[A Case of Squamous Cell Carcinoma of the Breast].

Squamous cell carcinoma(SCC)of the breast is a rare disease. We encountered a case of SCC of the breast that relapsed in the early postoperative period and rapidly progressed thereafter. A 38-year-old woman visited our hospital presenting with a tumor in the left breast consisting of a 5-cm mass with an irregularly sharped wall. Fine needle biopsy examination showed squamous cell carcinoma. A modified radical mastectomy by Auchincloss's method was performed on the left breast. SCC was confirmed by histological examination. Two months later, local recurrence on the chest wall was found during adjuvant chemotherapy. Thereafter, the disease rapidly progressed, and finally, the patient died of respiratory failure caused by lung metastasis. The prognosis of SCC of the breast is recognized as being more unfavorable than that of invasive ductal carcinoma. We should develop an effective chemotherapeutic strategy for this disease.

Breast conserving surgery using volume replacement with oxidized regenerated cellulose: a cosmetic outcome analysis.

We evaluated the cosmetic outcome of volume replacement with oxidized regenerated cellulose (ORC) after breast-conserving surgery (BCS) and also examined factors that may have influenced the results. Ninety-four patients who underwent BCS with ORC replacement between January 2010 and August 2012 participated in this study. The cosmetic outcomes of these patients were evaluated using scores based on the criteria of the Japan Breast Cancer Society. We evaluated cosmetic scores with regards to several clinical factors and the occurrence of complications after this procedure. The mean score of the cosmetic outcome of all patients was 9.5 points of 12 points. Thirty-seven patients were categorized as "Excellent," 34 were "Good," 22 were "Fair," and 1 was "Poor." Patient age, body mass index, weight of the specimen, and ORC amount were not significantly different between patients with favorable cosmetic scores and those without. However, the weight of the removed specimen was slightly higher in patients with an unfavorable cosmetic score. Although acute dermatitis and eczema was observed in 15% and 3% of patients, all of them were improved with conservative treatment. Cosmetic scores were significantly higher in patients without complications than in patients with complications. In conclusion, ORC replacement after BCS is a simple and reliable procedure. The selection of indication and prevention of complications are important for obtaining a better cosmetic outcome. This is the first report to cosmetically evaluate a relatively large number of patients that have undergone ORC replacement after BCS.

Validation of online calculators to predict the non-sentinel lymph node status in sentinel lymph node-positive breast cancer patients.

PURPOSE: This study evaluated and compared the predictive values of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and the Stanford nomogram for predicting non-sentinel lymph node (SLN) metastasis in patients with SLN metastasis, which were the only nomograms available online, and verified their usefulness in the macrometastasis or micrometastasis/isolated tumor cell (ITC) subgroups. METHODS: Eighty-nine patients with a positive SLN biopsy who underwent axillary lymph node dissection were analyzed. The predicted probability of non-SLN metastasis was calculated using a computerized model from the websites for each nomogram. The results were compared using the area under the curve (AUC) of the receiver operating characteristics curve for each model. The false-negative and false-positive rates were also calculated. RESULTS: The AUC for the entire population was 0.701 with the MSKCC nomogram and 0.756 with the Stanford nomogram. The AUCs of macrometastasis and micrometastasis/ITC groups were 0.680 and 0.469 with the MSKCC nomogram, and were 0.676 and 0.574 with the Stanford nomogram, respectively. Although false-negative cases were not identified, the false-positive rates were high in both subgroups when using these nomograms. CONCLUSIONS: This independent comparison found no significant difference between the two nomograms. In this study, these nomograms could not reliably predict positive non-SLN in patients with SLN micrometastasis/ITC.

De-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low-risk pure HER2 breast cancer.

PURPOSE: Neoadjuvant trastuzumab combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse. METHODS: We treated patients with tumors measuring ≤ 3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for four cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted. RESULTS: Eighteen patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low. CONCLUSION: This less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk.

Axillary Reconstruction with a Posterior Circumflex Humeral Artery Perforator Flap as a Salvage Surgery for Axillary Invasion of Advanced Breast Cancer.

A case of advanced breast carcinoma with large skin invasion that extended from the breast to the axilla and which was reconstructed with a meshed split skin graft for the chest defect and a posterior circumflex humeral artery perforator flap for the axillary area was described. When skin invasion of the breast cancer extends to the axillary area, reconstruction methods of the defect are probably complicated. The purpose of reconstruction is not only to close defects, but also to protect important tissues, such as axillary vessels and the brachial plexus. Moreover, thinner flaps are preferred to prevent a bulky contour. Many reconstruction methods can be used; however, if total mastectomy causes a large tissue defect from the breast to the axilla involving the subscapular artery, and only limited reconstruction is possible, a posterior circumflex humeral artery perforator flap can be an option to reconstruct the axilla.

A phase II, multicenter, single-arm trial of eribulin as first- or second-line chemotherapy for HER2-negative advanced or metastatic breast cancer: evaluation of efficacy, safety, and patient-reported outcomes.

PURPOSE: Although eribulin is a suitable option for early-line treatment of metastatic breast cancer (MBC), data on first- or second-line use of eribulin for human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited. Therefore, we conducted a phase II trial to investigate the efficacy and safety of eribulin for first- or second-line chemotherapy for HER2-negative MBC. MATERIALS AND METHODS: We performed a phase II, open-label, single-arm, multicenter study in Japan. Eligible patients were women with histologically confirmed HER2-negative MBC without chemotherapy or only one chemotherapy line for MBC. The primary endpoint was the overall response rate (ORR) and the secondary endpoints included the clinical benefit rate (ORR + stable disease for 6 months; CBR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and health-related quality of life (HRQoL). RESULTS: A total of 35 patients with HER2-negative MBC were enrolled between March 2013 and February 2017 (data cut-off July 31, 2017). The ORR was 37.1% (95% CI 21.1-53.2%). The CBR was 54.3% (95% CI 37.8-70.8%). The median PFS was 6.2 months (95% CI 2.7-9.4 months) and median OS was 21.4 months (95% CI 11.5-32.9 months). Common grade 3/4 adverse events were neutropenia (42.9%) but febrile neutropenia (2.9%). Although the majority of non-hematological adverse events were mild in severity, one patient died of pneumonitis. In HRQoL analysis, eribulin appeared to maintain HRQoL of many patients. CONCLUSIONS: Eribulin as first- or second-line chemotherapy is effective and has manageable toxicity for patients with HER2-negative MBC.

Comparative proteomic analysis of paclitaxel resistance-related proteins in human breast cancer cell lines.

Paclitaxel is widely used to treat various cancers; however, resistance to this drug is a major obstacle to breast cancer chemotherapy. To identify the proteins involved in paclitaxel resistance, the present study compared the proteomes of MCF-7 human breast cancer cells and its paclitaxel-resistant subclone MCF-7/PTX. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry, 11 upregulated and 12 downregulated proteins were identified in MCF-7/PTX cells compared with the parental cell line. These 23 proteins were functionally classified as stress-induced chaperones, metabolic enzymes and cytoskeletal proteins. The anti-apoptotic proteins, stress-70 protein, 78-kD glucose-regulated protein, peptidyl-prolyl cis-trans isomerase A (PPIA) and heterogeneous nuclear ribonucleoprotein H3, were also upregulated in MCF-7/PTX cells. Notably, knockdown of the stress-response chaperone PPIA using small interfering RNA in MCF-7/PTX cells restored their sensitivity to paclitaxel. These findings indicated that PPIA may have an important role in paclitaxel resistance in MCF-7/PTX cells.

Outpatient management without initial assessment for febrile patients undergoing adjuvant chemotherapy for breast cancer.

The purpose of this study was to retrospectively analyze the feasibility of outpatient management without initial assessment for febrile patients undergoing adjuvant chemotherapy for breast cancer. A total of 131 consecutive patients with breast cancer treated with adjuvant or neoadjuvant chemotherapy from 2011 to 2013 at Osaka Medical College Hospital (Osaka, Japan) were retrospectively reviewed. In the case of developing a fever (body temperature, ≥38°C), the outpatients had been instructed to take previously prescribed oral antibiotics for 3 days without any initial assessment, and if no improvement had occurred by then, they were required to visit the hospital for examination and to undergo treatment based on the results of a risk assessment for complications. The primary aim of the present study was to assess the outcome of febrile episodes, while the secondary aim was to assess the incidence of febrile episodes, hospitalizations, and the type of chemotherapy. The 131 patients received 840 chemotherapy administrations. Fifty-five patients (42.0%) had a total of 75 febrile episodes after 840 chemotherapy administrations (8.9%). Treatment failure occurred in 12 of the 75 episodes (16.0%) in 11 of the 55 patients (20.0%). Only four episodes required hospitalization. Treatment success was achieved in 63 episodes (84.0%). In conclusion, the feasibility of outpatient management without initial assessment was evaluated in the present study for febrile patients undergoing adjuvant chemotherapy for breast cancer, and the outpatient strategy regimen may be safe and convenient for these patients.

Prevalence and characteristics of Cyprinid herpesvirus 3 (CyHV-3) infection in common carp (Cyprinus carpio L.) inhabiting three rivers in Kochi Prefecture, Japan.

Cyprinid herpesvirus 3 (CyHV-3) causes lethal disease in common and koi carp. Mortality by CyHV-3 disease has not been reported since 2011 in Kochi Prefecture, Japan. Here, we detected and quantified CyHV-3 in common carp inhabiting three rivers in the prefecture to examine if the carp are carriers of CyHV-3 as a source of infection. CyHV-3 DNA was detected in 16.7% (12/72) of brain samples in Kagami River, 3.9% (3/76) of brain and 3.9% (3/76) of gill samples in Monobe River, and 5.1% (4/79) of brain and 1.3% (1/79) of gill samples in Wajiki River. CyHV-3 genotypes identified in the 23 samples were classified as the J genotype A1 that has been found in Japan. The CyHV-3 DNA load did not differ statistically between sampling months, indicating that CyHV-3 has been silent in common carp, unlike Lake Biwa where the annual reactivation occurs in spring. Taken together, our results represented definitive evidence that seasonal changes in water temperature do not affect CyHV-3 activity in carp. Considering that infectious virus was not isolated from CyHV-3 DNA-positive samples, it was suggested that CyHV-3 establishes a latent infection in carp populations inhabiting Kagami River, Monobe River and Wajiki River. Further, the presence of circular or concatameric CyHV-3 DNA was detected in five of 23 CyHV-3 DNA-positive samples. Common carp inhabiting Lake Biwa were reported previously to harbor linear but not circular CyHV-3 DNA. This difference suggested that the CyHV-3 genome may be circularized for long-term maintenance without active viral replication.

Safety of nanoparticle albumin-bound paclitaxel administered to breast cancer patients with clinical contraindications to paclitaxel or docetaxel: Four case reports.

Taxanes, including paclitaxel (PTX) and docetaxel (DOC), are poorly soluble in water due to their hydrophobic properties and thus, require solvents. However, use of these solvents has been associated with toxic responses, including a hypersensitivity reaction (HSR). Nanoparticle albumin-bound paclitaxel (nab-PTX) is a novel formulation of PTX, which allows reconstitution of the agent with a saline solution instead of solvents and administration without premedication for HSRs. The current study reports the safe administration of nab-PTX to four breast cancer patients considered clinically to have contraindications to PTX or DOC. Two of the patients had previously experienced HSRs to PTX or DOC and the other two patients had contraindications to steroids as a premedication for HSRs, since one patient suffered from diabetes and the other was a carrier of the hepatitis B virus. All 4 patients were safely administered nab-PTX. In conclusion, administration of nab-PTX appears to be effective for patients that have previously experienced HSRs to other taxanes or in those with contraindications to steroids.

Association between body mass index and breast cancer intrinsic subtypes in Japanese women.

The purpose of this study was to examine the association between body mass index (BMI) and breast cancer intrinsic subtypes in Japanese women. A more complete understanding of the subtypes of breast cancer may elucidate the mechanisms affecting the etiology and mortality associated with each subtype. Tumor data on 531 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (Her2) status were obtained [luminal A, luminal B, triple-negative (TN) and Her2-type]. Demographics (age at diagnosis, menopausal status and BMI) were collected from medical records. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis. Of the 531 cases, 333 (62.7%) were luminal A, 85 (16.0%) were luminal B, 43 (8.1%) were Her2-type and 70 (13.2%) were TN. Compared with luminal A cases, premenopausal TN cases were more likely to be obese (OR, 4.11; 95% CI, 1.10-14.40), while postmenopausal TN cases were more likely to be underweight (OR, 3.14; 95% CI, 1.19-8.01). Premenopausal luminal B cases were likely to be underweight or obese, while luminal B and Her2-type cases were likely to be underweight. In the present study, significant heterogeneity of associations between BMI and tumor subtypes was observed. Breast cancer subtypes may have various etiologies associated with each subtype.

A case of solitary breast metastasis from malignant melanoma of the nasal cavity.

Metastatic breast tumors are rare; however, malignant melanoma is one of the primary tumors most commonly reported to metastasize to the breast. Among these, the primary tumors typically associated with metastasis to the breast are cutaneous melanomas. We present, herein, a very rare case of solitary metastasis to the left breast from malignant melanoma of the nasal cavity, which represents less than 1% of all malignant melanomas. The patient, a 78-year-old woman, was treated using a combination of surgery and radiotherapy. In the absence of therapeutic efficacy, disease progression was very rapid. No previous studies have described malignant melanoma of the nasal cavity with solitary breast metastasis. This case report aims to increase awareness of the need to establish treatment strategies based on an understanding of the etiology and pathophysiology.

Use of contrast-enhanced computed tomography in clinical staging of asymptomatic breast cancer patients to detect asymptomatic distant metastases.

The use of computed tomography (CT) with regards to the clinical staging of patients with asymptomatic breast cancer has been on the increase in clinical practice. However, the benefits of routine CT have yet to be fully clarified. This study investigated the value of employing contrast-enhanced CT (CECT) to screen for distant metastases in patients with asymptomatic breast cancer. The clinical records of 483 patients with asymptomatic breast cancer who underwent CECT at a single institution between April 2006 and January 2011 were reviewed retrospectively. The CECT results were classified into normal, true-positive (metastases) or false-positive findings. Abnormal CECT findings, including true- and false-positive results, were detected in 65 patients (13.5%). Of these, 26 patients (5.4%) showed confirmed true metastatic disease, including 18 lung metastases, 11 liver metastases and 13 bone metastases. Upstaging to stage IV due to the results of the CECT scan occurred in 0 of 155 patients at stage I, 5 of 261 patients (1.9%) at stage II and 21 of 67 patients (31.3%) at stage III. The false-positive rates were 7.7, 9.0 and 8.7% in stages I, II and III, respectively. The size of the lung or liver metastasis was significantly larger than the false-positive lesion. Routine CECT did not appear to be useful for detecting distant metastases in completely asymptomatic patients. Conversely, a small number of patients were upstaged from early to stage IV and a predictive factor beyond T and N stage alone appears to be needed in order to predict which asymptomatic patients have distant metastases.