Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer

IntroductionTriple-negative breast cancer (TNBC) is negative for hormone receptors and human epidermal growth factor receptor 2 (HER2). In stage I TNBC, adjuvant therapy or follow-up are performed according to risk factors, but clinical trial data is scarce. In recent years, it has been reported that HER2-low cases (1+/2+ and in situ hybridization negative) have different prognoses than HER2-0 cases. However, the risk of recurrence and risk factors in this HER2-low population for stage I TNBC have not yet been investigated.MethodsHerein, out of 174 patients with TNBC who underwent surgery from June 2004 to December 2009 at the National Cancer Center Hospital (Tokyo), we retrospectively examined 42 cases diagnosed as T1N0M0 TNBC after excluding those treated with preoperative chemotherapy.ResultsAll patients were female, the median age was 60.5 years, and 11 cases were HER2-low and 31 cases were HER2-0. The median follow-up period was 121 months. Postoperative adjuvant therapy was administered in 30 patients and recurrence occurred in 8 patients. HER2-low cases showed a significantly shorter disease-free survival (HR: 7.0; 95% CI: 1.2– 40.2; P=0.0016) and a trend towards shorter overall survival (hazard ratio [HR]: 4.2, 95% confidence interval [CI]: 0.58–31.4) compared with that of HER2-0 cases. HER2 was also identified as a factor for poor prognosis from the point- estimated values in univariate and multivariate analyses after confirming that there was no correlation between the other factors.ConclusionFor patients with stage I TNBC, the HER2-low population had a significantly worse prognosis than the HER2-0 population

Breast Cancer Brain Metastasis—Overview of Disease State, Treatment Options and Future Perspectives

Breast cancer is the second most common origin of brain metastasis after lung cancer. Brain metastasis in breast cancer is commonly found in patients with advanced course disease and has a poor prognosis because the blood–brain barrier is thought to be a major obstacle to the delivery of many drugs in the central nervous system. Therefore, local treatments including surgery, stereotactic radiation therapy, and whole-brain radiation therapy are currently considered the gold standard treatments. Meanwhile, new targeted therapies based on subtype have recently been developed. Some drugs can exceed the blood–brain barrier and enter the central nervous system. New technology for early detection and personalized medicine for metastasis are warranted. In this review, we summarize the historical overview of treatment with a focus on local treatment, the latest drug treatment strategies, and future perspectives using novel therapeutic agents for breast cancer patients with brain metastasis, including ongoing clinical trials

Prognostic impact of presumed breast or ovarian cancer among patients with unfavorable-subset cancer of unknown primary site

Abstract Background The clinical utility and prognostic impact of presumed primary breast or ovarian cancer among patients with an unfavorable subset of cancer of unknown primary site (CUP) remains unclear. We aimed to evaluate the clinical relevance of the presumed primary site of CUP and the clinical outcome of site-specific therapy based on such presumptions. Methods Patients referred to our center who were diagnosed with unfavorable-subset CUP and treated between April 2007 and March 2015 were enrolled in this study. Data were collected retrospectively from the hospital database and electronic medical records. Presumptive primary breast or ovarian cancer was based on histological and immunohistochemical analyses and metastatic patterns. The outcomes of patients with unfavorable-subset CUP with a putative primary site in the breast or ovary (P-CUP) and of patients with unfavorable-subset CUP, but without P-CUP (U-CUP), were assessed. Results A total of 780 patients were referred to our hospital with malignancy of unknown origin. Of these, 409 patients were diagnosed with CUP and 344 patients with unfavorable-subset CUP. Following clinicopathological examination, 40 (11.6%) of the 344 patients had P-CUP and the remaining 303 (88.3%) patients had U-CUP. In total, 136 patients received chemotherapy (22 with P-CUP and 114 with U-CUP). Among the 22 patients with P-CUP, three received hormonal therapy for breast cancer, and 19 received chemotherapy based on the presumed primary organ (breast, 4; ovaries, 15). Conventional platinum-based chemotherapy was administered to 105 patients with U-CUP and non-platinum drug treatment to nine patients. The objective response rates were 61.1% (95% confidence interval [CI]: 38.6–83.6) and 41.1% (95% CI: 31.8–50.4) for patients with P-CUP and U-CUP, respectively. The median overall survival durations were 50.0 months and 16.9 months (log-rank: P = 0.002) for patients with P-CUP and U-CUP, respectively. P-CUP was identified as an independent predictor of good prognosis according to multivariate analysis. Conclusions Patients with P-CUP had higher response rates and a better prognosis compared with patients with U-CUP. It might thus be reasonable to classify this subset as a new category of CUP with a favorable prognosis

Efficacy and safety of eribulin in patients with locally advanced or metastatic breast cancer not meeting trial eligibility criteria: a retrospective study

Abstract Background The efficacy and safety of eribulin in patients with locally advanced or metastatic breast cancer has been demonstrated in phase III trials. However, as patients receiving eribulin in daily practice do not necessarily meet all the eligibility criteria of clinical trials, data for such patients are limited. Methods We identified patients with locally advanced or metastatic breast cancer, treated with eribulin monotherapy between July 2011 and December 2015 at the National Cancer Center Hospital, Tokyo, Japan. Patients who would have met the following eligibility criteria from the EMBRACE trial were included in the eligible group, and the rest were included in the ineligible group: 1) Eastern Cooperative Oncology Group Performance status 0–2; 2) adequate function of principal organs; and 3) absence of active infection. We compared the relative dose intensity (RDI), tumor response, progression-free survival (PFS), overall survival (OS), and adverse events between the groups. Nominal and continuous values were compared using the Fisher’s exact test and Mann-Whitney U test, respectively. Survival outcomes were determined using Kaplan-Meier estimation, and between-group differences were assessed using the log-rank test. Results Of the 203 patients included, 34 were classified into the ineligible group and 169 into the eligible group. Initial dose reduction and treatment discontinuation due to adverse events (AEs) were more common in the ineligible group (initial dose reduction: 23.5% in the ineligible group vs. 7.7% in the eligible group, p = 0.011; treatment discontinuation due to AEs: 11.8% vs. 3.0%, p = 0.045). However, RDI (66% vs. 71%, p = 0.130), response rate (15.6% vs. 18.1%, p = 1.000), PFS (3.7 months vs. 4.0 months, p = 0.913), OS (11.5 months vs. 16.1 months, p = 0.743), AEs requiring hospitalization (5.9% vs. 6.5%, p = 1.000), and grade 3/4 AEs were similar in both groups. PFS, OS, AEs requiring hospitalization, and discontinuation due to AEs in the eligible group were comparable to those found in previous phase III trials. Conclusion The safety and efficacy of eribulin monotherapy was demonstrated in a broader patient population than that eligible for clinical trials. Eribulin may be a treatment option in these patients with locally advanced or metastatic breast cancer, considering dose reduction and pre-existing dysfunctions

Incidence of skeletal‐related events in patients with Ewing sarcoma: An observational retrospective study in Japan

Abstract Background Skeletal‐related events (SREs), including the pathological fracture, surgical treatment or radiation of bone lesions, malignant spinal cord compression, hypercalcemia, are important considerations when managing metastatic bone tumors; however, owing to their rarity, the incidence of SREs in patients with Ewing sarcoma remains unknown. Methods We retrospectively reviewed the clinical data from 146 patients with Ewing sarcoma treated at a single institution from 2005 to 2019. The median age at diagnosis was 22.7 years. Fifty patients (34.2%) had metastatic disease at diagnosis. The primary outcome was the SRE‐free rate among patients with Ewing sarcoma. Moreover, we identified the risk factors for SREs using univariate or multivariate analyses. Results During the observational period (median, 2.6 years), SREs occurred in 23 patients. Radiation to the bone, malignant spinal cord compression, and hypercalcemia were documented as the initial SREs in 12 patients (52.2%), 10 patients (43.5%), and one patient (4.3%), respectively. The SRE‐free rate was 94.2 ± 2.0, 87.3 ± 3.0, and 79.6 ± 3.8% at 1, 2, and 3 years after the initial visit, respectively. Multivariate analysis revealed bone metastasis at diagnosis (hazard ratio [HR] = 4.41, p = 0.007), bone marrow invasion (HR = 34.08, p < 0.001), and local progression or recurrence after definitive treatment (HR = 3.98, p = 0.012) as independent risk factors for SREs. Conclusions SREs are non‐rare events that can occur during the treatment course for Ewing sarcoma, with an especially high incidence of malignant spinal cord compression. Patients with metastatic disease at diagnosis, especially in the bone or bone marrow, or with local progression or recurrence after definitive treatment, should be carefully monitored for the occurrence of SREs. The most effective methods to monitor the occurrence of SREs and new preventative therapies for SREs should be investigated in the future

Clinical and biomarker factors affecting survival in patients with platinum-sensitive relapsed ovarian cancer receiving olaparib monotherapy: a multicenter retrospective study

Abstract The standard treatment for platinum-sensitive relapsed ovarian cancer (PSROC) is platinum-based chemotherapy followed by olaparib monotherapy. A retrospective study was conducted to identify factors affecting the survival of patients with PSROC undergoing olaparib monotherapy in real-world clinical settings. The study enrolled 122 patients who received olaparib monotherapy between April 2018 and December 2020 at three national centers in Japan. The study used the Kaplan–Meier method and univariable and multivariable Cox proportional hazards models to evaluate the associations between factors and progression-free survival (PFS). Patients with BRCA1/2 mutations had a significantly longer median PFS than those without these mutations. Both the BRCA1/2 mutation-positive and mutation-negative groups exhibited a prolonged PFS when the platinum-free interval (PFI) was ≥ 12 months. Cancer antigen 125 (CA-125) level within reference values was significantly linked to prolonged PFS, while a high platelet-to-lymphocyte ratio (≥ 210) was significantly associated with poor PFS in the BRCA1/2 mutation-negative group. The study suggests that a PFI of ≥ 12 months may predict survival after olaparib monotherapy in patients with PSROC, regardless of their BRCA1/2 mutation status. Additionally, a CA-125 level within reference values may be associated with extended survival in patients without BRCA1/2 mutations. A larger prospective study should confirm these findings