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PURPOSE: In PALOMA-2, palbociclib plus letrozole significantly improved progression-free survival (PFS) as initial treatment of estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer. We assessed the benefit of palbociclib plus letrozole in Asians. PATIENTS AND METHODS: Of 666 enrolled postmenopausal women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (no prior treatment of advanced disease), 95 were Asian. Patients were randomly assigned 2:1 to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was investigator-assessed PFS. Secondary end points were overall survival, objective response, patient-reported outcomes, pharmacokinetics, and safety. RESULTS: Median PFS was significantly longer in Asian patients who received palbociclib plus letrozole versus placebo plus letrozole (25.7 months [95% CI, 19.2 months to not estimable] v 13.9 months [95% CI, 7.4 to 22.0 months]; hazard ratio, 0.48; 95% CI, 0.27 to 0.87; P =.007). The most common toxicities with palbociclib were hematologic and more frequent among Asians versus non-Asians: neutropenia (any grade, 95.4% v 76.8%; grade 3/4, 89.2% v 62.5%), leukopenia (43.1% v 38.3%; 32.3% v 23.5%), and thrombocytopenia (27.7% v 13.5%; 4.6% v 1.1%). No Asians had febrile neutropenia. Discontinuation rates as a result of adverse events were similar among Asian and non-Asian patients who received palbociclib plus letrozole (10.8% and 9.5%). In Asians, quality of life (QOL) was maintained with no significant differences observed between treatments from baseline in breast cancer–specific QOL and general health status scores. Change from baseline in EuroQol five dimensions index scores was significantly higher with palbociclib plus letrozole (0.013 v –0.069; P =.0132). Geometric mean palbociclib trough concentration values were higher in Asians versus non-Asians (93.8 v 61.7 ng/mL). CONCLUSION: Consistent with the overall study population, the addition of palbociclib to letrozole significantly improved PFS in Asians. Hematologic toxicities were more frequent in Asians versus non-Asians but manageable with early dose modifications while maintaining QOL. [ABSTRACT FROM AUTHOR]

PURPOSE: In PALOMA-2, palbociclib plus letrozole significantly improved progression-free survival (PFS) as initial treatment of estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer. We assessed the benefit of palbociclib plus letrozole in Asians. PATIENTS AND METHODS: Of 666 enrolled postmenopausal women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (no prior treatment of advanced disease), 95 were Asian. Patients were randomly assigned 2:1 to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was investigator-assessed PFS. Secondary end points were overall survival, objective response, patient-reported outcomes, pharmacokinetics, and safety. RESULTS: Median PFS was significantly longer in Asian patients who received palbociclib plus letrozole versus placebo plus letrozole (25.7 months [95% CI, 19.2 months to not estimable] v 13.9 months [95% CI, 7.4 to 22.0 months]; hazard ratio, 0.49; 95% CI, 0.27 to 0.87; P =.007). The most common toxicities with palbociclib were hematologic and more frequent among Asians versus non-Asians: neutropenia (any grade, 95.4% v 76.8%; grade 3/4, 89.2% v 62.5%), leukopenia (43.1% v 38.3%; 32.3% v 23.5%), and thrombocytopenia (27.7% v 13.5%; 4.6% v 1.1%). No Asians had febrile neutropenia. Discontinuation rates as a result of adverse events were similar among Asian and non-Asian patients who received palbociclib plus letrozole (10.8% and 9.5%). In Asians, quality of life (QOL) was maintained with no significant differences observed between treatments from baseline in breast cancer–specific QOL and general health status scores. Change from baseline in EuroQol five dimensions index scores was significantly higher with palbociclib plus letrozole (0.013 v –0.069; P =.0132). Geometric mean palbociclib trough concentration values were higher in Asians versus non-Asians (93.8 v 61.7 ng/mL). CONCLUSION: Consistent with the overall study population, the addition of palbociclib to letrozole significantly improved PFS in Asians. Hematologic toxicities were more frequent in Asians versus non-Asians but manageable with early dose modifications while maintaining QOL. [ABSTRACT FROM AUTHOR]

Background Two global phase 3 trials (301 trial of first- or second-line eribulin, EMBRACE of third- or later-line eribulin) were carried out during development of eribulin for breast cancer treatment. In this post marketing observation study in Japan, efficacy and safety of eribulin in metastatic breast cancer patients were examined. Additionally, the results were compared with that of phase 3 trials. Method We conducted a prospective study in patients with inoperable or recurrent HER2-negative breast cancer. We enrolled a similar number of patients receiving eribulin as first- or second-line therapy (early line) and those receiving eribulin as third- or later line therapy (later line), and followed the patients for two years (ClinicalTrials.gov Number: NCT02371174). For the overall survival and time to treatment failure, the estimated value of them were calculated by the Kaplan Meier method. The severity of adverse drug events was determined by CTCAE v 4.0. Results During September 2014 to February 2016, 651cases were registered at 182 facilities. In analysis set, 637 patients (319 patients of early line/317 patients of late line/1 patient of unknown) was median age of 62.7 (30 - 85) years. Performance status 0/1/2/3/4 was seen in 360/234/38/5/0 patients, respectively. Dose reduction were required in 33% of patients. The median overall survival (early line/late line) was 18.8 months/12.6 months, respectively, and median time to treatment failure was 4.4 months/3.8 months, respectively. Major side effects (early line/late line) were neutropenia (51%/56%), leucopenia (55%/57%), peripheral neuropathy (32%/22%). Grade 3≤ peripheral neuropathy was 2%. Conclusion The results of overall survival (18.8 months in early line, 12.6 months in later line) in this study is comparable to those of large phase 3 study (15.9 months in 301 trial, 13.1 months in EMBRACE). The incidence of Grade 3≤ peripheral neuropathy was lower than that of phase 3 trials. [ABSTRACT FROM AUTHOR]

Two global phase 3 trials (301 trial of first- or second-line eribulin, EMBRACE of third- or later-line eribulin) were carried out during development of eribulin for breast cancer treatment. In this post marketing observation study in Japan, efficacy and safety of eribulin in metastatic breast cancer patients were examined. Additionally, the results were compared with that of phase 3 trials. We conducted a prospective study in patients with inoperable or recurrent HER2-negative breast cancer. We enrolled a similar number of patients receiving eribulin as first- or second-line therapy (early line) and those receiving eribulin as third- or later line therapy (later line), and followed the patients for two years (ClinicalTrials.gov Number: NCT02371174). For the overall survival and time to treatment failure, the estimated value of them were calculated by the Kaplan Meier method. The severity of adverse drug events was determined by CTCAE v 4.0. During September 2014 to February 2016, 651cases were registered at 182 facilities. In analysis set, 637 patients (319 patients of early line/317 patients of late line/1 patient of unknown) was median age of 62.7 (30 - 85) years. Performance status 0/1/2/3/4 was seen in 360/234/38/5/0 patients, respectively. Dose reduction were required in 33% of patients. The median overall survival (early line/late line) was 18.8 months/12.6 months, respectively, and median time to treatment failure was 4.4 months/3.8 months, respectively. Major side effects (early line/late line) were neutropenia (51%/56%), leucopenia (55%/57%), peripheral neuropathy (32%/22%). Grade 3≤ peripheral neuropathy was 2%. The results of overall survival (18.8 months in early line, 12.6 months in later line) in this study is comparable to those of large phase 3 study (15.9 months in 301 trial, 13.1 months in EMBRACE). The incidence of Grade 3≤ peripheral neuropathy was lower than that of phase 3 trials. [ABSTRACT FROM AUTHOR]

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 ). [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to measure adherence rate to the quality indicators (QI) in clinical practice to evaluate the quality of care for breast cancer patients in Japan.Design: A retrospective record review.Setting: Two hundred twenty-four designated breast cancer care hospitals throughout Japan.Participants: A total of 15 227 patients diagnosed with breast cancer in 2005.Main Outcome Measures: The adherence rate of seven items that correspond to QIs of medical care, which were developed using an adaptation of RAND/UCLA (University of California, Los Angeles) appropriateness method.Results: The lowest quality score was the drug therapy adherence to the St. Gallen consensus recommendations, for which the overall quality score 52.8%. The highest quality score was the adherence rate of hormone receptor testing, for which overall quality score was 97.8%. The greatest variations across facilities were for HER-2 testing and for radiation therapy after breast-conserving surgery. The least variation was for hormone receptor testing.Conclusions: There was a range of measurements for the adherence rate to each QI, suggesting that the desired standards of care had not necessarily pervaded all facilities. It is necessary to strive for widespread implementation of QIs and realization of the significance of measuring the medical care quality among physicians treating breast cancer. [ABSTRACT FROM AUTHOR]

HER2-positive breast cancers that achieve pathological complete response (pCR) after HER2-directed therapy consistently have good survival. We previously identified HSD17B4 methylation as a marker for pCR by methylation screening. Here, we aimed to identify a new marker by conducting a multi-omics analysis of materials prepared by laser capture microdissection, and adding 71 new samples. In the screening set (n = 36), mutations, methylation, and expression were analyzed by targeted sequencing, Infinium 450 K, and expression microarray, respectively, and 15 genes were identified as differentially expressed and eight genomic regions as differentially methylated between cancer samples with and without pCR. In a validation set (n = 47), one gene showed differential expression, and one region had differential methylation. Further, in the re-validation set (n = 55), all new samples, only HSD17B4 methylation was significantly different. The HSD17B4 methylation was at the transcriptional start site of its major variant, and was associated with its silencing. HSD17B4 was highly expressed in the vast majority of human cancers, and its methylation was present only in breast cancers and one lymphoblastic leukemia cell line. A combination of estrogen receptor-negative status and HSD17B4 methylation showed a positive predictive value of 80.0%. During HER2-directed neoadjuvant therapy, HSD17B4 methylation was the most reliable marker to monitor response to the therapy. These results showed that HSD17B4 methylation is a candidate predictive and response marker of HER2-positive breast cancer to HER2-directed therapy. [ABSTRACT FROM AUTHOR]

While pertuzumab was added to adjuvant therapy for high-risk HER2-positive breast cancer according to APHINY trial, definition of "high risk of recurrence" is still unclear. Because neoadjuvant chemotherapy (NAC) including anti-HER2 drugs showed potent efficacy to achieve pCR and better survival, one lymph node metastases may show survival outcomes equivalent to node-negative cases. Hence, we examined the risk factors of recurrence in HER2-positive breast cancer and determined whether one lymph node metastasis after NAC is true predictor of recurrence. From May 1993 to March 2017, patients who underwent radical mastectomy/partial mastectomy after NAC for breast cancer in our institution were retrospectively examined. Among those patients, HER2-positive patients were 253, 23% of all patients. Breast cancer recurrence occurred in 46 (18.2%) of HER2-positive patients who underwent NAC and radical mastectomy. Multivariate analysis was performed on tumor size, lymph node metastasis, hormone receptor, Ki-67, preoperative chemotherapy regimen for recurrence risk factor. The risk of recurrence was significantly higher in one lymph node metastasis group than in the node-negative group (HR 6.157, p=.0006, 95%CI 2.175-17.435). Likewise, the risk of recurrence was significantly higher in the group with two or more lymph node metastases than in the node-negative group (HR 3.877, p=.0107, 95%CI 1.370-10.972). The presence of even one lymph node metastasis was suggested as a risk factor of recurrence, likely representing metastatic potential of the disease. [ABSTRACT FROM AUTHOR]

Background Eribulin demonstrated longer overall survival for pretreated metastatic breast cancer. Several factors are reported to be associated with their survival outcomes of breast cancer patients, and scarce of predictors are determined for each agent. Previous reports have demonstrated that high neutrophil to lymphocyte ratio (NLR) is related to poor survival outcomes of cancer. We hypothesized that low NLR is predictor of longer survival of breast cancer patients. We investigated whether baseline NLR before chemotherapy is associated with overall survival, and explored possible mechanism of better survival in patients with metastatic breast cancer. Methods We extracted female patients with metastatic breast cancer who received Eribulin for metastatic disease at NCCHE. We included HER2-negative disease, and those treated with standard chemotherapy including eribulin. We retrieved patient and disease characteristics; age, disease location, de novo stage IV or recurrent disease, hormone receptor status. Result We identified 135 patients between July 2012 and December 2018 with a median age of 57.9 (34-77), of which 106 (78.5%) had HR positive disease, 104 (77.0%) had recurrent disease, and 114 (84.4%) had visceral disease. Log rank test showed hormone receptor status and visceral disease were significant variable for candidate for multivariate analysis. COX regression model demonstrated that decreasing of NLR was associated with better OS [HR = 1.145, 95% confidence interval (95% CI)=1.073-1.223]. We showed low NLR at the administration of eribulin was independent predictor of OS [HR = 1.048, 95% confidence interval (95% CI)=1.004-1.093]. Conclusion We showed low NLR is better prognostic factor of any chemotherapy for metastatic breast cancer. Our exploratory research also showed low NLR at eribulin administraton was suspected to be better OS indicator regardless of pretreated chemotherapy. [ABSTRACT FROM AUTHOR]

While pertuzumab was added to adjuvant therapy for high-risk HER2-positive breast cancer according to APHINY trial, definition of "high risk of recurrence" is still unclear. Because neoadjuvant chemotherapy (NAC) including anti-HER2 drugs showed potent efficacy to achieve pCR and better survival, one lymph node metastases may show survival outcomes equivalent to node-negative cases. Hence, we examined the risk factors of recurrence in HER2-positive breast cancer and determined whether one lymph node metastasis after NAC is true predictor of recurrence. From May 1993 to March 2017, patients who underwent radical mastectomy/partial mastectomy after NAC for breast cancer in our institution were retrospectively examined. Among those patients, HER2-positive patients were 253, 23% of all patients. Breast cancer recurrence occurred in 46 (18.2%) of HER2-positive patients who underwent NAC and radical mastectomy. Multivariate analysis was performed on tumor size, lymph node metastasis, hormone receptor, Ki-67, preoperative chemotherapy regimen for recurrence risk factor. The risk of recurrence was significantly higher in one lymph node metastasis group than in the node-negative group (HR 6.157, p=.0006, 95%CI 2.175-17.435). Likewise, the risk of recurrence was significantly higher in the group with two or more lymph node metastases than in the node-negative group (HR 3.877, p=.0107, 95%CI 1.370-10.972). The presence of even one lymph node metastasis was suggested as a risk factor of recurrence, likely representing metastatic potential of the disease. [ABSTRACT FROM AUTHOR]