The rare case of synchronous bilateral breast metastasis from a lung neuroendocrine tumor (small cell lung carcinoma): a case report and literature review.

BACKGROUND: Breast metastasis from small cell neuroendocrine carcinoma (SNEC) is very rare. In the present report, we describe a case of a female patient who was initially diagnosed with triple negative primary bilateral breast cancer, but during systemic examination, the diagnosis was bilateral breast metastasis from SNEC. CASE PRESENTATION: A 62-year-old woman with no history of smoking presented to the Department of General Medicine with left-sided chest pain, and computed tomography revealed masses in both breasts and left pleural thickening that was further confirmed by mammography and ultrasound of the breasts. A needle biopsy was performed, and triple negative primary bilateral breast cancer was diagnosed. Because progastrin-releasing peptide (ProGRP) 37,300 pg/ml (normal range, 0-81.0 pg/ml) and neuron-specific enolase 35.0 ng/ml (normal range, 0-16.3 ng/ml) levels were elevated, thoracoscopic biopsy was performed, and SNEC was diagnosed. Pathological examinations showed that the bilateral breast masses were also positive for immunohistochemical staining of chromogranin A, synaptophysin, and CD56, leading to a diagnosis of bilateral breast metastasis of neuroendocrine tumor. CONCLUSION: Although very rare, the possibility of breast metastasis should be considered when malignancy is suspected in other organs.

Percutaneous ultrasound-guided cryoablation for early-stage primary breast cancer: a follow-up study in Japan.

BACKGROUND: Ultrasound-guided percutaneous cryoablation (PCA) for early-stage breast cancer (ESBC) can be performed under local anesthesia in an outpatient clinic. This study continues a pilot stage to examine local control, safety, patient quality of life (QoL), satisfaction and cosmetic outcomes of cryoablation for ESBC. METHODS: PCA was performed under local anesthesia for patients with primary ESBC, followed by radiation and endocrine therapies. Oncologic outcomes were examined by imaging (mammography, ultrasound, MRI) at baseline and 1, 6, 12, 24, 36, and 60 months post-cryoablation. EQ-VAS, EQ-5D-5L, subjective satisfaction and Moiré topography were used to measure health-related QoL outcomes. RESULTS: Eighteen patients, mean aged 59.0 ± 9.0 years, mean tumor size 9.8 ± 2.3 mm, ER + , PR + (17/18), HER2-, Ki67 < 20% (15/18), underwent PCA and were followed for a mean of 44.3 months. No serious adverse events were reported, and no patients had local recurrence or distant metastasis in the 5-year follow-up. Cosmetic outcomes, satisfaction level, and QoL all improved post-cryoablation. Five-year average reduction rates of the cryolesion long, short, and depth diameters, on US, were 61.3%, 42.3%, and 22.8%, respectively, compared to the 86.2% volume reduction rate on MRI. The correlation coefficient between MRI and US measurement criteria was highest for the long diameter. During follow-up, calcification of the treated area was observed in 13/18 cases. CONCLUSION: Cryoablation for ESBC is an effective and safe procedure with excellent cosmetic outcomes and improved QoL. This study contributes to the growing evidence supporting cryoablation as a potential standard treatment for ESBC, given compliance to pre-defined patient selection criteria.

An approach for improvement of the accuracy of cancer gene panel testing.

BACKGROUND: Tissue-based comprehensive genomic profiling (CGP) is increasingly being employed for genotype-directed therapies in patients with advanced cancer. However, tissue availability may limit their potential applications. In Japan, the cost of cancer gene panel tests is covered by public insurance for patients diagnosed with advanced solid tumors once in their lifetime. Therefore, it is essential to improve the success rate (reportability) and accuracy of CGP tests. The purpose of this study was to identify the factors associated with efficient and accurate CGP testing using relevant information obtained from real-world data. METHODS: This study included 159 samples analyzed using tumor-only panel FoundationOne® CDx cancer genome profiling (F1CDx) and 85 samples analyzed using matched-pair panel OncoGuide™ NCC Oncopanel system (NCCOP) at St. Marianna University Hospital. Sample characteristics (fixation conditions, storage period, histology, tumor cell ratio, and genomic tumor cell content), CGP performance, and quality control status were evaluated across all 244 tested samples. RESULTS: In 237/244 samples (97.1%), CGP testing results were successfully obtained [F1CDx, 99.4% (158/159) and NCCOP, 92.9% (79/85)]. An increased number of fibroblasts, inflammatory cells, and necrotic tumor cells, long-term storage, and/or prolonged fixation of tissue sections were involved in the unreported results and/or qualified CGP results. In addition, a negative correlation between median insert size values and ΔΔCq was observed in the NCCOP system. CONCLUSION: We identified various factors associated with efficient and accurate CGP testing using relevant information obtained from real-world data, suggesting that thorough selection and preparation of tissue sections could optimize CGP and maximize useful information.

Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast.

In a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.

[Clinical Significance of the Curative Effect after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer-Correlation to Prognosis].

We investigated factors related to the recurrence and prognosis of patients with triple-negative breast cancer (TNBC)after neoadjuvant chemotherapy(NAC). Of the 545 patients who underwent surgery after NAC between January 2013 and December 2016, 131 patients had TNBC. An analysis of each TNBC case indicated that the presence or absence of clinical lymph node metastasis(cN)before treatment might be a predictive factor of prognosis. There were 57(43.5%)pathological complete response(pCR)(ypT0 or ypTis/N0)cases after NAC. Overall survival(OS)and disease free survival(DFS) were significantly better in pCR cases than in non-pCR cases. However, recurrence was observed in 8 of 57(14%)pCR cases and 29 of 74(39%)non-pCR cases. The factors defining DFS from the univariate analysis of the non-pCR group were cN, ypT, ypN, and vascular invasion. The multivariate analysis of these factors suggested that residual cN and vascular invasion might be independent factors predicting DFS. Residual vascular invasion was found to predict OS, and was considered to be a poor prognostic factor.

Trastuzumab Emtansine (T-DM1) Plus S-1 in Patients with Trastuzumab-Pretreated HER2-Positive Advanced or Metastatic Breast Cancer: A Phase Ib Study.

BACKGROUND: In treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, the efficacy of capecitabine combined with HER2-directed agents such as trastuzumab and lapatinib is supported by some evidence. The combination of T-DM1 and S-1, another oral 5-FU, may be a safe alternative treatment for metastatic breast cancer. OBJECTIVES: The optimal dose of S-1 was evaluated in combination with T-DM1 for patients with HER2-positive advanced or metastatic breast cancer. The safety and clinical response of this combination treatment were also assessed. METHODS: This 3 + 3 dose-escalation study of S-1 given for the first 2 of 3 weeks, in combination with T-DM1 (3.6 mg/kg given every 3 weeks) to patients with trastuzumab-pretreated HER2-positive advanced or metastatic breast cancer was designed to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. We also evaluated the safety and clinical activity of this combination treatment in multiple cycles. Two different dose levels of S-1 (65 and 80 mg/m2/day) were planned, although the capecitabine arm was abandoned because of slow recruitment. RESULTS: Twelve out of the 13 patients enrolled were evaluable for DLT. One DLT (grade ≥3 non-hematological adverse events) occurred at dose level 0, leading to the expansion of this cohort to 6 patients, with an additional DLT (≥7 days discontinuation of medication), while no DLT occurred at dose level 1. As a result, the maximum tolerable dose of S-1 was determined to be 80 mg/m2/day for 14 days with T-DM1 3.6 mg/kg, repeated every 3 weeks. Two patients had grade 3 thrombocytopenia at dose level 0, and 1 patient at dose level 1. CONCLUSIONS: S-1 can be safely combined with the clinically relevant dose of T-DM1 in patients with HER2-positive advanced or metastatic breast cancer. Further evaluation with a larger sample size is required for efficacy assessment.

Histopathological and immunohistochemical evaluations of breast cancer treated with radiofrequency ablation.

BACKGROUND: Although RF ablation is a promising non-surgical ablation technique for the treatment of breast cancer, assessment of the efficacy requires not only imaging of tumor necrosis but also histological confirmation. METHODS: Two series of patients were treated with RF ablation. In the first series, 17 patients underwent surgical resection immediately and 17 underwent delayed mammotome excision in the second series. The ablated tumor tissue was examined histologically with H&E staining and NADH-diaphorase staining. Furthermore, ssDNA was immunohistochemically stained in the specimen where tumor cells were histologically detected. RESULTS: In the first series, mild response was histologically seen in 14 of 17 patients (82%), whereas complete response was observed in 8 of 16 patients (50%) in the second series. However, NADH-diaphorase staining did not demonstrate any viable tumor tissues in any patient in either the first or the second series. ssDNA staining was positive (non-viable) in 13 of 16 cases in the first series, but it was positive in all 8 cases tested in the second series. CONCLUSION: Although NADH-diaphorase staining is essential to evaluate tumor cell viability immediately after RF ablation, ssDNA may be useful for the assessment of cell viability after some interval following RF ablation.

Radiofrequency ablation therapy for small breast cancer followed by immediate surgical resection or delayed mammotome excision.

BACKGROUND: There is increasing demand for minimally invasive treatment approaches. Although radiofrequency (RF) ablation therapy is promising for the local treatment of small, well-localized breast cancer, the problem of determining tumor cell death after RF ablation remains. METHODS: In the first series of this study, 17 patients underwent surgical resection immediately after RF ablation and 7 patients received delayed mammotome excision in the second series. The ablated tumor tissue was examined histologically with hematoxylin-eosin (H&E) staining and nicotinamide adenine dinucleotide (NADH)-diaphorase staining to assess tumor cell viability. RESULTS: Histological examination with H&E staining revealed a spectrum of changes ranging from complete coagulation necrosis to normal-appearing tumor cells, although the degenerative changes were more remarkable in the second than in the first series. However, NADH-diaphorase staining revealed no viable tumor cells in the ablated lesion in either series. CONCLUSIONS: NADH-diaphorase staining is essential to assess the effects of RF ablation. However, further studies are needed to determine whether RF ablation may provide equivalent local control and survival compared with conventional BCT for patients with small breast cancer.