with trastuzumab (TCH) or with dual HER2 blockade (TCHP). According to the present guidelines of the National Comprehensive Cancer Network (NCCN), polychemotherapy without anthracycline is preferred, which is justified because of its lower toxicity, especially cardiotoxicity. Currently, a pathologically confirmed complete response (pCR) is usually the primary objective in clinical trials dedicated to preoperative systemic treatment in breast cancer. pCR became a surrogate of treatment effectiveness. That is why oncologists eagerly use polychemotherapy combined with dual HER2 blockade as preoperative treatment to increase the patient's chance to achieve pCR, sometimes even when the patient's risk of relapse is relatively small. The goal of this article is to review current evidence-based knowledge about the effectiveness and toxicity of polychemotherapy with or without anthracycline combined with trastuzumab or dual HER2 blockade used as preoperative treatment in HER2-positive breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: (Neo-)adjuvant chemotherapy for breast cancer is effective but has deleterious side effects on muscle tissue, resulting in reduced skeletal muscle mass, muscle function, and cardiorespiratory fitness. Various exercise regimens during cancer treatment have been shown to counteract some of these side effects. However, no study has compared the effect of high-intensity training versus low-to-moderate intensity training on muscle tissue cellular outcomes and physical function in patients with breast cancer during chemotherapy. Objective: The aim of this substudy within the Physical Training in Cancer (Phys-Can) consortium is to evaluate and compare the effects of high and low-to-moderate intensity exercise on muscle cellular outcomes, muscle function, and cardiorespiratory fitness in women with breast cancer undergoing (neo-)adjuvant chemotherapy. We further aim to investigate if the effects of chemotherapy including taxanes on muscles will be different from those of taxane-free chemotherapy. Methods: Eighty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to a combination of strength and endurance training, either at high intensity or at low-to-moderate intensity. Testing of muscle function and cardiorespiratory fitness and collection of muscle biopsies from the vastus lateralis muscle will be performed before the first cycle of chemotherapy (or after 1 week, when not possible) (T0), halfway through chemotherapy (T1), and after completion of chemotherapy (T2). It is estimated that approximately 50% of the participants will be willing to undergo muscle biopsies. To separate the effect of the treatment itself, a usual care group with no supervised training will also be included, and in this group, testing and collection of muscle biopsies will be performed at T0 and T2 only. Results: This study is funded by Active Against Cancer (Aktiv mot kreft) (May 2013) and the Norwegian Cancer Society (December 2018). Inclusion started in December 2016 and the last participant is expected to be recruited in December 2022. As of June 2022, we enrolled 38 (19 with biopsies) participants to the high-intensity training group, 36 (19 with biopsies) participants to the low-to-moderate intensity training group, and 17 (16 with biopsies) participants to the usual care group. Data analyses will start in fall 2022. The first results are expected to be published in spring 2024. Conclusions: This study will generate new knowledge about the effects of different training intensities for women with breast cancer during chemotherapy treatment. It will give further insight into how chemotherapy affects the muscle tissue and how physical training at different intensities may counteract the treatment side effects in muscles. The results of this study will inform the development and refinement of exercise programs that are effective and compatible with the multidisciplinary management of breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective observational study aims at highlighting the response to pertuzumab, trastuzumab and docetaxel treatment (THP), without using anthracycline, in patients with HER2-positive early breast cancer. We add evidence to the suitability of THP in real life to reach higher pathological complete response rates, with a good safety profile for patients. An exploratory analysis of the mutational status of PIK3CA was performed as well, and 21% mutated samples were identified, with overall higher pCR rates in PIK3CA mutant patients and, particularly, in those who were THP-treated. Our original results open the door to further studies focused on more in-depth analysis of the molecular and clinical features related to the response to anthracycline-free neoadjuvant treatment in HER2-positive early breast cancer patients. HER2 is considered one of the most traditional prognostic and predictive biomarkers in breast cancer. Literature data confirmed that the addition of pertuzumab to a standard neoadjuvant chemotherapy backbone (either with or without anthracyclines), in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), leads to a higher pathological complete response (pCR) rate, which is known to correlate with a better prognosis. In this retrospective analysis, 47 consecutive patients with HER2-positive EBC received sequential anthracyclines and taxanes plus trastuzumab (ATH) or pertuzumab, trastuzumab and docetaxel (THP). Despite the limited sample size, this monocentric experience highlights the efficacy (in terms of pCR) and safety of THP in the neoadjuvant setting of HER2-positive EBC as an anthracycline-free approach. Given the role of PIK3CA as a prognostic and therapeutic target in breast cancer, tumors were also analyzed to assess the PIK3CA mutational status. Thirty-eight out of forty-seven patients were evaluated, and PIK3CA variants were identified in 21% of tumor samples: overall, one mutation was detected in exon 4 (2.6%), two in exon 9 (5.3%) and four in exon 20 (10.5%). Of note, one sample showed concurrent mutations in exons 9 (codon 545) and 20 (codon 1047). Among patients reaching pCR (n = 13), 38.5% were PIK3CA mutants; on the other hand, among those lacking pCR (n = 25), just 12% showed PIK3CA variants. Regarding THP-treated mutant patients (n = 5), 80% reached pCR (three hormone-receptor-negative, one hormone-receptor-positive). Interestingly, the only patient not achieving pCR had a tumor with two co-occurring PIK3CA mutations. In conclusion, this study provides new evidence about the efficacy and good safety profile of THP, compared to the ATH regimen, as an anthracycline-free neoadjuvant treatment of HER2-positive EBC. Further studies on larger/multicentric cohorts are planned for more in-depth analysis to confirm our molecular and clinical results. [ABSTRACT FROM AUTHOR]

What is known and Objective: Compared with other molecular subtypes, hormone receptor‐positive breast cancer often shows worse neoadjuvant chemotherapy efficacy. This study aims to explore the relationship between the oestrogen receptor (ER)‐related genes carbonic anhydrase 12 (CA12) and trefoil factor 3 (TFF3) and their predictive value of neoadjuvant chemotherapy for breast cancer. Methods: We investigated the relationships between CA12, TFF3 and ER status and their predictive value of anthracycline‐taxane neoadjuvant chemotherapy in 115 female breast cancer patients via real‐time polymerase chain reaction (RT‐PCR) and 4 GEO datasets: GSE41998, GSE25065, GSE20194 and GSE20271. Then, the effects of CA12 and TFF3 on the chemotherapy drugs doxorubicin and docetaxel were verified in vitro in the breast cancer cell lines MCF‐7 and BT474. Results and Discussion: The GEO datasets and RT‐PCR results showed that the relative expression of both CA12 and TFF3 was higher in oestrogen receptor‐positive samples compared with the other samples (p < 0.05). CA12 was significantly correlated with TFF3 (p < 0.05). In MCF‐7 cells, inhibition of TFF3 induced downregulation of CA12 and ESR1 (p < 0.05) at both the mRNA and the protein levels, while inhibition of CA12 also downregulated TFF3 and ESR1 (p < 0.05). In BT474 cells, inhibition of TFF3 downregulated CA12 and ESR1 (p < 0.05) at both the mRNA and the protein levels, while inhibition of CA12 led to slight upregulation of TFF3 and ESR1 (p > 0.05). Moreover, GEO datasets and RT‐PCR results showed that CA12 and TFF3 were more highly expressed in nonpathological complete response (non‐pCR) samples than in pCR samples (p < 0.05). Cell viability assays of MCF‐7 and BT474 cells showed that inhibiting CA12 and TFF3 could enhance sensitivity to doxorubicin and docetaxel (p < 0.05). What is new and Conclusion: CA12 and TFF3 were correlated with each other, and their high expression might explain the worse efficacy of neoadjuvant chemotherapy in oestrogen receptor‐positive breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Despite great success as a targeted breast cancer therapy, trastuzumab use may be complicated by heart failure and loss of left ventricular contractile function. This review summarizes the risk factors, imaging, and prevention of cardiotoxicity associated with trastuzumab and other HER2-targeted therapies. Findings: Cardiovascular disease risk factors, advanced age, and previous anthracycline treatment predispose to trastuzumab-induced cardiotoxicity (TIC), with anthracycline exposure being the most significant risk factor. Cardiac biomarkers such as troponins and pro-BNP and imaging assessments such as echocardiogram before and during trastuzumab therapy may help in early identification of TIC. Initiation of beta-adrenergic antagonists and angiotensin converting enzyme inhibitors may prevent TIC. Cardiotoxicity rates of other HER2-targeted treatments, such as pertuzumab, T-DM1, lapatinib, neratinib, tucatinib, trastuzumab deruxtecan, and margetuximab, appear to be significantly lower as reported in the pivotal trials which led to their approval. Conclusions: Risk assessment for TIC should include cardiac imaging assessment and should incorporate prior anthracycline use, the strongest risk factor for TIC. Screening and prediction of cardiotoxicity, referral to a cardio-oncology specialist, and initiation of effective prophylactic therapy may all improve prognosis in patients receiving HER2-directed therapy. Beta blockers and ACE inhibitors appear to mitigate risk of TIC. Anthracycline-free regimens have been proven to be efficacious in early HER2-positive breast cancer and should now be considered the standard of care for early HER2-positive breast cancer. Newer HER2-directed therapies appear to have significantly lower cardiotoxicity compared to trastuzumab, but trials are needed in patients who have experienced TIC and patients with pre-existing cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Abstract Background Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the “Essence of the kidney is reflected on the hair”. Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction. Methods/design Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine. Discussion This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development. Trial registration Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.

Aim To compare the effect of neoadjuvant chemotherapy based on taxane and/or anthracycline to the extent of an objective response in female patients with unresectable breast cancer with evaluation of the toxic profile of applied chemotherapy. Methods One hundred patients with histologically verified breast cancer, treated with neoadjuvant chemotherapy were divided into two groups: a study group A (50 patients), who had received 4 to 6 cycles of taxane-based chemotherapy, and control group B (50 patients), who had received 4 to 6 cycles of anthracyclines-based chemotherapy. Pathohistological response was evaluated after tumour excision and axillary resection at the end of chemotherapy and it was defined as pathologic complete (pCR), partial (pPR), or no response (pNR). Toxic effects were evaluated and quantified by the Common Terminology Criteria for Adverse Events v4.0. Results After neoadjuvant chemotherapy, 8% of patients in the group A achieved pCR, 54% achieved pPR, while 38% of patients had no tumour response to applied chemotherapy. In the group B pCR was achieved in 6%, pPR in 42% of patients, while 51% of patients were pNR to the administered chemotherapy. Significant reduction of tumour mass was achieved in the group of patients treated with taxanes: 20.00 (7.75-30.25) vs. 13.50 (6.00-25.00) mm (p=0.024). Toxicity of chemotherapy in group A and group B was within the limits of grade 2. Conclusion The addition of taxane to anthracycline-based neoadjuvant chemotherapy in patients with breast cancer resulted in a significant reduction in tumour mass compared to the group of patients treated with anthracyclines, but without increasing the overall side effects.

Primary analysis of the phase III trial BG01-1323L demonstrated that utidelone plus capecitabine significantly improved progression-free survival (PFS) and overall response rate (ORR) versus capecitabine alone in heavily-pretreated patients with metastatic breast cancer (MBC). Here, we report the final overall survival (OS) analysis and updates of other endpoints. In total, 405 patients were randomised 2:1 to receive utidelone (30 mg/m2 IV daily, days 1-5, over 90 min) plus capecitabine (1000 mg/m2 orally b.i.d., days 1-14) or capecitabine alone (1250 mg/m2 orally b.i.d., days 1-14) every 21 days. The secondary endpoint, OS, was estimated using the Kaplan–Meier product-limit approach at a two-sided alpha level of 0.05 after the prespecified 310 death events had been reached. Exploratory analyses of the primary endpoint, PFS, and the secondary endpoint, ORR, were also done. Safety was analysed in patients who had at least one dose of study drug. At the final OS analysis, the median duration of follow-up was 19.6 months in the utidelone plus capecitabine group and 15.4 months in the capecitabine alone group. In the intention-to-treat population, 313 deaths had occurred at data cut-off, 203 of 270 patients in the combination group and 110 of 135 in the monotherapy group. Median OS in the combination group was 19.8 months compared with 16.0 months in the monotherapy group [hazard ratio (HR) = 0.75, 95% confidence intervals (CI) 0.59-0.94, P = 0.0142]. The updated analysis of PFS and ORR showed that the combination therapy remained superior to monotherapy. Safety results were similar to those previously reported with respect to incidence, severity and specificity. No late-emerging toxicities or new safety concerns occurred. For heavily-pretreated, anthracycline- and taxane-resistant MBC patients, utidelone plus capecitabine significantly improved OS versus capecitabine alone. These results support the use of utidelone plus capecitabine as a novel therapeutic regimen for patients with MBC. • The phase III study evaluated utidelone plus CAP versus CAP alone in patients with anthracycline- and taxane-refractory MBC. • In this final analysis of OS, utidelone plus CAP significantly improved OS compared with CAP alone. • No significant differences were observed in the safety profiles of the treatment groups. • Of note, utidelone caused only mild myelosuppression and no significant hepatic toxicity. • Although peripheral neuropathy was common, it was generally manageable and reversible with dose modifications. [ABSTRACT FROM AUTHOR]

Background. Nowadays there are no any standards of treatment for patients with locally advanced and metastatic breast cancer resistant to treatment with anthracyclines, taxanes and capecitabin. Ixabepilone has proved successful as a single agent for treatment of these patients. Methods. Eribulin was chosen as an alternative strategy. Efficacy criteria were overall and progression-free survival. Cost-effectiveness analysis is performed on the basis of published data and Markov modeling for 1.5 year time horizon. Results. Total expenditures for ixabepilone strategy were 18.2% less than those for eribulin treatment. Administration of ixabepilone instead of eribulin will allow treating additionally up to 222 patients per year. Price elasticity analysis revealed that total expenditures on ixabepilone will be 20% less than on eribulin treatment at a price of ixabepilone equal to 63 000 rubles per 45 mg vial and 21 691.23 rubles per 15 mg vial of ixabepilone. Conclusion. Ixabepilone as a single agent appeared to be economically reasonable as compared to eribulin in case of ineffective pretreatment with taxanes, anthracyclines and capecitabine.

Angiosarcoma is a subset of soft-tissue sarcomas with poor 5-year survival rate. Given its rarity, limited large cohort data is available for this disease. Therefore, the present study evaluated data from patients with angiosarcoma treated at a provincial Institution (BC Cancer) to determine potential modifiable predictors of survival. A retrospective review of patients across British Columbia (Canada) was conducted at the Sarcoma Outcome Unit of BC Cancer from January 1, 1969 to September 19, 2017. Cox proportional hazard models were used to calculate hazard ratios (HR) for the overall survival (OS) and progression free survival (PFS) of patients. A total of 145 patients with angiosarcoma were identified, of which 68 were metastatic/unresectable at presentation. Of the 145 patients included, 38 received chemotherapy, with 15 receiving taxane. A single patient received chemotherapy in a neoadjuvant setting. Of the resectable patients, 71 had first line surgery and 38 had curative-intent radiation during their treatment. Of the study cohort, 38 patients received prior radiation for an unrelated cancer and 4 patients had pre-existing chronic lymphedema. Resectable disease (HR, 0.22; P<0.01), first treatment with either surgery (HR, 0.08; P<0.01), radiation (HR, 0.19; P<0.01) or chemotherapy (HR, 0.22; P<0.01) were predictors of improved OS. First line surgery resulted in improved OS (HR, 0.36; P<0.01) and PFS (HR, 0.48; P<0.01). In addition, OS was positively impacted by the extent of surgery [complete (R0) vs. microscopic residual tumor (R1); HR, 0.26; P<0.01; R0 vs. macroscopic residual tumor (R2); HR, 0.08; P<0.01) resection. Extent of surgery and any radiation treatment were determined to be important predictors of OS. The results also revealed that patient outcome was improved following any treatment compared with supportive care alone. In conclusion, multidisciplinary care is critical for the treatment of patients diagnosed with angiosarcoma. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a highly aggressive disease and of poor prognosis. It is very important to identify novel biomarkers to predict therapeutic response and outcome of TNBC. We investigated the association between polymorphisms in PARP1 gene and clinicopathological characteristics or survival of 272 patients with stage I-III primary TNBC treated with anthracycline/taxane based adjuvant chemotherapy. We found that after adjusted by age, grade, tumor size, lymph node status and vascular invasion, rs7531668 TA genotype carriers had significantly better DFS rate than TT genotype carriers, the 5 y DFS was 79.3% and 69.2% (P = 0.046, HR 0.526 95% CI 0.280–0.990). In lymph node negative subgroup, DFS of rs6664761 CC genotype carriers was much better than TT genotype carriers (P = 0.016, HR 0.261 95% CI 0.088–0.778) and DFS of rs7531668 AA genotype carriers was shorter than TT genotype carriers (P = 0.015, HR 3.361 95% CI 1.259–8.969). In subgroup of age ≤ 50, rs6664761 TC genotype predicted favorable DFS than TT genotype (P = 0.042, HR 0.405 95% CI 0.170–0.967). Polymorphisms in PARP1 gene had no influence on treatment toxicities. After multivariate analysis, tumor size (P = 0.037, HR = 2.829, 95% CI: 1.063–7.525) and lymph node status (P < 0.001, HR = 9.943, 95% CI: 2.974–33.243) were demonstrated to be independent prognostic factors. Our results suggested that polymorphisms in PARP1 gene might predict the DFS of TNBC patients treated with anthracycline/taxane based adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Cognitive impairment is one of the most deleterious effects of chemotherapy treatment in cancer patients, and this problem sometimes remains even after chemotherapy ends. Common classes of chemotherapy-based regimens such as anthracyclines, taxanes, and platinum derivatives can induce both oxidative stress in the blood and in the brain, and these effects can be reproduced in neuronal and glia cell cultures. In rodent models, both the acute and repeated administration of doxorubicin or adriamycin (anthracyclines) or cisplatin impairs cognitive functions, as shown by their diminished performance in different learning and memory behavioural tasks. Administration of compounds with strong antioxidant effects such as N-acetylcysteine, gamma-glutamyl cysteine ethyl ester, polydatin, caffeic acid phenethyl ester, and 2-mercaptoethane sulfonate sodium (MESNA) counteract both oxidative stress and cognitive alterations induced by chemotherapeutic drugs. These antioxidant molecules provide the scientific basis to design clinical trials in patients with the aim of reducing the oxidative stress and cognitive alterations, among other probable central nervous system changes, elicited by chemotherapy in cancer patients. In particular, N-acetylcysteine and MESNA are currently used in clinical settings and are therefore attracting scientific attention.

This article represents data on economic evaluation of treatment with ixabepilone (Ixempra) as a single agent for patients with metastatic breast cancer with ineffective pretreatment with taxanes, anthracyclines and capecitabine. Two health technologies were evaluated: Ixabepilone as a single agent at the 1st day of a 21-day cycle of chemotherapy versus eribulin also as a single agent at the 1st and the 8th days of a 21-day cycle. Cost-effectiveness analysis is performed on the basis of published data and Markov modeling. As a result, ixabepilone as a single agent appeared to be economically reasonable as compared to eribulin as a single agent in case of ineffective pretreatment with taxanes, anthracyclines and capecitabine. Total expenditures for Ixabepilone strategy were 13.6% less than those for eribulin treatment. Furthermore, ixabepilone was found 16% more effective in terms of median progression-free survival, as compared to eribulin as a single agent. Sensitivity analysis has proved the results obtained in the main scenario. Price elasticity analysis revealed the equality of total expenditures on ixabepilone and eribulin treatment at a price of ixabepilone equal to 88 000 rubles per 45 mg vial and 30 298.87 rubles per 15 mg vial of ixabepilone.

Background: Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the "Essence of the kidney is reflected on the hair". Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction.Methods/design: Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine.Discussion: This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development.Trial Registration: Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy with anthracyclines/taxanes is considered as an effective treatment option for breast cancer. Adjuvant chemotherapeutic options with anthracyclines or taxanes have improved disease free survival and overall survival rates in early breast cancer. The study is aimed to compare the therapeutic efficacy of anthracyclines containing regimen and sequential administration of taxanes with anthracyclines regimen for NODE positive breast cancer patients and to assess the Health-Related Quality of Life (HRQOL) of treated patients. Methods: This prospective open label study involved 14 patients who were treated with 6 cycles of 5-Fluorouracil (500mg/m2), Doxorubicin (50mg/m2), Cyclophosphamide (500mg/m2) [FAC] and 10 patients with 6 cycles of FAC plus 4 cycles of Paclitaxel (225mg/m2) [PAC]. Paired sample T test was used to assess the disease-free survival and reoccurrence rate. Time to progression was assessed by Kaplan Meir analysis and independent sample T test was used for assessing all the HRQOL parameters. Results: The disease-free survival was evaluated between the baseline and after 2 months of the chemotherapy which showed significant difference (p<0.05) in the patients treated with FAC regimen. Further, significant difference (p<0.05) was also seen in the comparison of the first and end reports of chest x-ray during stage 3b. There was a significant improvement (p<0.05) in the quality of life in the patients treated with FAC with adjuvant Paclitaxel during the 3rd cycle. Conclusion: The study outcomes recommend that sequential administration of Paclitaxel with FAC can give more treatment benefit in stage 3 breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Standard adjuvant chemotherapy for HER2-negative breast cancer consists generally in an anthracycline and taxane-based regimen (A+T). The TC (docetaxel and cyclophosphamide) regimen arises as a potential alternative, although individual randomized controlled trials (RCTs) could not demonstrate the non-inferiority of TC over A+T. This is a systematic review and meta-analysis of RCTs comparing 6 cycles of TC versus sequential A+T in the adjuvant treatment of HER2-negative breast cancer.Methods: A systematic literature search was performed to identify RCTs comparing TC versus A+T. Disease-free survival (DFS) and overall survival (OS) were assessed. Subgroup analyses of DFS according to hormone receptor status, lymph node involvement, and menopausal status were performed. Hazard ratios (HRs) and 95% confidence intervals (CI) for DFS and OS were extracted from each trial, and a pooled analysis was conducted using the random-effect model. The Higgins' I-Squared Test was used to quantify heterogeneity.Results: Seven RCTs were included (12,741 patients). Overall, no difference was observed between TC and A+T in DFS (HR 1.08, 95% CI 0.96-1.20) and OS (HR 1.05; 95% CI 0.90-1.22). A trend favoring A+T was observed in hormone receptor-negative (HR 1.12, 95% CI 0.93-1.34) and N2 patients (HR 1.25; 95% CI 0.82-1.90). Emesis/vomiting, mucositis, thrombocytopenia and sensory neuropathy were significantly more frequent with A+T.Conclusion: As adjuvant treatment of HER2-negative breast cancer, sequential A+T regimen was associated with increased risk of toxicities and no clear survival benefit as compared to 6 cycles of TC. Higher-risk patients may benefit the most from A+T, whilst TC may be an efficacious and less toxic alternative for lower-risk patients. [ABSTRACT FROM AUTHOR]

Treatment of patients with metastatic breast cancer (BC) with a triple-negative phenotype represents the most difficult challenge for clinicians. The optimal chemotherapy regimens for triple-negative BC (TNBC) have not been determined for a long time. However, in the later periods were found molecular agents of application (6 subtypes of TNBC) for the specific therapeutic agent and were performed many studies and subunit analysis, examined appropriate drugs for TNBC. Cell lines of these subtypes have different anticancer drug sensitivity. The results of further studies of targeted drugs using as monotherapy or in combination with chemotherapy in patients with TNBC, in spite of molecular genetic evidence for their application, have fallen short of expectations, although have shown increase in progression-free survival and overall survival. The development of eribulin (nontaxane microtubule dynamics inhibitor) in 2010 significantly increased the possibility of therapy in patients with locally advanced and metastatic BC who had already received chronic treatment. According to the joint analysis of the randomized phase III EMBRACE trial and Study 301, which included data about 1864 patients, it was demonstrated that eribulin statistically significant improve overall survival compared with other drugs using as monotherapy in the general population and among patients with TNBC [statistically significant differences in overall survival was associated with the subgroup of TNBC in patients who had been treated with eribulin, in comparison with the control arm: 12.9 and 8.2 months, respectively (relative risk 0.74; 95% confidence interval, 0.60 to 0.92, p=0.006)]. This article deals with the own experience of successful and long-term eribulin application in young woman with TN metastatic BC who have had already received chronic treatment.

Background: Capecitabine monotherapy is usually used for advanced breast cancer (ABC) resistant to anthracycline and taxane, but there are still many other options too. Our meta-analysis assessed whether capecitabine monotherapy was superior or noninferior to the other regimens in ABC pretreated with anthracycline and taxane. Materials and Methods: PubMed databases and abstracts from the proceedings of American Society of Clinical Oncology and San Antonio Breast Cancer Symposium were searched for randomized controlled trials that compared capecitabine monotherapy with other regimens for ABC progression after anthracycline- and taxane-treatment. Hazard ratios (HRs) were used for progression-free survival (PFS) and overall survival (OS). Risk ratios (RRs) were used for overall response rate (ORR) and Grade 3–4 drug-related adverse events. All statistical analyses were conducted with RevMan 5.3 software, and statistical significance was defined as P < 0.05. Results: In total, 4671 patients from eight trials were included. Target therapy as treatment group was involved in four trials, and the other four trials were merely chemotherapy in treatment group. Our study indicated that capecitabine monotherapy was not superior but also noninferior to the other regimens in ORR (RR = 1.32−95% confidence interval [CI] 0.98–1.77, P = 0.07), PFS (HR = 1.03, 95% CI 0.85–1.25, P = 0.76), and OS (HR = 0.96, 95% CI 0.88–1.05, P = 0.40). Subgroup analysis showed that both the other chemotherapy regimens and target drugs failed to improve efficacy compared with capecitabine monotherapy, and target drugs could shorten PFS (HR = 1.22, 95% CI 1.06–1.39, P = 0.004). Incidences of Grade 3–4 hematology toxicity in other regimens group significantly increased compared with capecitabine monotherapy. Conclusions: Our meta-analysis demonstrated that capecitabine monotherapy could be the first choice for ABC pretreated with anthracycline and taxane due to its efficacy and low toxicity. [ABSTRACT FROM AUTHOR]

Background: Capecitabine monotherapy is usually used for advanced breast cancer (ABC) resistant to anthracycline and taxane, but there are still many other options too. Our meta-analysis assessed whether capecitabine monotherapy was superior or noninferior to the other regimens in ABC pretreated with anthracycline and taxane.Materials and Methods: PubMed databases and abstracts from the proceedings of American Society of Clinical Oncology and San Antonio Breast Cancer Symposium were searched for randomized controlled trials that compared capecitabine monotherapy with other regimens for ABC progression after anthracycline- and taxane-treatment. Hazard ratios (HRs) were used for progression-free survival (PFS) and overall survival (OS). Risk ratios (RRs) were used for overall response rate (ORR) and Grade 3-4 drug-related adverse events. All statistical analyses were conducted with RevMan 5.3 software, and statistical significance was defined as P < 0.05.Results: In total, 4671 patients from eight trials were included. Target therapy as treatment group was involved in four trials, and the other four trials were merely chemotherapy in treatment group. Our study indicated that capecitabine monotherapy was not superior but also noninferior to the other regimens in ORR (RR = 1.32-95% confidence interval [CI] 0.98-1.77, P = 0.07), PFS (HR = 1.03, 95% CI 0.85-1.25, P = 0.76), and OS (HR = 0.96, 95% CI 0.88-1.05, P = 0.40). Subgroup analysis showed that both the other chemotherapy regimens and target drugs failed to improve efficacy compared with capecitabine monotherapy, and target drugs could shorten PFS (HR = 1.22, 95% CI 1.06-1.39, P = 0.004). Incidences of Grade 3-4 hematology toxicity in other regimens group significantly increased compared with capecitabine monotherapy.Conclusions: Our meta-analysis demonstrated that capecitabine monotherapy could be the first choice for ABC pretreated with anthracycline and taxane due to its efficacy and low toxicity. [ABSTRACT FROM AUTHOR]

Abstract This study identified chemotherapeutic agents that up-regulate programmed cell death ligand-1 (PD-L1) and galectin-9 (Gal-9) in breast cancer cells. Immunohistochemical (IHC) staining was used to evaluate changes in PD-L1 and Gal-9 expression in the tumor tissue of triple-negative breast cancer (TNBC) patients who received anthracycline- and taxane-based neoadjuvant chemotherapy. To determine whether PD-L1 and Gal-9 expression changes were attributable directly to chemotherapeutics, MDA-MB-231 cells and HS578T cells were treated with different concentrations of anthracycline and taxane. Expression levels of PD-L1 and Gal-9 were evaluated and the activation status of NFκB in MDA-MB-231 and HS578T cells was determined to identify the PD-L1 and Gal-9 up-regulation mechanism. Three cases of increased PD-L1 expression and two of increased Gal-9 expression were observed among the TNBC patients. PD-L1 and Gal-9 expression were up-regulated by anthracycline and taxane in MDA-MB-231 cells, but not in HS578T cells. Increased nuclear levels of NFκB were observed in MDA-MB-231 cells treated with 0.5 μM epirubicin. Anthracycline and taxane up-regulated PD-L1 and Gal-9 expression in some subtypes of TNBC. This study provides useful reference data for clinical trials investigating combination treatments with immune checkpoint inhibitors and chemotherapy. [ABSTRACT FROM AUTHOR]

Cardiotoxic effects of chemotherapy and targeted drugs are ubiquitous and challenging in the field of oncology therapeutics. The broad spectrum of toxicities ranging from ischemic, hypertensive, cardiomyopathic, and arrhythmic complications can present as a significant challenge for clinicians treating cancer patients. If early diagnosis and intervention of cardiotoxic complications is missed, this can lead to delay or abrogation of planned treatment, which can potentially culminate to significant morbidity due to not only the cardiotoxic complications but also the progression of cancer. Hence, full knowledge of cardiovascular complications of chemotherapeutic agents, essential diagnostics tests to order, and appropriate management is paramount to oncologist, oncology pharmacists, and scientific clinical investigators. The aforementioned is particularly true in the current oncology era of plenteous early clinical trials studying several pathway/molecular-targeting agents with an increased cardiotoxic potential and the rapid expedited approval of those drugs by the FDA. Herein, we present a review discussing cardiotoxic effects of drugs and guidelines for management of the toxicities to assist the medical field in general managing patients with cancer. [ABSTRACT FROM AUTHOR]

The article deals with the results of the administration of new cytostatic - eribulin (Halaven). In EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) phase III clinical study, Halaven had been administrated to 6 patients (between 6 and 35 cycles), at that, partial tumor regression was observed in 3 patients and other 3 patients achieved stabilization. Median progression-free survival (PFS) was 15,3 months and median duration of response (DOR) was 13 months in eribulin group, in group of treatment of physician's choice - median PFS was 5,3 and median DOR was 3,3 months. This article demonstrates 3 clinical cases. The authors concluded that eribulin showed high effectiveness and meaningful improvement in overall survival, maintaining the high quality of life.

S-1 and irinotecan combination is attractive for breast cancer refractory to anthracyclines and taxanes. Patients with advanced human epidermal growth factor receptor 2 ( HER2)-negative breast cancer previously treated with anthracyclines and taxanes were eligible. Patients with brain metastases and homozygous for UGT1A1 *6 or *28 or compound heterozygous (* 6/ *28) were excluded. A dose-escalation design was chosen for the phase I portion (level 1: irinotecan 80 mg/m2 days 1-8 and S-1 80 mg/m2 days 1-14 every 3 weeks; level 2: irinotecan 100 mg/m2 and S-1 80 mg/m2). Study objectives included determination of the recommended dose for phase II, response rate, progression-free survival ( PFS), and safety. Pharmacokinetics and CD34+ circulating endothelial cells ( CECs) as pharmacodynamics were also analyzed. Thirty-seven patients were included. One patient at each level developed dose-limiting toxicities; therefore, level 2 was the recommended dose for phase II. Diarrhea was more common in patients possessing a *6 or *28 allele compared with wild-type homozygous patients (46% and 25%). Among 29 patients treated at level 2, PFS was longer for UGT1A1 wt/*6 and wt/*28 patients than for wt/ wt patients (12 vs. 8 months, P = 0.06). PFS was significantly longer in patients with a larger-than-median SN-38 area under the curve ( AUC) than in those with a smaller AUC ( P = 0.039). There was an association between clinical benefit and reduction in baseline CD34+ CECs by S-1 ( P = 0.047). The combination of irinotecan and S-1 is effective and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: To better predict the likelihood of response to chemotherapy, we have conducted a study comparing the gene expression patterns of primary tumours with their corresponding response to systemic chemotherapy in the metastatic setting.Methods: mRNA expression profiles of breast carcinomas of patients that later developed distant metastases were analyzed using supervised and non-supervised classification techniques to identify predictors of response to chemotherapy. The top differentially expressed genes between the responders and non-responders were identified and further explored. An independent dataset which was generated to predict response to neo-adjuvant CT was utilized for the purpose of validation. Response to chemotherapy was also correlated to the clinicopathologic characteristics, molecular subtypes, metastatic behavior and survival outcomes.Results: Anthracycline containing regimens were the most common first line treatment (58.4%), followed by non-anthracycline/non-taxane containing (25.8%) and taxane containing (15.7%) regimens. Response was achieved in 41.6% of the patients to the first line CT and in 21.8% to second line CT. Response was not found to be significantly correlated to tumour type, grade, lymph node status, ER and PR status. Patients with HER2+ tumours showed better response to anthracycline containing therapy (p: 0.002). Response to first and second line chemotherapy did not differ among gene expression based molecular subtypes (p: 0.236 and p: 0.20). Using supervised classification, a 14 gene response classifier was identified. This 14-gene predictor could successfully predict the likelihood of better response to first and second line CT (p: <.0001 and p: 0.761, respectively) in the training set. However, the predictive value of this gene set in data of response to neoadjuvant chemotherapy could not be validated.Conclusions: To our knowledge, this is the first study revealing the relation between gene expression profiles of the primary tumours and their chemotherapy responsiveness in the metastatic setting. In contrast to the findings for neoadjuvant chemotherapy treatment, there was no association of molecular subtype with response to chemotherapy in the metastatic setting. Using supervised classification, we identified a classifier of chemotherapy response; however, we could not validate this classifier using neoadjuvant response data.Trial Registration: Non applicable. Subjects were retrospectively registered. [ABSTRACT FROM AUTHOR]

The 3rd International Consensus Conference for Breast Cancer in Young Women (BCY3) took place in November 2016, in Lugano, Switzerland organized by the European School of Oncology (ESO) and the European Society of Medical Oncologists (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY2 with incorporation of new evidence to inform the guidelines, and areas of research priorities were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA). [ABSTRACT FROM AUTHOR]

Purpose The effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC. Methods We retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m 2 at baseline were considered obese, whereas those with a BMI <30 kg/m 2 were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure. Results Among 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42–13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47–15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10 −4 –0.81; p = 0.025). Conclusions Obese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity. [ABSTRACT FROM AUTHOR]

Anthracycline- or taxane-based regimens are commonly used in the treatment of breast cancer, often in the (neo)adjuvant and first-line metastatic settings. However, to date, there is no single accepted standard of care after failure of these cytotoxic agents. Following the promising results obtained in the Phase III EMBRACE study, eribulin mesylate was approved for the treatment of metastatic breast cancer patients after progression with anthracyclines and taxanes unless contraindications. This case report describes a chemo-pretreated woman with important pleural effusion, nodal, locoregional involvement from breast cancer who had a disease response after treatment with eribulin in second line. This case underlines how this well-tolerated monochemotherapy may be able to obtain a prolonged disease control and a good clinical outcome. [ABSTRACT FROM AUTHOR]

Anthracyclines are used in breast cancer both in early and advanced stages and their recommendation together with taxanes, either concurrently or sequentially, is debatable and individualized by phenotype. Circulating biomarkers have already been introduced in clinical practice for metastatic disease monitoring. We questioned whether it might be a role for these markers in neoadjuvant and adjuvant settings too and a general review was conducted. CK18 and CTC were found predictive for anthracycline related response in preoperative setting. Soluble E-cadherin is promising, a retrospective analysis showing a direct correlation with clinical response. CEA, CA 15-3 and HER2 ECD are not of interest for their predictive role. [ABSTRACT FROM AUTHOR]

Objectives Despite the survival benefit and acceptable tolerability of eribulin for advanced/metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes, there is limited evidence of the clinical benefit of early eribulin use. We investigated the efficacy and safety of first- to third-line eribulin use in patients with MBC. Materials and methods In this phase II, open-label, single-arm study conducted at 14 sites in Kyushu, Japan, women with histologically confirmed human epidermal growth factor receptor 2–negative MBC were enrolled between December 1, 2011 and November 30, 2013 (Data cut-off: November 30, 2014). Objective response rate (ORR; primary endpoint), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety were evaluated. Results Of 53 recruited patients, 47 were enrolled. The ORR was 17.0% (95% confidence interval, 7.6–30.8), DCR was 66.0% (51.2–77.8), median PFS was 4.9 months (3.5–7.0), DOR was 6.6 months (1.9–14.3), and median OS was 17.4 months (10.1–not evaluable). The common grade 3/4 adverse events were neutropenia (25 patients; 53.2%), leucopenia (16 patients; 42.1%) and febrile neutropenia (4 patients; 8.5%). Toxicity did not increase during the long-term treatment. Subgroup analysis indicated that first-line treatment led to higher ORR and prolonged PFS and OS than second-/third-line treatment and that incidence of adverse events in patients of second-/third-line treatment was not higher than that in patients of first-line treatment. Conclusion Eribulin exhibited efficacy and manageable tolerability in Japanese women with pretreated MBC in first- to third-line use. (ID: UMIN000007121). [ABSTRACT FROM AUTHOR]

Aim: This study was designed to verify the efficacy of breast cancer treatment and its cardiac toxicity in population with significant cardiac comorbidities.Materials& Methods: Prospective observational study was conducted in 48 patients.Results: The increase and dependence of echocardiographic parameter early/late were observed on hemoglobin level in all patients, and white blood cells and cholesterol in patients with diabetic were reported. Patients undergo left ventricle diameter change on treatment.Conclusion: Use of potentially cardiotoxic chemo regimens in breast cancer patients with cardiac comorbidities, with optimized cardiac therapy accordingly can save patients from development of early myocardial dysfunction induced by chemotherapy - limiting factor to minimize the risk is optimization of lipid level, red blood cell count and platelets count. [ABSTRACT FROM AUTHOR]

Background. Adjuvant chemotherapy for high-risk early-stage breast cancer patients significantly improves longterm treatment results. The decision to administer chemotherapy is made based primarily on prognostic factors (defined by the pathological characteristics of the primary tumour and regional lymph nodes) and also on patientrelated factors, such as age, menopausal status and comorbidities. The guidelines on adjuvant chemotherapy have been established and reviewed for many years by several medical societies (NCCN, ESMO, PTOK, PUO) and experts of St. Gallen International Breast Cancer Conference. The aim of this study was to assess the pattern of adjuvant chemotherapy administration that had been routinely prescribed in four cancer centres in various regions of Poland (Opole, Kraków, Białystok, Poznań). Methods. 218 early-stage breast cancer patients treated in selected cancer centres during 3 consecutive months of 2014 have been included in the analysis. The medical charts of the patients have been carefully evaluated. Data on the adjuvant chemotherapy administration have been reviewed retrospectively. Results. The percentage of IHC tests in the analysed group was satisfactory. As much as 8 different chemotherapy regimens have been recorded. 98% of patients received anthracycline-based chemotherapy. Almost half of the patients (48.6%; 106/218) received taxanes. However, up to 27% (30/111) of patients with involved lymph nodes (pN+) did not received taxanes in the adjuvant setting. Trastuzumab was most frequently administered sequentially, which may be considered suboptimal. [ABSTRACT FROM AUTHOR]

Background: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients.Methods and Findings: We performed whole exome sequencing on 29 TNBC cases from the MD Anderson Cancer Center (MDACC) selected because they had either pCR (n = 18) or extensive residual disease (n = 11) after neoadjuvant chemotherapy, with cases from The Cancer Genome Atlas (TCGA; n = 144) and METABRIC (n = 278) cohorts serving as validation cohorts. Our analysis revealed that mutations in the AR- and FOXA1-regulated networks, in which BRCA1 plays a key role, are associated with significantly higher sensitivity to ACT chemotherapy in the MDACC cohort (pCR rate of 94.1% compared to 16.6% in tumors without mutations in AR/FOXA1 pathway, adjusted p = 0.02) and significantly better survival outcome in the TCGA TNBC cohort (log-rank test, p = 0.05). Combined analysis of DNA sequencing, DNA methylation, and RNA sequencing identified tumors of a distinct BRCA-deficient (BRCA-D) TNBC subtype characterized by low levels of wild-type BRCA1/2 expression. Patients with functionally BRCA-D tumors had significantly better survival with standard-of-care chemotherapy than patients whose tumors were not BRCA-D (log-rank test, p = 0.021), and they had significantly higher mutation burden (p < 0.001) and presented clonal neoantigens that were associated with increased immune cell activity. A transcriptional signature of BRCA-D TNBC tumors was independently validated to be significantly associated with improved survival in the METABRIC dataset (log-rank test, p = 0.009). As a retrospective study, limitations include the small size and potential selection bias in the discovery cohort.Conclusions: The comprehensive molecular analysis presented in this study directly links BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in TNBC and suggests that functional RNA-based BRCA deficiency needs to be further examined in TNBC. [ABSTRACT FROM AUTHOR]