The Cyclin-Dependent Kinase 4/6 Inhibitor Abemaciclib Is Tolerated Better than Palbociclib by Advanced Breast Cancer Patients with High Serum Albumin Levels.

The cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib, have been approved in Japan. However, the selection criteria for these drugs have not been established. Hence, we aimed to identify the risk factors for CDK4/6 inhibitor-induced intolerable adverse events requiring dose reduction or therapy cessation and to establish useful markers for choosing the appropriate CDK4/6 inhibitor, based on the incidence of the intolerable adverse events. This retrospective cohort analysis included patients with advanced breast cancer who received 125 mg/d palbociclib or 300 mg/d abemaciclib. We defined significant adverse events (SAEs) as side effects requiring dose reduction or therapy cessation. Thirty-six percent of the patients who received palbociclib (9/25) and 27.3% of those who received abemaciclib (9/33) experienced SAEs. In palbociclib and abemaciclib groups, baseline white blood cell (WBC) counts and serum albumin (ALB) levels, respectively, were significantly lower in patients who experienced SAEs than in those who did not (palbociclib: p = 0.007; abemaciclib: p = 0.004). According to the receiver operating characteristic curve analysis, the optimal cutoff values for baseline WBC count and ALB level were 5700/µL and 4.0 g/dL, respectively. Among patients with ALB levels >4.0 g/dL, the incidence of abemaciclib-induced SAEs was significantly lower than that of the palbociclib-induced SAEs (1/17 (5.9%) vs. 6/14 (42.9%), odds ratio: 11.0, 95% confidence interval: 1.07-583, p = 0.0281). Thus, a baseline WBC count ≤5700/µL and ALB level ≤4.0 g/dL may be risk factors for palbociclib and abemaciclib-induced SAEs, respectively. Also, high ALB levels can serve as a useful marker for choosing abemaciclib.

[A Case of Liver Abscess during Treatment for Abemaciclib-Induced Interstitial Lung Disease].

The patient was a 64-year-old woman. The patient was operated for left breast cancer(pT2N0M0, stage ⅡA, Luminal A). Eight years after surgery, CT findings revealed lung metastasis in the S8 and S9 areas of the left lung. The patient was treated with a combination of abemaciclib and letrozole, which resulted in a partial response(PR). One year after treatment, the lung metastases remained small, but multiple interstitial shadows appeared in both lower lung fields. The patient was diagnosed with drug-induced interstitial lung disease(Grade 1), and abemaciclib withdrawal and steroid therapy were initiated. After 3 months of treatment with prednisolone at 30 mg/day, the interstitial shadows tended to improve on CT, but a liver abscess was found in the S8 area of the right lobe of the liver. Prednisolone was tapered and abemaciclib was resumed at a dose of 200 mg/day, resulting in scarring of the lung injury and resolution of the liver abscess. The patient's PR was maintained for 18 months after relapse. We report a case of liver abscess during treatment of abemaciclib-induced interstitial lung disease.

Treatment of anaplastic thyroid cancer with tyrosine kinase inhibitors targeted on the tumor vasculature: initial experience in clinical practice.

Anaplastic thyroid cancer (ATC) is a rarely occurring refractory disease. While recent clinical trials have demonstrated the efficacy of tyrosine kinase inhibitor (TKI) therapy for ATC, evidence is scarce in clinical practice. In this study, we reviewed our initial experiences with TKI treatment in ATC patients with the aim of revealing the efficacy and safety of the same in clinical practice. We retrospectively reviewed our experiences with TKI treatment use in ATC patients diagnosed at our institute from 2014 to 2019. Changes in the patients' neutrophil-to-lymphocyte ratio (NLR) by TKI therapy introduction as well as their clinical factors to indicate the efficacy were examined. Seven patients showed no indication for TKI treatment, while 13 (65%) received treatment. The median duration of TKI treatment was 1.9 months. All patients died, and the overall survival period from diagnosis was 4.7 (95% confidence interval: 2.0-11.5) months. Adverse events ≥Grade 3 were observed commonly (92.3%), and resulted in the termination of TKI treatment in six cases (46.1%). Existence of multiple unfavorable characteristics (higher Prognostic Index) was associated with poor survival. The NLR decreased after the introduction of TKIs and increased again when treatment failed. The response rate to TKI among the ATC patients were approximately 30% in practice. Although the duration of the response was short, several patients demonstrated long survival durations when TKI treatment was provided after successful multidisciplinary treatment to control local disease. Decreases in high NLR values during treatment may suggest the continued effect of TKIs.

[A Case of a Malignant Phyllodes Tumor in the Breast with Lymph Node Metastasis].

A 52-year-old woman experienced right breast pain and detected a mammary tumor 6 months ago. She then noticed rapid enlargement of the tumor, which was suspected to be a borderline malignant phyllodes tumor. The tumor size was approximately 15 cm and presented with skin congestion but without infiltration. The tumor showed internal heterogeneous echo and rich blood flow signals on breast ultrasonography. Ultrasonography also showed swelling of the axillary lymph node. Lymph node cytology revealed the presence of atypical cells in the lymph node, and CT scan showed lymph node metastasis in the right axilla and no distant metastases. We performed mastectomy with lymph node sampling. Pathological examination of the specimens confirmed a malignant phyllodes tumor and a metastatic lymph node. One month later, a subcutaneous mass and multiple pulmonary nodules were identified on a chest CT scan. Chest wall irradiation(45 Gy)and chemotherapy were performed, but the number of pulmonary nodules, pleural effusion, and size of the subcutaneous mass continued to increase. Although she underwent another chemotherapeutic treatment, she died 5 months after the surgery. Thus, we report a case of a malignant phyllodes tumor with an extremely rare lymph node metastasis, which rapidly progressed even though multimodal therapy was performed.

[Experience with BD EleVationTM in Vacuum-Assisted Biopsy].

For qualitative diagnosis of breast mass, core needle biopsy(CNB)and fine-needle aspiration biopsy cytology(FNAC)are widely used. Overseas, vacuum-assisted biopsy(VAB)is often the first choice for qualitative diagnosis, and its proper use has become a clinical issue. In addition, with the progress of diagnostic imaging in recent years, the chances of finding micro-lesions such as ductal carcinoma in situ(DCIS)are increasing. Since a sufficient amount of tissue sample is required for these diagnoses and abundant biopsy materials are required, tissue biopsy by VAB may be desirable. The advantage of tissue biopsy with VAB is that accurate definitive diagnosis is possible by collecting a sufficient amount of tissue to obtain pretreatment tissue information. On the other hand, there is concern that patient stress may occur, such as hematoma formation after puncture and invasion by a thick puncture needle. It is lightweight and has an ergonomic design that provides stable grip. New technological innovations in this device may contribute to the reduction of patient stress, and are expected to be used in the future. We outline the experience of using BD EleVationTM in breast suction tissue biopsy at our institution.

[A Case of Metastatic Invasive Lobular Carcinoma of the Breast Initially Presenting with Periorbital Swelling].

The patient was 54 years old, female. She was aware of gradually worsening right peri-eyelid swelling 2 years before the first presentation to our dermatology department. She underwent biopsy of eyelid skin 2 times. Nevertheless, definitive diagnosis was not obtained. Two months after the initial examination, right anterior thoracic swelling appeared, and right axillary, right subclavian, and interpectoral lymphadenopathy were detected. She was referred to our department for diagnosing metastatic breast cancer. Ultrasonography showed hypoechoic lesion with distortion(largest lesion>2 cm)in right breast, which was suspected to be a breast cancer. The results of breast core needle biopsy, the third time's eyelid skin biopsy and additional imaging studies confirmed T2N3M1, Stage Ⅳ right mammary invasive lobular carcinoma with metastasis to the eyelid skin, right axillary lymph nodes, right subclavian lymph nodes and the subcutaneous tissue of the right back. Immunohistochemical studies showed ER-positive, PgR-negative, HER2-negative, and low Ki-67 expression. Endocrine therapy with letrozole was initiated, which maintained stable disease without compromising the quality of life.

[Clinical Significance of Inflammatory Markers in Recombinant Human-Soluble Thrombomodulin Therapy for DIC in Solid Tumors].

BACKGROUND: The peripheral blood neutrophil-lymphocyte ratio(NLR), platelet-lymphocyte ratio(PLR), and lymphocyte- monocyte ratio(LMR)of cancer patients have been proposed as indicators of systemic inflammatory response. Recombinant human-soluble thrombomodulin(rTM)has also been reported its efficacy in DIC associated with solid tumors. In this study, we investigated the clinical significance of inflammatory markers in rTM therapy for DIC associated with solid tumors. PATIENTS AND METHOD: A retrospective study of 63 patients with solid tumors with DIC was performed. We examined the correlation between NLR, LMR, PLR and DIC withdrawal rate and 28-day survival rate. RESULTS: The DIC withdrawal rate was not correlated in LMR(p=0.655), and significantly higher in low NLR and low PLR cases(p=0.037, p=0.024). Furthermore, 28-day survival rate was not correlated in LMR(p=0.632), and significantly higher in low NLR and low PLR cases(p= 0.046, p=0.014). CONCLUSIONS: It was suggested that NLR and PLR may be useful as predictive markers of DIC withdrawal rate and 28-day survival rate in rTM therapy for DIC associated with solid tumors.

[A Case of Dermatitis Caused by Metronidazole Gel That Needed to Be Differentiated from Breast Cancer Skin Metastasis].

Seventy years old woman noticed a mass in her right breast before 3 years. Since she had ulcer bleeding, she visited our hospital. In physical findings, a hemorrhagic about 8 cm mass with an ulcer was found in the upper right breast. Breast ultrasonography revealed a large tumor of approximately 8 cm in the right A area, and needle biopsy revealed invasive ductal carcinoma(ER positive, PgR positive, HER2 positive, Ki-67 low expression). Right axillary lymph node metastasis was confirmed, but no clear distant metastasis was observed. Pretreatment diagnosis was right breast cancer, cT4bN1M0, Stage ⅢB, Luminal HER. Chemotherapy was started with pertuzumab, trastuzumab, and docetaxel, and the tumor was reduced after 6 cycles. Due to side effects, the drug was changed to a molecular targeted drug only and the treatment was continued. However, redness was observed in the entire right breast, and breast cancer skin metastasis was suspected. Since the dermatitis caused by metronidazole gel was also distinguished, the redness was improved when the application was stopped. When confirmed by a patch test, a reaction to metronidazole gel was observed, leading to the diagnosis of dermatitis caused by metronidazole gel.

[Effectiveness of Atezolizumab Combination Therapy for PD-L1(SP142)Positive Lung and Breast Double Cancer-A Case Report].

The anti-PD-L1 antibody atezolizumab has become the standard of immunochemotherapy with the results of the international phase Ⅲ trials in lung cancer and breast cancer. We report a case in which atezolizumab was efficiency in PD-L1 (SP142)-positive lung and breast double cancer. A 56-years-old woman. She noticed a lump in her right breast and visited a nearby doctor, who referred her to our hospital for close examination and treatment. Ultrasonography revealed about 5 cm mass on the right mammary gland and axillary lymph nodes swelling. Core-needle biopsy was confirmed invasive ductal carcinoma( ER negative, PgR negative, HER2 negative, Ki-67 high expression). CT findings showed right mammary mass, right axillary lymph nodes swelling, liver mass, and lung tumor with mediastinal lymph nodes swelling. Therefore, a bronchoscopic biopsy was performed and a diagnosis of primary lung cancer was obtained. Pretreatment diagnosis was lung adenocarcinoma, cT2a, N2/3, M1b/1c(HEP, OSS), Stage ⅢA/B or ⅣA/B(PD-L1 positive), and right breast cancer, T4b, N2, M0/1 (HEP, OSS, LYM), Stage ⅢB or Ⅳ triple-negative(PD-L1 positive)double cancer. We underwent surgery(mastectomy with axillar lymph nodes dissection), followed by immunochemotherapy(atezolizumab, carboplatin, paclitaxel)and it was efficiency.

[A Case of Cervical Metastasis from Breast Cancer].

A 59-year-old female was performed a left mastectomy with axillary lymph node dissection. Final diagnosis of the surgical specimen was left breast cancer pT2N1M0, Stage ⅡB, Luminal type. She was treated with adjuvant endocrine therapy, however, chest wall recurrence was identified at 1 year and 3 months after surgery, and curative resection of this tumor and radiotherapy were performed. Nine months later, she was admitted to the hospital for cervical pain and dyspnea, and magnetic resonance imaging showed bone metastasis in cervical vertebra which compressed spinal cord. Although cervical fusion therapy was performed, she died 39 days later. Metastasis spinal cord compression in breast cancer patients may result in irreversible spinal cord injury if treatment is delayed. Rapid diagnosis and systemic treatment for oncologic emergency are significant.

[A Case in Which Re-Administration of Pertuzumab/Trastuzumab with Eribulin Therapy Was Useful for Recurrent HER2 Breast Cancer].

Pertuzumab plus trastuzumab plus docetaxel regimen is the first choice for the initial treatment of HER2-positive recurrent breast cancer. However, docetaxel causes many adverse events. A 48-year-old woman was admitted to our hospital for a left breast tumor and was diagnosed with left breast cancer(T1N0M0, Stage Ⅰ, Luminal A). We performed a breast-conserving surgery and sentinel lymph node biopsy, followed by irradiation of the remaining parts of the mammary gland and adjuvant therapy with tamoxifen. Three and a half years after the first surgery, she underwent local resection due to chest wall recurrence of breast cancer. The recurrent tumor was HER2-positive, and we administered fluorouracil, epirubicin, cyclophosphamide( FEC)and paclitaxel plus trastuzumab. Liver metastases were confirmed on completion of cycle 11 of trastuzumab administration, and the regimen was changed to pertuzumab plus trastuzumab plus docetaxel. A partial response was seen following this regimen. The next line of treatment was the administration of 5 cycles of T-DM1, which resulted in stabilizing the disease. The liver metastases progressed, and the regimen was changed to pertuzumab plus trastuzumab plus eribulin. Partial response was seen following this regimen for liver metastases without serious adverse events(20 cycles).

Effectiveness and safety of the pre-prescription of garenoxacin in comparison to moxifloxacin for low-risk febrile neutropenia in breast cancer patients undergoing adjuvant and neoadjuvant chemotherapy.

PURPOSE: The purpose of this study was to compare the efficacy of the pre-prescription of garenoxacin mesylate hydrate (GRNX) with that of moxifloxacin hydrochloride (MFLX) in the management of breast cancer patients with low-risk febrile neutropenia. METHODS: Data from female patients who had been instructed to take previously prescribed oral GRNX or MFLX for 3 days during adjuvant and neoadjuvant chemotherapy if their body temperature exceeded 38 °C were analyzed. This study compared the effectiveness between these fluoroquinolones using a propensity score matching analysis. RESULTS: The 330 patients received 1192 administrations of chemotherapy between May 2007 and April 2014 and 136 (41.2%) patients had a total of 212 (17.8%) febrile episodes. The frequencies of febrile episodes were 19.5% (113/579) and 16.2% (99/613) in the GRNX and MFLX groups, respectively. After propensity score matching, 384 episodes were matched in each group. Febrile events occurred in 80 and 56 cases in the GRNX and MFLX groups, respectively. Treatment success was identified in 80.0% (64/80) of cases in the GRNX group and 64.3% (36/56) of cases in the MFLX group (P = 0.0494). Additionally, the therapeutic use of granulocyte-colony stimulating factor was 6.3% (5/80) of cases in the GRNX group and 17.9% (10/56) of cases in the MFLX group (P = 0.0498). There were few differences in the frequency of adverse effects between the two groups. CONCLUSIONS: These results indicate that the pre-prescription of GRNX may be a more effective option for the management of low-risk febrile neutropenia during adjuvant and neoadjuvant chemotherapy for breast cancer.

[Two Cases of Orbital Metastasis from Breast Cancer].

Orbital metastasis from breast cancer is a rare condition. Here, we describe 2 cases of orbital metastasis from breast cancer. The first patient was a 26-year-old woman diagnosed with triple-negative invasive ductal carcinoma. She underwent surgery after neoadjuvant chemotherapy. One year after surgery, she had multiple bone metastases and then multiple liver metastases developed. During chemotherapy for metastatic disease, she complained ofheadaches and visual disturbances. Findings ofa MRI scan suggested a metastatic tumor in the left orbit. A total of 30 Gy of radiation therapy was administered, but she died a month after the orbital metastasis was discovered. The second patient was a 42-year-old woman, who had advanced breast cancer with bone metastasis. Diplopia developed 8 months after initiation of chemotherapy. Meningeal dissemination was suspected because ophthalmological examination revealed swelling ofbilateral optic discs. She lost her sight within a month. She died 2 months after the diagnosis oforbital metastasis. There was no evidence ofcentral nervous system metastasis in either case. Loss ofvision severely impairs patients' quality oflif e. It is important to know that there is rarely such a rapid progression ofdisease, especially in young patients with triple-negative disease.

[Late Recurrence of Breast Cancer 32 Years after Surgery-A Case Report].

An 86-year-old woman visited her nearby hospital for a mass on the left side of her sternum. She had undergone total mastectomy for left breast cancer 32 years prior and multiple small nodules had been found in both lungs 2 years ago. She was sent to our hospital for suspected breast cancer recurrence. Chest computed tomography showed multiple small nodules in both lungs and a mass with sternal sclerosis on the parasternal bone of her left 2-3 intercostal space. A core needle biopsy was performed on the chest wall tumor by ultrasonography. Not only pathological but also immunohistological examination findings were similar to those of the surgical specimens 32 years ago(estrogen receptor: positive, progesterone receptor: positive, HER2: negative, Ki-67 score: low). Therefore, she was diagnosed with a late recurrence of her breast cancer. She started letrozole but the disease had progressed 6 months later. We experienced a case of late breast cancer recurrence 32 years after surgery.

[A Case of Recurrent Breast Cancer Treated with Local Irradiation Using Leadless Pacemaker Implantation].

A 68-year-old woman noticed a tumor in her left breast and visited our hospital. She was diagnosed with left breast cancer cT2N2M0, stage ⅢA, and surgery was performed after the neoadjuvant chemotherapy. Although this case was indicated for radiation therapy(PMRT)after total mastectomy, postoperative radiation was not performed due to an implantable pacemaker placed in the left anterior chest. Therefore, postoperative adjuvant therapy with endocrine therapy was started. After 3 years of treatment, her left axillary lymph node was enlarged, and needle biopsy confirmed metastasis and recurrence. When local excision was performed, postoperative irradiation was deemed necessary because residual microlesions were suspected. Irradiation planning did not deny the possibility that the pacemaker in the anterior chest indwelling could become the irradia- tion range. Therefore, a leadless pacemaker was inserted, and local irradiation(50 Gy/20 Fr)was performed without complications. The next treatment is fulvestrant, and no recurrence has been observed 6months postoperatively.

[A Case of Advanced Breast Cancer with Altered Biology by Eribulin Chemotherapy].

In the treatment of advanced breast cancer, onlya few drugs confer overall survival(OS)benefit. Eribulin is a drug that was shown to extend OS in an international phase Ⅲtrial; however, the underlying mechanism is thought to involve cancer microenvironment regulation. The concept of "breast cancer subtype discordance" implies the biological changes that accompany treatment. Herein, we encountered a case of advanced breast cancer in a 54-year-old woman that showed biological changes after eribulin chemotherapy. The patient noticed a lump in her left breast and visited a nearby doctor, who referred her to our hospital for close examination and treatment. Ultrasonographyrevealed a large mass at the center of the left mammarygland and axillaryly mph node swelling. Core-needle biopsyconfirmed an invasive ductal carcinoma(ER stronglypositive, PgRnegative, HER-2 negative, Ki-67 low expression). CT findings showed multiple lung metastases. Letrozole was administered for cT4N2M1, stage Ⅳ, Luminal A, which showed progression to the left side with advances in breast cancer. Six months later, the primarytumor and axillaryly mph nodes showed progression. Subsequent treatment with eribulin was started, and partial response was obtained; however, new lymph node metastasis developed in the axilla after 11 cycles. The primary tumor and axillaryly mph nodes showed stronglypositive ER expression, were PgR-negative and HER2-positive, and showed Ki-67 low expression and HER2-positive conversion.

[Secondary osteoporosis. Surgical treatment for patients with secondary osteoporosis.]

In the etiology of secondary osteoporosis, only primary hyperparathyroidism is the one to which osteoporosis itself is indicated for surgery. However, there are several diseases that may give bone a good environment by surgical treatment for primary diseases such as hyperthyroidism or Cushing's syndrome, and secondary osteoporosis may improve. It is important to properly conduct differential diagnosis and to discuss and determine surgical indication.

[A Case of Multiple Lung Metastases from Breast Cancer Successfully Treated with Endocrine Therapy].

A 40-year-old woman underwent right partial mastectomy and axillary lymph node dissection. Pathological examination confirmed right breast cancer(T2N0M0, Stage ⅡA, mucinous, ly3, v0, weakly positive ER and PgR). After surgery, she received radiotherapy for residual mammary gland cancer and endocrine therapy as adjuvant treatment for 5 years. Seven years after the first surgery, computed tomography showed multiple lung tumors. Transbronchial lung biopsy revealed lung metastasis from breast cancer(strongly positive ER and PgR, negative HER2). She received first-line endocrine therapy, and the response was classified as stable disease(SD). Three years later, the disease control became poor. Second-line endocrine therapy was then administered, and the response was classified as partial response(PR)for 3 years. After that, we modified the regimen to monotherapy of letrozole, and she achieved PR for a further 3 years. In the treatment for patients with metastatic hormone receptor-positive breast cancer, it is important to consider the sensitivity of endocrine therapy, such as relapse-free survival or the expression of hormone receptors in metastatic tumors.

[A Case of a Malignant Phyllodes Tumor That Was Difficult to Distinguish from Stromal Sarcoma].

A 72-year-old woman visited our hospital with the chief complaint of a mass in the right breast. Breast ultrasonography revealed a hypoechoic area with a distinct border in the right breast. A core needle biopsy showed the proliferation of spindle cells in the stroma, and she was diagnosed with stromal sarcoma or malignant phyllodes tumor. Right lumpectomy was performed. Pathological examination revealed a malignant phyllodes tumor with a sarcomatous lesion. Although she did not receive adjuvant chemotherapy, she is alive without any recurrence 2 years after the surgery. It is difficult to distinguish phyllodes tumors from stromal sarcoma, based on core needle biopsy, and the prognosis of malignant phyllodes tumors with distant metastases is poor. Rapid surgery to determine an accurate diagnosis and careful follow-up after surgery are impor- tant.

[A Case of Breast Neuroendocrine Carcinoma].

A 73-year-old woman visited our hospital with the chief complaint of a mass in the left breast. Breast ultrasonography revealed a hypoechoic area in the left breast. A core needle biopsy showed the proliferation of solid tumor cells. Immunohistochemistry indicated strongly positive expression of E-cadherin, synaptophysin, and chromogranin A. We then diagnosed her with breast neuroendocrine carcinoma. The expression of estrogen receptor(ER)and progesterone receptor(PgR)were also strongly positive, and the expression of human epidermal growth factor receptor 2(HER2)was negative. Computed tomography( CT)and bone scintigraphy revealed no metastasis. Simple mastectomy of the left breast and sentinel lymph node biopsy were performed. Final pathological examination of the tumor also led to the diagnosis of breast neuroendocrine carcinoma(T2N0M0, StageⅡA, Luminal A-like). After surgery, endocrine therapy is planned, considering the breast cancer subtype. Breast neuroendocrine carcinoma is rare. It is important to consider the possibility of metastasis from other organs to the breast.