Innovative use of magnetic resonance imaging-guided focused ultrasound surgery for non-invasive breast cancer: a report of two cases.

OBJECTIVE: This report describes the first clinical experience with magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) using the ExAblate 2100 system for non-invasive breast cancer. METHODS: Two women with non-invasive breast cancer underwent MRgFUS treatment. One week after the MRgFUS treatment, US-guided vacuum-assisted biopsy was performed for the ablated lesions at the same time as breast-conserving surgery. RESULTS: The patients experienced good cosmetic outcomes and did not experience any severe adverse events, such as skin burns. Pathological examination of the surgical specimens revealed a few degenerated intraductal lesions around the breast biopsy markers. CONCLUSION: Performing MRgFUS with the new ExAblate 2100 system appears to be safe and feasible. The histopathological results revealed that adequate ultrasound energy in the appropriate location can induce tumor necrosis.

Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma.

Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry. RhoA, ROCK, mTOR, AKT1, and PIK3CA mRNA expression were conducted using laser microdissection and semi-nested quantitative reverse transcription-polymerase chain reaction. RhoA expression was stronger on the tumor interface of IDCs than the tumor center (P<0.001). RhoA expression was correlated with ROCK expression only in HER2-subtype IDC (P<0.05). In IDCs co-expressing RhoA and ROCK, F-actin expression was stronger on the tumor interface, particularly at the edges of tumor cells, than it was in ROCK-negative IDCs (P<0.0001). In conclusion, RhoA expression was not correlated with EMT in IDC, but enhanced F-actin expression was localized on the edge of tumor cells that co-expressed ROCK. RhoA/ROCK signaling may be associated with collective cell invasion, particularly in HER2-subtype IDC.

[A Study of Therapy for Locally Advanced Breast Cancer with Metastasis].

We reviewed 21 patients with locally advanced breast cancer with distant metastasis.The median age was 61 years.The median time to presentation at hospital was 13 months, and the median neoplasm diameter on the first visit was 10 cm.The main histological type was scirrhous carcinoma.Sixteen cases tested positive for hormone receptor(76%), 4 tested positive for HER2(19%), and 3 were triple negative(14%).Four patients underwent surgery.The techniques performed included mastectomy and axillary lymph node dissection.Three patients experienced local recurrence.The first-line treatment was surgery for 1 patient, chemotherapy for 12 patients, hormonal therapy for 7 patients, and trastuzumab for the HER2 positive patients.The median follow-up period was 49 months.The patients for where an operation was performed were 49 months and the operation not- enforcement patients were 54 months.If treatment is possible for patients with locally advanced breast cancer with distant metastasis, multidisciplinary treatment according to individual patient characteristics is recommended. In the case of surgical treatment, careful consideration must also be given to these characteristics.

[Report of a Successful Case of Combined Modality Therapy for a Patient with Local Recurrence of Rectal Cancer].

A 67-year-old man underwent abdominoperinealresection for rectalcancer (Rb, tub2>muc, A, N1, H0, P0, M0, Cy1, Stage III a). We administered mFOLFOX6 as adjuvant chemotherapy for 6 months. Twenty-seven months after surgery, his serum tumor marker level was increased, and local recurrence in the left rear of the prostate was detected by pelvic CT. The patient selected radiation(50 Gy/25 Fr), after rejecting resection for the local recurrence. After radiation, we performed chemotherapy combined with bevacizumab. Seventeen months from the start of chemotherapy, 47 months after surgery, chemotherapy was stopped because his tumor maker levels normalized and pelvic CT revealed a partial response. At present, his progression-free survival is 7 months after completion of chemotherapy. We conclude that combined modality therapy is an option for a patient with locally recurrent rectal cancer.

[Effectiveness of Lenvatinib for Thyroid Cancer with Lung Metastases - Report of a Case].

A 73-year-old woman visited our hospital 1 year 4 months ago because of multiple lung masses that were incidentally detected on CT. We subsequently conducted a whole body examination. Ultrasonography revealed multiple masses in her thyroid. We performed fine needle aspiration biopsy cytology(ABC), and the cytological diagnosis was papillary carcinoma. Total thyroidectomy and modified radical neck dissection were performed. Two months after the operation, cervical lymph nodes were enlarged, and she received I -131 radioisotope therapy. However, the lung masses became enlarged. Five months after operation, she was stared on lenvatinib therapy. The lung lesions did not progress during the 10 months after starting this therapy. In this case, lenvatinib was effective against metastatic thyroid cancer.

Immunohistochemical co-expression status of cytokeratin 5/6, androgen receptor, and p53 as prognostic factors of adjuvant chemotherapy for triple negative breast cancer.

Triple negative breast cancer (TNBC) is immunohistochemically characterised by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2). TNBC is known for its poor prognosis and high recurrence probability. There is no effective targeted treatment for TNBC, but only adjuvant chemotherapies. There are two TNBC subtypes, basal-like and non-basal-like, which are defined based on positive cytokeratin (CK) 5/6 and/or epidermal growth factor receptor (EGFR) expression. In particular, CK5/6 expression is reported to correlate with TNBC recurrence. TNBC lacks ER-α expression, but some TNBCs are known to express the androgen receptor (AR). Moreover, although p53 accumulation is detected in various malignant tumors, its influence on adjuvant chemotherapy for patients with TNBC remains unclear. The aim of this study was to assess the combined immunohistochemical expression of CK 5/6, AR, and p53 as a potential prognostic marker of adjuvant chemotherapy for patients with TNBC. The expression of CK5/6, AR, and p53 in formalin-fixed and paraffin-embedded (FFPE) surgical sections from 52 patients with TNBC was analysed by immunohistochemistry (IHC) and the co-expression patterns in individual cells were investigated by immunofluorescent (IF) staining. Low AR expression was correlated with high clinical stage (P < 0.05) and low nuclear grade (P < 0.05). The expression of CK5/6 and p53 did not correlate with clinicopathological features. Patients who needed adjuvant chemotherapy presented the worst prognosis. In particular, when the IHC expression pattern was CK5/6 (-), AR (-), and p53 (+), the disease free survival (DFS) and overall survival (OS) were the worst. On the other hand, patients with AR (+) and p53 (-) TNBC presented a good prognosis. The analysis of the co-expression status of these three markers showed that no cells presented both AR and CK5/6 expression. Furthermore, TP53 mRNA expression was higher in patients with AR-negative TNBC (P < 0.05) and in patients with the worst prognosis (P < 0.05) than in the other patients. These results suggested that, in patients with CK5/6-negative TNBC, AR expression correlated with good prognosis, but p53 accumulation correlated with poor prognosis. The present IHC markers allowed us to predict the post-surgery prognosis of patients with TNBC. In conclusion, TNBCs are heterogeneous. Patients with the CK5/6 (-), AR (-), and p53 (+) TNBC subtype, evaluated by IHC, presented the worst prognosis. These IHC markers will be helpful to follow patients with TNBC.

[Indoleamine 2,3-Dioxygenase Activity during Fulvestrant Therapy for Aromatase Inhibitor-Resistant Metastatic Breast Cancer].

We evaluated the clinical significance of indoleamine 2,3-dioxygenase (IDO) during fulvestrant therapy for aromatase inhibitor (AI)-resistant metastatic breast cancer. IDO activity can be measured by the tryptophan (Trp)/kynurenine (Kyn) ratio. Trp and Kyn were measured with high performance liquid chromatography (HPLC). Patients with AI resistant metastatic breast cancer had a 28.6% response rate to fulvestrant therapy, and the clinical benefit rate was 76.2%. AI-resistant metastatic breast cancer patients with distant metastases had a lower serum Trp/Kyn level than patients who had local recurrences. During fulvestrant therapy, IDO activity significantly decreased in the fulvestrant responder group compared to that in the fulvestrant non-responder group. During fulvestrant therapy, the IDO activity correlated with the number of metastatic lesions. These results suggest that measuring the Trp/Kyn ratio is useful for evaluating immunological metastatic status during endocrine therapy.

[Examination of the Response Rate of Paclitaxel and Bevacizumab Therapy for Metastatic Advanced Breast Cancer According to the Lymphopenia Grade].

Bevacizumab is a well-established anti-VEGF monoclonal antibody that inhibits angiogenesis. Herein, we examined the response rates according to the grade of lymphopenia in metastatic breast cancer patients treated with bevacizumab+paclitaxel therapy. The objective responses were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) Guideline v1.1. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Twenty study patients were divided into group A (grade 2-4 lymphopenia) and group B (grade 1 lymphopenia or no decreased lymphocyte count) and compared. The mean progression-free survival (PFS)was 77.7 days in group A (n=7) and 56.8 days in group B (n=13). There was no significant difference between both groups (p=0.67, logrank test). The response rate (RR) was 14.3% (CR=0, PR=1, SD=3, PD=3) in group A, while in group B, it was 23.0% (CR=0, PR=3, SD= 6, PD=4). Furthermore, the clinical benefit rate (CBR) bwas 57.1% in group A and 69.2% in group B.

[Study of the Response Rate and Neutrophil Lymphocyte Ratio in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy].

The neutrophil lymphocyte ratio (NLR) is associated with the outcomes of some cancer patients such as those with digestive cancer. Herein, we examined the relationship between the response rate following neoadjuvant chemotherapy and NLR in breast cancer patients. We recruited 19 primary breast cancer patients who were administered neoadjuvant chemotherapy. We evaluated the effects of this treatment and classified the patients into responder (CR and PR) and non-responder (SD and PD) groups. We measured the value of NLR before or at the start of nab-PTX treatment, and 7 days after nab-PTX (1-1) and nab-PTX (4-3) treatment. The average age was 58.6 years. The responder and non-responder groups comprised 14 and 5 cases, respectively. The average values of NLR before or at the start of the nab-PTX phase were 4.33 and 5.05 in the responder and non-responder groups, respectively. The average NLR values 7 days after nab-PTX (1-1) were 6.72 and 5.60 in the responder and non-responder groups, respectively. The NLR values 7 days after nab-PTX (4-3) were 2.40 and 2.65 for the responder and non-responder groups, respectively. There were no significant differences between the responder and non-responder groups for each treatment phase.

Altered intracellular region of MUC1 and disrupted correlation of polarity-related molecules in breast cancer subtypes.

MUC1 glycoprotein is overexpressed and its intracellular localization altered during breast carcinoma tumorigenesis. The present study aimed to clarify the relationship of cytoplasmic localization of MUC1 with the breast cancer subtype and the correlation of 10 molecules associated with cell polarity in breast cancer subtypes. We immunostained 131 formalin-fixed and paraffin-embedded breast cancer specimens with an anti-MUC1 antibody (MUC1/CORE). For 48 of the 131 tumor specimens, laser-assisted microdissection and real-time quantitative RT-PCR were performed to analyze mRNA levels of MUC1 and 10 molecules, ß-catenin, E-cadherin, claudin 3, claudin 4, claudin 7, RhoA, cdc42, Rac1, Par3 and Par6. Localization of MUC1 protein varied among breast cancer subtypes, that is, both the apical domain and cytoplasm in luminal A-like tumors (P < 0.01) and both the cytoplasm and cell membrane in luminal B-like (growth factor receptor 2 [HER2]+) tumors (P < 0.05), and no expression was found in triple negative tumors (P < 0.001). Estrogen receptor (ER)+ breast cancers showed higher MUC1 mRNA levels than ER- breast cancers (P < 0.01). The incidence of mutual correlations of expression levels between two of the 10 molecules (55 combinations) was 54.5% in normal breast tissue and 38.2% in luminal A-like specimens, 16.4% in luminal B-like (HER2+), 3.6% in HER2 and 18.2% in triple negative specimens. In conclusion, each breast cancer subtype has characteristic cytoplasmic localization patterns of MUC1 and different degrees of disrupted correlation of the expression levels between the 10 examined molecules in comparison with normal breast tissue.

[Usefulness of Local Therapy in Elderly Breast Cancer Patients with Distant Metastases].

We investigated the usefulness of local therapy in elderly breast cancer patients with distant metastases. Sixty-four elderly breast cancer patients were encountered during 10 years. Fifty-one patients had complications. The proportion of endocrine receptor-positive tumors was 95.2%. Patients who had metastases at the first visit represented 22.6% of the study group. Advanced-stage cancers were recognized in elderly patients than other patients. The mean observation time for all the patients was 7.4 years. The mortality from cancer was 6.5%, and the mortality from other diseases was 58.1%. We divided the patients into 2 groups, the non-metastases group (group A, n=48), and the metastases group (group B, n=14). There were no significant differences between groups A and B in the rates of endocrine receptor-positive tumors, surgery rate, and survival rate. These results suggest that endocrine therapy without surgery should be considered in elderly breast cancer patients with endocrine receptor-positive tumors.

[Examination of the Cases Given Primary Tumor Resection after Systemic Therapy for Metastatic Breast Cancer].

We examined the records of patients with stage Ⅳ breast cancer who underwent primary tumor resection after systemic therapy. In our department, in 2013, there were 8 such cases. The average local tumor diameter was 59 mm. There was 1 case of metastases to the liver, 2 cases to the lung, 3 cases to the bone, and 1 case to the kidney. Three cases had lymph node metastases. Two cases were treated with hormonal therapy, and 6 cases received chemotherapy as preoperative systemic therapy. All cases underwent Bt plus Ax. Approximately 2 years after the surgery, 5 of the 8 patients were alive. The postoperative local control was good and we were able to continue systemic treatment for the distant metastases in all cases. We think that resection of the primary tumor improved the quality of life of the patients. However, for 1 fatal case, a brain metastasis was detected shortly after surgery. Therefore, we need to consider the patient's condition carefully before we operate.

[A Case of an Older Patient with Metastatic Breast Cancer Effectively Treated with Capecitabine, with Achievement of cCR].

A case: An 82-year-old woman underwent Bp plus Ax enforcement for carcinoma of the right breast (T2N1M0, StageⅡB) about 5 years previously. Letrozole was administered, but right pleura tuberculum and pleural dissemination was noted in the fifth postoperative year. The hormone therapy was changed, but mediastinal lymph node metastases were observed with tumor marker elevation and bilateral metastases in the lung and right pleural fluid retention. Capecitabine 1,800 mg/day for 3 weeks was started in the sixth postoperative year. The response to treatment was classified as cCR and no side effects were noted. For approximately 1 year and 6 months, no recurrence or metastasis has been observed. Consecutive therapy such as onset of the side effect or an injection method change, dosage weight loss is difficult though chemotherapies is performed for the recurrence metastasis breast cancer case of the older patient. Because capecitabine is isolated, and a continuous administration is had without a side effect, and it was with cCR for this case, in addition, discussion of the literature is reported because it seemed that it may be in effective therapy for an older patient breast cancer case in future.

[A Case of Pure Type Mucinous Carcinoma Recurrence after Local Control].

The patient was a 44-year-old woman. Mastectomy and sentinel lymph node biopsy had been performed for carcinoma of the left breast approximately 1 year previously. The diagnosis was mucinous carcinoma, T3N0M0, stage ⅡB, ER(+), PgR(+), HER2 score 0, Ki-67 20%. Hormone therapy was administered postoperatively. Four months after the surgery, left axilla lymphadenopathy was observed. Chemotherapy with EC and nab-PTX was started for the postoperative lymph node recurrence. To achieve local control, axillary lymphadenectomy was performed within 1 year postoperatively, and 1 metastatic lesion in the lymph nodes was observed. Hormone therapy was started sequentially, with no subsequent recurrence or metastasis. Mucinous carcinomas are classified as a breast cancer subtype. Mixed type, including breast ductal carcinoma, form a large proportion of mucinous carcinomas and the therapy for breast ductal carcinoma is usually administered in such cases. Conversely, pure type mucinous carcinomas rarely show metastasis and have a good prognosis. In this case, however, metastasis was noted and chemotherapy was not completely effective, and local control was achieved with surgical resection.

[Experience with a Thyroid Carcinoma in Which Symptoms Were Moderated by Local Excision].

Thyroid carcinoma have almost improvement of thing ingredient doing sacculation in a portion is most. We report a case of a giant thyroid carcinoma with a cyst that was operated on. A 64-year-old man showed giant cyst characteristics on cervical ultrasonography, with a mass with calcification on the left lobe. The findings showed an exclusion of tracheal deviation and the esophagus and left total jugular veins were shown. We observed giant calcification in the left lobe center, and the cervical CT laboratory findings showed sacculation on the outside. The cyst showed partial exclusion of the total jugular veins. We preliminarily diagnosed class Ⅳ papillary cancer by cytology. The chosen treatment was hypervolemia control on the bottom, plus total thyroidectomy and a lymphodectomy. A perioperative portion of the cyst ingredients was washed away. The whole thyroid gland was firm, and the right lobe showed a tumor. We left one part of the cyst that stuck to a blood vessel in situ. The cervical intracranial pressure, which was the palliative purpose of operating, seemed significantly improved.

[Interval Breast Cancer with Neuroendocrine Differentiation].

We report a case of interval breast cancer that was an invasive ductal carcinoma of the breast with neuroendocrine differentiation. The patient was a 66-year-old woman who had a breast lump. She had received breast cancer screening every other year. The last screening was 1 year and 6 months prior to diagnosis. A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma. Breast conserving surgery plus sentinel lymph node biopsy was performed. The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma with neuroendocrine differentiation, positive for ER and PgR, and negative for HER2/neu protein expression. The surgical margins were negative, and there was no metastasis in the sentinel lymph node. She was administered radiation therapy and adjuvant endocrine therapy. Two years after surgery, she is well without metastasis.

[Axillary Lymph Nodes Metastases from Occult Breast Cancer Recurrence at Ten Years after Resection--Case Report].

We encountered a case of axillary lymph nodes metastases from occult breast cancer recurrence at 10 years after resection. Ten years previously, a 71-year-old woman had undergone surgery (dermabrasion+full thickness skin graft+axillary lymph node dissection) for axillary lymph nodes metastases from occult breast cancer. After the operation, she had received chemotherapy and hormone therapy for 5 years. Then, in the recent 5 years, she had stopped attending our hospital. Ten years after the first operation, she came back to our hospital with a lump in her axillary region. She underwent resection for the subcutaneous mass and the axillary lymph nodes. The pathological diagnosis implied metastases from breast carcinoma. We checked up a hole her body. However, we could not detect the original lesion.

[Study of the Identification Rate of Sentinel Lymph Node Biopsy after Partial Breast Resection].

Sentinel lymph node biopsy using the dye method is generally performed for patients with breast cancer. However, identification of the sentinel lymph node in the mammary gland is occasionally difficult after breast partial resection, as lymph flow is changed under the influence of surgery. Sentinel lymph node biopsy for patients with breast cancer who underwent partial mastectomy without axillary lymph node dissection is grade C1 in the breast cancer clinical practice guideline ver.2 2013. We examined the identification rate of the sentinel lymph node for patients with breast cancer who underwent lumpectomy or partial mastectomy. Lumpectomy and partial mastectomy were performed in 4 and 3 patients, respectively. It was possible to identify the sentinel lymph node in 6 patients, and no metastasis of cancer cells was identified in any patient. In 1 patient who underwent partial mastectomy, it was impossible to identify the sentinel lymph node, and thus, Level Ⅰlymph node sampling was performed. However, the pathological diagnosis was no metastasis of cancer cells. This patient underwent partial mastectomy of the C area and a smaller volume of the mammary gland. Therefore, we consider that lymph flow changed under the influence of surgery. Sentinel lymph node biopsy using the dye method after partial breast resection is useful, but partial mastectomy of the C area makes it difficult to perform sentinel lymph node biopsy.

Overexpression of PGC1α and accumulation of p62 in apocrine carcinoma of the breast.

Apocrine carcinoma is categorized as a special type of breast carcinoma because of its specific morphological features. To clarify the characteristics of apocrine carcinoma from the point of view of the mitochondrial profile, we conducted a comparative study between apocrine and non-apocrine carcinomas. The expressions of mitochondrial related factors (PGC1α, Nrf1, Nrf2, mtTFA and COX4) were examined in a testing set of breast cancer tissue. Apocrine carcinomas showed a clear tendency towards higher mRNA expression levels of PGC1α than non-apocrine carcinomas. The expression of the selected factor, PGC1α, as well as that of p62 was further examined. The results revealed that apocrine carcinomas showed a higher immunohistochemical positivity rate for PGC1α (21.3% vs. 3.2%; P = 0.008), and that the mRNA expression level of PGC1α was significantly higher in apocrine carcinoma than in non-apocrine carcinoma (P = 0.007). The immunohistochemical positivity rate for p62 protein was also higher in apocrine carcinomas (44.7% vs. 21.0%; P = 0.015), although no significant difference in the p62 mRNA expression level was detected between the two types of carcinoma (P = 0.633). In conclusion, this study revealed that apocrine carcinoma overexpressed PGC1α contributing to mitochondrial biogenesis, and also p62 protein accumulation.

[CD147 expression in non-invasive and invasive breast carcinoma].

CD147 is a multifunctional membrane glycoprotein involved in tumor invasion, and is overexpressed in many solid tumors. However, the role of CD147 in breast cancer is not well understood. The aim of this study was to evaluate CD147 expression in non-invasive and invasive ductal carcinomas. We recruited 156 breast cancer patients who underwent radical operations at our hospital up until 2002. We performed immunohistochemistry on their tumor specimens, and compared these data with clinicopathological factors. We divided the patients into two groups: group A was comprised of non-invasive ductal carcinomas and group B, invasive ductal carcinomas. The CD147-positive rate was 62.8% for all patients and was higher in group B than group A. In all cases, the CD147-positive rate correlated with clinical stage, number of metastatic lymph nodes, and tumor size. These results implied that CD147 may be involved in the process of breast cancer invasion.