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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten previously untreated postmenopausal women with metastatic breast cancer, none of whom had received prior systemic therapy, were treated with the luteinising hormone releasing hormone (LHRH) analogue D-Ser(But)6, Azgly10-LHRH (ICI 118630). Two obtained an objective partial remission, one in bone metastases and one in lung metastases. One patient proved unassessable. Amongst the seven failures, incomplete pituitary gonadotrophin suppression over the relatively short treatment period with the daily injections was noted. The seven patients failing ICI 118630 received tamoxifen and two with high tumour oestrogen receptor values responded. LHRH analogues may provide a novel endocrine therapy for postmenopausal breast cancer although more data are needed. In this study, the monthly depot injection proved superior to daily injections with regard to gonadotrophin suppression, although it is not clear that this provides the mechanism of action.
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PMID:Remission of postmenopausal breast cancer during treatment with the luteinising hormone releasing hormone agonist ICI 118630. 294 37

Although breast carcinomas are considered to originate from glandular epithelial cells, some exhibit 'squamoid features', comprising stratification with a gradient in the nuclear-cytoplasmic ratio within individual cancer cell nests on microscopy. In parallel with a histological review of squamoid features, we immunohistochemically investigated the expression of involucrin, a marker of terminal squamous differentiation, in 223 breast carcinomas with one to three regional nodal metastases but no distant metastases and analysed their association with other clinicopathological parameters to explore their clinical and biological implications. Squamoid features and involucrin expression, detected in 22% and 27% of cases respectively, correlated with each other and were associated with high-grade atypia, a solid-nest pattern, cancer cell necrosis on histology and negative oestrogen receptor status. The incidence of regional recurrences was higher in patients with involucrin expression, whereas bone metastases were less frequent in groups with squamoid features or with diffuse (> or = 10%) involucrin expression. Both squamoid features and involucrin expression, which were considered to be derived either from differentiation into keratinocytes or from some kind of cellular degeneration caused by high turnover rate, are suggested to influence the biological behaviour of breast cancer cells in vivo, and they may be effective in predicting the most likely recurrence sites.
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PMID:Squamoid features and expression of involucrin in primary breast carcinoma associated with high histological grade, tumour cell necrosis and recurrence sites. 916 48

Three hundred and sixty-seven women presenting to the Breast Unit at Guy's Hospital between 1975 and 1990 whose first distant metastasis was in the skeleton were identified and the influence of a number of patient and tumour characteristics on the development and subsequent prognosis of bone metastases was assessed. One hundred and thirty-nine women had disease that remained clinically confined to the skeleton. They were more likely to be older, with lobular carcinoma and to have presented initially with little or no axillary lymph node involvement. The 228 women who subsequently developed disease at extra-osseus sites were more likely to have poorly differentiated ductal tumours and heavy lymph node involvement at primary diagnosis. On multivariate analysis, the clinical and pathological factors of greatest prognostic importance for survival after the development of bone metastases were histological grade (P = < 0.0001), oestrogen receptor status (P = < 0.0001), bone disease at initial presentation (P = < 0.0001), disease-free interval (P = 0.002) and age (P = 0.006).
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PMID:Clinical course and prognostic factors following bone recurrence from breast cancer. 982 86

Bone metastases can present to a number of different specialties and their successful management requires a coordinated approach with good liaison between the specialists. Patients who respond to systemic therapy for their metastases have a good chance of being alive at 3 years, and 20% will be alive at 5 years. This means that it is worth palliating these patients properly. With this in mind, the intention of this document is to try and improve the process of care for women with metastatic bone disease from breast cancer. These guidelines consider all aspects of care from diagnosis to assessment of response to treatment, and describe the Quality Objectives that should be addressed at each stage. The level of available evidence is indicated throughout the document where possible. In considering diagnosis, the guidelines emphasize the value of having a dedicated orthopaedic surgeon specifically linked to each Cancer Unit. The attachment of a dedicated orthopaedic surgeon will ensure that mechanical problems are correctly identified, and that actual or imminent fracture is correctly managed. The latter is particularly important as the management of pathological fractures is not the same as that of traumatic fractures. The orthopaedic surgeon should also act as the liaison between his/her own Unit and the tertiary spinal or neurosurgical centres as necessary. In addition, empowering the radiologist means that the diagnostic process can be accelerated and refined. The place of different investigations in diagnosis, including tumour markers, is discussed. The guidelines emphasize the need for a definitive diagnosis before treatment in the (rare) case of a solitary metastasis. The treatment section discusses orthopaedic management, radiotherapy and systemic treatments (endocrine therapy, chemotherapy and bisphosphonates). The guidelines emphasize the emergency nature of spinal cord compression, describing the need for fast access to assessment and for good liaison between specialists. It is essential that these are available and widely publicized to ensure effective management. The role of radiotherapy in both local pain relief and spinal cord compression is discussed, and various techniques are described. Endocrine therapy and chemotherapy are discussed in relation to the disease-free interval, performance status, extent and site of metastatic disease, and oestrogen receptor status. Specific chemotherapy regimes are not discussed as these are subject to change and local protocols should be followed. The increasing evidence behind the role of bisphosphonates is reviewed. With many unanswered questions about the long-term use of this group of drugs, the guidelines offer a scoring system for deciding which patients might benefit most from long-term bisphosphonate therapy. The guidelines describe the possible ways of assessing response to treatment and the difficulties that may be encountered, including a discussion of the role of tumour markers in assessment of response. A final section looks at palliative care principles in bone pain management, acknowledging the need for continuation of good care throughout the patient's journey, from diagnosis onwards. We very much hope these guidelines will stimulate individuals and institutions to improve the process of delivering care to this group of patients.
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PMID:British Association of Surgical Oncology Guidelines. The management of metastatic bone disease in the United Kingdom. The Breast Specialty Group of the British Association of Surgical Oncology. 1018 49

Postoperative radiotherapy (RT) forms an intrinsic part of breast conservation therapy, substantially reducing the risk of breast relapse. It is given 4-6 weeks postoperatively using medial and lateral beams to achieve a near homogeneous dose to the breast while minimising the dose to adjacent structures. Typically, a dose of 40 Gy in 15 daily fractions over three weeks or 50 Gy in 25 fractions over five weeks is given, with a boost of 10 Gy using low energy electrons or superficial X-rays. RT is delivered to the chest wall after mastectomy in patients with large tumours (> 5 cm), close surgical margins, or significant axillary node involvement and may result in an additional 10% survival benefit. Early complications of RT include tiredness, skin erythema and moist desquamation. Late reactions, breast fibrosis, telangiectases and peau d'orange are reduced if more treatment fractions are given. Lung irradiation is minimised by careful treatment planning and < 1% of patients experience radiation pneumonitis or pulmonary fibrosis. Patients with locally advanced breast cancer may be offered a combination of systemic therapy, endocrine, chemotherapy and radical RT. Preoperative systemic and radiation therapy reduces the mastectomy rate but at present does not improve survival. Those who are unfit for radical treatment and have large ulcerating or fixed cancers are offered either endocrine or cytotoxic therapy, depending upon the oestrogen receptor status, followed by RT, which is unlikely to cure but may achieve local control for a variable duration. RT forms part of the multidisciplinary approach to palliative treatment for metastatic disease. Bone metastases occur in 75% of women with metastatic disease and RT provides effective pain relief and reducing risk of pathological fractures. Patients with brain metastases need high-dose steroids followed by cranial RT.
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PMID:Radiotherapy for early and advanced breast cancer. 1177 Mar 58

Adjuvant systemic treatments have greatly improved the prognosis of women with early breast cancer. Combination chemotherapy and, for patients with oestrogen receptor-positive (ER+) tumours, endocrine treatment has been found to reduce the frequency of relapse and improve survival. New adjuvant strategies include the introduction of taxanes into adjuvant chemotherapy schedules, the use of aromatase inhibitors in place of, or in addition to, tamoxifen, and the use of adjuvant bisphosphonates. Combination chemotherapy has been found to reduce the annual odds of recurrence and death in pre- and postmenopausal women. The benefits, however, are on average less in older patients. Anthracycline-based regimens are more effective than traditional regimens of cyclophosphamide, methotrexate, and fluorouracil (CMF). The benefits of adjuvant cytotoxic and endocrine treatments are additive. There is considerable debate as to the role of taxanes in adjuvant therapy. Improved outcome has been observed in one large trial, especially in those patients with ER-negative tumours. High-dose chemotherapy has not fulfilled its early promise. Ovarian suppression and/or tamoxifen remain the treatments of choice. The annual odds of relapse and death have been reduced by approximately one-third and one-quarter, respectively. Several very large studies are in progress to assess the potential of aromatase inhibitors in the adjuvant setting. Direct comparisons with tamoxifen, as well as switching after several years from tamoxifen to an aromatase inhibitor, are strategies under evaluation. Early results from one of these trials evaluating anastrozole (the Arimidex, Tamoxifen, Alone or in Combination [ATAC] trial) has reported a reduced relapse rate after a median follow-up of 3 years in favour of anastrozole. However, this was at the expense of accelerated bone loss, and strategies to minimise this side effect of aromatase inhibitors are under investigation. Although many studies have indicated that bisphosphonates prevent the development of metastatic bone disease in animals, the clinical role of prophylactic bisphosphonates in early breast cancer is not clearly defined. Three studies with oral clodronate have been published, two of them indicating a protective effect on the development of bone metastases and improved survival, and one suggesting a disadvantage to the use of adjuvant clodronate. Further large adjuvant trials with clodronate and zoledronic acid are in progress. Adjuvant bisphosphonates also have been found to reduce bone loss associated with cancer treatments and preserve skeletal health. It may be possible to replace the current oral regimens for prevention of bone loss with a single annual infusion of the highly potent bisphosphonate zoledronic acid.
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PMID:Current and future status of adjuvant therapy for breast cancer. 1254 90

The aim of this study was to identify factors that may be associated with the development of bone metastases in patients with metastatic breast carcinoma and to see if any of these factors had a bearing on subsequent survival. In total, 492 patients presented to the Nottingham City Hospital with metastatic breast carcinoma between July 1997 and December 2001. Of these, 267 patients had bone metastases at presentation with metastatic disease, 91 patients in this group had bone as their only site of metastatic disease. Sites of first presentation of metastatic disease were prospectively recorded, as were histological features of the primary tumour (tumour type, histological grade, lymph node stage, tumour size and oestrogen receptor (ER) status). The radiological features of the bone metastases, the metastasis-free interval and serological tumour marker levels at presentation with metastases were all recorded. There was a significant association between the development of bone metastases and lower grade tumours (P=0.019), ER-positive tumours (P<0.0001) and the lymph node stage of the primary tumour (P=0.047). A multivariate analysis found that metastasis-free interval, additional sites of metastatic disease other than bone, ER status and serological tumour marker levels all independently contributed to survival from time of presentation with bone metastases.
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PMID:Bone metastases from breast carcinoma: histopathological - radiological correlations and prognostic features. 1291 74

Endocrine therapy remains important in the adjuvant treatment of pre- and postmenopausal women. Adjuvant ovarian ablation with or without tamoxifen produces effects which are equivalent to those of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy in premenopausal women with oestrogen receptor (ER) and/or progesterone receptor (PgR) positive breast cancer. Tamoxifen alone is also effective in these women. Concurrent use of tamoxifen and ovarian ablation may be even more effective, but more studies are needed. Tamoxifen remains a standard adjuvant therapy for postmenopausal women with ER and/or PgR positive tumours. Current information supports the use of 5 years of tamoxifen but additional studies comparing 5 years to longer duration are ongoing. The aromatase inhibitor (AI) anastrozole has now been demonstrated to be better than tamoxifen in preventing recurrence in early reports from the Arimidex vs Tamoxifen And the Combination (ATAC) Trial. Ongoing trials of this and other AIs before, after, concurrent with, or substituted for tamoxifen in the adjuvant setting may soon revolutionize our approach for postmenopausal women. Adjuvant bisphosphonates have been shown to reduce the incidence of bone metastases and improve survival in two of three published adjuvant trials and are being further studied. Her-2 neu status is being explored as a predictive factor for selection of endocrine therapy, but is not yet considered standard for this purpose.
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PMID:The best use of adjuvant endocrine treatments. 1465 27

Tamoxifen is the standard first-line endocrine therapy for breast cancer, but recent data indicate that it is likely to be replaced by the effective aromatase inhibitors (AIs), in both the metastatic and adjuvant settings. Aromatase inhibitors induce complete oestrogen deprivation that leads to clinically significant bone loss. Several ongoing or planned trials combine AIs with bisphosphonates, even more so that recent data reveal that clodronate may reduce the incidence of bone metastases and prolong survival in the adjuvant setting. Bisphosphonates can inhibit breast cancer cell growth in vitro, but they have never been studied in steroid-free medium (SFM), an in vitro environment that mimics the effects of AIs in vivo. Quite surprisingly, in SFM, clodronate stimulated MCF-7 cell growth in a time- and dose-dependent manner by up to two-fold (crystal violet staining assay), whereas it had no mitogenic activity in complete medium. The bisphosphonate similarly increased the proliferation of IBEP-2 cells, which also express a functional oestrogen receptor (ER), while it weakly inhibited the growth of the ER-negative MDA-MB-231 cells. Expectedly, 17beta-oestradiol stimulated the growth of MCF-7 and IBEP-2 cells cultured in SFM, and had no effect on MDA-MB-231 cells. Moreover, partial (4-OH-tamoxifen) and pure antioestrogens (fulvestrant, ICI 182,780), in combination with clodronate, completely suppressed the mitogenic effect of the bisphosphonate, suggesting that it was mediated by an activation of ER. In accordance with this view, clodronate induced ER downregulation, weakly increased progesterone receptor expression, and stimulated the transcription of an oestrogen-responsive reporter gene. In conclusion, we report a previously unknown stimulatory effect of clodronate on MCF-7 cells grown in SFM, in vitro conditions that are potentially relevant to the use of AIs for breast cancer. Moreover, our data suggest that ER is involved in these effects of clodronate on cancer cell growth.
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PMID:Steroid-free medium discloses oestrogenic effects of the bisphosphonate clodronate on breast cancer cells. 1547 66

Ten-year follow-up results are presented of an adjuvant clodronate trial in patients with primary breast cancer. Between 1990 and 1993, 299 women with primary node positive breast cancer were randomized to oral clodronate 1600 mg daily (149) or controls (150) for 3 years. All patients received adjuvant chemo- or endocrine therapy. Within 10 years bone metastases were detected at the same frequency in the clodronate and control groups: 44 (32%) vs. 42 (29%), respectively, (p=0.35). The frequency of non-skeletal recurrences (visceral and local) was significantly higher in the clodronate group 69 (50%) as compared with the controls 51 (36%) (p=0.005). Ten-year disease-free survival (DFS) remained significantly lower in the clodronate group (45% vs. 58%, p=0.01, respectively). This was especially seen in oestrogen receptor negative patients (25% vs. 58%, p=0.004, respectively). No significant overall survival difference was found between the groups. As previously reported 3-year adjuvant clodronate treatment did not prevent the development of bone metastases in node-positive breast cancer patients. A negative effect of clodronate on DFS by increasing the development of visceral metastases was still seen at 10 years, but this did not significantly compromise overall survival.
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PMID:Ten-year follow-up of a randomized controlled trial of adjuvant clodronate treatment in node-positive breast cancer patients. 1584 10


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