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)

In 1987/88 a prospective study was undertaken of 750 patients with postoperative carcinoma of the breast but no evidence as yet of skeletal metastases. A thorough history regarding pain was taken with pre-set questions and an exact clinical examination conducted to reveal any skeletal pain. Subsequently whole-body skeletal scanning was performed, plus additional X-ray films, determination of tumour markers CA-15-3 and CEA, and further tests as indicated. Clinical and imaging results agreed in 649 patients. In 70 patients the clinical suspicion or questionable finding of metastases was not confirmed by radiology or a scan. Bone metastases would have been missed in only 14 patients (1.9%) without a skeletal scan. Eleven of these 14 patients were in high-risk groups (negative hormone receptor status; axillary lymph node metastases). Skeletal metastases were undiscovered in only three of the 750 patients (0.4%). It is thus sufficient to limit skeletal scans to high-risk groups, as long as a careful history of pain is taken and a thorough clinical examination conducted.
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PMID:[The value of skeletal scintigraphy in the aftercare of breast carcinoma. A prospective study of 750 cases]. 253 82

Specific high affinity receptors for 1,25-dihydroxyvitamin D3 are present in several human breast cancer cell lines, and this hormone can regulate the replication of these cells. These receptors are also present in primary breast carcinomas. The present study has resulted from the follow-up for up to 68 mo of 263 women, who had had 1,25-dihydroxyvitamin D receptor (1,25-DR) levels measured in their primary tumors. Survival data on 191 women were correlated with the levels of 1,25-DR and other steroid hormone receptors, menopausal status, and age by life table analysis. Survival was not affected by 1,25-DR level in either absolute terms or relative levels. However, the late development of lymph node metastases in eight of 47 individuals was correlated with the 1,25-DR level (P = 0.05). There was no correlation between 1,25-DR or other hormone receptor levels and the development of hypercalcemia or bone metastases in the small number of individuals so affected. As we had observed previously, there was no correlation between the level of 1,25-DR and that of the other steroid hormones. These data show that the presence of 1,25-DR in primary breast cancers is independent of other prognostic indicators and, inasmuch as it correlated with late lymph node metastasis, may be an adverse prognostic indicator.
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PMID:Significance of 1,25-dihydroxyvitamin D3 receptor in primary breast cancers. 301 26

In 114 patients with metastatic breast cancer resistant to chemo- and hormonal therapy another attempt was made to treat these patients with the hormone combination of aminoglutethimide (AG) 1000 mg daily and medroxyprogesteroneacetate (MAP) 1500 mg daily for 6 weeks, than 500 mg MAP daily. At present, the following results were obtained from 100 evaluable patients: Complete remission (CR) 4,4% [median remission duration (MRD) 34,8 weeks], partial remission (PR) 18,5% (MRD 34,5 weeks), a no change status (NC) in 44,5% (MRD 17,2 weeks), in 32,6% of the cases there was no response. 19 patients with hormone receptor positive tumors obtained CR + PR in 26,3%, NC 68,4%. Bone metastases seem to respond best to this therapy. 2/3 of all patients suffered from cerebral side effects, particularly contemporary personality disorders and depressive syndromes, 53% showed a short increase of their liver values. During the first 6 weeks the side effects were most pronounced. In 16 cases - entirely patients primarily in bad general condition - the therapy had to be stopped due to heavy subjective side effects. The combination AG/MAP represents a new highly effective therapeutic modality with a relatively broad therapeutic index. The treatment results are described. MAP can replace cortisone generally applied together with AG and seems to have an additive effect with AG.
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PMID:[Medroxyprogesterone acetate (MAP) and aminoglutethimide (AG) in metastatic breast carcinoma. Preliminary report on a phase II study of the German Cancer Society's Internal Medicine Oncology Task Force]. 621

It has been suggested that tamoxifen may improve the efficacy of medical castration with luteinising hormone-releasing hormone analogues, but very few data have so far been published concerning the clinical and endocrinological activity of this therapeutic modality. In this phase II multicentre trial conducted by the Italian Trials in Medical Oncology group (ITMO), 64 premenopausal patients with hormone receptor-positive or unknown breast cancer were treated with monthly s.c. injections of goserelin 3.6 mg, in association with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced disease. All of the patients were evaluable for efficacy and there was an overall response rate of 41% (95% confidence interval 28-52%), with 7 of the 26 responders achieving complete remission. The median time to response was 4 months (range 2-17), and the median response duration was 13 months (range 6-37 +). Better responses were observed in soft tissues (51%); the response in visceral and bone metastases was respectively 19% and 37%. Serum concentrations of gonadotrophins and oestradiol were significantly decreased by the treatment, oestrogen levels being constantly suppressed to within the range observed in post-menopausal women. No significant change was detected in serum testosterone levels. In our experience, although it was not associated with any increased clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a feasible approach in the management of premenopausal advanced breast cancer.
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PMID:Combination goserelin and tamoxifen therapy in premenopausal advanced breast cancer: a multicentre study by the ITMO group. Italian Trials in Medical Oncology. 773 10

Although metastasis is a frequent event in breast cancer patients, insight into the clinical course, prognosis and therapy with respect to the site of the first metastases has been poor and contradictory in former investigations. Follow-up data from 648 patients with metastatic breast cancer were statistically analyzed. Patients with bone metastases at first relapse had better overall survival (median 71 vs. 48 months; p < 0.001) and survival after first metastases (median 24 vs 12 months; p < 0.001) than patients with visceral metastases at first relapse. Bone was the site of first metastasis in 46%, and 71% of patients with metastatic breast cancer developed bone metastases. The localization of the second metastatic site was of prognostic relevance in patients with first visceral metastases, but not in patients with first bone metastases. The presence of osseous metastases correlated significantly with estrogen and progesterone receptor positivity, tumor grading I/II and S-phase fraction <5%. The better prognosis of patients with bone metastases is not determined exclusively by hormone receptor status. The disease is significantly more stable in patients with first bone metastases than in those with first visceral metastases.
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PMID:Metastatic breast cancer: clinical course, prognosis and therapy related to the first site of metastasis. 1083 97

The prognosis for patients with metastatic breast cancer remains poor. Metastatic breast cancer confined to the bones may have a better prognosis, especially hormone receptor-positive disease. We performed a prospective, randomized clinical trial to compare immediate consolidation with high-dose chemotherapy and hematopoietic support versus observation with high-dose consolidation at the time of disease progression in women with metastatic breast cancer and only bone metastases. The patients received chemotherapy with doxorubicin, 5-fluorouracil and methotrexate before randomization. In all, 85 patients were enrolled and 69 were randomized. The median follow-up is 8.1 years from randomization. The median event-free survival (EFS) for the immediate transplant arm is 12 months and for the observation arm is 4.3 months (P<0.0001). The median overall survival for the immediate transplant arm is 2.97 years and for the observation arm 1.81 years, a difference that is not statistically significant. Immediate high-dose chemotherapy and radiation therapy as consolidation offers a clinically and statistically significant improvement in EFS compared with radiation therapy alone following induction chemotherapy for women with metastatic breast cancer confined to the bones.
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PMID:A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy. 1670 60

The purpose of this study was to evaluate technical success, technique effectiveness, and survival following radiofrequency ablation for breast cancer liver metastases and to determine prognostic factors. Forty-three patients with 111 breast cancer liver metastases underwent CT-guided percutaneous radiofrequency (RF) ablation. Technical success and technique effectiveness was evaluated by performing serial CT scans. We assessed the prognostic value of hormone receptor status, overexpression of human epidermal growth factor receptor 2 (HER2), and presence of extrahepatic tumor spread. Survival rates were calculated using the Kaplan-Meier method. Technical success was achieved in 107 metastases (96%). Primary technique effectiveness was 96%. During follow-up local tumor progression was observed in 15 metastases, representing a secondary technique effectiveness of 86.5%. The overall time to progression to the liver was 10.5 months. The estimated overall median survival was 58.6 months. There was no significant difference in terms of survival probability with respect to hormone receptor status, HER2 overexpression, and presence of isolated bone metastases. Survival was significantly lower among patients with extrahepatic disease, with the exception of skeletal metastases. We conclude that CT-guided RF ablation of liver metastases from breast cancer can be performed with a high degree of technical success and technique effectiveness, providing promising survival rates in patients with no visceral extrahepatic disease. Solitary bone metastases did not negatively affect survival probability after RF ablation.
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PMID:CT-guided radiofrequency ablation in patients with hepatic metastases from breast cancer. 1857 33

Aromatase inhibitors have largely replaced tamoxifen as the first-line treatment for postmenopausal women with metastatic, hormone receptor-positive (HR+) breast cancer. However, many patients develop clinical resistance with prolonged treatment, and oestrogen deprivation following aromatase inhibition can result in loss of bone mineral density. Furthermore, most patients with metastatic breast cancer develop bone metastases, and the resulting adverse skeletal-related events are a significant cause of patient morbidity. Src, a non-receptor tyrosine kinase, is a component of signalling pathways that regulate breast cancer cell proliferation, invasion and metastasis as well as osteoclast-mediated bone turnover. Preclinical evidence also suggests a role for Src in acquired endocrine resistance. As such, Src inhibition represents a logical strategy for the treatment of metastatic breast cancer. In vitro, combination therapy with Src inhibitors and endocrine agents, including aromatase inhibitors, has been shown to inhibit the proliferation and metastasis of both endocrine-responsive and endocrine-resistant breast cancer cell lines more effectively than either of the therapy alone. Src inhibition has also been shown to suppress osteoclast formation and activity. Combination therapy with aromatase inhibitors and Src inhibitors therefore represents a novel approach through which the development of both acquired resistance and bone pathology could be delayed. Data from clinical trials utilising such combinations will reveal if this strategy has the potential to improve patient outcomes.
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PMID:Combining Src inhibitors and aromatase inhibitors: a novel strategy for overcoming endocrine resistance and bone loss. 2047 23

Biopsies of metastatic tissue are increasingly being performed. Bone is the most frequent site of metastasis in breast cancer patients, but bone remains technically challenging to biopsy. Difficulties with both tissue acquisition and techniques for analysis of hormone receptor status are well described. Bone biopsies can be carried out by either by standard posterior iliac crest bone marrow trephine/aspiration or CT-guided biopsy of a radiologically evident bone metastasis. The differential yield of these techniques is unknown. Results from three prospective studies of similar methodology were pooled. Patients underwent both an outpatient posterior iliac crest bone marrow trephine/aspiration and a CT-guided biopsy of a radiologically evident bone metastasis. Samples were assessed for the presence of malignant cells and where possible also for estrogen (ER) and progesterone receptor (PgR) expression. 40 patients were enrolled. Bone marrow aspiration/trephine biopsy was completed in 39/40 (97.5%) and CT-guided biopsy was completed in 34/40 (85%) of patients. Sufficient tumor cells for hormone receptor analysis were available in 19/39 (48.8%) and 16/34 (47%) of and bone marrow aspiration/trephine and CT-guided biopsies, respectively. Significant discordance in ER and PgR between the primary and the bone metastasis was also seen. Nine patients had tissue available from both bone marrow and CT-guided bone biopsies. ER and PgR concordance between these sites was 100 and 78%, respectively. Performing studies on human bone metastases is technically challenging, with relatively low yields regardless of technique. Given resource issues and similar success rates when comparing both techniques, bone marrow examination may be utilized first and if inadequate tissue is obtained, CT-guided biopsies can then be used.
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PMID:Acquisition of metastatic tissue from patients with bone metastases from breast cancer. 2111 56

We report the case of an 82-year-old female diagnosed with HER2-negative, hormone receptor (HR)-positive metastatic breast cancer. Upon biochemical disease progression of the initially HR-receptor positive disease under anti-hormonal treatment with tamoxifen and letrozole, she received combination chemotherapy with paclitaxel/gemcitabine. Due to her suffering from severe toxicity, therapy was switched to nab-paclitaxel/gemcitabine. From April 22, 2013, to July 15, 2013, the patient received 5 cycles of nab-paclitaxel/gemcitabine as a 30-min infusion every 3 weeks, with excellent biochemical responses to treatment. Tumor marker levels as well as bilirubin were reduced to baseline levels. Chemotherapy with nab-paclitaxel/gemcitabine was well tolerated. At a follow-up visit immediately after the end of chemotherapy, the patient reported well-being and presented with a Karnofsky performance status (KPS) of 100%. At the last follow-up in October 2013, she was alive with multiple metastatic sites in the liver and bone metastases in the spine without risk of fracture and a KPS of 90%. She has received palliative single agent chemotherapy with capecitabine (14/7 regimen, 1,500 mg b.i.d.) since August 2013 and continued to show a good biochemical treatment response at the last follow-up in October 2013. Since August 2013, the patient has also received denosumab (120 mg sc, q4w) for her metastatic bone disease. As of July 2014, treatment has not been changed and the patient reports her well-being.
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PMID:Excellent biochemical response to polychemotherapy with nab-paclitaxel/gemcitabine in an 82-year-old female with metastatic breast cancer. 2540 57


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