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ABSTRACT: BACKGROUND: Conventional imaging does not always accurately depict the pathological response to neoadjuvant chemotherapy (NAC). Diffusion-weighted imaging (DWI) may provide additional insight into the chemotherapeutic effect. This study assessed whether the apparent diffusion coefficient (ADC) correlated with pathological outcome and prognosis in breast cancer patients receiving NAC. METHODS: Fifty-six patients with locally advanced breast cancer received surgery after NAC. Dynamic contrast-enhanced (DCE) and DWI were performed before and after NAC. The pathological response was classified into five categories from no response to complete response according to amount of residual cancer. The correlation between ADC and postoperative pathologic and prognostic outcome was assessed. RESULTS: The distribution of the pathological response classification was as follows: no response, 3 cases; mild response, 22 cases; moderate response, 12 cases; marked response, 11 cases; complete response, 8 cases. ADC after NAC correlated with pathological response, but ADC before NAC did not. The change in ADC after chemotherapy had better correlation coefficient (r = 0.67) than change in size (r = 0.58) and ADC after NAC (r = 0.64). Although the group with larger change of tumor size showed only marginal significance compared with the smaller change group (p = 0.089), the group with higher change of ADC showed significantly better prognosis than the lower one (p = 0.038). CONCLUSIONS: Change in ADC after chemotherapy better correlated with pathological outcome and prognosis than change in tumor size. DWI has potential in evaluating the pathological outcome of NAC in breast cancer patients.
Breast Cancer 02/2013; · 1.36 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 09/2012; 70 Suppl 7:360-4.
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Masahiro Sakakibara,
Toshihiko Fujimori,
Tetsutaro Miyoshi,
Takeshi Nagashima, Hiroshi Fujimoto,
Hiroshi Tiberu Suzuki,
Yohsuke Ohki,
Koya Fushimi,
Jissei Yokomizo,
Yukio Nakatani,
Masaru Miyazaki
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ABSTRACT: Aldehyde dehydrogenase 1 (ALDH1)-positive cells exhibit stem-like or progenitor ability and have been considered a clinically important diagnostic and therapeutic target in patients with breast cancer. In this study, the authors evaluated responsiveness to chemotherapy of ALDH1-positive cells in primary and metastatic lesions and its relation to prognosis for patients with lymph node-positive breast cancer.
In total, 115 patients who had breast cancer with cytologically confirmed lymph node metastases and who underwent surgery after neoadjuvant chemotherapy (NAC) were evaluated. By using ALDH1 immunohistochemistry in core-needle biopsy specimens of the primary tumor, cytology samples of axillary lymph nodes before NAC, and pathologic samples of each after NAC, the clinical significance of ALDH1-positive cell status was evaluated in primary and metastatic lesions before and after NAC.
The presence of ALDH1-positive cancer cells, but not ALDH1-negative cancer cells, in primary and metastatic lesions after NAC was associated with a worse prognosis. In multivariate analysis, only ALDH1-positive cells in metastatic lesions after NAC correlated with overall survival. The responsiveness of ALDH1-positive cells to chemotherapy differed between primary and metastatic lesions, and the findings indicated that ALDH1-positive cells in metastatic lesions after NAC may clinically precede those in the primary lesion.
The responsiveness of ALDH1-positive cells to chemotherapy in primary and metastatic lesions and its prognostic significance were clarified in patients with breast cancer. The authors concluded that ALDH1-positive status may represent a surrogate marker as a new concept in patients with lymph node-positive breast cancer.
Cancer 12/2011; 118(16):3899-910. · 4.77 Impact Factor
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ABSTRACT: There is increasing demand for minimally invasive treatments for small breast cancer mainly because of the desire for better cosmetic results. Although radiofrequency ablation (RFA) is an attractive approach as a local control method for small breast cancer, the problems of histological effectiveness and safety management remain.
A total of 29 patients including one patient with bilateral breast cancer were enrolled in this study. The mean tumor size of 30 breasts was 12.8 mm (range 5-19 mm). Under general anesthesia, RFA was performed with a Cool-tip RF system (Valleylab, Boulder, CO, USA) after sentinel lymph node biopsy. Postoperative evaluation with magnetic resonance imaging (MRI) and vacuum-assisted core needle biopsy was done 3-4 weeks after RFA before radiotherapy. Ablated tumors were evaluated with hematoxylin-eosin (H&E) and nicotinamide adenine dinucleotide (NADH)-diaphorase staining. If needed, adjuvant chemo and/or endocrine therapy was performed.
All patients except one completed one session of RFA. The mean temperature near the center of the tumors was 89.6°C (range 78-100°C). Postoperative MRI showed the ablated zone clearly in all patients. MRI revealed no hypervascularity of the tumors in the ablated zone. Evaluation with H&E staining of the tumors showed remarkable degenerative changes in only three patients. NADH-diaphorase staining showed no viable tumor tissue in 24 patients out of 26 examined. Three patients received small diameter grade 3 skin burns, two on the outside of the thigh from the grounding pad and one on the breast skin. One patient had a breast lesion like a chronic granulomatous mastitis resulting from overreaction of the ablated zone.
RFA therapy appeared relevant and applicable for patients with small breast cancer. Because small skin burns were observed as adverse events, close attention should be paid in the course of the RFA procedure.
Breast Cancer 03/2010; 18(1):3-9. · 1.36 Impact Factor
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ABSTRACT: Radiofrequency ablation (RFA) has recently been used to treat small breast cancer. However, there are no data on the long-term morphological features after the procedure. The present study attempts to clarify the characteristics of and changes in the ablated lesion.
A total of 17 breast cancer patients underwent RFA using a single needle featuring an internally cooled electrode; this was followed by whole-breast irradiation and adjuvant systemic therapy. Magnetic resonance imaging (MRI) using a 1.5-T system was performed before and 1, 3, 6, and 12 months after ablation, and the morphological characteristics and the size of the ablated lesion were evaluated. Mammography was also performed for a comparison with the MRI measurement.
MRI displayed no residual enhancement of the tumor after RFA; there was an altered signal intensity with peripheral enhancement, however, and the area decreased in size gradually at a rate of 3.3% per month. Mammography showed a ring surrounding a roundish area whose size was equal to that seen with MRI.
Our current series demonstrated the morphological characteristics on breast imaging after RFA plus radiation therapy. The size of the ablated area decreased over time. These findings are valuable for clinical follow-up of breast cancer patients undergoing RFA.
Japanese journal of radiology 07/2009; 27(5):197-204. · 0.65 Impact Factor
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ABSTRACT: There is growing evidence that tumor-associated macrophages (TAMs) promote tumor growth and dissemination. Many individual reports have focused on the protumor function of molecules linked to the recruitment of macrophages, but little is known about which factor has the strongest impact on recruitment of macrophages in breast cancer. To elucidate this question, we performed RT-PCR using species-specific primers and evaluated tumoral and stromal mRNA expression of macrophage chemoattractants separately in human breast tumor xenografts. The correlation between the tumoral or stromal chemoattractant mRNA expression including monocyte chemoattractant protein-1 (MCP-1) (CCL2), MIP-1alpha (CCL3), RANTES (CCL5), colony-stimulating factor 1, tumor necrosis factor alpha, platelet-derived growth factor (PDGF)-BB and macrophage infiltration were compared. There was significant positive correlation between stromal MCP-1 expression and macrophage number (r = 0.63), and negative correlation between tumoral RANTES expression and macrophage number (r = -0.75). However, no significant correlation was found for the other tumoral and stromal factors. The interaction between the tumor cells and macrophages was also investigated. Tumor cell-macrophage interactions augmented macrophage-derived MCP-1 mRNA expression and macrophage chemotactic activity in vitro. Treatment of immunodeficient mice bearing human breast cancer cells with a neutralizing antibody to MCP-1 resulted in significant decrease of macrophage infiltration, angiogenetic activity and tumor growth. Furthermore, immunohistochemical analysis of human breast cancer tissue showed stromal MCP-1 had a significant correlation with relapse free survival (p = 0.029), but tumoral MCP-1 did not (p = 0.105). These findings indicate that stromal MCP-1 produced as a result of tumor-stromal interactions may be important for the progression of human breast cancer and macrophages may play an important role in this tumor-stroma interaction.
International Journal of Cancer 03/2009; 125(6):1276-84. · 5.44 Impact Factor
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ABSTRACT: In this study, we report a breast-conserving surgery (BCS) approach that uses projection and reproduction techniques of breast MRI obtained in the surgical position to the breast surface in patients with ductal carcinoma in situ (DCIS) of the breast.
Between February 2005 and January 2007, a total of 104 patients with operable breast cancer at our hospital had surgical-position breast MRI examinations. The 24 patients with relatively localized DCIS received BCS using the projection and reproduction techniques of the surgical-position breast MRI. During the same time period, 28 patients with relatively localized DCIS in whom prone-position breast MRI was performed, had conventional BCS using mammography-guided hookwires. In this study, we compared the surgical outcomes of our surgical approach with those of the conventional approach in a total of 52 patients with relatively localized DCIS.
Average volume of the pathologic specimens in the new technique group (27.5 cm(3)) was substantially smaller than that in the conventional BCS group (57.6 cm(3), p = 0.0007). In addition, the positive margin rate was substantially lower in the new technique group (12.5%) than in the conventional BCS group (39.3%; p = 0.029).
This study demonstrates that BCS can be done guided by the precise projection and reproduction techniques of the lesion obtained by surgical-position breast MRI. To the best of our knowledge, this is the first report of BCS technique for DCIS in this manner. Our surgical approach can be clinically useful in surgical planning and management in patients with DCIS.
Journal of the American College of Surgeons 08/2008; 207(1):62-8. · 4.55 Impact Factor
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Rikiya Nakamura,
Takeshi Nagashima,
Masahiro Sakakibara,
Takafumi Sangai, Hiroshi Fujimoto,
Manabu Arai,
Takashi Shida,
Katsuhiko Kaneoya,
Takuya Ueda,
Yukio Nakatani,
Hideyuki Hashimoto,
Masaru Miyazaki
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ABSTRACT: Success of breast-conserving surgery (BCS) following neoadjuvant chemotherapy (NAC) depends on accurate assessment of the initial lesion. We developed a new procedure (NIPR) in which initial naked magnetic resonance images are projected onto the skin before BCS.
Thirty-five breast cancer patients underwent supine oblique MRI of the operative area. In 20 DCIS patients, the metallic clips were reproduced by projection on the skin using NIPR, and discrepancies between the projection site and clip were measured on X-rays. Fifteen patients (T1;3,T2;8,T3;4 cases) treated with NIPR were compared to 20 (T1;5 , T2;15 cases) treated using the conventional method with regard to excision area and additional excision rate of BCS after NAC.
The median discrepancy (linear distance) was 2.6 mm. NIPR significantly reduced the excision area and additional excision rate in T1 and T2 compared to the conventional method (P<0.05).
NIPR is a reliable technique for BCS following NAC with significant reductions in excision area and additional excision rate and superior cosmetic results.
The Breast 06/2008; 17(3):245-51. · 2.49 Impact Factor
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ABSTRACT: Human breast cancer frequently metastasizes to bone, and effective therapies for patients with bone metastasis are required.
However, the molecular mechanism for the bone metastasis of human breast cancer has not yet been fully elucidated. The present
study aimed to evaluate the importance of active osteoclasts and bone-derived insulin-like growth factors (IGFs) for the survival
and growth of breast cancer cells in bone. Human breast cancer cell line MCF-7 cells were injected into human adult bone (HAB)
implanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The mice were then treated with recombinant
human osteoclastogenesis inhibitory factor/osteoprotegerin (rhOCIF/OPG), a decoy receptor for receptor activator of NF-kappaB
ligand (RANKL), or an anti-human IGF monoclonal antibody. Histomorphometric analyses revealed that both treatments significantly
decreased the tumor area of MCF-7 cells in cross-sections of the implanted HAB to about 30% of the tumor area in control mice,
but had no effect on the growth of subcutaneously injected MCF-7 cells. Consistent with the results for the tumor area in
HAB, there were fewer osteoclasts in the implanted HAB in rhOCIF/OPG-treated mice than in vehicle-treated mice. However, treatment
with the anti-human IGF monoclonal antibody had no effect on the number of osteoclasts in HAB. The results indicate that the
active osteoclasts induced by RANKL and the IGFs released as a result of bone resorption by these osteoclasts play crucial
roles in the survival and growth of human breast cancer cells in bone and suggest that neutralization of bone-derived IGFs
will be effective in preventing the development of bone tumors in breast cancer patients.
Clinical and Experimental Metastasis 05/2008; 25(4):401-410. · 3.52 Impact Factor
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ABSTRACT: Intramolecular cyclic etherification of 1,3-diols was investigated using iodine as a catalyst under solution reaction conditions. Compounds containing five-membered ether rings were obtained. Propella ether (11-oxatricyclo[4.4.3.0(1,6)]tridecane) was conveniently synthesized from 1,3-diol (6-(2-hydroxyethyl)spiro[4.5]decan-6-ol) in 97% yield via carbon skeleton rearrangement. Spiroethers and bicyclic ethers were also obtained from the corresponding 1,3-diols in yields of over 77%. The most suitable reaction conditions were a temperature of 80 degrees C, a 1:0.2 molar ratio of 1,3-diol:iodine, and a time period of 8 h. In addition, terpenoic ethers were efficiently synthesized from the corresponding 1,3-diols, derived from (+)-camphor and (-)-fenchone, via skeleton rearrangement. In particular, the reaction of the 1,3-diol derived from (+)-camphor proceeded smoothly at room temperature with a yield of 91%. The yield of the cyclic ether using iodine as a catalyst was comparable to the method using sulfuric acid.
Journal of oleo science 02/2008; 57(8):437-43. · 1.42 Impact Factor
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ABSTRACT: Human breast cancer frequently metastasizes to bone, and effective therapies for patients with bone metastasis are required. However, the molecular mechanism for the bone metastasis of human breast cancer has not yet been fully elucidated. The present study aimed to evaluate the importance of active osteoclasts and bone-derived insulin-like growth factors (IGFs) for the survival and growth of breast cancer cells in bone. Human breast cancer cell line MCF-7 cells were injected into human adult bone (HAB) implanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The mice were then treated with recombinant human osteoclastogenesis inhibitory factor/osteoprotegerin (rhOCIF/OPG), a decoy receptor for receptor activator of NF-kappaB ligand (RANKL), or an anti-human IGF monoclonal antibody. Histomorphometric analyses revealed that both treatments significantly decreased the tumor area of MCF-7 cells in cross-sections of the implanted HAB to about 30% of the tumor area in control mice, but had no effect on the growth of subcutaneously injected MCF-7 cells. Consistent with the results for the tumor area in HAB, there were fewer osteoclasts in the implanted HAB in rhOCIF/OPG-treated mice than in vehicle-treated mice. However, treatment with the anti-human IGF monoclonal antibody had no effect on the number of osteoclasts in HAB. The results indicate that the active osteoclasts induced by RANKL and the IGFs released as a result of bone resorption by these osteoclasts play crucial roles in the survival and growth of human breast cancer cells in bone and suggest that neutralization of bone-derived IGFs will be effective in preventing the development of bone tumors in breast cancer patients.
Clinical and Experimental Metastasis 02/2008; 25(4):401-10. · 3.52 Impact Factor
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ABSTRACT: Recent animal data have suggested that cancer-induced stroma consists of blood-borne fibroblasts as well as tissue-derived fibroblasts. In this study, mononuclear cells isolated from the pulmonary vein blood of lungs resected from lung cancer patients were cultured to confirm the presence of blood-borne fibroblast. In 34% (16 of 47) of the cases, spindle cells with fibroblast morphology proliferated in a disarrayed fashion and were positive for vimentin and collagen type I but negative for both specific myogenic and endothelial markers. The cDNA profiles of blood-borne fibroblasts, tissue-derived (lung) fibroblasts, human vascular smooth muscle cells (HSMCs), and umbilical vein endothelial cells (HUVECs) were clustered with a hierarchical classification algorithm. The profiles of the blood-borne fibroblasts were clearly isolated from those of the tissue-derived fibroblasts, HSMCs, and HUVECs. When carboxyfluorescein succinyl ester (CFSE)-labeled human mononuclear cells from the blood of lung cancer patients were transferred into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice engrafted with a human lung cancer xenograft, CFSE-labeled fibroblasts were found around the cancer nests. We investigated the several clinicopathological factors of blood-borne fibroblast-positive patients. The blood-borne fibroblast-positive cases had a significantly larger central fibrotic area in primary lung cancer than in the negative cases (123 +/- 29 vs. 59 +/- 13 mm(2); p = .02). Our results indicated that the blood in the vicinity of human lung cancer contains fibroblast progenitor cells that have the capacity to migrate into the cancer stroma and differentiate into fibroblasts having biological characteristics different from those of tissue-derived fibroblasts. Disclosure of potential conflicts of interest is found at the end of this article.
Stem Cells 07/2007; 25(6):1469-77. · 7.78 Impact Factor
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Rikiya Nakamura,
Takeshi Nagashima,
Masahiro Sakakibara,
Shigeharu Nakano,
Naoto Tanabe, Hiroshi Fujimoto,
Manabu Arai,
Masami Kadowaki,
Takashi Oide,
Toru Tanizawa,
Masaru Miyazaki
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ABSTRACT: We report a case of angiosarcoma arising in the breast following breast-conserving surgery with radiation therapy for breast carcinoma. The patient, a 49-year-old postmenopausal woman, had undergone breast-conserving surgery for invasive ductal carcinoma of the left breast (pT2 pN0 M0 Stage IIA). Adjuvant radiotherapy (50 Gy with a booster dose to the tumor bed of 10 Gy) was then performed for the residual breast tissue and the patient was treated with hormone therapy (tamoxifen, 20 mg daily) for 5 years. She presented with skin erosion with bleeding 10 years after the initial operation. Incisional biopsy revealed angiosarcoma of the breast, and total mastectomy was subsequently performed. The patient was the treated with chemotherapy (weekly paclitaxel, 80 mg/m2 x cycles) and has remained well without evidence of local or distant recurrence.
Breast Cancer 02/2007; 14(2):245-9. · 1.36 Impact Factor
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ABSTRACT: Intramolecular cyclization of 3-hydroxy acids was investigated using iodine as a catalyst under solvent-free conditions. The reaction proceeded to completion in the heterogeneous system. Lactones were obtained by intramolecular cyclization of 3-hydroxy acids. Propella lactone (11-oxatricyclo[4.4.3.0(1,6)]tridecan-12-one) was conveniently synthesized from 3-hydroxy acid ((6-hydroxyspiro[4.5]dec-6-yl)acetic acid) in 88% yield with carbon skeleton rearrangement. Spiro lactones and bicyclic lactones were also obtained from the corresponding 3-hydroxy acids in yields of over 75%. The most suitable reaction conditions were a temperature of 80 degrees C, a molar ratio of 3-hydroxy acid:iodine = 1:0.1, and a time period of 6 h. In addition, terpenic lactones were efficiently synthesized from the corresponding 3-hydroxy acids, derived from (+)-camphor, (-)-fencone, and (-)-pulegone, with skeleton rearrangement. The yield of the solvent-free reaction was as high as that of the corresponding reaction in solution.
Journal of oleo science 02/2007; 56(4):189-93. · 1.42 Impact Factor
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Masami Kadowaki,
Takeshi Nagashima,
Hiroto Sakata,
Masahiro Sakakibara,
Takafumi Sangai,
Rikiya Nakamura, Hiroshi Fujimoto,
Manabu Arai,
Yasuhide Onai,
Yuichirou Nagai,
Yukimasa Miyazawa,
Masaru Miyazaki
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ABSTRACT: Benign epithelial inclusions are uncommonly found in lymph nodes, and ectopic breast tissue in axillary lymph nodes is particularly uncommon. The patient is a 48-year-old woman who had an adenoma of the nipple removed 10 years previously. A swollen lymph node with amorphous calcifications in a clustered distribution on mammogram was found in the left axilla. Fine needle aspiration cytology showed only cystic change. Excisional biopsy was performed and microscopic examination demonstrated that the node contained benign mammary epithelial and glandular inclusions, and no evidence of malignancy. Such cases will be increasingly found due to the widespread use of mammography screening and biopsy of axillary sentinel lymph nodes. Ectopic breast tissue in lymph nodes may be mistaken for malignant lesions. It is most important to identify correctly the epithelial inclusions in lymph nodes to prevent an erroneous diagnosis.
Breast Cancer 02/2007; 14(4):425-8. · 1.36 Impact Factor
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ABSTRACT: Recent reports have revealed that bone marrow (BM)-derived cells can be constituents in a number of organs, especially in remodeling tissue. Using bone marrow transplantation (BMT) technique, we found that BM can serve as a source of both myoepithelial cells and periductal fibroblasts in the mammary gland. The numbers of BM-derived myoepithelial cell were 4.8-fold, and those of periductal fibroblast were 2.4-fold higher in the mice when BMT which was performed at the pubertal stage, as compared with BMT was performed at the postpubertal stage. Treatment with estrogen+progesterone pellet increased numbers of BM-derived myoepithelial cells and periductal fibroblasts, to levels 4.5- and 2.6-fold higher than in placebo mice, respectively. In situ hybridization revealed BM-derived periductal fibroblasts expressed insulin-like growth factor I mRNAs that are known to regulate mammary gland. These results suggest that drastic structural change that is induced by hormonal stimulation increased the recruitment of BM-derived myoepithelial cells and periductal fibroblasts to the mammary gland context.
Biochemical and Biophysical Research Communications 09/2006; 346(4):1173-80. · 2.48 Impact Factor
