Purpose
We present the English version of The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer, 2018 edition.
Methods
The JBCS formed a task ...force to update the JBCS Clinical Practice Guidelines, 2015 edition, according to Minds Handbook for Clinical Practice Guideline Development 2014. First, we set multiple outcomes for each clinical question (CQ). Next, quantitative or qualitative systematic review was conducted for each of the multiple outcomes, and the strength of recommendation for the CQ was taken into consideration during meetings, with the aim of finding a balance between benefit and harm. Finalized recommendations from each session were confirmed through discussion and voting at the recommendation decision meeting.
Results
The recommendations, the strength of recommendation and the strength of evidence were determined based on systemic literature reviews and the meta-analyses for each CQ.
Conclusion
The JBCS updated the Clinical Practice Guidelines for systemic treatment of breast cancer.
Circulating tumor DNA (ctDNA) consists of DNA fragments released from cancer cells into the blood circulation with quick clearance. Analysis of ctDNA can enable real-time assessment of the presence ...of cancer cells and their genomic characteristics. Therefore, ctDNA is expected to be one of the most useful biomarkers for cancer. In recent years, several ultra-sensitive assays for ctDNA analysis have been developed, and many clinical trials are using these assays to investigate the efficacy of ctDNA-based therapeutic strategies. In the perioperative phase, real-time identification of minimal residual disease at the molecular level with ctDNA analysis can help evaluate the risk of recurrence to inform escalation or de-escalation of perioperative drug therapy. Many trials have examined whether therapeutic strategies using ctDNA analysis to predict treatment efficacy or resistance to molecular targeted agents can improve prognosis in metastatic breast cancer. In this review, we discuss the most recent ctDNA assays, the significance of introducing ctDNA assays to clinical practice, and the research on their application in perioperative and metastatic phases.
No standard options existed for human epidermal growth factor receptor 2 (HER2)‐positive advanced breast cancer that progresses after second‐line trastuzumab emtansine therapy before 2020. The ...purpose of this study was to examine the efficacy of pertuzumab retreatment after disease progression following pertuzumab‐containing therapy for HER2‐positive locally advanced or metastatic breast cancer for the first time. This randomized, open‐label, multicenter phase III trial was undertaken in 93 sites in Japan. Eligible patients with HER2‐positive breast cancer who had received pertuzumab, trastuzumab, and chemotherapy as first‐ and/or second‐line therapy were randomly assigned (1:1) to: (i) pertuzumab, trastuzumab, and physician's choice chemotherapy (PTC), or (ii) trastuzumab and physician's choice chemotherapy (TC). The primary end‐point was investigator‐assessed progression‐free survival (PFS). Between August 1, 2015 and December 31, 2018, 219 patients were randomized to PTC (n = 110) or TC (n = 109). Median follow‐up was 14.2 months (interquartile range, 9.0–22.2), and median PFS was 5.3 months (95% confidence interval CI, 4.0–6.6) with PTC and 4.2 months (95% CI, 3.2–4.8) with TC (stratified hazard ratio 0.76 95% CI upper limit 0.967; p = 0.022). Progression‐free survival was improved by adding pertuzumab in all prespecified subgroups. The PTC arm showed a trend towards better overall survival and duration of response, but similar objective response and health‐related quality of life. The incidence of treatment‐related adverse events was similar between groups except for diarrhea. Pertuzumab retreatment contributes to disease control for HER2‐positive locally advanced or metastatic breast cancer previously treated with pertuzumab‐containing regimens.
This randomized, open‐label, multicentre phase 3 trial examined the efficacy of pertuzumab retreatment after disease progression following pertuzumab‐containing therapy for HER2‐positive locally advanced or metastatic breast cancer for the first time. Patients randomly assigned to pertuzumab, trastuzumab and physician #x2019;s choice chemotherapy had improved progression‐free survival compared with those who received trastuzumab and physician #x2019;s choice chemotherapy (5.3 vs 4.2 months; p=0.022). Pertuzumab retreatment also showed a trend towards better overall survival and duration of response, and contributes to disease control for HER2‐positive locally advanced or metastatic breast cancer previously treated with pertuzumab‐containing regimens.
Background
Everolimus is a mechanistic-target-of-rapamycin (mTOR) inhibitor bearing a potent antitumor effect against hormone receptor-positive breast cancer. Here, we report the case of a patient ...with recurrent breast cancer who developed osteomyelitis during the treatment with everolimus plus exemestane.
Case presentation
A 56-year-old woman with early-stage breast cancer underwent right mastectomy and axillary lymph node dissection at the age of 45. Four years after the surgery, she experienced relapse at the chest wall. Radiotherapy was performed on the chest wall, including the sternum, and denosumab was administered. After several regimens of hormonal therapies, everolimus in combination with exemestane was administered. Three months later, the patient visited our clinic because of continuous fever. A computed tomography scan showed an osteolytic change in the sternal bone with pneumomediastinum, which indicated sternal osteomyelitis. Extensive debridement followed by secondary reconstruction of the chest wall was successfully performed.
Conclusions
Everolimus may cause osteomyelitis of the affected bone as a result of tumor necrosis. Everolimus-induced osteomyelitis may be manageable by extensive debridement performed without delay.
Background Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding ...post-T-DM1 treatments is currently lacking. We evaluated the effectiveness of post-T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer. Methods In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post-T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken. Results Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval CI) rwPFS, TTF, and OS were 5.7 (4.8-6.9) months, 5.6 (4.6-6.4) months, and 22.8 (18.2-32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8-56.7) and 23% (15.1-31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, greater than or equai to12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months. Conclusions In the real-world setting in Japan, several post-T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings. Trial registration UMIN000038296; registered on 15 October 2019. Keywords: Retrospective observational study, HER2-positive, Unresectable and/or metastatic breast cancer, KBCSG-TR 1917, T-DM1/trastuzumab emtansine
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We experienced a case of breast cancer in which liver metastases spread rapidly and the patient died of pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a fatal cancer-associated ...respiratory complication disease. To reveal genetic alterations of the clinical course, we performed next generation sequencing of the serial specimens using the Ion AmpliSeqTM Comprehensive Cancer Panel and RNA sequencing for transcriptomic data, followed by gene set analysis. The analysis revealed an oncogenic
TP53
R213* mutation in all specimens and
STK11
loss in tissues sampled after disease progression. Immunohistochemistry with an anti-STK11 antibody confirmed no STK11 expression in the samples after progression. Transcriptome analysis showed a significant downregulation of proteins associated with apoptosis in the specimens with STK11 loss.
STK11
loss may have triggered the rapid progression of PTTM from a comprehensive genomic analysis.
Breast cancer tumors frequently have intratumoral heterogeneity (ITH). Tumors with high ITH cause therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in ...response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to a poor prognosis for HER2-targeted adjuvant therapy resistance in primary breast cancers.
This study included patients with primary breast cancer (
= 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with the HER2 gene copy number within a tumor sample. Each tumor was classified into a biphasic grade graph (high heterogeneity HH) group or a monophasic grade graph (low heterogeneity LH) group based on heterogeneity. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up.
Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS:
< 0.001 (HH:63% vs. LH:91% at 10 years) and for the OS:
= 0.012 (HH:78% vs. LH:95% at 10 years).
High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach to heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.
Background
Since humoral hypercalcemia of malignancy (HHM) in breast cancer patients without bone metastasis is rare, the clinical features of this condition are not fully understood.
Case ...presentation
During the recent 12 years, 3602 patients were diagnosed with breast cancer in our institution, and only three patients developed HHM without bone metastasis. They were all recurrent breast cancer patients with visceral metastases including the lung and the liver. It took no more than 2 months since symptomatic onset to hospitalization because of hypercalcemia. The maximum serum calcium concentrations were 15.0 mg/dL or higher. All patients had symptoms related to hypercalcemia. Treatment of hypercalcemia including hydration, calcitonin, bisphosphonate, and diuretics was initially effective in the three patients. However, two of three cases were eventually fatal because of unsuccessful treatment of breast cancer.
Conclusions
The common features of HHM without bone metastasis in breast cancer patients include acute onset, severe symptomatic hypercalcemia, and presence of visceral metastasis. Treatment of hypercalcemia decreased serum calcium level in a short period, while successful treatment of breast cancer was essential for a long-term management of HHM. This report provides a consideration to help elucidate the pathophysiology and medical care of breast cancer patients with HHM without bone metastasis.
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