A case of phyllodes tumor with rapid growth during pregnancy and lactation period: a case report.

BACKGROUND: The age of onset of the phyllodes tumor is generally in the late 40 s, and diagnosis and treatment during pregnancy and lactation are rare. We herein present a case of a phyllodes tumor that rapidly increased in size during the pregnancy and lactation period. CASE PRESENTATION: A 39-year-old woman was referred to our hospital with a mass in the right breast that increased in size during the pregnancy and lactation period. On ultrasound (5 week postpartum), a well-defined lobulated mass with internal septations and fluid retention was observed. Magnetic resonance imaging of the breast at 8 week postpartum revealed a 70-mm-sized smooth-margin mass with multilocular cystic components. Marked proliferation of stromal cells with high cell density was observed in a biopsy specimen taken at the previous hospital. We diagnosed the mass as a phyllodes tumor of borderline malignancy and excised it at 13 week postpartum. The excised tumor was 85 mm in diameter and its interior was filled with a milk-like substance. Histologically, there was only a mild increase in stromal cell density but fibrosis with associated degeneration was prominent. The final diagnosis was benign phyllodes tumor with degeneration. CONCLUSIONS: We report a case of a phyllodes tumor that rapidly increased in size during pregnancy and the lactation period. The accumulation of a milk-like substance was thought to be responsible for the rapid growth of the tumor.

BRCAness of brain lesions reflects a worse outcome for patients with metastatic breast cancer.

PURPOSE: Breast cancer often metastasizes to the central nervous system. Although the prognosis of brain metastases from breast cancer has been considered poor, and systemic therapy has not contributed to an improved prognosis, newer agents are expected to be more effective. BRCAness is defined as the status of homologous recombination deficiency (HRD) in tumor tissue, regardless of the presence of pathogenic germline BRCA1/2 variants. A study employing next-generation sequencing analysis showed that HRD was found relatively frequently in brain metastases of breast cancer patients. However, there have been no studies evaluating BRCAness in brain metastases of breast cancer with more efficient, rapid, and cost-effective methods. METHODS: We retrospectively investigated 17 brain metastases of breast cancer that were surgically resected at our hospital from January 2007 to December 2022. Of these, samples from 15 patients were evaluable for BRCAness by employing multiplex ligation-dependent probe amplification (MLPA) assay. RESULTS: Of the 15 patients, five patients (33%) had tumors with BRCAness. Clinicopathological factors of patients with brain metastases with BRCAness were not statistically different from those of patients who possessed tumors without BRCAness. Patients with brain metastases with BRCAness had shorter overall survival compared to those without BRCAness (BRCAness, median 15 months (95% CI 2-30) vs. non-BRCAness, median 28.5 months (95% CI 10-60); P = 0.013). CONCLUSION: In this study, we evaluated BRCAness in brain metastases of breast cancer with the MLPA method, and found that about one-third of patients had BRCAness-positive tumors. The analysis of BRCAness using MLPA has the potential for practical clinical use.

Relationship Between Daily Dose of Everolimus and Treatment Effect in Patients With Luminal HER2-negative Metastatic Breast Cancer.

BACKGROUND/AIM: Everolimus (EVE)-based treatment is an option for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), but a predictive marker has not yet been established. The recommended dose of EVE in combination with endocrine therapy is 10 mg/day, but due to adverse effects, patients are frequently forced to reduce the dose. However, the correct maintenance dose to achieve a therapeutic effect is still under debate. Employing real-world data, we examined clinicopathological factors to predict the efficacy of EVE-based treatment, particularly focusing on daily dose intensity (DDI). PATIENTS AND METHODS: Ninety-five patients with MBC who received EVE-based treatment in combination with exemestane during the period from 2014 to 2022 were retrospectively investigated. Doses of EVE were reduced as needed and DDI was calculated with total doses of EVE and the duration of the treatment. RESULTS: Mean time-to-treatment-termination (TTT) was 25.4 weeks. Patients with tumors with a high Ki67 labeling index, low absolute lymphocyte count, and small DDI of EVE had significantly shorter TTT (p=0.006, 0.043, and 0.030, respectively). When patients were categorized based on DDI of EVE, patients with DDI ≤5 mg/day had significantly shorter TTT (p=0.002). There were no correlations between RDI and factors such as age, body weight, and numbers of previous treatments for MBC. CONCLUSION: Maintaining a DDI of at least 5 mg/day seems crucial to achieving a therapeutic effect. Our data might be useful for determining the dosage of EVE in clinical practice.

Encapsulated Papillary Carcinoma in an Elderly Male Whose Diagnosis Was Difficult before Surgery: A Case Report.

Encapsulated papillary carcinoma (EPC) is a relatively rare histologic type of breast cancer. It is sometimes difficult to obtain a definitive diagnosis by needle biopsy, reflecting its characteristics as an intracystic lesion. Herein, we report a case of EPC in an elderly male that was difficult to diagnose before surgery. A 70-year-old man visited our hospital after a mass just under his right nipple that gradually increased in size. Ultrasonography revealed a well-defined intracystic 50 mm-sized tumor and a papillary-shaped solid component arising from the cyst wall. Cytology revealed small clusters of atypical cells suggestive of malignancy, but we did not reach a definitive diagnosis with subsequent vacuum-assisted needle biopsy due to the small amount of specimen. Given the imaging findings strongly suggested a malignant tumor, a mastectomy was performed. Histologically, there was a thick fibrous capsule and mildly atypical cells showed papillary growth, and we diagnosed the case as EPC (pTisNXM0). Sometimes, EPC is difficult to discriminate from intracystic papilloma before surgery, but clinicians should always keep in mind that this histological type exists with a certain frequency in male patients.

Difference in the Care of Patients with Amyotrophic Lateral Sclerosis With and Without Intervention from the Palliative Care Team: Observations from a Center in Japan.

Background: Despite the significant palliative care needs for people living with amyotrophic lateral sclerosis (ALS), palliative medicine in Japan is mainly focused on oncologic disease. Objective: To compare the care provided to patients with ALS with and without intervention from the palliative care team (PCT and non-PCT groups, respectively). Design: This is a retrospective case-control study. Setting: One ALS center in Japan. Participants: Sixty patients with clinically definite ALS treated until death from January 2012 to December 2019. Measurements: We compared the two groups based on the presence of advance directives, patient age, use of noninvasive and invasive ventilation, maximum opioid dosage, and use of nonopioid palliative medications such as antidepressants and anxiolytics. We also compared the prescribing practices of the attending physicians. Results: There was no difference in the rate of advance directive completion between the PCT and non-PCT groups. Although all but one patient in the PCT group used opioids, only half of the patients in the non-PCT group used opioids (p < 0.001). The mean maximum opioid dosage was higher in the PCT group than in the non-PCT group (p = 0.003). Moreover, 79.2% and 41.7% of the PCT and non-PCT groups, respectively, received antidepressants or antianxiety agents (p = 0.004). Maximum opioid dosages were not different on the basis of attending physician's experience level. Conclusions: Opioid and nonopioid medications intended for symptom management were more likely to be prescribed to patients with ALS who received intervention from a PCT.

Amelioration of rheumatoid arthritis in a breast cancer patient treated with palbociclib: a case report.

Rheumatoid arthritis is a common autoimmune disease that requires new therapeutic agents. Cyclin-dependent kinase 4/6 inhibitors have recently been approved for metastatic breast cancer patients and have also been reported to improve the arthritis score in collagen-induced arthritis mouse models. We report a 56-year-old woman who had previously been diagnosed with rheumatoid arthritis and treated with methotrexate. At age 40, she underwent surgery with curative intent for breast cancer but subsequently developed lung metastases. Palbociclib, a cyclin-dependent kinase 4/6 inhibitor, was administered in combination with fulvestrant (anti-oestrogen drug) for metastatic breast cancer. One month later, serum matrix metalloproteinase-3 and C-reactive protein levels were markedly decreased, and her rheumatoid arthritis symptoms, which had worsened just prior to the detection of metastatic lung disease, showed amelioration. Methotrexate, which had been used to treat her rheumatoid arthritis, could subsequently be administered in a reduced dose. The cyclin-dependent kinase 4/6 inhibitor was also effective for the metastatic breast cancer, and, to date, the patient's disease has remained stable for more than one year. Based on the results of basic research, cyclin-dependent kinase 4/6 inhibitors are promising new therapeutic agents for rheumatoid arthritis patients, although these drugs have not, as yet, been used in a clinical setting. To the best of our knowledge, this is the first report to describe a patient whose rheumatoid arthritis responded to a cyclin-dependent kinase 4/6 inhibitor administered for metastatic breast cancer.

A Gastric Metastatic Lesion That Resembled Early-Stage Gastric Cancer on Endoscopy during Treatment for Recurrent Breast Cancer: A Case Report.

Breast cancer metastasis to the gastrointestinal tract is relatively rare. Patients with such disease often develop gastrointestinal symptoms, but it is sometimes asymptomatic. Endoscopic findings of gastric metastasis from breast cancer markedly vary from benign to malignant, and even in suspected malignant cases, it is often difficult to differentiate between primary and metastatic disease. We experienced a case in which an endoscopic examination performed during the treatment for metastatic breast cancer resembled an early-stage gastric cancer. A 71-year-old woman underwent curative surgery for right breast cancer 16 years previously. She underwent endoscopic submucosal dissection for early-stage gastric cancer 5 years ago. Two years ago, she developed metastatic disease in the lungs and mediastinal lymph nodes, and endocrine therapy was administered. At the same time, a follow-up endoscopy revealed a new elevated lesion, suspected to be an early-stage gastric cancer. However, histological diagnosis of the biopsy was metastasis of breast cancer. One and a half years later, a follow-up endoscopy revealed a gastric lesion that had reduced in size. She is still alive, having received a variety of systemic treatments. Patients with metastatic breast cancer are experiencing prolonged survival. Thus, follow-up endoscopy should be considered after the diagnosis of gastrointestinal metastasis considering the risk of lethal conditions, such as gastrointestinal bleeding and perforation. Our case serves as a reminder to clinicians how difficult it is to determine whether a gastric lesion is primary or metastatic based on endoscopic findings and the importance of communication with endoscopists and pathologists.

Short somatic alterations at the site of copy number variation in breast cancer.

Copy number variation (CNV) is a polymorphism in the human genome involving DNA fragments larger than 1 kb. Copy number variation sites provide hotspots of somatic alterations in cancers. Herein, we examined somatic alterations at sites of CNV in DNA from 20 invasive breast cancers using a Comparative Genomic Hybridization array specifically designed to detect the genome-wide CNV status of approximately 412 000 sites. Somatic copy number alterations (CNAs) were detected in 39.9% of the CNV probes examined. The most frequently altered regions were gains of 1q21-22 (90%), 8q21-24 (85%), 1q44 (85%), and 3q11 (85%) or losses of 16q22-24 (80%). Gene ontology analyses of genes within the CNA fragments revealed that cascades related to transcription and RNA metabolism correlated significantly with human epidermal growth factor receptor 2 positivity and menopausal status. Thirteen of 20 tumors showed CNAs in more than 35% of sites examined and a high prevalence of CNAs correlated significantly with estrogen receptor (ER) negativity, higher nuclear grade (NG), and higher Ki-67 labeling index. Finally, when CNA fragments were categorized according to their size, CNAs smaller than 10 kb correlated significantly with ER positivity and lower NG, whereas CNAs exceeding 10 Mb correlated with higher NG, ER negativity, and a higher Ki-67 labeling index. Most of these findings were confirmed or supported by quantitative PCR of representative DNA fragments in 72 additional breast cancers. These results suggest that most CNAs are caused by gain or loss of large chromosomal fragments and correlate with NG and several malignant features, whereas solitary CNAs of less than 10 kb could be involved in ER-positive breast carcinogenesis.

Primary breast non-Hodgkin's lymphoma in a 14-year-old girl: a case report.

BACKGROUND: Primary breast lymphoma is rare. Occurrence rates of malignant breast tumors in children are also quite low. We herein report a B-lymphoblastic lymphoma of the breast arisen in an adolescent girl. To the best of our knowledge, this is the youngest case with primary breast non-Hodgkin's lymphoma. CASE PRESENTATION: A 14-year-old Japanese girl felt a lump in her right breast and came to our hospital. A circumscribed soft mass, 30 mm in diameter, was palpable. Histological examination revealed atypical lymphoid cells diffusely spreading into the breast tissue. Based on results of immunohistochemistry and flow cytometry, her disease was diagnosed as B-lymphoblastic lymphoma (stage I). She was then referred to the pediatric department and received combination chemotherapy, based on a chemotherapy regimen for children with acute lymphoblastic leukemia. Following remission induction therapy, we confirmed no FDG uptake in the right breast on PET-CT scan. CONCLUSIONS: We have described a rare malignant lymphoma arising in the breast of an adolescent female. Histological assessment is necessary for diagnosis of breast lymphoma. However, it can be challenging with several reasons, and clinical information may contribute to the assessment. Moreover, treatments for lymphoma vary according to disease types. Thus, surgeons should collaborate closely with pathologists, pediatricians, and hematologists.

Neutrophil-to-lymphocyte ratio and histological type might predict clinical responses to eriburin-based treatment in patients with metastatic breast cancer.

BACKGROUND: Metastatic breast cancer (MBC) is generally considered to be incurable. Although many options are available for treating MBC, physicians often encounter difficulties in choosing the most appropriate treatment because the MBCs of individual patients respond differently even to the same treatments. Thus, predictive markers for therapeutic efficacy are urgently needed. Neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR, respectively), have been studied and established as prognostic markers for breast cancer patients but whether either or both of these markers are predictive of treatment responses is still unclear. Herein, we investigated predictive markers for eribulin-based treatment responsiveness in patients with MBC, by examining clinicopathological features, including several markers of immunocompetent cells in peripheral blood. METHODS: Clinicopathological features of the 104 patients with metastatic/Stage IV breast cancer given eribulin-based regimens were investigated in relation to clinical responses to eribulin-based treatments and progression-free-survival (PFS). RESULTS: Special histological types and high NLR at baseline were independently related to poor clinical responses to the treatments (p = 0.023 and 0.039, respectively). The Cox hazard model revealed that patients with oestrogen receptor (ER)-negative tumours and high NLR, monocyte-to-lymphocyte ratio (MLR) and PLR showed significantly shorter PFS (p = 0.021, 0.005, 0.008 and 0.030, respectively). On multivariate analysis, only ER status and NLR remained independent factors related to PFS (p = 0.011 and 0.003, respectively). CONCLUSIONS: Our data revealed that special histological types and high NLR might be factors related to low responsiveness to eribulin-based regimens in patients with MBC.

Impact of circulating tumour cells on survival of eribulin-treated patients with metastatic breast cancer.

Several clinical studies have examined circulating tumour cells (CTCs). However, the application of CTCs as a predictive/prognostic marker for breast cancer patients has yet to be established, particularly the selection of suitable markers for detecting CTCs. We recently investigated CTCs, including mesenchymal status, from metastatic breast cancer patients who had received eribulin-based treatment. We found that assessment of both mesenchymal and epithelial CTCs might be important for predicting eribulin responsiveness. In the current study, we followed up the outcomes of these patients after eribulin treatment and investigated the possibility of CTC analysis results serving as prognostic markers for this patient population. Twenty-one patients were enrolled and peripheral blood samples were collected before eribulin-based treatments. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Overall survival (OS) was assessed in relation to the number of CTCs and clinicopathological factors. During the observation period, 13 patients (62%) died due to breast cancer and the median OS was 18 months. Patients with high-grade tumours and a high total number of CTCs showed significantly shorter OS than those with low-grade tumours and smaller CTC burdens (p = 0.026 and 0.037, respectively). Patients who received eribulin as the first chemotherapy for metastatic disease showed longer OS (p = 0.006). Our data suggest that determining numbers of both mesenchymal and epithelial CTCs might predict survival for patients receiving eribulin.

Multiple Surgical Treatments for Repeated Recurrence of Skull Base Mesenchymal Chondrosarcoma.

We report a case of a young male who received multiple surgical treatments for repeated recurrence of skull base mesenchymal chondrosarcoma (MC). When the patient was 18 years old, we subtotally removed the skull base MC and he was treated with stereotactic radiosurgery for remnant tumors in the left cavernous sinus. After 30 months, we removed residual tumors that had regrown partially, via combined endonasal endoscopic and orbitozygomatic approaches. Over the next 65 months, the patient refused radical resection, and received six salvage surgeries, two stereotactic radiotherapies, and five stereotactic radiosurgeries for repeated recurrence. At 95 months after initial surgery, the tumors had extended to the skull base and nasal cavities. As a result, the left eye had been blinded and right visual acuity was deteriorated. We performed left anterior-middle cranial base resection, removal of nasal and intradural tumors, high flow bypass, en-bloc resection of the left cavernous sinus and clivus, and reconstruction using an abdominal flap. Even though the main tumors were removed with safety margins, tumors around the right optic nerve were removed by piecemeal to preserve right eye function. Six months after the radical resection, tumors in the right orbital apex recurred because we had been unable to remove the tumor with adequate safety margins. Skull base MC has a high tendency to recur locally, so these tumors should be radically removed with safety margins as early as possible to prevent recurrence.

Analysis of circulating tumour cell and the epithelial mesenchymal transition (EMT) status during eribulin-based treatment in 22 patients with metastatic breast cancer: a pilot study.

BACKGROUND: Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. However, the development of CTCs as a predictive marker for treatment effects on breast cancer remains an enormous task. We investigated CTCs, including epithelial mesenchymal transition (EMT) status, from metastatic breast cancer patients who had received eribulin-based treatment, which reportedly suppresses EMT as a means of tumour suppression. Our aim was to test the possibility of this method serving as a tool predicting eribulin efficacy. METHODS: Twenty-two patients were enrolled and peripheral blood samples were collected before eribulin treatment. CTCs were then examined using a Microfluidic Chip device. CTCs positive for vimentin and pan-cytokeratin were defined as mesenchymal and epithelial CTCs, respectively. Progression-free survival (PFS) and clinical response were assessable in 20 and 18 patients, respectively, in relation to the number of CTCs. RESULTS: Numbers of total CTCs were significantly increased in patients with progressive disease during treatment (p = 0.006). Median PFS was 14.6 weeks and patients with more total and mesenchymal CTCs at baseline had significantly shorter PFS (p = 0.0013 and 0.013, respectively). Multivariate logistic regression analysis revealed small number of total baseline CTCs and long disease-free survival to be related to long PFS (p = 0.0004 and 0.020, respectively). CONCLUSIONS: Our data suggest that determining both mesenchymal and epithelial CTCs at baseline might be a good tool for predicting eribulin responsiveness. Evaluation of mesenchymal CTC can be considered as a parameter in larger studies, while most clinical trials are currently employing only the detection of the epithelial cellular adhesion molecule (EpCAM).

Steroid-resistant autoimmune myelofibrosis in a patient with autoimmune hepatitis and Evans syndrome complicated with increased expression of TGF-ß in the bone marrow: a case report.

We here report a 47-year-old female with autoimmune myelofibrosis (AIMF) associated with liver damage caused by autoimmune hepatitis and Evans syndrome. Bone marrow biopsy revealed hypocellular marrow with grade 2 reticulin fibrosis and increased levels of B lymphocytes (CD20+), T lymphocytes (CD3+, CD8+), and plasma cells (CD138+). Immunohistochemical analysis revealed increased expression of transforming growth factor-ß (TGF-ß) in infiltrating lymphocytes and macrophages in the bone marrow. She was initially treated with oral prednisolone (PSL) for 2 months, which had a limited effect. However, after treatment with rituximab, the patient's pancytopenia showed improvement, allowing us to rapidly reduce the PSL dosage. The present case suggests the possibility that increased expression of TGF-ß in infiltrating lymphocytes and macrophages of bone marrow may contribute to the pathogenesis of AIMF. Prednisolone combined with rituximab may thus be an effective option for steroid-refractory cases.

[A Case of Primary Poorly Differentiated/Small Cell Carcinoma of the Breast in a Patient with Von Recklinghausen's Disease].

We report a case of neuroendocrine carcinoma and poorly differentiated/small cell carcinoma ofthe breast in a patient with von Recklinghausen's disease. The patient was a 46-year-old woman who was diagnosed with von Recklinghausen's disease when she was 22 years old. She presented with left breast pain, and physical examination revealed a firm mass in the left breast. A core needle biopsy of the tumor revealed triple negative breast cancer with neuroendocrine features. We performed a simple mastectomy with lymph node dissection. We did not plan neoadjuvant chemotherapy because the tumor would be possibly inoperative if neoadjuvant chemotherapy was not effective for this neuroendocrine cancer. The tumor was diagnosed as a neuroendocrine carcinoma and poorly differentiated/small cell carcinoma. The patient was treated with CDDP and CPT- 11, which is a regimen often used to treat small cell lung cancer.