In this single-group, phase 2 study, the use of trastuzumab deruxtecan resulted in a response in 60% of women with HER2-positive advanced breast cancer who had received a median of six previous lines ...of therapy. The drug was associated with myelosuppression and gastrointestinal toxicity; interstitial lung disease was reported in 13.6% of the patients.
Patients who complete neoadjuvant chemotherapy for breast cancer without a pathological complete response have a high risk of relapse. A randomized trial comparing capecitabine with no additional ...adjuvant therapy showed that capecitabine prolonged disease-free and overall survival.
Patients who have residual invasive breast cancer after the receipt of neoadjuvant chemotherapy have a high risk of relapse.
1
The rate of complete response as assessed on pathological testing (hereafter, pathological complete response) ranges from 13 to 22% among patients with human epidermal growth factor receptor 2 (HER2)–negative primary breast cancer.
1
Patients who do not have a pathological complete response after the receipt of neoadjuvant taxane and anthracycline chemotherapy have a 20 to 30% risk of relapse.
2
Patients with HER2-negative cancer who receive neoadjuvant chemotherapy often receive postoperative radiation therapy, whereas endocrine therapy is administered to patients with hormone-receptor–positive disease . . .
Purpose
High-density tumor-infiltrating lymphocytes (TILs) are a prognostic marker for triple-negative breast cancer (TNBC). However, lymphocytic infiltration is heterogeneous in its pattern. We ...aimed to explore the utility of TIL distribution patterns against TIL density for predicting TNBC prognosis and chemotherapeutic effects.
Methods
Primary invasive TNBC cases were retrieved from a single institutional cohort, and archived samples were reviewed by two board-certificated pathologists. We used 154 consecutive surgical specimens from patients with standard adjuvant therapy, and 80 biopsies taken before primary systemic chemotherapy. The average density of stromal TILs was scored at 10% intervals, while the distribution pattern of TILs was evaluated as diffuse or non-diffuse. The association between TILs and prognosis or pathological complete response (pCR) was statistically analyzed.
Results
A diffuse pattern of TILs at primary surgery correlated with better prognosis (relapse-free survival RFS, hazard ratio HR 3.71, 95% confidence interval CI 1.60–8.57; overall survival OS, HR 3.87, 95% CI 1.46–10.27), as well as high TIL density (≥ 50%; RFS, HR 4.51, 95% CI 2.06–9.90; OS, HR 3.28, 95% CI 1.32–8.14). Diffuse TIL pattern and nodal status were independent prognostic factors in multivariate analysis. Diffuse TIL pattern upon biopsy was associated with higher pCR rate (diffuse, 46%; non-diffuse, 21%;
P
= 0.032). All high TIL cases had diffuse patterns and the best outcome. Interobserver concordance was moderate (
k
= 0.53–0.55; distribution pattern) to good (weighted
k
= 0.67–0.69; density), and it was faster to assess the distribution pattern than to assess the density of TIL.
Conclusions
Showing similar clinical impacts to the TIL density, diffuse TILs could be a predictive marker for better prognosis and higher pCR. The assessment of TIL distribution pattern is simple, faster, and practical. Heterogeneous tumor immunity may contribute to further stratification of TNBC treatment.
Occupational exposure of anticancer agents during their preparation has been recognized as a serious hazard. Closed system drug transfer devices (CSTDs) enable "safe" preparation of agents for ...medical personnel and ensure a safe hospital environment. However, artificial particles of infusion materials have been reported during CSTD use. Here, the incidence of insoluble fine particles during preparation of anticancer agents using CSTDs was examined. Visible insoluble fine particles were found in 465 (9.4%) of 4948 treatment cases at Ehime University Hospital with CSTD use. Contaminants occurred more frequently during preparation of monoclonal antibodies than cytotoxic anticancer agents (19.4% vs. 4.1%, respectively, P < 0.01). A similar survey was conducted at nine hospitals to investigate the incidence of insoluble fine particles with or without CSTDs. Insoluble fine particles were detected in 113 (15.4%) of 732 treatment cases during preparation of monoclonal antibodies with CSTD use. In contrast, the occurrence of insoluble fine particles without CSTDs was found in only 3 (0.073%) of 4113 treatment cases. Contamination with CSTDs might cause harmful effects on patients during cancer therapy. We strongly recommend the use of in-line filters combined with infusion routes after CSTD use to avoid contamination-associated adverse events.
Endocrine therapy is standard treatment for estrogen receptor (ER)-positive breast cancer, yet long-term treatment often causes acquired resistance, which results in recurrence and metastasis. Recent ...studies have revealed that RNA-binding proteins (RBP) are involved in tumorigenesis. Here we demonstrate that PSF/SFPQ is an RBP that potentially predicts poor prognosis of ER-positive breast cancer patients by posttranscriptionally regulating ERα (ESR1) mRNA expression. Strong PSF immunoreactivity correlated with shorter overall survival in ER-positive breast cancer patients. PSF was predominantly expressed in a model of tamoxifen-resistant breast cancer cells, and depletion of PSF attenuated proliferation of cultured cells and xenografted tumors. PSF expression was significantly associated with estrogen signaling. PSF siRNA downregulated ESR1 mRNA by inhibiting nuclear export of the RNA. Integrative analyses of microarray and RNA-immunoprecipitation sequencing also identified SCFD2, TRA2B, and ASPM as targets of PSF. Among the PSF targets, SCFD2 was a poor prognostic indicator of breast cancer and SCFD2 knockdown significantly suppressed breast cancer cell proliferation. Collectively, this study shows that PSF plays a pathophysiological role in ER-positive breast cancer by posttranscriptionaly regulating expression of its target genes such as ESR1 and SCFD2. Overall, PSF and SCFD2 could be potential diagnostic and therapeutic targets for primary and hormone-refractory breast cancers.
A cross-sectional survey of working cancer survivors in Japan examined the timing of and reasons for job resignation and their work-related information/ support needs.
Abstract
Objective
Despite ...advances in work-related policies for cancer survivors, support systems for working survivors in healthcare settings in Japan remain underdeveloped. We aimed to reveal (i) the present situation of cancer survivors’ job resignation, the timing of resignation, and reasons for resignation; (ii) healthcare providers’ screening behaviors of cancer survivors’ work-related difficulties and (iii) changes to cancer survivors’ information/support needs over time since diagnosis.
Methods
We conducted an anonymous, cross-sectional survey using a convenience sample of re-visiting outpatients at three cancer centers in Japan in 2015. The questionnaire covered participants’ demographic and clinical characteristics, change to job status, timing of and reasons for job resignation, screening experience regarding work-related difficulties by healthcare providers, and information/support needs at four distinct timings (at diagnosis, between diagnosis and initial treatment, between initial treatment and return-to-work, and after return-to-work). The results of 950 participants were eligible for statistical analysis.
Results
Only 23.5% of participants were screened about work-related issues by healthcare providers despite 21.3% participants reporting resigning at least once. Among participants who resigned, 40.2% decided to do so before initial treatment began. Regarding reasons for resignation, self-regulating and pessimistic reasons were ranked highly. Respondents’ work-related information and support needs were observed to change over time. While treatment-related information (schedule and cost) was ranked highly at diagnosis, the need for more individually tailored information and support on work increased after treatment began.
Conclusions
This study provides important basic data for developing effective support systems for working survivors of cancer in hospital settings.
Summary Background Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT3 )-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing ...chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy. In this phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group, active-comparator trial, we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting, both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy. Methods Between July 5, 2006, and May 31, 2007, 1143 patients with cancer who were receiving highly emetogenic chemotherapy (ie, cisplatin, or an anthracycline and cyclophosphamide combination AC/EC) were recruited from 75 institutions in Japan, and randomly assigned to either single-dose palonosetron (0·75 mg), or granisetron (40 μg/kg) 30 min before chemotherapy on day 1, both with dexamethasone (16 mg intravenously) on day 1 followed by additional doses (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC) on days 2 and 3. A non-deterministic minimisation method with a stochastic-biased coin was applied to the randomisation of patients. Covariates known to effect emetic risk, such as sex, age, and type of highly emetogenic chemotherapy, were used as stratification factors of minimisation to ensure balance between the treatment groups. Primary endpoints were the proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) during the acute phase (0–24 h postchemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with a complete response during the delayed phase (24–120 h postchemotherapy; superiority comparison with granisetron). The non-inferiority margin was predefined in the study protocol as a 10% difference between groups in the proportion of patients with complete response. The palonosetron dose of 0·75 mg was chosen on the basis of two dose-determining trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses (modified intention to treat). This trial is registered with ClinicalTrials.gov , number NCT00359567. Findings 1114 patients were included in the efficacy analyses: 555 patients in the palonosetron group and 559 patients in the granisetron group. 418 of 555 patients (75·3%) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients (73·3%) in the granisetron group (mean difference 2·9% 95% CI −2·70 to 7·27). During the delayed phase, 315 of 555 patients (56·8%) had complete response in the palonosetron group compared with 249 of 559 patients (44·5%) in the granisetron group (p<0·0001). The main treatment-related adverse events were constipation (97 of 557 patients 17·4% in the palonosetron group vs 88 of 562 15·7% in the granisetron group) and raised concentrations of serum aminotransferases (aspartate aminotransferase: 24 of 557 4·3% vs 34 of 562 6·0%; alanine aminotransferase: 16 of 557 2·9% vs 33 of 562 5·9%); no grade 4 main treatment-related adverse events were reported. Interpretation When administered with dexamethasone before highly emetogenic chemotherapy, palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase, with a comparable safety profile for the two treatments. Funding Taiho Pharmaceutical (Tokyo, Japan).
Purpose
Scalp cooling during chemotherapy infusion to mitigate alopecia for breast cancer patients is becoming widespread; however, studies regarding hair recovery after chemotherapy with scalp ...cooling are limited. We conducted a prospective study of hair recovery after chemotherapy with scalp cooling.
Patients and methods
One hundred and seventeen Japanese female breast cancer patients who completed planned (neo)adjuvant chemotherapy using the Paxman Scalp Cooling System for alopecia prevention were evaluated for alopecia prevention in our prospective study. We evaluated their hair recovery 1, 4, 7, 10, and 13 months after chemotherapy. Primary outcomes were grades of alopecia judged by two investigators (objective grades) and patients’ answers to the questionnaire regarding the use of a wig or hat (subjective grades).
Results
Of 117 patients, 75 completed scalp cooling during the planned chemotherapy cycles (Group A), but 42 discontinued it mostly after the first cycle (Group B). Objective and subjective grades were significantly better in Group A than in Group B throughout 1 year, and at 4 and 7 months after chemotherapy. When we restricted patients to those with objective Grade 3 (hair loss of > 50%) at 1 month, Group A exhibited slightly faster hair recovery based on the objective grades than Group B. There was less persistent alopecia in Group A than in Group B.
Conclusions
Scalp cooling during chemotherapy infusion for Japanese breast cancer patients increased the rate of hair recovery and had preventive effects against persistent alopecia.
Background
The Japanese Breast Cancer Society Registry started in 1975; it was transferred to the registry platform of the National Clinical Database in 2012. We provide the annual data and an ...analysis of the Breast Cancer Registry for 2017.
Methods
Patients’ characteristics and pathological data of the 95,203 registered Japanese breast cancer patients from 1,427 institutes in 2017 were obtained. Trends in age at diagnosis and pathological stage were determined during the most recent 6 years (2012–2017).
Results
The mean onset age was 60.2 years with bimodal peaks at 45–49 years and 65–69 years. A short-term trend of the most recent 6 years of data caused the second, older peak. At diagnosis, 32.4% of breast cancer patients were premenopausal. The distribution of stages revealed that the proportion of early stage breast cancer (stage 0–I) increased up to 60%. At the initial diagnosis, 2.2% of patients presented with metastatic disease. Sentinel node biopsy without axillary node dissection was performed without neoadjuvant chemotherapy (NAC) in 68.8%, and with NAC in 31.1%, of patients. For patients without NAC, lymph node metastasis was less than 3% if the tumor size was less than 1 cm. The proportion of node-negativity decreased to 79.5% when tumor size was 2.1–5 cm.
Conclusions
This analysis of the registry provides new information for effective treatment in clinical practice, cancer prevention, and the conduct of clinical trials. Further development of the registry and progress in collecting prognostic data will greatly enhance its scientific value.
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