scholarly journals Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kanako Hagio ◽  
Toraji Amano ◽  
Hideyuki Hayashi ◽  
Takashi Takeshita ◽  
Tomohiro Oshino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Targeted Sequencing ◽  
Breast Cancer Patients ◽  
Somatic Gene ◽  
Estrogen Receptor Positive ◽  
Gene Alterations

AbstractClinical targeted sequencing allows for the selection of patients expected to have a better treatment response, and reveals mechanisms of resistance to molecular targeted therapies based on actionable gene mutations. We underwent comprehensive genomic testing with either our original in-house CLHURC system or with OncoPrime. Samples from 24 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer underwent targeted sequencing between 2016 and 2018. Germline and somatic gene alterations and patients’ prognosis were retrospectively analyzed according to the response to endocrine therapy. All of the patients had one or more germline and/or somatic gene alterations. Four patients with primary or secondary endocrine-resistant breast cancer harbored germline pathogenic variants of BRCA1, BRCA2, or PTEN. Among somatic gene alterations, TP53, PIK3CA, AKT1, ESR1, and MYC were the most frequently mutated genes. TP53 gene mutation was more frequently observed in patients with primary endocrine resistance compared to those with secondary endocrine resistance or endocrine-responsive breast cancer. Recurrent breast cancer patients carrying TP53-mutant tumors had significantly worse overall survival compared to those with TP53-wild type tumors. Our 160-gene cancer panel will be useful to identify clinically actionable gene alterations in breast cancer in clinical practice.

scholarly journals Prognostic effect of professional oral care in estrogen receptor-positive metastatic breast cancer patients treated with everolimus and exemestane enrolled in Oral Care-BC: a randomized controlled trial

2020 ◽  
Author(s):  
katsuhiko nakatsukasa ◽  
Naoki Niikura ◽  
Kosuke Kashiwabara ◽  
Takeshi Amemiya ◽  
Kenichi Watanabe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Oral Care ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Control Groups ◽  
Estrogen Receptor Positive ◽  
And Control

Abstract Background: The Oral Care BC-trial reported that professional oral care (POC) reduces the incidence and severity of oral mucositis in patients receiving everolimus (EVE) and exemestane (EXE). However, the effect of POC on clinical response among patients receiving EVE and EXE was not established. We compared outcomes for estrogen receptor-positive metastatic breast cancer patients that received POC to those that had not and evaluated clinical prognostic factors. All patients simultaneously received EVE and EXE. Methods: Between May 2015 and Dec 2017, 174 eligible patients were enrolled in the Oral Care-BC trial. The primary endpoint was the comparative incidence of grade 1 or worse oral mucositis, as evaluated by an oncologist over 8 weeks between groups. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collected after a follow-up period of 13.9 months. Results: There were no significant differences in PFS between the POC and Control Groups ( P = 0.801). A BMI < 25 mg/m 2 and non-visceral metastasis were associated with longer PFS ( P = 0.018 and P = 0.003, respectively) and the use of bone modifying agents (BMA) was associated with shorter PFS ( P = 0.028). The PFS and OS between the POC and control groups were not significantly different in the Oral-Care BC trial. Conclusions: POC did not influence the prognosis of estrogen receptor-positive metastatic breast cancer patients. Patients with non-visceral metastasis, a BMI < 25 mg/m 2 , and who did not receive BMA while receiving EVE and EXE may have better prognoses. Trial registration: The study protocol was registered online at the University Hospital Medical Information Network (UMIN), Japan (protocol ID 000016109), on January 5, 2015 and at ClinicalTrials.gov (NCT02376985).

scholarly journals Prognostic effect of professional oral care in estrogen receptor-positive metastatic breast cancer patients treated with everolimus and exemestane enrolled in Oral Care-BC: secondary endpoint results of a randomized controlled trial

2020 ◽  
Author(s):  
katsuhiko nakatsukasa ◽  
Naoki Niikura ◽  
Kosuke Kashiwabara ◽  
Takeshi Amemiya ◽  
Kenichi Watanabe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Oral Care ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Control Groups ◽  
Estrogen Receptor Positive ◽  
And Control

Abstract Background: The Oral Care BC-trial reported that professional oral care (POC) reduces the incidence and severity of oral mucositis in patients receiving everolimus (EVE) and exemestane (EXE). However, the effect of POC on clinical response among patients receiving EVE and EXE was not established. We compared outcomes for estrogen receptor-positive metastatic breast cancer patients who received POC to those who had not, and evaluated clinical prognostic factors. All patients simultaneously received EVE and EXE. Methods: Between May 2015 and Dec 2017, 174 eligible patients were enrolled in the Oral Care-BC trial. The primary endpoint was the comparative incidence of grade 1 or worse oral mucositis, as evaluated for both the groups over 8 weeks by an oncologist. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collected after a follow-up period of 13.9 months. Results: There were no significant differences in PFS between the POC and Control Groups (P = 0.801). A BMI < 25 mg/m2 and non-visceral metastasis were associated with longer PFS (P = 0.018 and P = 0.003, respectively) and the use of bone modifying agents (BMA) was associated with shorter PFS (P = 0.028). The PFS and OS between the POC and control groups were not significantly different in the Oral-Care BC trial. Conclusions: POC did not influence the prognosis of estrogen receptor-positive metastatic breast cancer patients. Patients with non-visceral metastasis, a BMI < 25 mg/m2, and who did not receive BMA while receiving EVE and EXE may have better prognoses.Trial registration: The study protocol was registered online at the University Hospital Medical Information Network (UMIN), Japan (protocol ID 000016109), on January 5, 2015 and at ClinicalTrials.gov (NCT02376985).

scholarly journals Secondary endpoints analysis in patients with estrogen receptor-positive metastatic breast cancer treated with everolimus and exemestane enrolled in Oral Care-BC

2021 ◽  
Author(s):  
Katsuhiko Nakatsukasa ◽  
Naoki Niikura ◽  
Kosuke Kashiwabara ◽  
Takeshi Amemiya ◽  
Kenichi Watanabe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Oral Care ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Control Groups ◽  
Estrogen Receptor Positive ◽  
Secondary Endpoints ◽  
And Control

Abstract Background: The Oral Care BC-trial reported that professional oral care (POC) reduces the incidence and severity of oral mucositis in patients receiving everolimus (EVE) and exemestane (EXE). However, the effect of POC on clinical response among patients receiving EVE and EXE was not established. We compared outcomes for estrogen receptor-positive metastatic breast cancer patients who received POC to those who had not, and evaluated clinical prognostic factors. All patients simultaneously received EVE and EXE. Methods: Between May 2015 and Dec 2017, 174 eligible patients were enrolled in the Oral Care-BC trial. The primary endpoint was the comparative incidence of grade 1 or worse oral mucositis, as evaluated for both the groups over 8 weeks by an oncologist. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collected after a follow-up period of 13.9 months. Results: There were no significant differences in PFS between the POC and Control Groups (P = 0.801). A BMI < 25 mg/m2 and non-visceral metastasis were associated with longer PFS (P = 0.018 and P = 0.003, respectively) and the use of bone modifying agents (BMA) was associated with shorter PFS (P = 0.028). The PFS and OS between the POC and control groups were not significantly different in the Oral-Care BC trial. Conclusions: POC did not influence the prognosis of estrogen receptor-positive metastatic breast cancer patients. Patients with non-visceral metastasis, a BMI < 25 mg/m2, and who did not receive BMA while receiving EVE and EXE may have better prognoses.Trial registration: The study protocol was registered online at the University Hospital Medical Information Network (UMIN), Japan (protocol ID 000016109), on January 5, 2015 and at ClinicalTrials.gov (NCT02376985).

scholarly journals A ‘one-two punch’ therapy strategy to target chemoresistance in estrogen receptor positive breast cancer

2020 ◽  
Author(s):  
Feng Chi ◽  
Jiayi Liu ◽  
Samuel W. Brady ◽  
Patrick A. Cosgrove ◽  
Aritro Nath ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Sequencing Analysis ◽  
Breast Cancer Patients ◽  
Chemotherapy Treatment ◽  
Single Cell Rna Sequencing ◽  
Estrogen Receptor Positive

AbstractBackgroundCancer cell phenotypes evolve over the course of a tumor’s treatment. The phenotypes that emerge and disappear over time will be specific to each drug regimen and type of cancer. Chemotherapy remains one of the most common and effective treatments for metastatic breast cancer patients; however, resistance to chemotherapy inevitably emerges. Cancer chemotherapy treatment regimens are not designed to target emerging chemo-resistance, despite its clear importance in progressive cancer. This study focuses on finding sequential treatment strategies that target acquired chemo-resistant states and optimize response to chemotherapy.MethodsIn this study, we used heterogeneous tumor samples from patients to identify subclones resistant to chemotherapy. Using flow cytometry for stem cell markers and DNA sequencing to define subclonal population changes, we measured the enrichment of cancer stem cell-like (CSL) phenotypes in subclones that survive chemotherapy. We then analyzed breast cancer patient tumor organoids and cell line acquisition of CSL traits following chemotherapy, as well as the ability of different drugs to reverse acquired resistance, using flow cytometry, mammosphere assays, and single cell RNA-sequencing analysis.ResultsWe show that in progressive estrogen receptor positive (ER+) metastatic breast cancer patients, resistant tumor subclones that emerge following chemotherapy have increased CSL abundance. Further, in vitro organoid growth of ER+ patient cancer cells also shows that chemotherapy treatment leads to increased abundance of ALDH+/CD44+ CSL cells. Chemotherapy induced CSL abundance is blocked by treatment with a pan-HDAC inhibitor, belinostat. Further, belinostat treatment diminished both mammosphere formation and size following chemotherapy, also indicating a decrease in progenitor CSL traits. HDAC inhibitors specific to class IIa (HDAC4, HDAC5) and IIb (HDAC6) were shown to primarily reverse the chemo-resistant CSL state. Single-cell RNA sequencing analysis with patient samples showed that HDAC targets and MYC signaling were promoted by chemotherapy and inhibited upon HDAC inhibitor treatment.ConclusionThese findings indicate that HDAC inhibition can block chemotherapy-induced drug resistant phenotypes with ‘one-two punch’ strategy in refractory breast cancer cells.

scholarly journals Secondary endpoints analysis in patients with estrogen receptor-positive metastatic breast cancer treated with everolimus and exemestane enrolled in Oral Care-BC

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Katsuhiko Nakatsukasa ◽  
Naoki Niikura ◽  
Kosuke Kashiwabara ◽  
Takeshi Amemiya ◽  
Ken-ichi Watanabe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Oral Care ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Control Groups ◽  
Estrogen Receptor Positive ◽  
Secondary Endpoints ◽  
And Control

Abstract Background The Oral Care BC-trial reported that professional oral care (POC) reduces the incidence and severity of oral mucositis in patients receiving everolimus (EVE) and exemestane (EXE). However, the effect of POC on clinical response among patients receiving EVE and EXE was not established. We compared outcomes for estrogen receptor-positive metastatic breast cancer patients who received POC to those who had not, and evaluated clinical prognostic factors. All patients simultaneously received EVE and EXE. Methods Between May 2015 and Dec 2017, 174 eligible patients were enrolled in the Oral Care-BC trial. The primary endpoint was the comparative incidence of grade 1 or worse oral mucositis, as evaluated for both the groups over 8 weeks by an oncologist. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collected after a follow-up period of 13.9 months. Results There were no significant differences in PFS between the POC and Control Groups (P = 0.801). A BMI <  25 mg/m2 and non-visceral metastasis were associated with longer PFS (P = 0.018 and P = 0.003, respectively) and the use of bone modifying agents (BMA) was associated with shorter PFS (P = 0.028). The PFS and OS between the POC and control groups were not significantly different in the Oral-Care BC trial. Conclusions POC did not influence the prognosis of estrogen receptor-positive metastatic breast cancer patients. Patients with non-visceral metastasis, a BMI <  25 mg/m2, and who did not receive BMA while receiving EVE and EXE may have better prognoses. Trial registration The study protocol was registered online at the University Hospital Medical Information Network (UMIN), Japan (protocol ID 000016109), on January 5, 2015 and at ClinicalTrials.gov (NCT02376985).

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