The effect of combined risk factors on breast cancer-related lymphedema: a study using decision trees.

BACKGROUND: The effect of combined risk factors on breast cancer-related lymphedema (BCRL) development has not yet been investigated. This study aimed to determine the combination of risk factors associated with BCRL development in patients who underwent breast cancer resection, including axillary lymph node dissection (ALND). METHODS: The participants included 129 women who were diagnosed with early-stage breast cancer and underwent breast cancer resection in this retrospective observational study. We performed a decision tree analysis to detect the combination of risk factors associated with BCRL development using age, body mass index (BMI), surgical side, mastectomy, the extent of ALND, and adjuvant therapy (chemotherapy, hormone therapy, and radiation therapy). RESULTS: Of the 129 participants, 11 (8.5%) developed BCRL. Postoperative chemotherapy was the optimal variable selected to classify patients who developed BCRL and those who did not. In participants with postoperative chemotherapy, the extent of ALND was selected as the second layer of the decision tree. When ALND was at level 3, BMI was selected as the third layer. We found that BCRL incidence was 44.4% in individuals with a BMI of 23.0 or higher. CONCLUSIONS: The combination of postoperative chemotherapy, level 3 ALND, and BMI of 23.0 or higher may further increase the risk of developing BCRL. The decision tree model will enable the identification of patients with a high risk of developing BCRL, and thus, preventive intervention, careful monitoring, and early treatment will be possible.

Differences in the Relationships Between Muscle Strength, Muscle Mass, Balance Function, and Quality of Life for Middle-Aged and Older Breast Cancer Survivors.

PURPOSE: The purpose of this study was to investigate the differences in muscle strength, muscle mass, balance function, and quality of life (QOL) among middle-aged breast cancer survivors (BCSs) and older BCSs. METHODS: The study included 53 middle-aged (<65 years old) BCSs and 49 older (≥65 years old) BCSs. Muscle strength was evaluated via handgrip and knee extensor strength, and muscle mass was assessed using a body composition test. Balance function was assessed using the Timed Up and Go test and the body sway test. QOL was assessed using the Medical Outcome Study 36-item Short-Form Health Survey. RESULTS: The older BCSs had significantly lower right grip strength, right knee extension strength, and muscle mass (P < .05) than the middle-aged BCSs. In addition, the body sway test showed that older BCSs had a significant increase in the length of center of pressure compared to middle-aged BCSs (P < .05). Older BCSs showed significantly lower physical functioning subscales in QOL compared to middle-aged BCSs (P < .05). The associations among muscle strength, muscle mass and QOL were more significantly observed in the older BCSs (P < .05). Furthermore, a significant correlation between QOL and balance function was observed in the older BCSs, but not in the middle-aged BCSs (P < .05). CONCLUSION: There may be associations among muscle strength, muscle mass, balance and QOL in older BCSs, but not in middle-aged BCSs. We believe that the findings of this study will be relevant in the context of planning rehabilitation for older BCSs.

[A Case of Locally Advanced Breast Cancer Successfully Treated with Local Control That Achieved a Pathological Complete Response after Bevacizumab and Paclitaxel Combination Chemotherapy].

A 68-year-old woman with a 5-year history of an untreated left breast tumor presented to our hospital. She was admitted for untreated diabetes and severe anemia. The cause of the anemia was bleeding from the tumor, and she was referred to our department. She was diagnosed with T4bN0M0, stage IIIb breast cancer. First, we initiated hormonal therapy. However, the tumor did not decrease in size. We then administered chemotherapy. The tumor markedly decreased in size, and mastectomy and axillary lymph node dissection were performed. The response was a pathological complete response. She is currently undergoing hormonal therapy at the time of this writing.

[A Case of Axillary Arterial Bleeding after Axillary Metastatic Lymph Node Necrosis during Treatment with Paclitaxel and Bevacizumabfor Breast Cancer].

A 44-year-old woman was diagnosed cT4bcN3cM1(LYM), Stage IV triple-negative breast cancer.Enhanced computed tomography revealed ipsilateral axillary lymph node metastasis, 10 cm in diameter.The supraclavicular and cervical lymph nodes also had metastases.She received paclitaxel(90mg/m2, on days 1, 8, and 15 every 4 weeks)in combination with bevacizumab(10mg/kg, on days 1 and 15 every 28 days).Her height was 165 cm, and her body weight was 100 kg.After 1 course of chemotherapy, a metastatic axillary lymph node with necrotic changes was removed spontaneously.A few days later, she experienced severe bleeding from her axillary artery, and she went into hypovolemic shock.Despite undergoing surgical hemostasis, the bleeding recurred twice, so we performed coil embolization of her subclavian artery.Thirty -five days after the first occurrence of bleeding, the patient died of sepsis and ARDS due to left arm necrosis.Bevacizumab is effective for the treatment of large tumors, but when the tumor is close to an artery, clinicians should be wary of fatal bleeding after necrosis.

Pathological aspects of the intraductal spread of breast cancer.

The intraductal spread of breast cancer is a major cause of local recurrence following breast-conserving therapy. To properly understand this pathology, three-dimensional (3D) cancer localization within the mammary ductal-lobular system (MDLS) is necessary. To this end we generated computer-assisted 3D reconstructions of all MDLSs using 2-mm-thick serial sections of surgically resected specimens. We then analyzed the characteristics of intraductal spread of breast cancer. In our study of quadrantectomy specimens from patients with primary invasive breast carcinoma, the intraductal spread of breast cancer was found to be continuous from the invasive tumor and spreading along the mammary glandular tree. The pattern is categorized into three types: the central type, the peripheral type, and the extensive type. The central type was found to be most common. A 3D analysis of total mastectomy specimen from a patient with primary non-invasive breast carcinoma revealed regional intraductal spread extending within and filling a single MDLS. The analysis also revealed the presence of ductal anastomoses connecting adjacent MDLSs. These ductal anastomoses were found to be an anatomical risk factor for extensive intraductal spread of breast cancer across multiple MDLSs. To minimize residual non-invasive components of breast carcinoma in the conserved breast, which is strongly associated with the outcome of local control of breast-conserving therapy, it is necessary to determine the optimum surgical margins in a flexible, patient-specific manner. This determination should be based on anatomical characteristics of the MDLS, such as those identified in the present study.

[Myeloid-derived suppressor cells in cancer patients].

Myeloid-derived suppressor cells (MDSCs) are one of the major cell populations responsible for regulating immune responses. MDSCs have been reported to accumulate in the blood, lymph nodes, and at tumor sites in most patients during tumor progression and chronic infection, where they potentially suppress T cell functions. We analyzed MDSCs (CD11b+ CD14- CD33+) in peripheral blood mononuclear cells by flow cytometry in 222 patients with esophageal, gastric, colorectal, hepatocellular, cholangiocellular, pancreatic, breast, ovarian, thyroid, and lung cancer, and 18 healthy volunteers. MDSCs were significantly higher in patients with esophageal, gastric, colorectal, hepatocellular, pancreatic, and breast cancer than in healthy volunteers, and the differences were not significant in patients with cholangiocellular, ovarian, thyroid, and lung cancer. Production of the cytokines IFN-γ and IL-6 in response to phytohemagglutinin was assayed using enzyme-linked immunosorbent assay (ELISA) test kits. Serum concentrations of sIL-2R were measured by ELISA. The percentages of MDSCs in patients with colorectal cancer positively correlated with neutrophil counts and the concentration of sIL-2R(both p<0.05), and inversely correlated with the production of IFN-γ( p<0.0001), serum albumin concentration(p<0.005), and lymphocyte counts (p<0.05). These data suggested that MDSCs are strongly related to chronic inflammation and nutritional impairment.

[Changes in myeloid-derived suppressor cells in malignant effusions of cancer patients following cancer chemotherapy].

Myeloid-derived suppressor cells(MDSCs) have been reported to be induced by inflammation, to suppress immune function, and promote tumor progression, and to be found in circulating blood, tumor tissue, and lymph nodes. MDSCs were found in pleural effusions and ascites of patients with malignant diseases and these results are described in this report. Changes in the levels of MDSCs during clinical responses to cancer chemotherapy are also reported. MDSC levels in malignant effusions have also been shown to change with the levels of MDSCs in peripheral blood and with clinical responses. MDSCs seem to play an important role in inflammation that is strongly related to advancing malignant diseases. The results also suggested that MDSCs may be reduced after effective chemotherapy, which may be effective as an adjuvant treatment with cancer immunotherapy.

[Myeloid-derived suppressor cells in patients with breast cancer].

Myeloid-derived suppressor cells (MDSC) are one of the major cell populations responsible for regulating immune responses. These cells have been reported to accumulate in the blood, lymph nodes, and tumor sites in most patients during tumor progression and in chronic infection. They are also reported to potently suppress T-cell functions. We studied MDSC in the peripheral blood mononuclear cells(PBMC)by flow cytometry using blood samples from 29 patients with breast cancer, and from 11 healthy donors. The cell level was significantly high for patients compared to the 11 healthy donors (5. 68±6. 09% vs. 0. 91±0. 54%). MDSC was significantly higher in all of the breast cancer patients (5. 68±6. 09%), preoperative patients (5. 79±4. 92%) and recurrent disease patients (5. 59±7. 28%), compared to healthy donors, but not for postoperative patients (1. 50±0. 95%). Thus, MDSC was elevated in patients with breast cancer, but decreased to the range of healthy individuals after the removal of the tumor mass. However, MDSC increased again with recurrence. We also report that in 2 cases, MDSC in the peripheral blood and pleural effusion of patients with metastatic breast cancer decreased after chemotherapy with gemcitabine.

[Therapeutic effects of vinorelbine-based chemotherapy--retrospective study of 65 patients with metastatic or relapsed breast cancer].

PATIENTS: The subjects were 65 stage IV or relapsed breast cancer patients who received vinorelbine monotherapy or combination therapy at Fukushima Medical University between May 2002 and November 2006. METHOD: Chemotherapy was divided into the following 3 groups Vinorelbine monotherapy (group A), Trastuzumab combination therapy (group B), MMVC (mitomycin C, methotrexate, vinorelbine and cyclophosphamide) therapy(group C). RESULTS: There were 33 patients in group A, 15 patients in group B, and 17 patients in group C. The percentage of patients who had received more than 3 prior chemotherapy regimens were 69. 7% in group A, 66. 7% in group B, and 82. 4% in group C. No complete responses were observed. Partial responses was observed 6 patients in group A, 5 patients in group B, and 2 patients in group C. Overall response rate was 18. 2% in group A, 33. 3% in group B, and 11. 8% in group C. Clinical benefit rate was 24. 2% in group A, 46. 7% in group B, and 23. 5% in group C. The median overall survival time was 267, 522, and 275 days in group A, B, and C respectively. DISCUSSION: Vinorelbine-based chemotherapy was considered as a new treatment option for patients with metastatic or relapsed breast cancer. It is necessary to examine the use at the early stage or more to obtain a high response rate and duration of response.

[Efficacy and safety of high-dose toremifene for hormone-responsive advanced or metastatic breast cancer patients with failed prior treatment by aromatase inhibitors].

BACKGROUND: Recently, aromatase inhibitors (AI) are widely used in postoperative adjuvant therapy for breast cancer. Nevertheless, studies of postoperative therapeutic strategies for recurrent breast cancer are insufficient. SUBJECTS AND METHOD: Data on 12 post-menopausal advanced/recurrent breast cancer patients in our department during June 2003- April 2007 were used for this study. No patient had responded to high-dose toremifene (TOR), a third-generation AI. Their therapeutic outcomes were analyzed retrospectively. The median observation period of the subjects was 16.1 months (4.0-40.9 months). Subjects were all hormone-sensitive. Overexpression of HER2 protein was found in only one case. During AI therapy immediately prior, exemestane (EXE) and anastrozole (ANA) had been given in nine and three cases, respectively. RESULTS: The complete response rate of AI therapy was 16.7% (2/12). The clinical benefit rate was 58.3% (7/12). The median of time to progression (TTP) was 33.8 weeks. Neither the presence nor absence of past history of treatment with tamoxifen (TAM) or other chemotherapies affected the anti-tumor effect. Analysis by the site of metastasis or recurrence revealed that the therapeutic effects were better for non-life-threatening cases in the lung, pleura, soft tissue, etc. The severities of adverse effects were all less than grade 2; the major ones were flushing and sweating. CONCLUSION: Results show that high-dose TOR given at an early stage can provide clinical benefits for post-menopausal advanced/recurrent breast cancer not responding to AI.

[A patient with metastatic breast cancer associated with retention of pleural effusion with no response to both CMF and exemestane, whose life was saved by high-dose toremifene].

The patient was a 70-year-old woman, who became aware of a mass in her right breast in 2001, but left it untreated. On March 10, 2003, she visited a nearby doctor with the chief complaint of dyspnea. Since a large painful mass was palpable in the right breast, advanced right breast cancer was suspected, and the patient was referred to our department. Examination revealed the presence of right axillary lymph node metastasis, left pleural effusion, and left atelectasis, and the patient was admitted to our hospital on an emergency basis. Two cycles of CMF were begun on April 2, but CT indicated NC to PD. Therefore, exemestane (EXE, 25 mg/day), was administered on May 13. While the size of the primary lesion was partially decreased, the tumor marker levels were increasing markedly. Administration of EXE was therefore discontinued, and toremifene (TOR, 120 mg/day), was begun. The systemic condition began to improve one month after the start of TOR administration. Two months later, the primary lesion had decreased in size. At after 9 months of TOR treatment, the size of the primary lesion and the tumor marker levels continued to decrease, and both the left pleural effusion and the left atelectasis disappeared.

Primary breast diffuse large B-cell lymphoma shows a non-germinal center B-cell phenotype.

Primary breast diffuse large B-cell lymphoma has a poor prognosis relative to other extranodal diffuse large B-cell lymphoma. Recently, diffuse large B-cell lymphoma has been subclassified as germinal center B-cell-like and nongerminal center B-cell types using tissue microarrays. The 5-year overall survival rate of the germinal center B-cell group is better than that of the nongerminal center B-cell group. To elucidate the reason for which primary breast diffuse large B-cell lymphoma has a poor clinical outcome, we investigated 15 patients with primary breast diffuse large B-cell lymphoma (stage IE; 13 cases, stage IIE; two cases) by immunohistochemistry using various markers including CD10, Bcl-6, MUM1 and MIB-1 and by molecular analysis of the immunoglobulin heavy chain gene variable region. Immunohistochemistry showed 0/15 (positive cases/examined cases) for CD10, 5/15 for Bcl-6, 15/15 for MUM1, 10/15 for Bcl-2, 2/15 for CD5 and 4/15 for CD40. The expression pattern of CD10(-) MUM1(+) in primary breast diffuse large B-cell lymphoma corresponded to the nongerminal center B-cell group. Moreover, the MIB-1 index was distributed from 60 to 95% with a mean of 79%, indicating a high proliferation of the lymphoma cells. The immunoglobulin heavy chain gene variable region of primary breast diffuse large B-cell lymphoma had a mutation frequency of 1-10% (seven cases) and 0-1 additional mutations in ongoing mutation analysis (five cases). Primary breast diffuse large B-cell lymphoma had characteristics of the nongerminal center B-cell group. In conclusion, primary breast diffuse large B-cell lymphoma has a nongerminal center B-cell phenotype and has a high MIB-1 index. These features might therefore be associated with poor prognosis.

[A case of advanced gastric cancer with multiple liver metastases responding completely to hepatic arterial infusion and systemic chemotherapies].

A 41-year-old male complaining of epigastric discomfort visited another hospital for a medical checkup. Gastrointestinal fiberscopic examination revealed a type 3 lesion on the lesser curvature of the lower portion, and biopsy specimens showed tubular adenocarcinoma. Abdominal CT demonstrated multiple liver metastases. After receiving a low-dose FP chemotherapy via IVH catheter for 1 week, the patient undertook a distal gastrectomy accompanied by D2 lymph node dissection. From the 19th postoperative day (POD), hepatic arterial infusion chemotherapy (HAIC) using 5-FU (500 mg/day) plus CDDP (10 mg/day) was performed for about 14 months. On the 47th POD, oral administration of UFT began and continued for 2 years. After 4 months of HAIC, the metastatic lesions of the liver disappeared completely. The patient has been free from recurrence since then for about 2 years. In the peripheral blood, Th1/Th2 ratio and activity of NK/LAK (IL-2 induced) kept increasing during this period. IHAC using 5-FU plus CDDP seems to be an efficient and worthy therapeutic modality if there are no other lesions except multiple liver metastases and a curative gastric resection is indicated.