A pharmacogenetic analysis of peripheral sensory neuropathy related to administration of taxanes in breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13133-e13133
Author(s):  
Alyson Leonard ◽  
Vinay K. Gudena
Keyword(s):  
Breast Cancer ◽  
Sensory Neuropathy ◽  
Normal Function ◽  
Categorical Variables ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Peripheral Sensory Neuropathy ◽  
Metabolizing Enzymes ◽  
Significant Difference ◽  
Peripheral Sensory

e13133 Background: Commonly used in the treatment of breast cancer, the taxane class includes paclitaxel and docetaxel. Both medications are primarily metabolized by cytochrome P450 enzymes and transporters mediate drug membrane influx and efflux. Variability in metabolizing enzymes and drug transporter function can affect drug clearance. This study sought to determine if the presence of pharmacogenetic changes in metabolizing enzymes and transporters resulted in a patient experiencing peripheral sensory neuropathy. Methods: In this case-control study, patients were enrolled between April 13, 2018 and April 30, 2018. Electronic medical records of patients with current appointments at Cone Health Cancer Center- Wesley Long were reviewed to identify patients who completed treatment with taxanes for breast cancer after January 1, 2017 for evaluation for inclusion in the study. Buccal swabs for pharmacogenetics testing were collected. Genes of interest, ABCB1, CYP3A4, CYP3A5, and SLCO1B1, were evaluated and data was categorized by phenotype. Baseline characteristics and phenotype results were compared using Fisher's exact test for categorical variables and Wilcoxon Rank Sum for numeric variables as appropriate. Results: Thirty-three patients were included in the final analysis. The population was mainly white at 72% and all patients in the study were female. The average patient age was 57 years old. Most patients had stage 1 breast cancer. Most patients received docetaxel. Among patients with peripheral sensory neuropathy, nine were grade 1, five were grade 2, and seven were grade 3. Resulting phenotypes: CYP3A5, all patients were normal metabolizers. CYP3A5, 7 normal metabolizer, 4 intermediate, and 22 poor. SLCO1B1, 25 normal function, 8 intermediate, and no low. ABCB1, 13 normal function, 7 intermediate, and 13 low. For all genes, there was no statistically significant difference in phenotype between the neuropathy and no neuropathy study arms, CYP3A5 (p = 0.075) SLCO1B1 (p = 0.106), ABCB1 (p = 0.902). Conclusions: The findings of our study indicate that having pharmacogenetics changes in the genes, ABCB1, CYP3A4, CYP3A5, and SLCO1B1 did not influence the patients experience with peripheral sensory neuropathy.

Primary analysis of a randomized phase II, multicenter trial: Neoadjuvant weekly nab-paclitaxel 100mg/m2 followed by FE100C compared with docetaxel 75mg/m2 followed by FE100C for early breast cancer in Japan.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 136-136 ◽  
Author(s):  
Takashi Kuwayama ◽  
Hideko Yamauchi ◽  
Toshimi Takano ◽  
Koichiro Tsugawa ◽  
Takanobu Sato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Sensory Neuropathy ◽  
Operable Breast Cancer ◽  
Breast Cancer Patients ◽  
Peripheral Sensory Neuropathy ◽  
Peripheral Sensory

136 Background: Nanoparticle Albumin-Bound Paclitaxel (nab-PTX) is a new solvent free taxane-based anticancer drug. According to CA024 trial, nab-PTX 100mg/m2 demonstrated superior response to docetaxel (DTX) in patients with metastatic breast cancer. Besides, nab-PTX 100mg/m2 was less toxicity. In operable breast cancer, GeparSepto study was reported that the pCR rate were significantly higher with nab-PTX 125/150 mg/m2 compared to paclitaxel. We planned the randomized parallel design phase II trial to evaluate nab-PTX 100mg/m2in early breast cancer. Methods: Stage II-III HER2-negative breast cancer patients were included in this trial and received either 4 cycles of DTX (75 mg/m2 day1) q 3 w or 4 cycles of nab-PTX (100 mg/m2 day1/8/15) q4w followed by 4 cycles of FE100C. The primary end point is pCR (ypT0/is ypN0) rate, and the secondary end points are response rate, histological effect of treatment, breast conservation rate, and toxicity. Results: Between March 2011 to March 2014, 152 eligible patients were enrolled at 6 centers (75 pts were allocated for nab-PTX). Baseline characteristics were well balanced; median age was 51/49 years (DTX/nab-PTX), 61/61% of the patients with ER positive, 38/36% triple negative breast cancer, 57/65% Ki67 > 20%. Clinically response rate was similar to each drug. (53/57%) The pCR rate was 12/17% (p = 0.323). In TNBC group, the pCR rate was 28/30% (p = 0.866). In Ki67 > 20% group, the pCR rate was significantly higher, 16/48% (p = 0.021) with nab-PTX arm. The most common grade3-4 adverse event was neutropenia, which was observed in 40/36% of cases. Non-hematological adverse events of any grade were; 34/32% myalgia (DTX/nab-PTX), 42/35% arthralgia, 55/65% peripheral sensory neuropathy. No Grade3-4 peripheral sensory neuropathy was observed in nab-PTX arm. Infusion reaction of DTX occurred in 1 patient. Conclusions: In this initial effectively analysis, neoadjuvant weekly nab-paclitaxel 100mg/m2 were promising drug in HER2-negative operable breast cancer patients. Larger studies will be needed to evaluate neoadjuvant weekly nab-paclitaxel compared with DTX. Clinical trial information: 000005388.

Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine

2007 ◽  
Vol 25 (23) ◽  
pp. 3407-3414 ◽  
Author(s):  
Edith A. Perez ◽  
Guillermo Lerzo ◽  
Xavier Pivot ◽  
Eva Thomas ◽  
Linda Vahdat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Efficacy And Safety ◽  
Peripheral Sensory Neuropathy ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Peripheral Sensory

PurposeTo evaluate the efficacy and safety of ixabepilone in patients with metastatic breast cancer (MBC) resistant to anthracycline, taxane, and capecitabine, in this multicenter, phase II study.Patients and MethodsPatients with measurable disease who had tumor progression while receiving prior anthracycline, taxane, and capecitabine were enrolled. Ixabepilone 40 mg/m2monotherapy was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle. The primary end point was objective response rate (ORR), assessed by an independent radiology facility (IRF).ResultsA total of 126 patients were treated and 113 were assessable for response. Patients were heavily pretreated: 88% had received at least two lines of prior chemotherapy in the metastatic setting. IRF-assessed ORR was 11.5% (95% CI, 6.3% to 18.9%) for response-assessable patients. Investigator-assessed ORR for all treated patients was 18.3% (95% CI, 11.9% to 26.1%). Fifty percent of patients achieved stable disease (SD); 14.3% achieved SD ≥ 6 months. Median duration of response and progression-free survival were 5.7 and 3.1 months, respectively. Median overall survival was 8.6 months. Patients received a median of 4.0 treatment cycles (range, one to 16 cycles), and 25% of patients received ≥ eight cycles. Grade 3/4 treatment-related events included peripheral sensory neuropathy (14%), fatigue/asthenia (13%), myalgia (8%), and stomatitis/mucositis (6%). Resolution of grade 3/4 peripheral sensory neuropathy occurred after a median period of 5.4 weeks.ConclusionIxabepilone demonstrated clear activity and a manageable safety profile in patients with MBC resistant to anthracycline, taxane, and capecitabine. Responses were durable and notable in patients who had not previously responded to multiple prior therapies.

Prognostic significance of NLR kinetics in operable triple negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14201-e14201
Author(s):  
Ranga Raman Ganta ◽  
Srividya Nasaka
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Medical Records ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Small Sample ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Significant Difference

e14201 Background: Inflammatory response exacerbates mechanisms linked to tumor growth and dissemination. As an index of systemic inflammatory marker, neutrophil lymphocyte ratio (NLR) may be a predictive biomarker of both prognosis and outcome in several malignancies. However very few reports have addressed the association of change in NLR and outcome in operable breast cancer. We evaluated preoperative NLR and postoperative NLR to assess which one would be predictive of disease outcome in triple negative breast cancer patients. Methods: This study included 67 stage I-III triple negative breast cancer patients diagnosed at HCG Cancer center, between 2013 to 2015. Those patients who underwent upfront surgery were included in the study. Patients who received neoadjuvant chemotherapy and those without adequate medical records were excluded. The NLR was calculated from the differential count by dividing neutrophil percentage with lymphocyte percentage. All preoperative NLRs were calculated from medical records, at the first visit. Postoperative NLR was obtained before first cycle chemotherapy. The NLR was divided into high if ratio is > 3 and low if it is ≤ 3. We evaluated prognostic value of NLR on 3 year DFS. Results: The median preoperative NLR was 2.52 (Range 0.77-8.6). The pre op NLR was high in 19 patients (28%) and low in 48 patients (72%). There was no significant difference between two groups in baseline characteristics. Among the preoperative High and low NLR groups, 3 year DFS is statistically significant. The median postoperative NLR was 2.23 (Range 0.89-8.1). The post operative NLR was high in 7 patients (11%) and low in 60 patients (89%). Among the postoperative High and low NLR groups, 3 year DFS is statistically not significant. The 12 (63%) patients in the high preoperative NLR patients were converted to of the low NLR after surgery. Conclusions: Preoperative NLR correlated with outcome in operable triple negative breast cancer than postoperative NLR. The NLR kinetics might be an index of response to the treatment which needs to be evaluated in prospective studies. Drawbacks of the study: single centre, retrospective study and small sample size.[Table: see text][Table: see text]

scholarly journals Is nab-paclitaxel better than conventional taxanes as neoadjuvant therapy for breast cancer? A meta-analysis

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094347
Author(s):  
Yong Li ◽  
Xiaoju Lu ◽  
Qimou Lin ◽  
Weiwen Li
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Meta Analysis ◽  
Sensory Neuropathy ◽  
Cochrane Library ◽  
Peripheral Sensory Neuropathy ◽  
Paclitaxel Group ◽  
Peripheral Sensory

Objective This study compared the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with conventional taxanes as neoadjuvant chemotherapy for breast cancer. Methods We searched the literature using PubMed, the Cochrane Library, and Web of Science from their inception to December 15, 2019 based on predetermined inclusion and exclusion criteria. The relevant studies compared pathologic complete response (pCR) and adverse event rates. Results The meta-analysis included five studies and 2335 patients. Compared with conventional taxanes, neoadjuvant chemotherapy with nab-paclitaxel was associated with a higher pCR rate (odds ratio [OR] = 1.39, 95% confidence interval [CI] = 1.16–1.67), especially among patients with triple-negative breast cancer or Ki67 indices of >20%. Pooled outcomes also revealed better event-free survival in the nab-paclitaxel group (hazard ratio = 0.69, 95% CI = 0.57–0.85). However, all-grade (OR = 2.17, 95% CI = 1.38–3.40) and grade ≥3 peripheral sensory neuropathy (OR = 3.92, 95% CI = 2.44–6.28) were more frequent in the nab-paclitaxel group. Conclusions This meta-analysis implied that nab-paclitaxel more effectively improved pCR than conventional taxanes. Nab-paclitaxel may have greater benefits in patients with triple-negative breast cancer. However, additional attention is required for the early diagnosis and management of peripheral sensory neuropathy.

scholarly journals Preoperative Neoadjuvant Hormonal Therapy and Neoadjuvant Chemotherapy for Stage 3B and 4 Breast Cancer Patients in Dharmais Hospital-National Cancer Center, Indonesia: A Cohort Study

2019 ◽  
Vol 12 (4) ◽  
pp. 109
Author(s):  
Ramadhan Karsono ◽  
Denni Joko Purwanto ◽  
Samuel J. Haryono ◽  
Bambang Karsono ◽  
Lenny Sari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cohort Study ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Hormonal Therapy ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Neoadjuvant Hormonal Therapy ◽  
Significant Difference

Background: There are no data of efficacy comparison between primary systemic therapy in stage 3B and 4 breast cancer patients in Indonesia. This study compared long term outcomes of breast cancer patients treated with neoadjuvant hormonal therapy (NAHT) and those treated with neoadjuvant chemotherapy (NACT)Methods: This was a cohort study conducted from 2011 to 2017. A total of 122 patients with stage 3B and 4 breast cancer received NAHT (n = 62) or NACT (n = 60) within a 6 cycles for NACT and 6 months for NAHT were included. Patients were excluded if they had a mastectomy before treatment, were pregnant, had been given hormonal therapy or chemotherapy before, had a contra-indication of chemotherapy, had a contra-indication of salpingo-oophorectomy bilateral for premenopausal patients, and declined to enter this study. The primary outcome of this study was overall survival. The outcomes were analysed using Kaplan-Meier for survival analysis and cox proportional hazard regression to estimate the hazard ratio.Results: There was a statistically significant difference in overall survival (p = 0.038). Median overall survival for NAHT patients was 1265 days and for NACT patients was 654 days. The hazard ratio showed NACT patients had a higher risk than NAHT patients (1.7 95% CI 1.03 – 2.9). Pathological complete response rate was higher in the NACT group than in the NAHT group (3.3% vs. 0%).Conclusions: Neoadjuvant hormonal therapy was superior to neoadjuvant chemotherapy in term of overall survival.

Effects of cardioprotective medications on breast cancer survival: A retrospective study from an academic center from Southern Illinois.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12540-e12540
Author(s):  
Manjari Rani Regmi ◽  
Priyanka Parajuli ◽  
Asad Cheema ◽  
Odalys Estefania Lara Garcia ◽  
Nitin Tandan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Beta Blocker ◽  
Hazard Ratio ◽  
Categorical Variables ◽  
Rank Test ◽  
P Value ◽  
Breast Cancer Patients ◽  
Cardiovascular Risks ◽  
Significant Difference

e12540 Background: Cardiovascular disease is one of the leading causes of deaths in breast cancer patients. Pre-existing cardiac conditions and cardiovascular risks associated with chemotherapy affect the overall mortality of these patients. Cardio protective medications like beta-blocker, ACEIs, ARBs, statin, and potassium-sparing diuretics have shown to increase the survival odds. In our study, we investigated the survival of breast cancer patients who were on cardio protective medications. Methods: Our retrospective cohort study included breast cancer patients from Simmons Cancer Institute, Springfield, Illinois from January 1st, 2014 to December 31st, 2017. The first step comprised of screening patients using ICD code of breast cancer. Next, a retrospective chart review led to selecting eligible patients with biopsy proven breast cancer diagnosis within the aforementioned dates. We excluded patients who were diagnosed outside the give time frame. Data on age, gender, medical comorbidities, medications, and survival status were also collected. Comparisons between categorical variables were compared with the Chi-Squared test. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival are assessed with Cox proportional hazards regression analyses. Results: Screening using ICD codes resulted in 1618 patients. Of those, 478 had biopsy proven diagnosis within the dates mentioned. 301 out of 478 patients were on some kind of cardio protective medication (88 on beta-blockers, 73 on ACEIs, 41 on ARBs, 87 on statins, and 12 on potassium sparing diuretics). We looked into survival analysis in patients on different cardioprotective medications. ARBs and potassium sparing diuretics showed increased likelihood of survival as the hazard ratio (HR) was found to be 0.512 (95% Cl: 0.068-3.832, p-value:0.0919) and HR 0.390 (95% CI: 0.130-1.66, p-value:0.514) respectively. In contrast, other cardio protective medications showed decreased trends for survival. The HR of beta blocker was 1.734 (95% CI: 0.508-5.919, p-value: 0.379) and of ACEIs was 1.350 (95% CI: 0.395-4.613, p-value: 0.632). Similarly, statins had a hazard ratio of 1.534 (95% CI: 0.512- 4.594, p-value:0. 444). Conclusions: We found that the cardio protective medications showed no statistically significant difference in survival in breast cancer patients. Given the smaller sample size and single center study, further multi-center clinical trial is warranted to establish a stronger association.

scholarly journals Occurrence of tinnitus and peripheral sensory neuropathy in women during chemotherapy treatment of breast cancer

2021 ◽  
Vol 11 (1) ◽  
pp. 69-79
Author(s):  
Simone Yuriko Kameo ◽  
Ricardo Barbosa-Lima ◽  
Josilene Luciene Andrade ◽  
Bruno Ferreira Amorim ◽  
Glebson Moura Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Medical Records ◽  
Analytical Study ◽  
Outpatient Service ◽  
Sensory Neuropathy ◽  
Inclusion Criteria ◽  
Chemotherapy Treatment ◽  
Peripheral Sensory Neuropathy ◽  
Breast Cancer Chemotherapy ◽  
Peripheral Sensory

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 toxicities scores 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 and p = 0.001), as well as very weak between the number of complete cycles of chemotherapy and tinnitus (ρ = 0.195 and p = 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.

Contribution of Magnetic Resonance Imaging in Determining Lumpectomy Cavity in Breast Radiotherapy

2020 ◽  
Vol 16 (8) ◽  
pp. 997-1003
Author(s):  
Ozlem Demircioglu ◽  
Huseyin Tepetam ◽  
Ayfer Ay Eren ◽  
Zerrin Ozgen ◽  
Fatih Demircioglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Supine Position ◽  
Radiotherapy Planning ◽  
Breast Cancer Patients ◽  
Breast Radiotherapy ◽  
Lumpectomy Cavity ◽  
Breast Cancer Radiotherapy ◽  
Significant Difference ◽  
Mean Diameter ◽  
Ct And Mri

Background: Accurate localization of the lumpectomy cavity is important for breast cancer radiotherapy after breast-conserving surgery (BCS), but the LC localization based on CT is often difficult to delineate accurately. The study aimed to compare CT-defined LC planning to MRI-defined findings in the supine position for higher soft-tissue resolution of MRI. Methods: Fifty-nine breast cancer patients underwent radiotherapy CT planning in supine position followed by MR imaging on the same day. LC was contoured by the radiologist and radiation oncologist together by CT and MRI separately. T2 weighted MR images and tomography findings were combined and the LC volume, mean diameter and the longest axis length were measured after contouring. Subsequently, patients were divided into two groups according to seroma in LC and the above-mentioned parameters were compared. Results: We did not find any statistically significant difference in the LC volume, mean diameter and length at the longest axis between CT and MRI but based on the presence or absence of seroma, statistically significant differences were found in the LC volumes and the length at the longest axis of LC volumes. Conclusion: We believe that the supine MRI in the same position with CT will be more effective for radiotherapy planning, particularly in patients without a seroma in the surgical cavity.

Association of CYP2D6*10 (c. 100 C>T) Genotype with Z-END Concentration in Patients with Breast Cancer Receiving Tamoxifen Therapy in Indonesian Population

2019 ◽  
Vol 19 (8) ◽  
pp. 1198-1206 ◽  
Author(s):  
Yenny ◽  
Sonar S. Panigoro ◽  
Denni J. Purwanto ◽  
Adi Hidayat ◽  
Melva Louisa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Steady State ◽  
Ultra Performance Liquid Chromatography ◽  
Cross Sectional Study ◽  
Threshold Concentration ◽  
Breast Cancer Patients ◽  
Cross Sectional ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Liquid Chromatography Tandem Mass

Background: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen (Z-END). Objective: The purpose of the study was to determine the association between CYP2D6*10 (c.100C>T) genotype and attainment of the plasma steady-state Z-END minimal threshold concentration (MTC) in Indonesian women with breast cancer. Methods: A cross-sectional study was performed in 125 ambulatory patients with breast cancer consuming TAM at 20 mg/day for at least 4 months. The frequency distribution of CYP2D6*10 (c.100C>T) genotypes (C/C: wild type; C/T: heterozygous mutant; T/T: homozygous mutant) was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), the results of which were subsequently confirmed by sequencing. The genotypes were categorized into plasma Z- END concentrations of <5.9 ng/mL and ≥5.9 ng/mL, which were measured using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results: Percentages of C/C, CT, and T/T genotypes were 22.4%, 29.6%, and 48.8%, respectively. Median (25-75%) Z-END concentrations in C/C, C/T, and T/T genotypes were 9.58 (0.7-6.0), 9.86 (0.7-26.6), and 3.76 (0.9-26.6) ng/mL, respectively. Statistical analysis showed a significant difference in median Z-END concentration between patients with T/T genotype and those with C/C or C/T genotypes (p<0.001). There was a significant association between CYP2D6*10 (c.100C>T) genotypes and attainment of plasma steady-state Z-END MTC (p<0.001). Conclusion: There was a significant association between CYP2D6*10 (c.100C>T) and attainment of plasma steady-state Z-END MTC in Indonesian breast cancer patients receiving TAM at a dose of 20 mg/day.

Sign in / Sign up

Export Citation Format

Share Document