[A Case of Multicentric HER2-Positive Breast Cancer with Alterations of the Intrinsic Subtype].

In cases where there are 2 or more tumors, it is crucial to conduct core needle biopsies on each of them. A 39-year-old woman presented at our hospital with pain in her left breast. Ultrasonography(US)revealed the presence of 2 contiguous tumors: a 35 mm tumor(tumor 1)and a 20 mm tumor(tumor 2)in the AC area of the left breast. US-guided core needle biopsies(CNB)were performed. The histological findings confirmed an invasive ductal carcinoma, characterized by ER(-)/ PR(-)/HER2(3+). Neoadjuvant chemotherapy indicated tumor 1 as PD and tumor 2 as PR, and surgery was subsequently performed(Bt plus SLN). Upon histopathological examination, the findings demonstrated a non-pCR invasive ductal carcinoma, featuring an ER(+)/PR(-)/HER2(-)profile. Depending on the specific subtype identified, post-operative treatment included HER2-targeted therapy or ER/PR-targeting hormone therapy in conjunction with chemotherapy.

[Examination of Factors Related to Walking Ability in Patients with Abdominal Cancer].

It has been reported that preoperative rehabilitation reduces the risk of postoperative complications. We examined the factors impacting the efficacy of preoperative rehabilitation. Forty-three cancer patients who underwent abdominal surgery after preoperative rehabilitation at our hospital were assessed". Walkable"was defined as having the ability to walk to the toilet(distance>30 meters)without requiring support. Following the clinical path, if patients became"walkable"by the second day after surgery, they belonged to the smooth group, while the remaining patients belonged to the delayed group. We examined the factors influencing walking ability. The smooth group consisted of 34 patients(79%), and the delayed group consisted of 9 patients(21%). The significant factors related to delays in acquiring walking ability were old age and weakened lower limb function. Improving lower limb function through preoperative rehabilitation may lead to patients acquiring walking ability earlier after surgery, especially in older patients.

An Exploratory Phase II Study of Eribulin Re-challenge After Short Term Therapy of 5-Fluorouracil for HER2 Negative, Advanced or Recurrent Breast Cancer.

BACKGROUND/AIM: In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. RESULTS: Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. CONCLUSION: In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.

[Cancer Patient Response Conference by Co-Medical Staff].

Often, co-medical staff are asked questions or consultations that are difficult to answer from cancer patients. However, as for the reply contents, each co-medical staff responded in various ways, there was no place to discuss an appropriate reply. At our hospital, we decided to hold a"Cancer Patient Response Conference"to enable us to respond appropriately regardless of years of service or occupation. This time, we investigated the effect of"Cancer Patient Response Conference"on the approach at Ishikiriseiki Hospital. As a result, it is possible for the co-medical staff to respond to empathy of the patient's feelings and to confirm the understanding of the patient, but it seemed that the response from the attending physician was good for the question about the life expectancy and the treatment effect etc. However, it was suggested that collaborative staff sharing patient problems and information at"Cancer Patient Response Conference"will be useful for future cancer patient response.

[A Case of Male Mammary' Paget's Disease].

A 90-year-old male visited our hospital because redness of his left chest. An erythema of 25 mm in size with indistinct border was observed on the left nipple, and mammary' Paget's disease was diagnosed with a skin biopsy. Ultrasound examination revealed no significant findings in the mammary gland, so a left mastectomy was performed under local anesthesia. The final pathological diagnosis was mammary' Paget's disease with noninvasive ductal carcinoma in the duct. We have experienced a very rare male mammary' Paget's disease because both male breast cancer and mammary' Paget's disease are rare.

Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Trastuzumab Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide for HER2-positive Operable Breast Cancer: A Multicenter Phase II Trial.

AIM: This study was conducted in order to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus trastuzumab followed by 5-fluorouracil/ epirubicin/cyclophosphamide (FEC) in a neoadjuvant chemotherapy (NAC) setting for patients with human epidermal growth factor receptor 2 (HER2)-positive operable breast cancer. PATIENTS AND METHODS: Each patient received four cycles of 260 mg/m2 nab-paclitaxel with 6 mg/kg trastuzumab (8 mg/kg as the loading dose) every 3 weeks (q3w) followed by four cycles of FEC (500/100/500 mg/m2) q3w. The primary endpoint was pathological complete response (pCR) rate. RESULTS: Twenty-nine patients were analyzed for the efficacy and safety of this treatment. All patients completed four cycles of nab-paclitaxel and trastuzumab, and 28 patients completed four cycles of FEC. Twenty-seven patients subsequently underwent surgery. The pCR rate was 74.0%. The most frequent toxicity was sensory neuropathy (96.6%), but grade 3 neuropathy rate was 3.4%. CONCLUSION: Nab-paclitaxel plus trastuzumab followed by FEC in patients with HER2-positive operable breast cancer is considerably effective and well tolerated.

[Thyroid Metastasis of Rectal Cancer].

A 65-year-old woman underwent laparoscopic low anterior resection for rectal cancer with distant metastasis to the right lobe of her liver and mediastinal and right subclavian lymph nodes. Since the postoperative chemotherapy resulted in the disappearance of the lymph node metastasis and diminished hepatic metastasis lesion, the enlarged anterior segment of the liver was performed. She was administered chemotherapy for 1 year after the second surgery. Thoracoabdominal computed tomography performed 18 months after the end of the treatment revealed swelling of the left lobe of the thyroid. Ultrasonography showed a 23mm lobulated hypoechoic tumor in the left lobe of the thyroid gland. We suspected thyroid metastasis by aspiration biopsy cytology. Left thyroid lobectomy was performed for definitive diagnosis and local control. Histological examination revealed thyroid metastasis of the rectal cancer. We experienced a rare case of thyroid metastasis from rectal cancer.

[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 an Elderly Male with Breast Cancer with Synchronous Triple Cancer of the Lung and Stomach].

An 89-year-old male was diagnosed with advanced gastric cancer during an upper gastrointestinal endoscopy for gastric polyp follow-up. Positron emission tomography revealed tumors with 18F-fluorodeoxyglucose(FDG)accumulation in the right lung and right breast. Incisional biopsy of the right breast tumor was performed and the tumor was diagnosed as primary breast cancer(ER: 90%, PgR: 70%, HER2: 1+, Ki-67: 17%). Since it was difficult to distinguish whether the lung tumor was primary lung cancer or metastasis, a bronchoscopic biopsy was performed. Histopathological examination revealed that the lung tumor was primary lung cancer. Thus, this male patient had simultaneous triple gastric, breast, and lung cancer. Total mastectomy was performed for the breast cancer under local anesthesia and adjuvant endocrine therapy was started. Stereo- tactic body radiation therapy(48 Gy/4 Fr/4 days)for lung cancer and partial gastrectomy for gastric cancer were subsequently performed. Although male breast cancer itself is rare, we experienced a very rare case of male breast cancer with simultaneous lung and gastric cancer.

Safety and Efficacy of Low-dose Nanoparticle Albumin-bound Paclitaxel for HER2-negative Metastatic Breast Cancer.

BACKGROUND/AIM: Nab-paclitaxel (nab-PTX) is an albumin-bound paclitaxel formulation. Although nab-PTX has shown superior efficacy compared to conventional paclitaxel (PTX) in metastatic breast cancer (MBC), chemotherapy-induced peripheral neuropathy (CIPN) was more frequently observed in nab-PTX. In this study, we aimed to estimate the feasibility of the nab-PTX 175 mg/m2/3weeks regimen. PATIENTS AND METHODS: Patients having metastatic or inoperable HER2-negative breast cancer received 175 mg/m2 of nab-PTX every three weeks. The primary endpoint was safety and the secondary endpoints were response and survival. RESULTS: Seventeen patients were enrolled with a median age of 64 years. Ten patients had estrogen receptor positive disease and seven had triple-negative disease. CIPN was observed in seven patients (41%) however, grade 3 CIPN was only seen in one patient (6%). Objective response rate was 41% and progression-free survival was 23 weeks. CONCLUSION: Nab-PTX 175 mg/m2/3wks regimen has a good safety profile and less frequent CIPN. This regimen can contribute to the strategy of MBC treatment.

Mammary phyllodes tumor with six episodes of a relapse: a case report.

BACKGROUND: Phyllodes tumor is a rare breast mass. Most phyllodes tumors are benign, but occasionally some show malignancy. Even if the tumors are benign, they can easily show recurrence. CASE PRESENTATION: We report a case of a 48-year-old Asian woman, who had previously undergone a tumorectomy of her left breast 12 years before, with a pathological diagnosis of fibroadenoma. Five years after the initial tumorectomy, the patient presented with an abnormally enlarged left breast. A biopsy determined the growth to be a phyllodes tumor; subsequently, a partial mastectomy was conducted. However, the patient's left breast showed rapid enlargement in the next 5 months. The treating physicians suspected a relapse and subsequently consulted with our hospital. The breast mass was resected at our institution. After this surgery, the patient had repeated episodes of relapse and underwent four additional operations. Since then, the patient has not had any additional relapse so far. CONCLUSIONS: We present a case of a phyllodes tumor with multiple episodes of relapse. Although phyllodes tumors commonly show relapse, this case was unique because of the number of episodes of relapse. This case highlights the need to carry out tumorectomy with adequate margins with subsequent careful observation to check for relapse.

Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and trastuzumab in women with human epidermal growth factor receptor 2-overexpressing breast cancer.

Although the concurrent use of anthracycline-containing chemotherapy and taxane with trastuzumab are considered the treatment of choice for the primary systemic therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early breast cancer, non-anthracycline regimens, such as concurrent administration of docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a favorable safety profile compared with standard paclitaxel for metastatic breast cancer patients in another phase III study. Based on these results, a phase I study of combination therapy with nab-paclitaxel, carboplatin and trastuzumab was planned, in order to estimate its efficacy and safety for HER2-overexpressing locally advanced breast cancer. The present study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose and recommended dose of this combination treatment in women with HER2-overexpressing locally advanced breast cancer. The starting dose of nab-paclitaxel was 220 mg/m2 (level 1), and the dose was escalated to 260 mg/m2 (level 2). Nab-paclitaxel was administered with carboplatin (area under the curve, 6 mg/ml/min) and trastuzumab tri-weekly. A total of 6 patients were enrolled. Although no DLT was observed during the first cycle, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia and 3 exhibited a grade 4 decrease in hemoglobin levels. In the present phase I study, although no patients experienced DLTs, this regimen was associated with severe hematological toxicities and it was not well tolerated. However, considering the high efficacy and lower risk of cardiotoxicity and secondary carcinogenesis with taxane, platinum and trastuzumab combination therapy, further evaluation of another regimen including weekly administration or a more accurate dose setting should be conducted.

[A Case of Paget-Type Recurrence 20 Years after Breast Conserving Surgery for Invasive Ductal Carcinoma].

We report an 85-year-old female suffered Paget-type recurrence at right remnant breast. The patient had undergone breast conserving surgery(BCS)20 years ago in another hospital for invasive ductal carcinoma of the right breast(pT1N0M0, Stage I ). Her chief complain was a skin ulcer of the right nipple. The pathological diagnosis for biopsy specimen from the areola was Paget's disease. She underwent total mastectomy. Paget cells were detected pathologically in the epidermis of the nipple and nearby mammary duct connected with fibrous tissue after BCS, suggesting Paget-type recurrence of invasive breast carcinoma.

Platelet-Lymphocyte Ratio as a Useful Predictor of the Therapeutic Effect of Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The peripheral blood platelet-lymphocyte ratio (PLR) has been proposed as an indicator for evaluating systemic inflammatory responses in cancer-bearing patients. While some reports suggest a correlation between PLR and prognosis, few studies have examined the relationship between PLR and sensitivity to chemotherapy. We conducted a study on whether PLR could serve as a predictor of the therapeutic effects of neoadjuvant chemotherapy (NAC). METHODS: PLR was evaluated in 177 breast cancer patients treated with the NAC 5-fluorouracil, epirubicin and cyclophosphamide, followed by weekly paclitaxel and subsequent curative surgery. The correlation between PLR and prognosis, and between PLR and the efficacy of NAC, were evaluated retrospectively. RESULTS: The low PLR group had significantly more patients > 56 years old (p = 0.001) and postmenopausal women (p = 0.001) than the high PLR group. The low PLR group also had a higher pathologic complete response (pCR) rate (p = 0.019). On examining the correlation with prognosis, the low-PLR group was found to have significantly longer disease-free survival (p = 0.004) and overall survival (p = 0.032) than the high PLR group. Multivariate analysis also revealed that lymph node metastasis (p = 0.043, hazard ratio = 4.40) and a high PLR (p = 0.005, hazard ratio = 2.84) were independent, unfavorable prognostic factors. CONCLUSIONS: For patients with breast cancer treated with NAC, a low PLR indicated high chemotherapy sensitivity, suggesting that PLR could serve as a predictive marker of the therapeutic effect of NAC.

A phase II, multicenter, single-arm trial of eribulin as first-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer.

The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m(2) on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1-21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC.

Predictive Value of Neutrophil/Lymphocyte Ratio for Efficacy of Preoperative Chemotherapy in Triple-Negative Breast Cancer.

BACKGROUND: The neutrophil/lymphocyte ratio (NLR) has been reportedly associated with prognosis in cancer patients by influencing both cancer progression and chemosensitivity. However, the correlation between NLR and the outcome of neoadjuvant chemotherapy (NAC) in breast cancer patients remains unclear. METHODS: NLR was evaluated in 177 patients with breast cancer treated with NAC with 5-fluorouracil, epirubicin, and cyclophosphamide, followed by weekly paclitaxel and subsequent curative surgery. The correlation between NLR and prognosis, including the efficacy of NAC, was evaluated retrospectively. RESULTS: NLR ranged from 0.5 to 10.6. Fifty-eight patients with low NLR (<3.0) had a higher pathological complete response (pCR) rate (p < 0.001) and were more frequently diagnosed with ER-negative/progesterone receptor (PR)-negative/HER2-negative (triple-negative) breast cancer (TNBC; p < 0.001) compared with patients with high NLR (≥3.0). Among TNBC patients who achieved pCR, disease-free survival (p = 0.006) and overall survival (p < 0.001) were significantly longer in patients with low NLR than in those with high NLR. Low NLR was associated with a significantly favorable prognosis in TNBC patients who achieved pCR, according to univariate analysis (p = 0.044, hazard ratio = 0.06). CONCLUSIONS: Low NLR may indicate high efficacy and favorable outcome after NAC in patients with TNBC.

Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer.

The protein nestin, a neuronal stem cell marker, has been reported to indicate a poor prognosis in various tumours. Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its molecular background has not been identified. The present study evaluated the expression of nestin and its significance in ATC. Tissue samples from 23 patients with ATC were subjected to immunohistochemical staining and the staining intensity of nestin in the cytoplasm was evaluated. The expression of nestin in the tumour cytoplasm was confirmed in 6 of the 23 tissue samples (26.1%). Between the nestin-positive group (n=6) and the nestin-negative group (n=17), there were no significant differences in the clinicopathological factors of the patients. However, the nestin-positive group exhibited significantly worse prognoses than the nestin-negative group (median survival time, 86.5 vs. 306 days; P<0.01, log-rank test). The multivariate analysis indicated that nestin expression was a prognostic indicator for the ATC patients (hazard ratio, 5.59; 95% confidence interval, 1.63-19.50; P<0.01), which is independent of the known clinical indicators. Nestin expression has the potential to be an independent indicator of a poor prognosis for patients with ATC.

Partial mastectomy using manual blunt dissection (MBD) in early breast cancer.

BACKGROUND: Breast-preserving surgery (Bp) and sentinel lymph node biopsy (SNB) are established as standard treatment for axillary lymph node-negative early breast cancer. METHODS: A surgical technique using manual blunt dissection (MBD), in which use of electrocautery, an ultrasonically activated scalpel, and ligation is minimized, is described. This involves an approach from small incisions in the axilla or areola to avoid injury to skin flaps, and with adequate mobilization of the breast, so that regardless of the tumor site, surgical wounds are not noticeable. The usefulness and tolerability of this surgical technique were examined. RESULTS: This surgical technique was evaluated in 233 patients. Surgery could be performed rapidly, with a mean operative time of 67 ± 21 min and a low mean blood loss of only 35 ± 28 ml. There was little need for postoperative analgesia, and surgery was well tolerated without postoperative bleeding or wound infection. CONCLUSION: Our proposed technique for partial mastectomy using MBD provides good curative and cosmetic results.

Ambulatory sentinel lymph node biopsy preceding neoadjuvant therapy in patients with operable breast cancer: a preliminary study.

BACKGROUND: Sentinel lymph node biopsy (SNB)-oriented stepwise treatment under local anesthesia has been performed in the outpatient-ambulatory setting in patients receiving neoadjuvant therapy (NAT). We retrospectively reviewed our preliminary experience of ambulatory SNB in breast cancer patients scheduled to undergo NAT to evaluate the usefulness and feasibility of this method as a minimally invasive, stepwise treatment protocol. METHODS: We retrospectively identified 56 patients with breast cancer without obvious nodal involvement who were scheduled to receive NAT before breast surgery. SNB was performed under local anesthesia in an ambulatory outpatient setting before the initiation of NAT. RESULTS: The average number of removed sentinel lymph nodes was 1.9. Identification of the sentinel node was possible in all cases, and macrometastasis was observed in six cases (10.7%). Micrometastasis was observed in five cases, while isolated tumor cells were noted in six cases. There were no delays in the initiation of NAT as a result of complications of SNB. CONCLUSIONS: This pilot study demonstrated the safety and feasibility of ambulatory SNB prior to NAT. Further studies are warranted to assess the strict indications, patient satisfaction, and medical economics of this procedure.

T-stage and positive sentinel nodes ratio are the useful factors to predict non-sentinel node metastasis in breast cancer patients with macro-metastasis in the sentinel node.

INTRODUCTION: Current guidelines recommend completion axillary lymph node dissection (cALND) in case of a sentinel lymph node (SN) metastasis larger than 2 mm (macrometastasis). However in many patients of those, the non-sentinel lymph nodes (NSN) contain no further metastasis, indicating that axillary lymph node dissection provides no benefit. To identify cases who could have undergone omission of the ALND with confidence, we have retrospectively evaluated the predictive factors of NSN metastasis with positive macrometastasis in the SN. METHODS: This study was based on a retrospective database of 420 patients who underwent sentinel lymph node biopsy (SNB) for breast cancer, of whom 61 patients had SN macrometastasis intra- and postoperatively. We examined predictive factors of NSN involvement in 51 cases of these 61 patients who underwent cALND. All clinical and histological variables were analyzed according to NSN status, by using Mann-Whitney U test, univariate and multivariate logistic regression model. RESULTS: T stage and the proportion of involved SNs among all identified SNs (SN ratio) were correlated with NSN metastasis. Univariate and multivariate analysis showed that T stage and SN ratio were the independent predictive factor of NSN metastasis. The area under ROC curve for SN ratio was 0.71. The best cut off value of SN ratio was 0.667. Negative predictive value to NSN metastasis in cases with both T2 and more than 0.667 of SN ratio was 85.7%. CONCLUSION: In patients with invasive breast cancer and macrometastasis of SN, T stage and SN ratio were useful for prediction of NSN metastasis.