Pilot trial of an electronic patient-reported outcome monitoring system in patients with metastatic breast cancer undergoing chemotherapy.

BACKGROUND: Electronic patient-reported outcomes monitoring (ePROM) is a useful communication tool for patients and healthcare providers in cancer chemotherapy. In this study, we examined the feasibility of our newly developed ePROM system, which we refer to as "Hibilog". METHODS: An ePROM app was developed by extracting 18 items from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE). Symptom monitoring was conducted every two weeks for patients with metastatic breast cancer undergoing chemotherapy. The primary outcome was the response rate to the ePROM system. The secondary outcomes were response time, item missing rate, and distribution of responses for each symptom. RESULTS: A total of 71 cases (mean age 52.6 years) were analyzed. Performance status was 0 in 76% of the cases and 1 or higher in 24%. First-line treatment was being administered in 30% of cases, second-line treatment in 17%, and third-line or higher treatment in 53%. The response rate to the ePROM system from registration to week 40 remained high at around 80%, indicating good compliance. The average response time was 5.5 min and the missing rate for each item was below 0.4%. Among 1,093 responses, the top 3 symptoms causing interference with daily life were Fatigue (63%), Numbness and tingling (48%), and General pain (46%). CONCLUSION: Our developed ePROM system was able to capture symptoms accurately in patients with metastatic breast cancer undergoing chemotherapy while maintaining a high response compliance.

Long-Term Physical Activity and Body Composition After Exercise and Educational Programs for Breast Cancer: A Randomized Controlled Trial From the Setouchi Breast Project-10.

BACKGROUND: It is unclear what interventions can sustain long-term higher physical activity (PA) to improve breast cancer outcomes. Thus, this study aimed to evaluate the long-term effects of interventions on PA after breast cancer treatment. METHODS: This was a prospective randomized controlled trial for patients with stage 0 to III breast cancer evaluating the efficacy of exercise and educational programs on long-term PA compared with usual care. The primary endpoint was proportion of patients with recreational PA (RPA) ≥5 metabolic equivalents (METs)/week at 1 year after registration. RESULTS: From March 16, 2016, to March 15, 2020, breast cancer patients were registered in the control (n = 120), education (n = 121), or exercise (n = 115) group. There were no significant differences in proportion of RPA ≥5 METs/week at 1 year between the exercise and control groups (54% and 53%, P = .492) and between the education and control groups (62% and 53%, P = .126). Significant difference in reductions from baseline at 1 year were noted on body weight (P = .0083), BMI (P = .0034), and body fat percentage (P = .0027) between education and control groups. Similarly, the exercise group showed significant difference in reduction in body fat percentage (P = .0038) compared to control group. CONCLUSION: Although there were no significant effects on RPA 1 year after exercise and educational programs for breast cancer survivors, both interventions reduced body composition. Future studies on PA should investigate appropriate interventions to improve overall survival.

Systemic immunity markers are associated with clinical outcomes of atezolizumab treatment in patients with triple-negative advanced breast cancer: a retrospective multicenter observational study.

Immune checkpoint inhibitors (ICI) are reportedly efficacious against triple-negative breast cancer (TNBC) and are now recommended as first-line therapy. Systemic immunity markers, the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR), have been identified as predict ICI efficacy in patients with various cancers. We retrospectively enrolled 36 TNBC patients who received atezolizumab treatment between September 2019 and May 2021 at eight Japanese medical institutions. We evaluated systemic immunity markers, including dynamic changes in these markers, as predictors of survival benefit derived from atezolizumab treatment. Median time-to-treatment failure (TTF) and overall survival (OS) were 116 days and "not reached", respectively. Patients with low NLR at baseline and decreased NLR at the start of the second cycle (SO2nd) had significantly longer OS than those with high NLR at baseline and increased NLR (SO2nd) (log-rank P < 0.001 and log-rank P = 0.049, respectively). Multivariate analyses identified high ALC at baseline and decreased NLR (SO2nd) as independent predictive markers for longer TTF (P = 0.043 and P = 0.002, respectively), and low NLR at baseline and decreased NLR (SO2nd) as independent predictive markers for longer OS (P < 0.001 and P = 0.013, respectively). The safety profile was consistent with those of previous trials. This retrospective multicenter observational study showed the clinical efficacy and safety of atezolizumab treatment. Furthermore, systemic immunity markers, including their dynamic changes, were found to be associated with clinical outcomes of atezolizumab treatment in patients with advanced or metastatic TNBC.

[A Case Report of Multiple Endocrine Neoplasia Type 2A(MEN2A)Diagnosed with Medullary Thyroid Carcinoma].

We experienced a case of multiple endocrine neoplasia type 2A(MEN2A)diagnosed with medullary thyroid carcinoma. The patient was a 50s woman who was referred for a thyroid nodule detected in the right lobe during a carotid ultrasound examination. After undergoing a hemithyroidectomy, it was determined that the tumor was medullary carcinoma. RET gene test was performed, confirming a mutation at codon768, leading to the diagnosis of MEN2A. A completion thyroidectomy was performed to remove the remaining thyroid tissue. Postoperatively, the patient is undergoing systemic surveillance.

[A Case of Giant Phyllodes Tumor Treated with Breast Reconstruction].

A 62-year-old woman was diagnosed with right breast tumor 2 years ago, which she refused to undergo surgery. The patient experienced a rapid enlargement of the mass over the past 1 month, and visited hospital. The patient was diagnosed with a borderline phyllodes tumor by needle biopsy. Her right breast was occupied by an 18 cm mass. We conducted tumor resection and immediate reconstruction with DIEAP flap. The pathological diagnosis was a malignant phyllodes tumor, and the postoperative radiation to the chest wall was performed. During a year and a half follow up, she has no recurrence and highly satisfied with the reconstructed breast. Phyllodes tumors may recur locally regardless of whether they are benign or malignant, and we need strict follow-up.

[A Case of HER2-Positive Metastatic Breast Cancer Achieved a Complete Response to Paclitaxel and Trastuzumab in Combination with Pertuzumab in Fifth Therapy].

We report a case of HER2-positive metastatic breast cancer achieved a complete response(CR)to paclitaxel(PTX) and trastuzumab(HER) in combination with pertuzumab(PER) in 5th therapy. A 69-year-old woman was diagnosed left breast cancer and underwent mastectomy and sentinel lymph node biopsy in January 2011. Pathological examination revealed an invasive ductal carcinoma that was ER 0%, PgR 0%, HER2(3+), Ki-67 67% and node negative. Two years after the operation, she found multiple lung metastases in both lungs. She was administered drug treatment as HER2-positive metastatic breast cancer, but multiple lung metastases got worse after 4th treatment. Weekly PTX, trastuzumab and pertuzumab were administered as 5th therapy. After 2 months, lung metastases diminished significantly. After 44 courses of drug treatment, positron emission tomography computed tomography(PET-CT)scan revealed CR. She wanted to cease treatment, so she continues to get CT scan every half a year and the CR has been maintained.

Retropharyngeal hematoma presenting airway obstruction: A case report.

INTRODUCTION: Blunt neck trauma patients can suffer from an airway emergency and are necessary to careful observation. PRESENTATION OF CASE: A 79-year-old man under anticoagulation therapy presented to our hospital three hours after a fall. Shortly after arrival, he developed dyspnea. Oral intubation was attempted, but with no success; therefore, an emergency tracheotomy was performed. Contrast-enhanced computed tomography (CT) and subsequent angiography revealed active bleeding from a branch of the right ascending cervical artery. Subsequently, the right thyrocervical trunk, which is upstream from the ascending cervical artery, was embolized and hemostasis was achieved. He was discharged 52 days after the emergency admission. DISCUSSION: This is the first case report of an ascending cervical artery injury due to blunt trauma that resulted in an airway emergency. Contrast-enhanced CT and cervical angiography are useful for confirming the area of injury and size of the hematoma. Half of patients with respiratory distress accompanied by a cervical spine injury require definitive airway management within five hours of the injury and all by 24 h. Neck trauma can lead to fatal airway obstruction and careful monitoring is warranted to detect any signs of impeding respiratory obstruction. CONCLUSION: All emergency physicians need to keep their airway management skills updated in order to perform reliably and rapidly in difficult and urgent situations.

[Clinical Practice of the Efficiency and Safety of Palbociclib in Patients with Metastatic Breast Cancer].

We aimed to examine the effects of palbociclib and neutropenia in patients with metastatic breast cancer(MBC). From December 2017 to December 2019, 18 patients with estrogen receptor(ER)-positive, human epidermal growth factor receptor 2(HER2)-negative MBC were treated with palbociclib for at least 1 cycle. The most common adverse event(AE) was neutropenia, which occurred in 83% of all cases. With cessation and dose reduction, none of the patients had Grade 4 neutropenia. Palbociclib used in the first- or second-line treatment of MBC showed a higher efficacy than when used as the third-line treatment, which was observed as a longer duration to stay on treatment and higher efficacy.

A case of ectopic hamartomatous thymoma: controversy over the designation.

BACKGROUND: Ectopic hamartomatous thymoma, which usually occurs in the lower neck, is a rare benign tumor containing spindle cells, epithelial nests, and adipose tissue. Although the origin of this tumor is still unknown, recent reports suggest that the designation of this tumor is inappropriate. CASE PRESENTATION: A 38-year-old with an anterior cervical mass in the suprasternal region of her neck was referred to our hospital. An ultrasound examination showed that the well-defined oval mass was 31 × 23 × 17 mm in size. A non-enhanced computed tomography scan of the neck revealed that the distinct neck mass in the subcutaneous tissue had a mixture of soft tissue and fatty components. The cervical tumor was clinically diagnosed to be an unusual lipoma with degeneration. The patient underwent the neck mass extirpation. During the surgery, the cervical mass was well demarcated and did not adhere to the surrounding tissues. The postoperative course was uneventful. The gross pathology report showed that the neck mass measured 3.0 × 2.5 × 2.0 cm. Microscopically, the tumor was composed of spindle cells, epithelial nests, and mature adipose tissue. Immunohistochemical examination revealed that both spindle cells and epithelial nests were positive for cytokeratin AE1/AE3. These histopathological findings were consistent with the features of ectopic hamartomatous thymoma. Over a follow-up period of 30 months, this patient exhibited no evidence of recurrence. CONCLUSIONS: Ectopic hamartomatous thymoma should be considered in the differential diagnosis of subcutaneous tumors in the lower neck, when the CT shows the tumor has the mixed components of fat and soft tissues.

[A Case of the Locally Advanced Breast Cancer with Serious Comorbidities Obtained a Good Local Control].

A 66-years-old woman was referred to our hospital with the chief complaint of a huge exposed left breast mass, associated massive exudates, bleedingand foul-smelling discharge. Invasive ductal carcinoma was diagnosed by core needle biopsy. The computed tomography showed left axillary lymph node metastases and no distant metastasis. Her performance status(PS) was Grade 3. She had serious comorbidities such as non-alcoholic steatohepatitis and liver cirrhosis, renal dysfunction. DMpC therapy and Mohs paste therapy were started since her overall status was improved. The huge left breast tumor and left axillary lymph node metastases were reduced remarkably. Total mastectomy and axillary lymph node dissection and free skin grafting was perfomed, and PS was improved to Grade 0, She received DMpC therapy for 4 months postoperatively, and radiotherapy at left chest wall and supraclavicular fossa.

A phase 1, dose-finding and pharmacokinetic study of gemcitabine with nab-paclitaxel in patients with metastatic breast cancer.

PURPOSE: Gemcitabine (Gem) with paclitaxel (Pac) is used for patients with metastatic breast cancer who require cytoreduction with manageable toxicities. Nanoparticle albumin-bound (nab)-Pac exhibits better efficacy and reduces the risk of hypersensitivity reactions associated with solvent-based Pac. Therefore, Gem plus nab-Pac (GA) therapy may be effective for metastatic breast cancer. The purpose of this study was to determine the maximum tolerated dose for GA therapy. METHODS: The subjects were patients with metastatic breast cancer with performance status 0 or 1 and normal hepatic, renal and marrow function. Leukopenia, neutropenia or thrombocytopenia of grade 4, neutropenic fever, or non-hematological toxicity of grade 3 or higher during the 1st cycle, and chemotherapy-induced peripheral neurotoxicity of grade 2 or higher at the end of the 1st cycle were defined as dose-limiting toxicities (DLTs). Gem (1250 mg/m(2)) was administered on days 1 and 8. nab-Pac was administered at a starting dose of 180 mg/m(2) (cohort 1) and escalated to 220 mg/m(2) (cohort 2) and 260 mg/m(2) (cohort 3) on day 1 of the 21-day cycle, using a 3 + 3 design. RESULTS: Nine patients (n = 3, 3, and 3 in cohorts 1, 2, and 3, respectively) were included in the study (median age 56 years; range 43-75 years). DLTs did not occur in any cohorts. CONCLUSIONS: The initial recommend dose in GA therapy is 1250 mg/m(2) Gem and 260 mg/m(2) nab-Pac. It is well known that nab-Pac has cumulative toxicities, and thus the efficacy and safety of GA therapy require validation in a phase 2 study.

[Analysis of Treatment and Outcomes in Locally Advanced Breast Cancer].

Current treatment guidelines for locally advanced breast cancers recommend multimodality therapy consisting of chemotherapy followed by local treatment(surgery and radiotherapy). We retrospectively analyzed 35 cases oflocally advanced breast cancer at our institution between January 2004 and December 2014. Nine patients(25.7%)were treated with multimodality therapy consisting ofchemotherapy, surgery, and radiotherapy. Nineteen patients(54%)had disease recurrence and 9(26%)died. Factors that were significantly associated with recurrence were premenopausal, T1-3, and 4 or more lymph node metastases, and the number oflymph node metastases remained significant in the multivariable analysis. The median relapse-free survival was 1,147 days and the 5-year relapse-free survival rate was 49.7%. Survival rates were influenced by menopausal state and the number oflymph node metastases on the univariate analysis, but not in the multivariable analysis. Our results indicate that multimodality therapy is necessary particularly for patients with 4 or more lymph node metastases.

[Assessment of traumatic rib fractures caused by traffic accident].

We reviewed 66 cases of traumatic rib fracture by traffic accident between January 2009 and December 2011. The age of patients ranged from 18 to 88 years, with an average age of 55.6, and they were predominantly male. They met with traffic accident when driving automobiles in 30 cases, driving motorcycles in 15 cases, and walking in 9 cases. The average number of fractured ribs was 4.1±3.2.Multiple rib fractures were observed in 75.8% of patients. Injuries other than rib fractures were involved in all patients who suffered over 7 rib fractures. Except one who died of pneumonia 62 days after traffic accident, 7 of 8 patients died within 48 hours:6 in a shock state and 1 in cardiac pulmonary arrest on arrival. About 80 % of the patients with rib fractures were hospitalized. As traffic accidents could cause any type of injuries including rib fractures, it is important to examine the whole body when patients were transported to a hospital.

[Two cases of dural metastasis of breast cancer].

The first case of dural metastasis occurred in a 60s years old woman, who presented with bone metastasis to the right breast. Nine months later, disorientation and left hemiplegia developed, the right coronal bone metastasis enlarged, and dural metastases were detected close to the tumor, as observed by using cranial magnetic resonance imaging (MRI). Whole brain radiation and chemotherapy(weekly paclitaxel)were administered. The right coronal bone metastasis reduced remarkably, and the dural metastases almost disappeared, as observed on a cranial MRI scan. The second case of dural metastasis occurred in a 50s years old woman who presented with multiple bone metastases. Extensive bone metastases to the skull and dural metastases to the side of the head were observed on cranial MRI scans. Subsequently, the patient experienced a severe headache, and whole brain radiation and pharmacotherapy with anastrozole and trastuzumab were administered. Cranial MRI revealed that the skull bone metastasis reduced and the dural metastases almost disappeared. We report that radiotherapy and pharmacotherapy were effective in these 2 cases of dural metastases of breast cancer.

[Two cases of recurrence of breast cancer at the chest wall wherein chest wall complications were treated by ablation].

Case 1 involves a 60-year-old woman who underwent surgery (breast total resection[Bt]plus axillary lymph node resection [Ax]) for the treatment of carcinoma of the right breast when she was 37 years of age. She underwent another surgery due to cancer recurrence in the right musculus pectoralis major when she was 50 years of age. The right fourth rib and the sternum showed high fluorodeoxyglucose (FDG) accumulation on positron electron tomography (PET)-computed tomography (CT) scans. Thus, we diagnosed the patient with recurrence of breast cancer at the chest wall. Lumpectomy was performed at the right chest wall, whereas ablation was performed for the right fourth and fifth rib and sternal complications. However, mediastinal lymph node metastasis developed 1 year and 2 months after the surgery. Subsequently, the patient developed lymphangitic carcinomatosis and died at 4 years and 2 months after the surgery. Case 2 involves an 80-year-old woman who underwent surgery (Bt+Ax) for the treatment of carcinoma of the left breast when she was 62 years of age. She had the swelling of the left chest wall in the 18th year from surgery, and was diagnosed recurrence of breast cancer at the chest wall, lumpectomy was performed at the left chest wall, whereas ablation was performed for the left third and fourth rib and sternal complications. No signs of recurrence have been observed for 1 year and 7 months after the surgery. Thus, ablation was performed for the treatment of chest wall complications and local recurrence of the breast cancer at the chest wall, and pharmacotherapy and radiotherapy were administered subsequently. We thereby report our experience with these 2 cases wherein local control was eventually achieved.

[A case of a geriatric patient with stage IV anal canal cancer showing complete response to chemoradiation therapy].

We present a case in which chemoradiation therapy was effective in a geriatric patient with Stage IV anal canal cancer. The patient is an 81-year-old woman who complained of proctorrhagia and anal pain. She was referred to us by her family doctor who suspected rectal cancer. Tumors as large as 6.5 cm in diameter mainly on the right side of the rectum as well as 2 palpable enlarged lymph nodes on the right inguinal area, were found during the initial physical examination. Squamous cell carcinoma was elevated to 16 ng/mL. A CT scan revealed that irregularly shaped masses as large as 7 cm in diameter were externally exposed on the right side of the rectum along with enlarged lymph nodes on the right inguinal area and metastasis at S7 lesion in the liver. Squamous cell carcinoma was diagnosed from biopsy results. Due to her age, the chemotherapy regimen was S-1+CDDP with radiation therapy and 4-port irradiation (50.4 Gy) of the primary tumor, interior of the pelvis, and inguinal lymph nodes. Partial response was observed upon completion of treatment, and complete response was obtained after 6 months. She is currently an outpatient taking S-1: 60 mg/day orally. There is no indication of cancer recurrence after 1 year and 3 months, and she continues to visit an outpatient clinic for regular follow-ups. These results demonstrate the effectiveness of chemoradiation therapy for geriatric patients with Stage IV anal canal cancer.

[A case of recurrent breast cancer with solitary adrenal metastasis treated with surgery and endocrine therapy].

We present a case in which a 46-year-old woman underwent mastectomy (Bt+AX) for right breast cancer (T4bN0M0, Stage IIIB) at the age of 42. A histopathological examination confirmed her cancer to be an invasive ductal carcinoma n (-),ER (+), PgR (+),HER 2 (1+). For postoperative medication therapy, she was taking goserelin plus tamoxifen for 2 years and tamoxifen thereafter. A right adrenal tumor was discovered during a follow-up CT scan and MRI after the operation. There was no indication of metastasis in any other location. A laparoscopic right adrenalectomy was performed to establish a definitive diagnosis and to cure the cancer. According to the histopathological examination, the tumor was ER (+), PgR (+), and HER2 (0) and metastasized from the breast. After this operation, the regimen was changed to high- dose toremifene as endocrine therapy. No recurrence of the cancer has been reported 2 years and 4 months after the operation. In most cases, metastasis to the adrenal gland is due to systemic metastasis as seen in the last stage of breast cancer, and a solitary adrenal gland metastasis from breast cancer is extremely rare. The combination of surgical removal and medication for solitary distant metastasis from breast cancer may be effective in improving the long-term survival rate.

Clinical significance of preoperative lymphoscintigraphy for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Lymphoscintigraphy (LSG) has been widely used as an additional modality to sentinel lymph node biopsy (SLNB) using isotope. However, the significance of the number of LSG-visualized axillary nodes has not been fully understood. We analyzed this and discussed its potential as a modality to complement SLNB. METHODS: Ninety-one breasts and axillary lymph nodal status were evaluated retrospectively. All patients were examined by LSG using isotope and subsequently by SLNB. RESULTS: Nine patients (9.9%) had no LSG-visualized axillary node, while 61 patients (67.0%) had only 1 node, and 21 patients (23.1%) had multiple nodes. Overall, sentinel lymph node (SLN) identification rate was 96.7%, and the mean number of removed SLNs was 1.5 nodes per patient. In patients with nonvisualized nodes, 66.7% of SLNs were successfully identified, while 100% of SLNs were identified in those with LSG-visualized nodes. Compared with patients with less than one visualized node, significantly more SLNs were removed in patients with multiple visualized nodes. The number of LSG-visualized nodes correlated with that of metastatic nodes. CONCLUSIONS: Preoperative LSG is effective in evaluating SLN status, and the LSG status could be associated with the number of dissected SLN. Moreover, the results of LSG potentially reflect the histological nodal status.

Tumor inhibitory effect of gefitinib (ZD1839, Iressa) and taxane combination therapy in EGFR-overexpressing breast cancer cell lines (MCF7/ADR, MDA-MB-231).

Some kinds of breast cancer cell lines, similar to several types of solid tumors, express epidermal growth factor receptor (EGFR). However, gefitinib, an EGFR tyrosine kinase inhibitor, is not effective for all these cell lines. Similarly, taxane is effective for many of the cell lines, although some, such as the multidrug-resistant MCF7/ADR cell line, show taxane-resistance. Here, we examined the growth inhibitory effect of combination treatment with gefitinib and taxane on the breast cancer cell lines MDA-MB-231 (EGFR-positive) and MCF7/ADR (EGFR- and HER2-positive). To estimate the combined effect, a Combination Index was calculated for each cell line. The combination of gefitinib and taxane showed a strong synergistic effect on MCF7/ADR cells, but an invitro additive-antagonistic effect on MDA-MB-231 cells. Similarly, the combination treatment showed a significantly increased tumor inhibitory effect on MCF7/ADR xenografts, but not on MDA-MB-231 xenografts. Regarding the mechanism of the synergistic effect, Western blotting analysis revealed that taxane activated the EGFR-Akt pathway in MCF7/ADR cells but not in MDA-MB-231. To determine the optimal sequential administration of gefitinib and taxane for MCF7/ADR cells, we used flow cytometry to analyze the cell cycle and apoptosis; finding that taxane treatment followed by gefitinib produced a higher rate of G2 arrest and apoptosis than gefitinib treatment followed by taxane. These results suggest gefitinib overcomes the drug-resistance of these cells, thereby increasing the effects of taxane on MCF7/ADR cells. Further, activation of the EGFR-Akt pathway by taxane is related to this synergistic effect.