Bioinformatics analysis of breast cancer bone metastasis related geneCXCR4

Objective:To analyze breast cancer bone metastasis related gene-CXCR4.Methods:This research screened breast cancer bone metastasis related genes by high-flux gene chip.Results:It was found that the expressions of 396 genes were different including 165 up-regulations and 231 down-regulations.The expression of chemokine receptor CXCR4 was obviously upregulated in the tissue with breast cancer bone metastasis.Compared with the tissue without hone metastasis,there was significant difference,which indicated that CXCR4 played a vital role in breast cancer bone metastasis.Conclusions:The hioinformatics analysis of CXCR4 can provide a certain basis for the occurrence and diagnosis of breast cancer bone metastasis,target gene therapy and evaluation of prognosis.

Role of TGF-<i>β</i>in breast cancer bone metastases

Breast cancer is the most prevalent cancer among females worldwide leading to approximately 350,000 deaths each year. It has long been known that cancers preferentially metastasize to particular organs, and bone metastases occur in ~70% of patients with advanced breast cancer. Breast cancer bone metastases are predominantly osteolytic and accompanied by increased fracture risk, pain, nerve compression and hypercalcemia, causing severe morbidity. In the bone matrix, transforming growth factor-β (TGF-β) is one of the most abundant growth factors, which is released in active form upon tumor-induced osteoclastic bone resorption. TGF-β, in turn, stimulates bone metastatic tumor cells to secrete factors that further drive osteolytic bone destruction adjacent to the tumor. Thus, TGF-β is a crucial factor responsible for driving the feed-forward vicious cycle of cancer growth in bone. Moreover, TGF-β activates epithelial-to-mesenchymal transition, increases tumor cell invasiveness and angiogenesis and induces immunosuppression. Blocking the TGF-β signaling pathway to interrupt this vicious cycle between breast cancer and bone offers a promising target for therapeutic intervention to decrease skeletal metastasis. This review will describe the role of TGF-β in breast cancer and bone metastasis, and pre-clinical and clinical data will be evaluated for the potential use of TGF-β inhibitors in clinical practice to treat breast cancer bone metastases.

A nanoagent for concurrent therapy of breast cancer bone metastasis and cancer-induced bone pain through SLC7A11 interruption and photodynamic therapy

Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Place of Bone Scintigraphy in the Assessment of Extension and Follow-Up of Breast Cancer in Senegal: Study of 165 Cases in the Nuclear Medicine Department of Idrissa Pouye General Hospital (Dakar)

Introduction: Breast cancer is the most common cancer in women worldwide, accounting for an estimated 22% of all female cancers. It is the leading cause of cancer mortality in women, almost all of which is due to metastases, with 73% of metastases occurring in the bone. In oncology, metastable technetium 99-labelled methylene bisphosphonate bone scintigraphy (BS) remains the standard examination for detecting and assessing the extent of bone metastases. The aim of this study was to assess the role of BS in the evaluation and follow-up of breast cancer in Senegal. Methodology: This was a retrospective study of breast cancer patients who underwent bone scintigraphy with 99mTc-HMDP in the nuclear medicine department of Idrissa Pouye General Hospital (IPGHO), from July 2009 to June 2022. Results: We enrolled 165 patients, mean age 46.79 years (27 - 87 years). BS was performed in 94.37% of cases for post-therapeutic monitoring and in 5.63% for pre-therapeutic assessment. Results were contributory in 131 patients (92.25%), of whom 72 cases (50.70%) were normal and 59 cases (41.55%) positive or presenting bone metastases;and non-contributory or doubtful in 11 cases (7.75%). Secondary bone locations were multiple in 57 cases (96.61%) and single or solitary in 2 cases (3.39%). The scintigraphic appearance of bone metastases was hyper-fixative in 58 cases (98.31%) and mixed in 1 case (1.69%). Bone lesions were quantified using the Soloway’s grading classification. Conclusion: BS with 99mTc-labelled bisphosphonates remains the examination of choice for skeletal exploration, in the detection and extension of bone metastases in breast cancer. Performance has been enhanced by the development of SPECT coupled with CT (SPECT-CT).

Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets

Metastatic occurrence is the principal cause of death in breast cancer patients. The high osteotropism makes breast cancer the most common primary tumor type associated with metastatic bone disease. The peculiar clinical aspects associated with metastases limited to the skeletal system suggest considering these cases as a distinctive subset of metastatic patients with a better prognosis. Because bone is frequently the first metastatic site in disease relapse, it is feasible that the next improvement in therapeutic options for bone metastatic disease could be associated with an improvement of survival expectation and quality of life in breast cancer patients. Study of the molecular basis of bone remodeling and breast cancer osteotropism has allowed identification of several therapeutic candidates involved in formation and progression of bone metastases. These targets are frequently the determinants of positive feedback between the tumor and bone cells whose clinical outcome is osteolytic lesions. In this review, we discuss the physiopathologic features underlying targeted therapeutic strategies aimed at interfering with the aberrant bone remodeling associated with breast cancer metastases.

Pre-osteoblastic MC3T3-E1 cells promote breast cancer growth in bone in a murine xenograft model

The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cancer cells induce apoptosis in osteoblasts, which further exacerbates bone loss. However, in early stages, breast cancer cells induce osteoblasts to secrete inflammatory cytokines purported to drive tumor progression. To more thoroughly evaluate the role of osteoblasts in early stages of breast cancer metastasis to the bones, we used green fluorescent protein-labeled human breast cancer cell lines MDA-MB-231 and MDA-MB-435, which both induce osteolysis after intra-femoral injection in athymic mice, and the murine pre-osteoblastic cell line MC3T3-E1 to modulate osteoblast populations at the sites of breast cancer metastasis. Breast cancer cells were injected directly into the femur with or without equal numbers of MC3T3-E1 cells. Tumors grew significantly larger when co-injected with breast cancer cells and MC3T3-E1 cells than injected with breast cancer cells alone. Osteolysis was induced in both groups, indicating that MC3T3-E1 cells did not block the ability of breast cancer cells to cause bone destruction. MC3T3-E1 cells promoted tumor growth out of the bone into the extraosseous stroma. These data suggest that breast cancer cells and osteoblasts communicate during early stages of bone metastasis and promote tumor growth.

Analysis of Clinicopathological Factors Associated with Bone Metastasis in Breast Cancer

Breast cancer is the second leading cause of cancer death in women today. Once breast can- cer metastasizes to bone, mortality increases. Thus, there is an urgent need to identify patients with high risk of bone metastasis, and to find predictive factors for the occurrence of bone metastasis at an earlier stage of breast cancer. Three hundred and sixty patients with pathologically proved breast cancer visit- ing the Department of Nuclear Medicine for whole body bone scan from January 2006 and January 2009 were investigated in this study. Clinicopathological information was obtained, which consisted of age, menopausal status, clinical staging, lymph node stage, histological grade, the expression of estro- gen receptor （ER）, progesterone receptor （PR） and epidermal growth factor receptor 2 （HER2）. Correla- tion between bone metastasis and the associated factors was tested by using the Chi-square test. A Cox multivariate analysis was used to assess the factors which independently contributed to survival after bone metastasis in breast cancer patients. Survival curves were drawn for metastasis-free interval and the independent factors which contributed to survival, using the Kaplan-Meier method. Twenty-four pa- tients were excluded from subsequent analysis. Three hundred and thirty-six enrolled patients ranged in age from 22 to 77 years （mean, 47.8 years）. ER/PR status [ER（＋） vs. ER（-）, 2,2=4.328, P=0.037; ER（＋）PR（＋） vs. ER（＋）PR（-）, ;（2=4.425, P=-0.035] and histological grade （;（2=7.131, P=0.028） were sig- nificantly associated with bone metastasis. ER status （;（2=8.315, P=0.004） and metastasis-free interval （;（2=6.863, P=-0.009） were independent prognostic factors for survival in breast cancer patients with bone metastasis. Our study suggested that ER/PR status and histological grade are risk factors for the development of bone metastasis in breast cancer patients. However, ER status and metastasis-free inter- val are independent prognostic factors for survival in breast cancer patients with bone metastasis. Breast cancer bone metastasis has its unique characteristics, which is helpful to choose the appropriate treat- ment for breast cancer patients with bone metastasis.

Effects of Curcumin on Biological Behavior and NF-κB/TNF-α Pathway in Mice with Metastatic Bone Pain of Breast Cancer Induced by Walker 256 Cells

Background. The active ingredient curcumin of traditional Chinese medicine was selected as the research object to investigate the possible mechanism of breast cancer metastatic bone pain in mouse walker 256 cells and the effect of curcumin on the NF-κB/TNF-α pathway in order to provide a new idea for clinical treatment of breast cancer metastatic bone pain. Methods. By establishing an animal model of breast cancer bone metastasis in walker 256 cells, the biological behavior of nude mice was observed on the 8th day after successful modeling. Meanwhile, the low dose group, middle dose group and high dose group of mice were given 15 mg/kg, 25 mg/kg, 50 mg/kg of curcumin solution intraperitoneally in 21 days, and the right cavity bone and spinal cord distended in mice (L4-L6) tissues were used to detect related factors, Immunohistochemical method was used to detect c-fos in spinal cord. Expression levels of RANK, NF-κB and TNF-α were detected by RT-PCR and Western blot. Meanwhile, serum levels of Cox2, il-6, leukotriene and PGE2 were detected. Results. Observing the biological behavior index of nude mice, we found that the mechanical pain and thermal pain threshold decreased (p < 0.05), and the cold pain and spontaneous pain scores increased significantly (p < 0.05). After group study, the expression of c-fos in the cancer pain model group was significantly higher than that in the normal control group (p < 0.05), and with the increase of curcumin dose, the expression of c-fos in the high dose group was significantly lower than that in the solvent model group (p < 0.05). The expression of RANK, NF-κB, TNF-α was higher than that of the normal control group and decreased gradually with the increase of curcumin dose, among which the expression of high dose group was significantly lower than that of solvent group (p < 0.05). RANK, NF-κB, TNF-α protein expression was higher than that of normal control group and gradually decreased with the increase of curcumin dose. The levels of Cox2, IL-6, leukotriene and PGE2 in serum decreased with the increase of curcumin dose, and the high dose group decreased significantly (p < 0.05). Conclusions. On the 8th day after the success of the animal model of breast cancer bone metastasis in Walker 256 cells, abnormal biological behaviors such as heat pain, cold pain sensation and spontaneous hyperalgesia were observed. Further studies have found that the increased expression of rank on osteoclasts induced up-regulated expression of NF-κB and c-fos, induced expression of TNF-α gene, and could induce synthesis and release of leukotriene, PGE2 through direct activation of cyclooxygenase, inflammatory media IL-6 cascade reaction, resulting in pathological pain and hypersensitivity. Traditional Chinese medicine active ingredient curcumin could reduce RANK expression of osteoclast, inhibit cell NF-κB and spinal cord c-fos activity, reduce TNF-α expression, inhibit Cox2 activity, and reduce the synthesis and release of inflammatory factors leukotriene and PGE2, thus exerting its analgesic effect, which provides new ideas and methods for clinical treatment of metastatic bone pain in breast cancer.

Detection of micrometastases in bone marrow and sentinel lymph nodes of breast cancer patients

To study the sensitivity and clinical significance of HE-staining,IHC and RT-PCR in detecting breast cancer micrometastases in bone marrow and sentinel lymph nodes （SLNs）. Methods ：After general anesthesia, all patients underwent bone marrow puncture and sentinel lymph node biopsy （SLNB） by 1% isosulfan blue, and then HE-staining,IHC and RT-PCR were used to detect micrometastases. Results：Of 62 patients with breast cancer whose axillary lymph nodes showed negative HE-staining results, 15 cases presented with positive RT-PCR and 9 cases showed positive IHC results positive in bone marrow micrometastases detection. PT-PCR and IHC showed good uniformity（kappa=0.6945）and there was significant difference in detective rate between these two methods （X2=4.1667,P = 0.0412）. In SLN samples, 13 showed positive RT-PCR results, while 7 showed positive IHC results. PT-PCR and IHC showed good uniformity （kappa=0.64.83）and significant difference was also found in detective rate between these two methods （X^2=4.1667 ,P = 0.0412）. Both bone marrow and SLN samples were RT-PCR positive in 3 cases, which indicated that bone marrow did not always accompany SLN micrometastases（X^2=0.067,P = 0.796）. Conclusion： Even if no axillary lymph node involvement or distant metastases are present in routine preoperative examination, micrometastases can still be detected in bone marrow or SLNs. Because the bone marrow micrometastases and axillary node micrometastses are not present simultaneously, combination test of multiple indicators will detect micrometastases more accurately.

Long-term Efficacy and Safety of Pamidronate Disodium in Treatment of Bone Metastases in Breast Cancer

Objective： To evaluate the long-term efficacy and safety of pamidronate disodium in patients with bone lesions secondary to advanced breast carcinoma. Methods： A retrospective chart review was conducted of 62 patients receiving intravenous pamidronate disodium for metastatic breast cancer. The proportion of patients experiencing at least one skeletal related event （SRE） after 12 months of therapy was determined. Results： The proportion of patients who had an SRE was 29.00% （18 individuals） and the median time to first event was greater than 350 days. Radiotherapy（ll individuals）and pathologic fracture（6 individuals）were the most frequent type of SRE, while cord compression（1 individuals） and hypercalcaemia（0 individuals） were rare. A total of 37 individuals had transient hypocalcaemia without any clinical symptom. No significant creatinine abnormalities were encountered. There were no clinically relevant changes of calcium ,phosphate and creatinine before and after therapy. Conclusion： Long-term treatment with pamidronate disodium significantly reduces and delays skeletal morbidity from osteolytic metastases . Prolonged therapy was well tolerated. This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase llI clinical trials.

Identification of the Risk Factors of Bone Metastatic among Breast Cancer Women in Al-Bashir Hospital

Background: Bone metastasis with advance cancer stage forms approximately 85% of all cases. Breast cancer patients frequently suffer from bone pain, functional impairment due to bone metastasis which impacts negatively on their quality of life. Subjects and Methods: A retrospective study of breast cancer patients who have bone metastasis at diagnosis or developing bone metastasis during 5 years from breast cancer diagnosis (2011-2016) and who received zometa 4 mg monthly in radiotherapy department was included and conducted in 2017. We reviewed 107 female with breast cancer diagnosed by bone scan and/or PET scan as cases of bone metastasis enrolled. Questionnaire was designed to document all variables besides, demographic data which contain (age, histopathology reading invasive ductal carcinoma, invasive lobular carcinoma or others, ER status, PR status, Her2neu status and lymph node status & stage, Onset of metastasis, Menopausal Status & finally No. of metastasis site). Results: We noticed that the highest percentage of patients diagnosed as bone metastasis were 45 years and more, and 86% of them were invasive ductal carcinoma;regarding hormonal status we noticed that ER, PR status was positive in 90.7% and 82.2% of cases respectively, Her2neu receptors were amplified in 26.2% of them, positive lymph nodes were seen positive in 80.4% of cases and 31.8% of them were shown (N3) stage;we noticed that the only risk factor of bone metastasis is PR+ significantly associated with lesions multiplicity (0.049). There is no significant association between ER, PR, Her2neu, lymph nodes and menopausal status and onset of bone metastasis, also age, ER, Her2neu, lymph nodes and menopausal status are not associated significantly with No. of metastatic lesions. Conclusion: PR+ is significantly associated with lesions multiplicity (0.049), which is considered as a risk factor of bone metastasis in our study.

Optimization Diagnosis of Breast Cancer Vertebral Metastases

The article is describing results after analysis of research conducted in Osh Interregional Oncology Center under the Ministry of Health in the Kyrgyz Republic. X-ray computed tomography, magnetic resonance imaging analyses were made for optimization diagnosis determination in patients with breast cancer vertebral metastases. According to the obtained data, the frequency of vertebral metastases in breast cancer was observed as well as the timing of their detection depending on the detection of the primary tumor. In addition, the necessity for early screening of vertebral metastases was explained.

花宝金治疗乳腺癌骨转移癌性疼痛经验

“女子以肝为先天”,加之自身生理特点易肝气郁滞、肝气上逆,日久肾气亏损形成乳腺癌。乳腺癌现已成为女性恶性肿瘤最常见的一种,而且乳腺癌极其容易发生转移,最常见的转移方式是骨转移,最常见的远处转移部位是骨骼,在骨转移部位形成的恶性肿瘤病灶压迫周围软组织、神经血管,形成骨癌痛,严重影响患者的生活质量和生存质量。花宝金教授从事中医治疗恶性肿瘤事业20余年,积累了大量治疗骨转移癌性疼痛的临床经验,在临床上亦取得了很好的治疗效果。文章从疏肝行气止痛、化痰消瘀止痛、补肾壮骨止痛、温阳补气止痛等方面来介绍花宝金教授治疗乳腺癌骨转移癌性疼痛的经验。

乳腺癌骨转移危险因素的系统评价

目的系统评价国内外乳腺癌患者骨转移的发生率与危险因素,为临床降低骨转移的发生率提供依据。方法通过计算机检索中英文数据库中国知网、维普、万方、中国生物医学文献数据库、Pubmed、Medline、Scopus、The Cochrane Library、Web of Science、Embase,搜索从建库至2024年4月17日发表的有关乳腺癌骨转移危险因素或影响因素的文献,按照纳入和排除标准筛选文献,使用Revman 5.4、Stata 17.0进行系统评价。结果本研究共纳入27篇文献,包括乳腺癌患者307993例,其中发生骨转移的患者12283例。Meta分析结果显示,纳入的研究结果间存在明显的统计学异质性(I^(2)=99.1%,P<0.001)。采用随机效应模型进行合并,骨转移发生率为27.8%[95%CI(0.232,0.324),P<0.001]。骨转移发生率的危险因素是年龄(≤40岁、≥50岁)、淋巴结阳性、伴内脏转移、临床分期晚(Ⅲ、Ⅳ期)、肿瘤直径≥5 cm、Ki-67高表达、肿瘤标记物(CEA、CA125)水平升高、生物标记物(nm23蛋白)低表达、ALP水平升高、低Hb、分子分型(luminal型、TNBC)。结论医护人员应对高危患者给予重点关注,尽早采取预防措施与治疗。

雷公藤治疗乳腺癌及其骨转移的药理研究进展

乳腺癌是全球高发恶性肿瘤之一,骨转移是乳腺癌全周期的常见并发症,易形成“肿瘤-骨微环境”的恶性循环,从而导致骨相关事件的发生,如骨痛、病理性骨折和高钙血症等。研究发现雷公藤有效成分具有抗乳腺癌和调控骨微环境的作用,包括抑制肿瘤细胞增殖和迁移、抑制肿瘤血管生成、诱导肿瘤细胞自噬、调控成骨细胞的骨形成、抑制破骨细胞的骨吸收、促进骨髓间充质干细胞向成骨细胞分化以及调控免疫微环境等,有助于抑制乳腺癌及其骨转移。该文系统性地综述了雷公藤防治乳腺癌及其骨转移的药理研究进展,并分析了当前研究的局限性及应用前景。

阿仑膦酸钠联合基础用药预防绝经女性乳腺癌术后依西美坦所致骨丢失的临床研究

目的探讨阿仑膦酸钠联合基础用药预防绝经女性乳腺癌术后依西美坦所致骨丢失的临床疗效。方法回顾性选取2018年6月至2022年6月于首都医科大学附属北京友谊医院因乳腺癌行依西美坦治疗、门诊根据骨密度结果诊断为骨量减少的绝经女性患者45例。根据治疗方案不同分为两组:联合用药组(n=24)和基础治疗组(n=21)。联合用药组给予阿仑膦酸钠75 mg+钙+活性维生素D治疗,基础治疗组给予钙+活性维生素D治疗。比较两组患者治疗初始时、治疗后1年、治疗后2年的骨密度(腰椎骨密度、髋部骨密度);比较两组患者治疗初始时及治疗后2年的骨代谢指标,包括血清骨钙素、全段甲状旁腺素;并记录两组患者骨质疏松性骨折及泌尿系统结石的发生情况。结果联合用药组患者治疗后1年及治疗后2年的腰椎及髋部骨密度较治疗初始时均无明显变化,差异均无统计学意义(P>0.05);基础治疗组患者治疗后1年及治疗后2年的腰椎及髋部骨密度较治疗初始时均显著降低,差异均有统计学意义(P<0.05)。治疗初始时、治疗后1年,两组患者的腰椎及髋部骨密度比较,差异均无统计学意义(P>0.05);治疗后2年,联合用药组腰椎及和髋部骨密度分别为-1.91±0.23、-1.93±0.31,均明显高于基础用药组(-2.21±0.30、-2.15±0.18),差异均有统计学意义(P<0.05)。联合用药组患者治疗后2年骨钙素和全段甲状旁腺素水平均较治疗初始时明显降低,差异均有统计学意义(P<0.05);基础治疗组患者治疗后2年骨钙素水平较治疗初始时明显降低,差异有统计学意义(P<0.05),而全段甲状旁腺素水平与治疗初始时比较,差异无统计学意义(P>0.05)。两组患者治疗初始时与治疗后2年骨钙素、全段甲状旁腺素比较,差异均无统计学意义(P>0.05)。两组患者治疗后2年内均无骨质疏松性骨折的发生,无泌尿系统结石的变化。结论采用依西美坦治疗的乳腺癌术后患者,骨密度诊断骨量减少,早期应用阿仑膦酸钠,能够有效减缓骨流失的进程。

地舒单抗对比唑来膦酸治疗乳腺癌骨转移的疗效和安全性:一项倾向评分匹配队列研究

目的比较地舒单抗与唑来膦酸治疗乳腺癌骨转移患者的有效性与安全性。方法回顾性收集2020年9月至2022年7月南京医科大学第一附属医院肿瘤科收治的经骨改良药物治疗(地舒单抗90例,唑来膦酸86例)的晚期乳腺癌骨转移患者的临床资料。通过倾向评分后进行1∶1匹配,分为地舒单抗组66例和唑来膦酸组66例。比较两组患者无骨相关事件(skeletal-related event,SRE)生存率和不良事件的发生情况。结果截至2023年7月20日,中位随访时间为18.3个月,两组患者中位至首次SRE发生时间均未达到。地舒单抗组和唑来膦酸组治疗后1年无SRE生存率分别为80.3%(95%CI:68.7%~89.1%)和63.6%(95%CI:50.9%~75.1%)。与唑来膦酸组比较,地舒单抗组降低SRE发生风险(HR=0.48,95%CI:0.26~0.90,P=0.022)。两组发生的不良事件主要为低钙血症,唑来膦酸组关节痛发生率更高(P=0.028)。结论与唑来膦酸比较,地舒单抗治疗晚期乳腺癌骨转移患者可延迟SRE的发生,且关节痛不良事件的发生率更低。

亮丙瑞林对ER阳性绝经前乳腺癌化疗患者卵巢功能及骨密度的影响

目的:探讨亮丙瑞林对雌激素受体(ER)阳性绝经前乳腺癌化疗患者卵巢功能及骨密度(BMD)的影响。方法:选取2020年1月—2022年8月丰城市人民医院收治的82例ER阳性绝经前乳腺癌患者的病历资料进行回顾性分析,根据治疗方式分为化疗组(n=41)和亮丙瑞林组(n=41)。化疗组患者予以AC-T辅助化疗,亮丙瑞林组在化疗组的基础上联合亮丙瑞林治疗。比较两组患者疗效、卵巢功能、BMD及月经情况。结果:亮丙瑞林组的总有效率高于化疗组(P<0.05)。治疗后,两组血清雌二醇(E2)水平均明显降低,血清促黄体生成素(LH)、卵泡刺激素(FSH)水平均明显升高(P<0.05);亮丙瑞林组患者的血清LH、FSH水平均明显高于化疗组,血清E2水平明显低于化疗组(P<0.05)。治疗后,两组左髋部、腰椎的BMD水平均明显降低(P<0.05);两组比较差异均无统计学意义(P>0.05)。亮丙瑞林组的闭经时间、月经恢复正常时间均较化疗组短,月经复潮率较化疗组高(P<0.05)。结论:亮丙瑞林可保护ER阳性绝经前乳腺癌化疗患者卵巢功能,可有效提高疗效,但可能会导致患者BMD下降,需要在治疗期间注意监测BMD变化,降低骨质疏松发生风险。

血清维生素D结合蛋白、FGF23、Klotho与乳腺癌骨转移的相关性分析

目的骨转移是乳腺癌常见的并发症之一,严重影响患者的生存和预后。本研究旨在探究血清维生素D结合蛋白(vitamin D⁃binding protein,VDBP)、成纤维细胞生长因子23(fibroblast growth factor 23,FGF23)和Klotho蛋白在乳腺癌骨转移中的表达及临床意义。方法收集95例来自本院2019⁃08⁃01至2021⁃08⁃01的女性乳腺癌患者作为研究对象,经影像学和组织病理学方式诊断是否发生骨转移,将患者分为骨转移组36例,非骨转移组59例。分析两组患者的临床病理特征;采集患者外周血样本,通过ELISA对血清中VDBP、FGF23和Klotho进行定量分析;使用Spearman相关分析进行指标间的关联性分析;Logistic回归分析乳腺癌发生骨转移的影响因素;ROC曲线分析血清VDBP、FGF23和Klotho水平预测乳腺癌发生骨转移的价值。结果骨转移和非骨转移乳腺癌病理分级比较有统计学意义(P<0.05)。骨转移和非骨转移乳腺癌患者血清中VDBP、FGF23及Klotho的水平依次为:(80.35±29.34)和(115.18±48.69)ng/mL、(658.35±201.19)和(405.36±154.42)pg/mL以及(155.82±40.29)和(229.35±72.46)pg/mL,两组比较差异有统计学意义(P<0.05)。Spearman相关性分析显示,骨转移乳腺癌患者血清中VDBP水平与乳腺癌病理分级相关(P<0.05);FGF23和Klotho水平与病理分级、是否骨痛以及转移部位有关(P<0.05)。VDBP、FGF23和Klotho水平均为乳腺癌骨转移发生的独立影响因素(P<0.05)。ROC曲线结果显示,VDBP、FGF23及Klotho预测乳腺癌患者发生骨转移的曲线下面积依次为:0.733、0.806、0.761,最佳截断值为:81.56 ng/mL、573.501 pg/mL和201.193 pg/mL;3个指标联合诊断的曲线下面积为0.820,高于单一指标诊断的曲线下面积。结论血清VDBP、FGF23及Klotho水平可作为乳腺癌骨转移的参考指标,在乳腺癌骨转移的临床诊断上具有一定应用前景。