Pathological Complete Response Patients after Neoadjuvant Chemotherapy in Breast Cancer.

Cases of breast cancer metastasis after achieving a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) are sometimes encountered in clinical practice. We investigated the prognostic factors for pCR in patients with breast cancer after NAC. This retrospective cohort study included patients with localized breast cancer who underwent NAC followed by surgery between 2004 and 2020 and achieved a pCR. The associations between clinical factors and distant metastasis-free survival rate were statistically analyzed. We analyzed data for 127 patients. Twelve patients (9.4%) had distant metastases, and seven (5.5%) died. For estrogen receptor (ER)-positive patients, the distant metastasis-free survival rate was 94.6% for both 5 and 8 years. In contrast, ER-negative patients had a distant metastasis-free survival rate of 87.6% and 85.4% for 5 and 8 years (p=0.094), respectively. In cT0-2 patients, the distant metastasis-free survival rate was 92.4% for 5 years and 90.5% for 8 years, whereas in cT3-4 patients, the distant metastasis-free survival rate was 83.5% for 5 years and 83.5% for 8 years (p=0.301). This study suggested that patients with ER-negative, pre-NAC cT3 or T4 breast cancer who had achieved a pCR after NAC tended to have a worse prognosis.

[A Case of Breast Cancer during Pregnancy Treated with Neoadjuvant Chemotherapy during Pregnancy].

Although breast cancer during pregnancy is relatively rare, the number of such cases has risen in recent years owing to an increase in mean childbirth age and the increasing prevalence of breast cancer. Here we report the case of a 37-year-old breast cancer patient who received neoadjuvant chemotherapy during pregnancy. The woman previously consulted an outside physician after noting a mass in her right breast at 25 weeks' gestation. Breast ultrasonography revealed a right breast tumor and axillary lymphadenopathy. A histopathological examination indicated right breast cancer and axillary lymph node metastasis. She was referred to our department for pregnancy management. Chest X-rays and abdominal ultrasonography were utilized in the search for metastases. She received 2 courses of doxorubicin and cyclophosphamide(AC)therapy during pregnancy and gave birth via cesarean section at 35 weeks' gestation. After delivery, the AC was resumed. The patient completed a total of 4 courses of AC followed by 4 courses of docetaxel (dosed every 3 weeks). She underwent total right mastectomy and axillary dissection; because the tumor was BRCA2 mutation-positive, a risk-reducing salpingo- oophorectomy was also performed. Adjuvant therapy included radiotherapy and tamoxifen but no luteinizing hormone- releasing hormone agonists. At the time of this writing more than 1 year post-surgery, she has not experienced recurrence; although the infant has a congenital clubfoot, she suffers from no other cognitive or developmental delays.

Four magnetic resonance imaging surveillance-detected breast cancer cases in cancer-free BRCA1/2 mutation carriers.

BACKGROUND: Hereditary breast and ovarian cancer (HBOC) syndrome is a susceptibility syndrome for cancers, such as breast and ovarian cancer, and BRCA1/2 are its causative genes. Annual breast-enhanced magnetic resonance imaging (MRI) is recommended for BRCA1/2 mutation carriers aged over 25 years as a secondary prevention of breast cancer. However, breast MRI surveillance is rarely performed in Japan, and only four cases of breast cancer diagnosis triggered by MRI surveillance have been reported. CASE PRESENTATION: At our hospital, MRI triggered the diagnosis of breast cancer in four cancer-free BRCA1/2 mutation carriers. In one of our four cases, although MRI showed only a 3-mm focus, we could diagnose breast cancer by shortening the surveillance interval considering the patient's high-risk for developing breast cancer. CONCLUSIONS: Image-guided biopsy, including MRI-guided biopsy, depending on the size of the lesion, and shorter surveillance intervals are useful when there are potentially malignant findings on breast MRI surveillance for cancer-free patients with HBOC.

A Case of a Rapidly Growing Granulocyte Colony-Stimulating Factor-Producing Squamous Cell Carcinoma of the Breast.

A 34-year-old woman with a rapidly growing right breast mass visited our hospital. The mass was diagnosed as a right breast cancer (cT3N1M0 stage ⦀A). Her serum leucocyte count and C-reactive protein levels were high, and she had persistent fever. However, serum procalcitonin and ß-D-glucan levels were normal, and no apparent infection focus was detected, although her serum granulocyte colony-stimulating factor (G-CSF) level was markedly elevated to 42.7 pg/mL. Therefore, a G-CSF-producing breast cancer was suspected. A pathological analysis of the surgical specimen revealed a squamous cell carcinoma of the breast (pT2N0 [i+] M0 stage ∥A). Right mastectomy (with the resection of the pectoralis major muscle), axillary lymph node dissection, and split layer grafting were performed. The leucocyte count and serum G-CSF level decreased on postoperative day (POD) 1 and normalized on POD 6. As adjuvant chemotherapy, 4 cycles of a combination chemotherapy with adriamycin and cyclophosphamide and 12 cycles of weekly paclitaxel were administered. After chemotherapy, the patient also underwent postmastectomy radiotherapy. Currently, 30 months after surgery, the patient is alive and well with neither progression nor distant metastasis. G-CSF-producing breast cancers tend to rapidly grow such as in the current case; thus, surgery should be performed immediately, followed by appropriate adjuvant treatment.

Metaplastic carcinoma of the breast and BRCA1 germline mutation: a case report and review.

BACKGROUND: Metaplastic carcinoma of the breast consists of both invasive ductal carcinoma and metaplastic carcinoma. This rare subtype of cancer has a poor prognosis. The development of metaplastic breast cancer and relationship with BRCA1 are not well known. Here, we report a rare case of germline BRCA1 mutation-positive breast cancer with chondroid metaplasia. CASE PRESENTATION: A 39-year-old Japanese woman with a family history of breast cancer in her mother and ovarian cancer in her maternal grandmother consulted at our hospital with a left breast mass. Needle biopsy for the mass was performed, leading to a diagnosis of invasive breast cancer with chondroid metaplasia. We performed left mastectomy + sentinel lymph node biopsy + tissue expander insertion and replaced with a silicone implant later. Pathological examination revealed that the patient had triple-negative breast cancer. Four courses of doxorubicin+ cyclophosphamide therapy were performed as adjuvant therapy after surgery. We performed genetic counseling and genetic testing, and the results suggested the germline BRCA1 mutation 307 T> A (L63*). She has currently lived without a relapse for 2 years post-surgery. CONCLUSIONS: There have been only 6 cases of metaplastic breast carcinoma with germline BRCA1 mutations including our case. Patients with BRCA1 mutations may develop basal-like subtypes or M type of triple-negative breast cancer besides metaplastic breast cancers.

Effect of Cell Seeding Conditions on the Efficiency of In Vivo Bone Formation.

PURPOSE: To optimize methods for seeding cells on granular-type beta-tricalcium phosphate (ß-TCP). MATERIALS AND METHODS: Bone marrow stromal cells were obtained from rat long bones and cultured in flasks with Minimum Essential Medium, Alpha Modification (αMEM) supplemented with 10% fetal bovine serum (FBS), dexamethasone, ascorbic acid, ß -glycerophosphate, and antibiotics. The influence of differential cell seeding densities and dynamic cell seeding conditions (rotation) was investigated using different sizes of ß -TCP granules and a subcutaneous implantation model. RESULTS: Higher cell seeding densities contributed to efficient in vivo bone formation. The rotational seeding did not affect the efficiency but contributed to the uniformity. Although the granule size did not affect the efficiency under the conditions used in this study, large granules showed more uniform distribution of bone regeneration, while small granules showed nonuniform but dense bone formation. Mixtures of relatively large and small granules may be beneficial for both uniform and efficient bone regeneration. CONCLUSION: These findings may contribute to stable bone tissue engineering with bone marrow stromal cells and ß -TCP granules as a scaffold.

Hemopexin is upregulated in rat intestinal mucosa injured by indomethacin.

BACKGROUND AND AIMS: Recent advancements in capsule endoscopy and double-balloon endoscopy have revealed that non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, can induce small intestinal mucosal damage. However, the precise pathogenesis and therapeutic strategy have not been fully revealed. The aim of the present study was to determine the upregulated proteins in the small intestine exposed to indomethacin. METHODS: Indomethacin (10 mg/kg) was administered subcutaneously to male Wistar rats to induce small intestinal damage and the severity of the intestinal injury was evaluated by measuring the area of visible ulcerative lesions. The intestinal mucosal tissue samples were collected and then analyzed by two-dimensional gel electrophoresis, with matrix-assisted laser desorption/ionization time-of-flight spectrometer peptide mass fingerprinting being used to determine the differentially expressed proteins between normal and injured intestinal mucosa. RESULTS: Among several protein spots showing differential expression, one, hemopexin (HPX), was identified as upregulated in indomethacin-induced injured intestinal mucosa using the MASCOT search engine. CONCLUSION: HPX was identified as upregulated protein in the small intestine exposed to indomethacin. HPX may be responsible for the development of the intestinal inflammation induced by NSAIDs.

Detection of N-(hexanoyl)lysine in the tropomyosin 1 protein in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric cancer cells.

N(ε)-(Hexanoyl)lysine, formed by the reaction of lysine with n-6 lipid hydroperoxide, is a lipid peroxidation marker during the initial stage of oxidative stress. The aim of the present study is to indentify N(ε)-(hexanoyl)lysine-modified proteins in neoplastic transformed gastric mucosal cells by N-methyl-N'-nitro-N-nitrosoguanidine, and to compare the levels of these proteins between gastric mucosal cells and normal gastric cells. Much greater fluorescence of 2-[6-(4'-hydroxy)phenoxyl-3H-xanthen-3-on-9-yl]benzoic acid, an index of the intracellular levels of reactive oxygen species, was observed for gastric mucosal cells compared to normal gastric cells. N(ε)-(Hexanoyl)lysine-modified proteins were detected by SDS-PAGE or two-dimensional electrophoresis and Western blotting using anti-N(ε)-(hexanoyl)lysine polyclonal antibody, and a protein band of between 30-40 kDa was clearly increased in gastric mucosal cells compared to normal gastric cells. Two N(ε)-(hexanoyl)lysine-modified protein spots in gastric mucosal cells were identified as the tropomyosin 1 protein by mass spectrometry using a MASCOT search. The existence of N(ε)-(hexanoyl)lysine modification in tropomyosin 1 was confirmed by Western blotting of SDS-PAGE-separated or two-dimensional electrophoresis-separated proteins as well as by the immunoprecipitation with anti-tropomyosin 1 antibody. These data indicate that N(ε)-(hexanoyl)lysine modification of tropomyosin 1 may be related to neoplastic transformation by N-methyl-N'-nitro-N-nitrosoguanidine in gastric epithelial cells.

Identification of dihalogenated proteins in rat intestinal mucosa injured by indomethacin.

Previous studies have shown that activated neutrophils and their myeloperoxidase (MPO)-derived products play a crucial role in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-related small intestinal injury. The aim of the present study is to identify dihalogenated proteins in the small intestine on indomethacin administration. Intestinal damage was induced by subcutaneous administration of indomethacin (10 mg/kg) in male Wistar rats, and the severity of the injury was evaluated by measuring the area of visible ulcerative lesions. Tissue-associated MPO activity was measured in the intestinal mucosa as an index of neutrophil infiltration. The dihalogenated proteins were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) using novel monoclonal antibodies against dibromotyrosine (DiBrY), and they were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) peptide mass fingerprinting and a Mascot database search. Single administration of indomethacin elicited increased ulcerative area and MPO activity in the small intestine. 2D-PAGE showed an increased level of DiBrY-modified proteins in the indomethacin-induced injured intestinal mucosa and 6 modified proteins were found. Enolase-1 and albumin were found to be DiBrY modified. These proteins may be responsible for the development of neutrophil-associated intestinal injury induced by indomethacin.