[Phyllodes Tumor of the Breast Occurring near Postoperative Fibroadenoma Scar-A Case Report].

We report the case of a phyllodes tumor of the breast occurring near a postoperative scar of fibroadenoma of the breast. The patient was a 41-year-old female who had a lump in the left breast, and underwent surgical resection of the tumor 5 years ago at another hospital.The pathological diagnosis of the tumor was fibroadenoma, and surgical margin was negative. The patient underwent ultrasonography every year at the treatment hospital.Five years later, the patient noticed a tumor in her left breast and visited our hospital.The tumor was 30mm in diameter and situated near the postoperative scar.A core needle biopsy for breast tumor led to the diagnosis of a phyllodes tumor.Surgical resection was performed with 5mm margins, and pathological analysis of the surgical specimen revealed a benign phyllodes tumor.The surgical margins were not involved.One year and 6 months after surgery, no metastases or recurrence were reported.

[Breast Papilloma with Rapid Growth Difficult to Distinguish from Carcinoma-A Case Report].

We report a case of papilloma of the breast with rapid growth in a 39-year-old female who had a lump in the left breast. The follow-up for the breast tumor was performed at another hospital.Three years after her first visit, 3 tumors measuring 1.8 cm, 0.5 cm, and 0.3 cm in diameter were detected. The patient visited our hospital to diagnose these tumors. We performed core needle biopsy for the tumor, and the pathological diagnosis was benign papilloma.After 1 year, the tumor grew to 3.0 cm in diameter, and we repeated the core needle biopsy. The pathological diagnosis remained as benign papilloma; however, the ultrasonography and MRI results showed that the tumor was malignant.Surgical resection was performed for the tumors, and pathological analysis of the surgical specimen revealed 3 benign papillomas with no involvement of the surgical margin.Six years after surgery, no recurrence was reported.

[Treatment for Breast Cancer in an Elderly Male Patient-Report of a Case].

Breast cancer in male is comparatively rare. We encountered a case of breast cancer in an elderly male who was treated with consideration of age. A 78-year-old male consulted our hospital with a lump on his right breast. The tumor was 3 cm in diameter and was palpable in the E area of his right breast, accompanied by pain. Mammography showed an indistinct mass in the S area. Ultrasonography revealed a well-defined and rough, lobulated mass. Core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. Metastatic work-up revealed no evidence of metastasis. The patient underwent mastectomy with sentinel lymph node(SN)biopsy and axial lymph node dissection(Ax)because of positive metastasis in an SN. The pathological findings from the surgically resected specimens indicated solid-tubular carcinoma. Lymph node metastases were observed in an SN(1/1)and Ax(1/3). On immunohistochemistry, tumor cells tested positive for estrogen and progesterone receptors and negative for HER2/neu protein expression. The Ki-67 labeling index was 14%. Postoperatively, the patient has not received chemotherapy, but received hormone therapy as adjuvant therapy considering his age. Nine months after the surgery, the patient is well, and metastasis has not appeared.

[Advanced-Stage Breast Cancer Discovered by Cervical Lymphadenopathy in an Elderly Patient-Report of a Case].

Breast cancer spreading beyond the regional lymph nodes from the primary lesion is considered to be difficult to cure. Although systemic therapy is common for the treatment of metastatic breast cancer, standard therapy is difficult in some cases. We encountered a case of advanced-stage breast cancer detected by cervical lymphadenopathy in an elderly patient. An 82-year-old woman consulted an otolaryngologist for left cervical lymphadenopathy. On receiving the biopsy result, she was referred for a suspected metastatic lymph node from breast cancer. The tumor was 40mm in diameter and was palpable in the CD area of her left breast, accompanied by pain. Ultrasonography showed an irregular-shaped mass. Core needle biopsy was performed, and the pathological diagnosis was invasive lobular carcinoma. Her body check-up revealed multiple enlarged lymph nodes from the left axilla to the supraclavicular and cervical areas. We diagnosed her clinical stage with T2N3cM1, stage Ⅳ(LYM). We proceeded with surgery to alleviate the symptom. Breast reduction surgery was performed for the left breast. The pathological findings from the surgically resected specimens indicated invasive lobular carcinoma. After the surgery, 5-fluorouracil(5-FU)drug was orally administered. Cervical lymphadenopathy decreased, and visceral metastasis has not appeared.

[Usefulness of Automated Breast Ultrasound for Deciding on a Surgical Approach in a Patient with Breast Cancer- A Case Report].

Since breast reconstruction has been covered by health insurance, we can choose a procedure that combines the cosmetic satisfaction of patients with curability. We report about a patient with breast cancer that who underwent nipple-sparing mastectomy after evaluating the intraductal spread by automated breast ultrasound system(ABUS), while hand held ultrasound( HHUS)showed only limited information on the intraductal spread of the lesion. A 52-year old woman with an abnormal screening finding was referred to our hospital. HHUS showed an irregular and poorly defined hypoechoic mass lesion with a lactiferous duct extending to directly under the nipple. A core needle biopsy revealed invasive ductal carcinoma. We performed ABUS to assess the intraductal spread in the lesion because the patient requested breast reconstruction. The coronal section of the breast in the ABUS did not showintraductal spread. We, therefore, decided to perform a nipple-sparing mastectomy and sentinel lymph node biopsy. Intraoperative evaluation by frozen and permanent sections showed negative margins. The ABUS findings helped in the evaluation of the intraductal spread of the lesion and in the choice of the optimal procedure for the patient.

[Usefulness of Breast Ultrasound in Follow-Up of Post-Operative Metachronous Contralateral Breast Cancer-A Case Report].

Mammography is the standard screening toolfor post-operative breast cancer, with annualcheck -ups recommended; however, it misses some cancers. We report a case a metachronous contralateral breast cancer detected by breast ultrasound 8 years and 6 months after operation. A 72-year-old women visited our hospital for follow-up 8 years and 6 months after the operation. She was diagnosed with right breast cancer at 63 years of age and underwent partial mastectomy with axially lymph node dissection. The pathological diagnose was scirrhous carcinoma. After chemotherapy and radiation therapy, she underwent screening with annual examinations. The mammography finding was normal, but an ultrasound showed a mass lesion in the contralateral breast. The pathological diagnosis of the biopsy specimen was mucinous carcinoma. A history of breast cancer is known to suggest an increased risk of metachronous contralateral breast cancer. Therefore, regular follow-up with breast ultrasound, not only mammography, is recommended.

[A Case of an Elderly Individual with Breast Cancer Diagnosed as Paget's Disease after Mastectomy].

We report here a case of a 78-year-old woman, who underwent mastectomy for breast cancer. Mammography showed a mass in the right MO area with an unclear boundary. Ultrasound examination revealed an irregular mass of 40×29×19mm in the right C region. Dynamic contrast-enhanced MRI showed a 34mm tumor with contrast effect in the C area of the right breast. We performed a core needle biopsy on the mass, and the histopathological diagnosis was apocrine carcinoma(ER-, PgR-, HER2 3+, and Ki-67 30%)of clinical T2N0M0, stageⅡA. Right mastectomy and sentinel lymph node biopsy were performed. In the postoperative pathological examination, the main lesion was apocrine carcinoma(ER-, PgR-, HER2 3+, Ki-67 20%)and Paget's disease(ER-, PgR-, HER2 3+, Ki-67 30%). After surgery, the patient was given trastuzumab therapy.

[A Case of Sentinel Lymph Node Biopsy for Breast Cancer in an Elderly Man].

A 75-year-old man noted an elastic hard tumor under his left areola.Mammography showed a microlobulated mass, so he was diagnosed with category Ⅳ breast cancer.Ultrasonography showed a circular hypo-echoic mass that was 21mm in diameter with a moderately indistinct border.Based on core needle biopsy, the tumor was diagnosed as invasive ductal carcinoma.We performed a whole-body check-up, and he was diagnosed with T1N0M0, StageⅠ breast cancer.The patient underwent mastectomy and sentinel lymph node biopsy.The pathological diagnosis based on the resected surgical specimen was invasive ductal carcinoma, positive for ER and negative for PgR and HER2/neu protein expression, and the Ki-67 positive cell index was 20%.The surgical margins were negative, and there was no metastasis in the sentinel lymph nodes.He was administered endocrine therapy as adjuvant therapy.Two years after the surgery, he remains well without metastases.

[A Case of Duplicated Cancer Simultaneously Causing Breast and Endometrial Cancer].

Recently, with the increase in the number of young cancer patients, we often encounter multiple primary cancer(MPC). In MPC, careful examination is necessary because the treatment order and policies change greatly depending on the stage and prognosis of each tumor. We report a case of synchronous MPC of endometrialcancer and breast cancer. The patient was a 40-year-old woman who underwent endometrial cytology by a previous doctor due to illicit bleeding. As a result of the diagnosis of classⅢB, she underwent gynecological examination in our hospital. Endometroid adenocarcinoma Grade 2 was diagnosed based on endoscopic findings. On pelvic MRI, a lesion adjacent to the neck showed a low signal in the uterine body compared to that in the endocardium. During the preoperative examination, CT showed contrast nodules in the right breast, and ultrasonography was performed at the department of breast surgery. Ultrasonography showed a low-echo mass of 23 mm in the right upper midline region. The needle biopsy results were papillotubular cancer(ER-negative, PgR-negative, HER2 1+, Ki-67 77%). Based on these findings, right breast cancer and endometrial cancer were diagnosed. Initially, we performed right mastectomy and sentinel lymph node biopsy; we then performed pancreatectomy in the gynecology department 2 weeks after discharge. After surgery, gynecology studied 6 courses of TC therapy, and currently, EC is undergoing breast surgery.

[The Diagnostic Problem of Automated Breast Volume Scanner(ABUS)for a Breast Cancer Patient with Dementia-A Case Report].

The patient was an 84-year-old woman.She had presented with a mass on her right breast.Mammography revealed an illdefined mass.Handheld ultrasonography(HHUS)revealed a low echoic mass, 25mm in diameter, on the AC area of her right breast.An automated breast volume scanner(ABUS)was not useful for detecting the lesion because the patient had dementia and restless body movements.A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma, which was positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.We examined her whole body and made a diagnosis of T2N0M0, StageⅡA.She underwent a muscle-preserving mastectomy plus sentinel lymph node biopsy.The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma, positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.The surgical margins were negative for malignancy, and no metastasis was observed in the sentinel lymph node.She was given endocrine as adjuvant therapies.Three years after the surgery, she was well without metastases.Patients with dementia could not use ABUS.HHUS will be useful for these patients.

[The Diagnostic Problem of the Automated Breast Volume Scanner(ABUS) for Paget Disease-A Case Report].

The patient, a 41-year-old woman, presented with an elastic soft tumor on her left breast. Sore skin was observed on the left nipple and areola. Mammography revealed poor extension at the left nipple surrounding skin. A hand-held ultrasonography( HHUS)device and automated breast volume scanner(ABUS)did not detect the thickening of the skin. Surgical biopsy was performed. The skin lesion was diagnosed as Paget disease. We examined her whole body and made a diagnosis of Tis N0 M0, stage 0. The patient underwent a mastectomy and sentinel lymph node biopsy. The pathological diagnosis on the basis of the resected surgical specimen was invasive ductal carcinoma, negative for ER and PgR, and positive for HER2/neu protein expression, and the Ki-67-positive cell index was 30%. The surgical margins were negative, and no metastasis was found in the sentinel lymph node. She was given trastuzumab as adjuvant therapy. Two years after the surgery, she was well without recurrence.

[A Case of Synchronous Bilateral Breast Cancer in an Elderly Patient].

We encountered a case of synchronous bilateral breast cancer in an elderly patient. A 75-year-old woman visited our hospital because she was identified with an abnormality on mammography during breast cancer screening. An elastic hard tumor 2.0 cm in diameter was detected in the A area of her right breast. Mammography showed an irregular tumor shadow with spicula in the right breast and micro-calcifications in her left breast. Ultrasonography showed a low echoic lesion 20mm in size in the A area of her right breast and a low echoic area 5mm in size in her left breast. Histological examination of core needle biopsy specimens revealed invasive ductal carcinoma in both breasts. Synchronous bilateral breast cancer was diagnosed. Bilateral muscle-preserving mastectomy with sentinel lymph node biopsy was performed. Postoperative histology revealed bilateral invasive ductal carcinoma without lymph node metastasis that was positive for ER and PgR, was negative for HER2, and had a Ki-67-positive cell index of 20% in the right breast(T1N0M0, Stage Ⅰ), and that was positive for ER, was negative for PgR and HER2, and had a Ki-67-positive cell index of 5% in the left breast(T1N0M0, Stage Ⅰ). The surgical margins were negative. She was administered endocrine therapy as adjuvant therapy for 5 years after the surgery. Eight years after the surgery, she was well without metastasis.

[Breast Cancer Operation for a Patient Administered Immunosuppressive Drug-A Case Report].

A 57-year-old woman with a history of interstitial pneumonia since 5 years ago was diagnosed with a 10mm diameter tumor during the medical examination and consultation at the hospital. The tumor was palpable in the AC area of her right breast. An ultrasonography showed an irregular-shaped mass. A vacuum-assisted biopsy was performed, and the pathologicaldiagnosis was suspicious for malignancy. Then, we performed an excisionalbiopsy and confirmed the definitive diagnosis of invasive ductalcarcinoma. However, surgicalmargins were positive on the skin and lateralside; therefore, we conducted a two-stage surgery. Interstitialpneumonia was in the active phase, and she was administered sufficient amount of immunosuppressive drugs. Therefore, we performed additionalresection under localanesthesia, not generalanesthesia. Interstitial pneumonia did not worsen perioperatively, and the postoperative course was uneventful. Surgeries performed while the patient is administered with immunosuppressive drugs may cause infections and delayed wound healing. Thus, perioperative complications should be carefully considered.

[Indoleamine 2,3-Dioxygenase Activity during Long-Term Letrozole Therapy for Hormone Receptor-Positive Breast Cancer].

Endocrine therapy is effective for elderly patients who are diagnosed with estrogen receptor-positive breast cancer and cannot receive surgical treatment or chemotherapy because of advanced age. The duration of response in patients receiving letrozole is approximately 10.3 months. There are few cases with more than 3 years of response. We evaluated the significance of indoleamine 2,3-dioxygenase(IDO)during letrozole therapy in long-term response. We measured IDO activity based on the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn levels were measured using high-performance liquid chromatography(HPLC). The Trp/Kyn ratio decreased along with tumor reduction after letrozole therapy. These results suggest that measuring the Trp/Kyn ratio may be useful for evaluating immunological status during endocrine therapy in elderly patients with locally advanced breast cancer.

[Neuroendocrine Carcinoma of the Breast Encountered in the General Hospital without the Breast Department-A Case Report].

Neuroendocrine carcinoma(NEC)is a rare disease. We report a case of NEC encountered in the general hospital without a breast department. The patient was a 69-year-old woman. She had received breast cancer screening and a mass on her left breast was found. Mammography revealed an ill-defined mass. Ultrasonography showed a low echoic mass, 11mm in diameter, on the A area of her left breast. A core needle biopsy of the breast tumor(A area)led to a diagnosis of an invasive ductal carcinoma, positive for estrogen receptor and progesterone receptor, but negative for HER2/neu. The Ki-67 positive cell index was 5%. We then examined her whole body and diagnosed her with T1N0M0, Stage Ⅰ. She underwent muscle-preserving mastectomy plus sentinel lymph node biopsy. The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma(NEC), positive for estrogen receptor and progesterone receptor, but negative for HER2/neu. The Ki-67 positive cell index was 5%. The surgical margins were negative, and no metastasis was found in the sentinel lymph node. She was administered endocrine therapy as adjuvant therapy. Two years postoperatively, she was well without metastases.

[Treatment Experience of Palbociclib as a New Checkpoint Inhibitor].

We encountered a case of multiple metastases from breast cancer. The patient was administered palbociclib, which was a new checkpoint inhibitor. The patient received various chemotherapies and endocrine therapies. We observed episode of care, a harm phenomenon, and tolerability. We did not recognize adverse events more severe than Grade 3 during the 6 weeks after initiating palbociclib therapy. Diagnostic imaging showed that the metastatic lesions maintained stable disease during the 6 weeks after initiating palbociclib therapy. This case suggested that palbociclib therapy is useful for patients with metastatic breast cancer.

Premature senescence is regulated by crosstalk among TFEB, the autophagy lysosomal pathway and ROS derived from damaged mitochondria in NaAsO2-exposed auditory cells.

Age-related hearing loss (ARHL) is one of the most prevalent types of sensory decline in a superaging society. Although various studies have focused on the effect of oxidative stress on the inner ear as an inducer of ARHL, there are no effective preventive approaches for ARHL. Recent studies have suggested that oxidative stress-induced DNA damage responses (oxidative DDRs) drive cochlear cell senescence and contribute to accelerated ARHL, and autophagy could function as a defense mechanism against cellular senescence in auditory cells. However, the underlying mechanism remains unclear. Sodium arsenite (NaAsO2) is a unique oxidative stress inducer associated with reactive oxygen species (ROS) that causes high-tone hearing loss similar to ARHL. Transcription factor EB (TFEB) functions as a master regulator of the autophagy‒lysosome pathway (ALP), which is a potential target during aging and the pathogenesis of various age-related diseases. Here, we focused on the function of TFEB and the impact of intracellular ROS as a potential target for ARHL treatment in a NaAsO2-induced auditory premature senescence model. Our results suggested that short exposure to NaAsO2 leads to DNA damage, lysosomal damage and mitochondrial damage in auditory cells, triggering temporary signals for TFEB transport into the nucleus and, as a result, causing insufficient autophagic flux and declines in lysosomal function and biogenesis and mitochondrial quality. Then, intracellular ROS derived from damaged mitochondria play a role as a second messenger to induce premature senescence in auditory cells. These findings suggest that TFEB activation via transport into the nucleus contributes to anti-senescence activity in auditory cells and represents a new therapeutic target for ARHL. We have revealed the potential function of TFEB as a master regulator of the induction of oxidative stress-induced premature senescence and the senescence-associated secretion phenotype (SASP) in auditory cells, which regulates ALP and controls mitochondrial quality through ROS production.

Heat-Killed Levilactobacillus brevis as a Candidate Postbiotics Through Immunostimulation Mediated by Macrophage-Inducible C-Type Lectin.

To understand the beneficial health-promoting effects of lactic acid bacteria (LAB) on immune cells, it is necessary to understand the relationship between LAB and innate immune receptors. We investigated the possible involvement of C-type lectin receptors (CLRs) in the immune-stimulating function of LAB in several strains. We found that levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 were reduced by the addition of inhibitors for spleen tyrosine kinase (syk), a signaling molecule used by several CLRs. Furthermore, employing CLR-Fc fusion proteins and reporter cells, we found that macrophage-inducible C-type lectin (Mincle) binds to Levilactobacillus brevis strain La37. Interestingly, this interaction was only observed in heat-killed L. brevis and disappeared after proteinase K treatment. Seven strains of L. brevis from different sources were also examined; among them, six strains showed Mincle reactivity, and the characteristics of the ligand were similar to those of La37. These results may facilitate a better understanding of the immunomodulatory effects of LAB for the development of functional foods.

Effectiveness of Changing the Class of Molecularly Targeted Agent after Disease Progression during Initial Molecularly Targeted Therapy for Luminal Advanced/Metastatic Breast Cancer.

BACKGROUND: The emergence of molecularly targeted agents (MTAs) has altered the treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC) /metastatic breast cancer (MBC). Multiple guidelines recommend molecularly targeted therapy as first-line treatment for HR+/HER2- ABC/MBC. However, optimal treatment for disease progression during MTA therapy remains undetermined. This study evaluated the suitability of different MTA types for this patient subgroup. METHODS: In this retrospective study, we analyzed the electronic health records of 56 patients with HR+/HER2- ABC/MBC receiving treatment with palbociclib, abemaciclib, or everolimus in our center between April 2014 and June 2021. RESULTS: Overall, 39, 14, and 35 regimens using palbociclib, abemaciclib, and everolimus, respectively, were identified. Three and 53 patients were premenopausal and postmenopausal, respectively. MTAs were included in the 1st-11th lines of treatment. Time to failure (TTF) was significantly different among the three MTAs. In contrast, TTF did not significantly differ among the 50 regimens that included CDK4/6 inhibitors, with/without prior mTOR inhibitor use, and the 35 regimens that included mTOR inhibitors, with/without prior CDK4/6 inhibitor use. CONCLUSIONS: The sequential use of different MTA classes did not affect the TTF of another MTA. mTOR inhibitor + exemestane is a favorable treatment option after CDK4/6 inhibitor + hormone therapy, and CDK4/6 inhibitor + hormone therapy is suitable for patients previously treated with mTOR inhibitor + exemestane. Although this study was retrospective and conducted at a single center, the present findings are useful for treatment selection in clinical practice.

Molecular targeted drugs resistance impairs double-strand break repair and sensitizes ER-positive breast cancer to PARP inhibitors.

BACKGROUND: There are various treatments for estrogen-positive breast cancer, mainly hormone therapy and molecular-targeted drugs. Acquiring resistance to these drugs is a major clinical problem. Additionally, little is known about the effect of drug resistance on the DNA repair mechanism. Poly ADP ribose polymerase (PARP) inhibitors currently used for treating HER2-negative metastatic breast cancer with BRCA mutations have been shown to be effective in BRCA-deficient cells with impaired homologous recombination repair. Here, we investigated the effect of drug resistance acquisition on the DNA repair mechanism and the effect of PARP inhibitors on ER (estrogen receptor) -positive breast cancer. METHODS: We investigated changes in the expression of DNA repair mechanism-related factors and repair ability of double-strand breaks (DSB) in various drug-resistant cell lines established in our laboratory. Additionally, PARP inhibitor susceptibility was investigated using olaparib. RESULTS: DSB repairs in MCF-7 and hormone therapy-resistant model cells were normal, and these cells demonstrated low sensitivity to olaparib. The resistant cell lines against CDK4/6 inhibitors, fulvestrant and mTOR/PI3K inhibitors showed decreased DSB repair ability and high olaparib sensitivity. They showed low sensitivity to CDK4/6 inhibitors, a close link between acquiring resistance to CDK4/6 inhibitors and hypersensitivity to olaparib. CONCLUSIONS: Our study suggests some cases of acquiring drug resistance impairs DSB repair ability and sensitizes ER-positive breast cancer to PARP inhibitors.