Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report that single agent therapy with trastuzumab had a significant effect on metastatic breast cancer, which was confirmed to be HER2 positive by Herceptest showing 2+staining, and gene amplification positively detected by FISH analysis. A 48-year-old woman underwent extended radical mastectomy (T2N0M0 stage II). Three years after the operation supraclavicular lymph node metastasis was noted. Bone scintigraphy showed metastases to the left ribs 5 years after operation. She was treated with chemo-endocrine therapy, but nonetheless could not bear the back pain caused by the bone metastases. Another chemotherapy course could not be permitted because of leukopenia. Immunohistochemistry (IHC) analysis with Herceptest showed 2+staining for HER2 and FISH analysis showed gene amplification of HER2. We started single agent therapy with trastuzumab and she subsequently had remarkably improved back pain. Physical examination and ultrasonography showed disappearance of the previous palpable supraclaviclar lymph nodes. Serum tumor markers were also reduced after the first administration of trastuzumab. The patient is currently alive, with no further progression of the lymph node or bone metastases.
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PMID:Metastatic breast cancer of HER2 scored 2+ by IHC and HER2 gene amplification assayed by FISH has a good response to single agent therapy with trastuzumab: a case report. 1273 73

The finding that EGF receptor (Epidermal Growth Factor Receptor) and PDGF receptor (Platelet-Derived Growth Factor Receptor) are involved in bone metastases opens up new therapeutic prospects. This new approach should allow the development of new therapeutic agents: EGF R/HER2 inhibitors and PDGF R antagonists.
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PMID:[Potential therapeutic implications of EGF R/PDGF R signalling pathways in bone metastases of prostate cancer]. 1645 73

HER-2 is an important prognostic factor in breast cancer, and its overexpression is observed in 20-60% of cases with micrometastases in the bone marrow. The aim of this study was to explore the potential functional role of HER-2 in primary breast tumors with bone metastases. Forty-eight primary breast tumors with simultaneous or non-simultaneous bone metastases were studied. The expression of hormone receptors, and metastasis and growth factor-related proteins were assessed by immunohistochemical staining. The correlation in statistical significance was assessed by the Chi-square test. Of the 48 breast tumors, 11 (22.9%) were HER-2-positive and 37 were HER-2-negative. There was no significant difference in HER-2 status and clinicopathologic factors between the two groups. Of the 11 HER-2-positive tumors, there were 2 and 3 cases that showed positive nuclear expression for estrogen and progesterone receptors, respectively. No extranuclear expression of HRs was detected in these tumors. For metastasis-related proteins such as c-Met, VEGF, and MTA-1, which are activated by HER-2, only some insignificant focal expression of these proteins was observed. An increased level of pAkt was observed in 9 (81.8%) of 11 tumors, and an increased expression of CXCR4 was observed in 6 (54.5%) of 11 tumors. The frequency of increased levels of pAkt and CXCR4 was not significant between HER-2-positive and -negative tumors. The increased levels of pAkt and CXCR4 are induced by factors that are both dependent and independent of HER-2, and the activation of HER-2/CXCR4/ Akt signaling pathway in primary breast tumors may contribute to the formation of bone metastases in breast cancer.
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PMID:Potential role of HER-2; in primary breast tumor with bone metastasis. 1668 82

Two women, aged 57 and 55 years, with metastatic breast cancer were admitted for uncontrolled pain due to bone metastases. Despite the fact that progressive disease was evident, a change in antitumour therapy had not been recommended. The pain control was optimised in both patients. In one patient, palliative chemotherapy was installed, combined with trastuzumab because of HER2/neu overexpression. She was still alive after one and a half year of treatment. The other patient could not adjust mentally to the fact that her palliative therapy was changed to antitumour therapy; she died one month later. It is important to be aware of the various kinds of therapy in metastatic breast cancer because palliative treatment is more than just symptomatic treatment. Systemic antitumour therapy includes hormone therapy, chemotherapy and targeted therapy. Furthermore, in patients with bone metastases, radiotherapy combined with bisphosphonates results in pain relief and can reduce skeletal complications. Because of the ensuing complexity of the treatment of metastatic breast cancer, these patients should be regularly managed by a breast-cancer care team in order to improve the quality of care.
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PMID:[Palliation in patients with metastatic breast cancer often better with antitumour treatment than with only symptomatic treatment]. 1744 91

A 60-year-old woman was admitted to the hospital with left thigh pain. She had undergone mastectomy and axillary lymph node dissection for right breast cancer (T3N2M0) five years and two months earlier. The pathological diagnosis then was invasive ductal carcinoma with axillaryly mph node metastases. Hormone receptors and HER2 status were negative and positive (3+), respectively. The patient received adjuvant chemotherapy and radiotherapy, but bone metastases appeared 18 months after surgery. Although trastuzumab-combination chemotherapy with taxane and/or capecitabine was given, bone metastases in thoracic vertebra resulted in incomplete paralysis in both legs. She underwent thoraco-lumbar vertebral fixation 10 months before admission. A PET/CT revealed multiple bone metastases in the left femur as well as vertebrae, and CEA rose markedly. She received radiotherapy and trastuzumab monotherapy in addition to bisphosphonate. Temporarily, CEA decreased, but because recurrence nests were recognized in the supraclavicle and mediastinum after the eight-month treatment, trastuzumab monotherapy was followed by trastuzumab plus vinorelbine combined therapy. This regimen markedly reduced CEA after three months, but it rose again over the following three months. As S-1-combined therapy was not effective, trastuzumab+gemcitabine (1 g/week and two weeks on/one week off) combined therapy was started. CEA decreased markedly after 4 cycles, and FDG accumulation in the recurrence region was markedly improved. The adverse event during this treatment was minor, and PS was sufficiently maintained. These results suggest that trastuzumab plus gemcitabine combination therapy is effective for HER2-positive metastatic breast cancer.
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PMID:[A case of HER2-positive metastatic breast cancer responding to trastuzumab plus gemcitabine combination therapy]. 1840 45

In most human breast cancers, lowering of TGFbeta receptor- or Smad gene expression combined with increased levels of TGFbetas in the tumor microenvironment is sufficient to abrogate TGFbetas tumor suppressive effects and to induce a mesenchymal, motile and invasive phenotype. In genetic mouse models, TGFbeta signaling suppresses de novo mammary cancer formation but promotes metastasis of tumors that have broken through TGFbeta tumor suppression. In mouse models of "triple-negative" or basal-like breast cancer, treatment with TGFbeta neutralizing antibodies or receptor kinase inhibitors strongly inhibits development of lung- and bone metastases. These TGFbeta antagonists do not significantly affect tumor cell proliferation or apoptosis. Rather, they de-repress anti-tumor immunity, inhibit angiogenesis and reverse the mesenchymal, motile, invasive phenotype characteristic of basal-like and HER2-positive breast cancer cells. Patterns of TGFbeta target genes upregulation in human breast cancers suggest that TGFbeta may drive tumor progression in estrogen-independent cancer, while it mediates a suppressive host cell response in estrogen-dependent luminal cancers. In addition, TGFbeta appears to play a key role in maintaining the mammary epithelial (cancer) stem cell pool, in part by inducing a mesenchymal phenotype, while differentiated, estrogen receptor-positive, luminal cells are unresponsive to TGFbeta because the TGFBR2 receptor gene is transcriptionally silent. These same cells respond to estrogen by downregulating TGFbeta, while antiestrogens act by upregulating TGFbeta. This model predicts that inhibiting TGFbeta signaling should drive the differentiation of mammary stem cells into ductal cells. Consequently, TGFbeta antagonists may convert basal-like or HER2-positive cancers to a more epithelioid, non-proliferating (and, perhaps, non-metastatic) phenotype. Conversely, these agents might antagonize the therapeutic effects of anti-estrogens in estrogen-dependent luminal cancers. These predictions need to be addressed prospectively in clinical trials and should inform the selection of patient populations most likely to benefit from this novel anti-metastatic therapeutic approach.
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PMID:Transforming growth factor-beta signaling: emerging stem cell target in metastatic breast cancer? 1884 63

Docetaxel is one of the most active cytotoxic drugs against breast cancer, but data are lacking on specific activity in molecularly selected subgroups. This retrospective study was aimed at assessing the outcome and prognostic factors for survival of patients with HER2-negative tumors receiving first-line docetaxel-based chemotherapy for advanced breast cancer (ABC). The medical charts of all 162 patients with prospectively proven HER2-negative ABC and having received docetaxel as first-line chemotherapy for metastatic disease at our institution were retrospectively reviewed with special emphasis on docetaxel efficacy. Potential prognostic factors were sought using multivariate analysis. Median progression-free survival (PFS) was 12 months (95% confidence interval 9.7-14.8) and median overall survival (OS) was 34.9 months (95% confidence interval 28.1-52.1). Hormone receptor (HR) status was the strongest prognostic factor in the univariate analysis for both PFS [hazard ratio = 0.23; P = 0.00000063] and OS (hazard ratio = 0.35; P = 0.0000079). After multivariate analysis, only three independent variables for PFS (HR-positive tumor, no prior adjuvant/neoadjuvant chemotherapy, and isolated bone metastases) and two for OS (HR-positive tumor and isolated bone metastases) remained predictive of a favorable outcome. HER2-negative, HR-positive ABC patients have a relatively good prognostic after docetaxel-containing first-line therapy. The subset of HER2-negative, HR-negative (triple-negative) has a very poor outcome, and innovative therapies are eagerly awaited for these patients.
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PMID:Docetaxel first-line therapy in HER2-negative advanced breast cancer: a cohort study in patients with prospectively determined HER2 status. 1974 2

The first case was a 40-year-old woman who was referred to our hospital with a complaint of left breast tumor. She was diagnosed as invasive ductal carcinoma (T2N0M0, Stage IIA). The tumor was ER-negative, PR-negative and HER2-positive. After primary systemic chemotherapy with 6 courses of 5-fluorouracil+epirubicin+cyclophosphamide(FEC)and 3 courses of weekly paclitaxel (PTX)+trastuzumab, the efficacy of chemotherapy was judged as a complete response (CR). After chemotherapy, radiotherapy for her left breast was performed without surgery. At 21 months after CR, local efficacy was judged as CR, but liver and bone metastases appeared, and were treated by capecitabine and trastuzumab. The efficacy of chemotherapy was judged as a partial response (PR). The second case was a 26-year-old woman referred to our hospital with a complaint of right breast tumor. She was diagnosed as invasive lobular carcinoma (T2N0M0, Stage IIA). The tumor was ER-positive, PR-negative and HER2-positive. After primary systemic chemotherapy with 4 courses of FEC and 6 courses of docetaxel+trastuzumab, the efficacy of chemotherapy was judged as CR. Then, 4 courses of weekly PTX+trastuzumab were performed. After chemotherapy, radiotherapy for her right breast was performed without surgery. The efficacy of treatment was judged as CR for 15 months.
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PMID:[Two cases of breast cancer responding to primary systemic chemotherapy containing trastuzumab without surgery]. 2008 43

A series of 159 tests on HER2 ECD in blood serum from breast cancer patients established the following correlations: enhanced levels of the marker occurred more often in patients with multiple metastases to different organs alongside those with bone metastases; patients in loco-regional relapse tended to show elevated levels too. It is suggested that the method be used for prognosis and monitoring.
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PMID:[An investigation of extracellular HER-2/NEU domain level in blood serum from breast cancer patients]. 2036 18

We experienced a case of anthracycline- and taxane-resistant recurrent breast cancer with multiple liver metastases and multiple bone metastases showing marked improvement by S-1. A 52-year-old woman visited our hospital because of her liver dysfunction in May 2008. She underwent a partial mastectomy preserving chest muscles in another hospital in 2000, but further details were unknown. Radiographic imaging tests revealed multiple metastases to the liver and bones in May 2008, and she was referred to our hospital for management of metastatic lesions. Tumor of the liver was diagnosed as metastases from the breast carcinoma, ER+, PgR+, HER2 (0), and histopathologically by core needle biopsy under ultrasonography. She received 4 courses of EC after 4 courses of biweekly docetaxel treatment. She showed a partial response (PR), so she was treated by the same course of treatment again. But she was diagnosed with an enlargement of liver metastases and recurrence of bone metastases by PET examination. Then the oral treatment with S-1 was started, and at the end of the second course, a significant reduction of abnormal accumulation in PET was noted. She has been quite well without any adverse effects from S-1. S-1 monotherapy was thus considered to be an effective treatment for advanced or recurrent breast cancer resistant to anthracyclines and taxanes.
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PMID:[A case of anthracycline- and taxane-resistant recurrent advanced breast cancer successfully treated with S-1 monotherapy]. 2064 19


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