乳腺癌芳香化酶抑制剂治疗期间骨丢失的长期随访结果

目的 评估绝经后激素受体阳性早期乳腺癌患者术后5年芳香化酶抑制剂（aromatase inhibitor,AI）辅助内分泌治疗过程中的骨丢失情况,为骨健康管理提供依据。方法 本研究为前瞻性观察性研究,入组绝经后激素受体阳性早期乳腺癌患者,接受股骨颈、全髋和腰椎L1-L4等部位的双能X线骨密度检测。AI辅助内分泌治疗前进行基线骨密度检查,治疗期间每年检查骨密度1次。分析AI治疗过程中骨密度变化以及骨质疏松发生率。结果 2013年11月至2016年8月共纳入131例患者,中位年龄60岁,中位绝经年龄50岁,AI治疗时间60～100个月。中位随访86个月,AI治疗5年期间患者腰椎、股骨颈、全髋骨密度逐年下降,5年骨密度总下降率分别为6.90%、5.68%、7.14%,其中第1年骨密度下降最快,第2～5年骨密度平稳下降。腰椎骨密度第1年变化率显著高于第2～5年骨密度变化率（P＜0.01）。进一步分层分析显示,基线骨密度、年龄以及体质量指数值未影响患者骨密度下降率。5年间共17例（17%）患者新发骨质疏松,其中15例为基线骨量低下患者,76%出现在腰椎（13/17）,骨折发生率2%（2/100）。结论 绝经后早期乳腺癌患者5年AI辅助内分泌治疗期间骨密度呈持续下降趋势。应加强AI治疗期间的骨健康管理,早期干预减少骨质疏松的发生。     

乳腺癌患者化疗前后血脂血糖及体质量指数的变化

目的:探讨乳腺癌患者化疗前后血脂、血糖及体质量指数(BMI)水平的变化。方法:选取收治的141例乳腺癌患者,记录化疗前后的血脂水平,包括甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),同时收集化疗前后的血糖及BMI,分析以上指标化疗前后的变化。结果:全组患者(不论绝经状态)化疗后TG、TC、LDL-C、血糖水平均明显升高,而HDL-C、BMI水平明显降低(均P0.05)。在绝经前患者中,化疗后TG、TC、LDL-C水平升高,HDL-C水平降低(均P0.05),血糖水平和BMI变化不明显(均P0.05);在绝经后患者中,化疗后TG、血糖水平明显升高(均P0.05),但TC、HDL-C、LDL-C水平无明显变化(均P0.05)。结论:乳腺癌患者总体上表现为化疗后血脂、血糖水平升高,BMI下降,但绝经前与绝经后患者表现有所不同,应针对患者具体情况考虑进行适当的干预。     

乳腺癌治疗后高骨质疏松患病率及相关因素分析

目的探索乳腺癌治疗后患者的骨质疏松患病率及相关影响因素。方法回顾性分析147例治疗后并已绝经的乳腺癌患者的临床资料,采用双能X线骨密度吸收仪进行骨密度检测(包括腰椎正位L1~4、股骨颈以及全髋的骨密度测定),分析乳腺癌受体不同表达(ER、PR、HER-2)、年龄、体质量指数(bone mass index,BMI)、绝经时间、术后时间、治疗方法对骨质疏松的影响。结果147例乳腺癌患者治疗后的骨质疏松患病率为40.8%;单因素分析显示年龄、BMI、绝经时间、治疗(内分泌治疗+化疗)、术后时间与骨密度减低呈显著相关(P<0.05),多因素Logistic回归分析显示影响治疗后乳腺癌患者骨密度的主要因素是年龄、BMI、术后时间(P<0.05)。结论乳腺癌治疗后患者具有较高的骨质疏松患病率,乳腺癌治疗的多种因素都能够降低骨密度。     

阿仑膦酸钠预防乳腺癌患者来曲唑辅助治疗所致骨质丢失的临床研究

目的 观察阿仑膦酸钠能否阻止绝经后妇女早期乳腺癌患者以芳香化酶抑制剂作为辅助治疗药物所导致的骨密度下降.方法 绝经后妇女早期乳腺癌术后患者40例,随机对照分组,所有患者每日口服来曲唑2.5 mg,碳酸钙1500 mg+维生素D3 125 U,持续1年.实验组患者每周口服阿仑膦酸钠70 mg.实验开始前和实验1年后用双能X线骨密度仪测量腰椎骨密度.实验开始前检测血常规,肝、肾功能,电解质,血清特异性碱性磷酸酶,尿Ⅰ型胶原N末端肽/肌苷比值,实验期间每3个月检测1次,同时记录患者的不适症状并监测乳腺癌进展.结果 实验组1年后腰椎骨密度较对照组增加4.3%,血清特异性碱性磷酸酶、尿Ⅰ型胶原N末端肽/肌苷比值分别较对照组下降39% 和55%,两组间比较差异具有显著性,无严重不良反应.结论 阿仑膦酸钠用于防止绝经后妇女早期乳腺癌患者以芳香化酶抑制剂作为辅助治疗药物所导致的骨密度下降,近期结果安全有效.     

乳腺癌术后辅助治疗进展

近年来 ,乳腺癌的研究进展很快 ,特别是内科治疗的飞速发展 ,使乳腺癌的疗效得到了显著提高。1　辅助化疗术后辅助治疗包括化疗与内分泌治疗。目前认为 ,对淋巴结阳性的患者 ,应给予术后辅助化疗。回顾性研究表明 ,无论对绝经前或绝经后患者 ,化疗均能够降低死亡率。EBCTCG(earlybreastcancertrialist’collaborativegroup)的最新研究也表明 ,化疗不但能延长绝经前患者的生存期 ,而且对绝经后的乳腺癌亦有效。对腋窝淋巴结阴性的患者 ,是否行辅助治疗应根据预后指标判断。一般认为 ,对肿块直径大于 1.0cm、雌激素受体 (ER)阴性、组织学…     

乳腺癌患者术后一年骨质疏松的相关因素分析

目的探讨乳腺癌患者术后1年合并骨质疏松症的相关因素。方法选取41例乳腺癌术后1年合并骨质疏松症患者为骨质疏松组(OP组),年龄53~75岁;56例骨密度正常的乳腺癌患者为非骨质疏松组(NOP组),年龄46~64岁。采用美国GE公司产的双能X线骨密度仪测定入组患者左侧股骨颈、腰椎1-4(L1-4)骨密度,并分析其与年龄、体重指数(BMI)、生产、绝经、绝经年限、雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER-2)等的相关性。结果 OP组年龄、体重指数(BMI)、绝经及绝经年限与NOP组比较,差异有统计学意义(P0.05),而两组雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER-2)阳性及是否生产之间比较无明显差异(P0.05)。相关性分析显示腰椎BMD与BMI呈正相关,而与年龄、绝经年限呈负相关。结论乳腺癌妇女骨质疏松症患病率较高,年龄、绝经年限、BMI为影响骨质疏松的关键因素。     

绝经前乳腺癌患者新辅助化疗相关闭经的影响因素及临床意义探讨

目的分析绝经前乳腺癌患者接受新辅助化疗后闭经的相关影响因素,了解新辅助化疗相关的闭经（NCRA）与新辅助化疗后肿瘤降期的关系。方法回顾性随访观察我院2006年3月至2011年3月期间224例绝经前乳腺癌患者接受新辅助化疗后月经状态的改变及新辅助化疗后彩超下乳房肿瘤的变化情况,分析新辅助化疗时患者年龄、化疗方案、肿瘤病理组织学特征（ER/PR和Her-2）、术后服用他莫昔芬（tamoxifen,TAM）与NCRA及其随后月经恢复的关系,以及新辅助化疗后肿瘤的变化与NCRA的关系。结果 224例患者中有166例（74.11%）患者出现NCRA,其中有15例停经但雌激素水平增高而行卵巢切除或接受戈舍瑞林治疗,余151例NCRA患者中有40例（26.49%）出现月经恢复。单因素及多因素分析结果显示,NCRA的发生及随后的月经恢复均与患者的年龄有关（P〈0.001,P=0.001）;不同化疗方案对NCRA的发生无明显影响（P〉0.05）,但是对NCRA后月经恢复有重要影响（P〈0.001）;肿瘤的ER/PR和Her-2表达和是否服用TAM对NCRA发生及其随后的月经恢复均无明显影响（P〉0.05）。发生NCRA时的化疗周期数随患者年龄的增长而减少,与NCRA后月经的恢复无关（P〉0.05）。NCRA的发生与新辅助化疗后肿瘤的降期无关（P〉0.05）。结论大多数绝经前乳腺癌患者接受新辅助化疗后会出现闭经,年龄越大的患者越容易发生NCRA,而且发生NCRA时接受化疗的周期数更少;年龄和化疗方案都会影响NCRA后月经的恢复;NCRA的发生未影响新辅助化疗的近期疗效。     

绝经后女性类风湿关节炎患者骨质疏松影响因素的回顾性研究

目的 通过分析绝经后女性类风湿性关节炎(RA)患者骨密度与临床资料的相关性,探讨影响骨密度的相关因素。方法 收集64例绝经后女性RA患者一般临床资料、腰椎及股骨的平均骨密度（BMD)、骨代谢指标、实验室检查指标,根据骨密度分为骨质疏松组和非骨质疏松组,比较临床资料并分析可能影响骨密度的因素。结果 64例患者平均年龄(58. 47 ±5.81) 岁,平均病程5.5(2.0,12.0)年。骨质疏松比例为62.5% (40/64)。骨质疏松组的绝经时间、ESR、纤维蛋白原、DAS28高于非骨质疏松组,绝经年龄、体重、BMI、ALB、DMARDs及抗骨吸收药物使用率低于非骨质疏松组,病程2年以上的患者骨质疏松发病率较高,其炎症指标亦高于同病程非骨质疏松组。简单相关分析提示BMD与绝经年龄、体重、BMI、ALB正相关,与 DAS28负相关。Logistic回归分析提示绝经年龄（OR = 4. 750,95%CI：1. 30247. 327,P = 0. 018)是影响绝经后女性RA患者 BMD的独立因素。多重线性回归方程提示BMD与BMI正相关,与DAS28负相关。结论 绝经后RA患者BMD受绝经年龄、BMI、DAS28的影响。绝经年龄是影响绝经后女性RA患者BMD的独立因素。     

绝经前雌激素受体阳性乳腺癌患者三苯氧胺辅助治疗的临床价值

三苯氧胺 (ｔａｍｏｘｉｆｅｎ ,ＴＡＭ)是最常用的一线乳腺癌内分泌治疗药物。临床大量应用于绝经后雌激素受体阳性乳腺癌患者。文献报道绝经前雌激素受体 (ｅｓｔｒｏｇｅｎｒｅｃｅｐｔｏｒ ,ＥＲ)阳性乳腺癌患者单用ＴＡＭ辅助治疗可进一步提高患者的无瘤生存率 (ｄｉｓｅａｓｅ ｆｒｅｅｓｕｒｖｉｖａｌ,ＤＦＳ)或总生存率 (ｏｖｅｒａｌｌｓｕｒ ｖｉｖａｌ,ＯＳ) ,但在绝经前ＥＲ阳性乳腺癌患者ＴＡＭ能否进一步提高ＣＭＦ辅助化疗的疗效一直存在争议[1] ,我们回顾性分析了从 1990年 1月至 1999年 12月我院 40 2例绝经前ＥＲ阳性乳…     

益气养血颗粒对绝经前乳腺癌患者内分泌功能的调节作用

目的：探讨绝经前乳腺癌患者内分泌功能变化及中药益气养血颗粒对其调节作用。方法：采用放射免疫分析法对１２５ 例乳腺疾病患者的性激素孕酮（Ｐ） 、雌三醇（Ｅ３） 、睾酮（Ｔ） 和促性腺激素促卵泡生成素（ＦＳＨ） 、促黄体生成素（ＬＨ） 及催乳素（ＰＲＬ） 进行检测研究。同时给予化疗和中药治疗。结果：绝经前乳腺癌患者体内Ｅ３ 和Ｐ水平明显降低,Ｔ和ＰＲＬ明显升高,化疗后患者在一定程度上出现了类似绝经后的改变。结论：绝经前乳腺癌患者内分泌功能明显异常,化疗对绝经前患者的治疗作用可能一部分是通过影响机体内分泌机制实现的。益气养血颗粒对患者激素水平具有调节作用,与化疗对内分泌机制的影响具有协同作用。     

Longitudinal patterns of weight gain after breast cancer diagnosis: observations beyond the first year

Many, but not all patients experience weight gain 1 year after a breast cancer diagnosis; clearly defined, clinically relevant groups at risk of weight gain have yet to be described. We set out to determine the factors associated with weight gain over time in patients with invasive breast cancer during a period of predominantly anthracycline-based adjuvant chemotherapy and to identify groups with differing weight gain risks. Breast cancer patients (stage I-IIIB) were identified in a retrospective chart review. Evaluated parameters included weight at diagnosis and 1, 2, and 3 years later, height, body mass index (BMI), age, menopausal and change in menopausal status, as well as therapy and pathologic stage. Regression models identified significant independent predictors of weight change. Recursive partitioning analysis (RPA) was employed to divide the dataset into relevant and significant groups. In 185 identified patients, regression models and RPA demonstrated that weight gain at 1 year was associated with younger age, adjuvant chemotherapy, and lower BMI. Weight gain at 2 years (n = 176) was greater than at year 1, and in addition to weight gain at year 1, was associated with younger age and adjuvant chemotherapy in regression analysis; RPA found that anthracycline therapy, age, and BMI were important. Weights at 3 years were similar to those seen at 2 years. Early-stage breast cancer patients treated with chemotherapy continue to gain weight 2 years after diagnosis, and this weight gain appears to be persistent at year 3. Observation beyond 1 year is needed to adequately evaluate weight gain in early-stage breast cancer patients, particularly for those receiving contemporary adjuvant chemotherapy.     

Improving bone health in patients with early breast cancer by adding bisphosphonates to letrozole: the Z-ZO-E-ZO-FAST program

Women undergoing treatment for breast cancer often have a number of pre-existing risk factors for bone loss, including existing or induced postmenopausal status. Long-term anticancer treatments may further augment this risk, inducing further bone-loss, increasing the incidence of bone fractures, associated morbidity and mortality, and healthcare costs. Long-term treatment with third-generation antiaromatase agents (AAAs) is used more and more instead of or after the selective estrogen-receptor modulator tamoxifen for the adjuvant treatment of postmenopausal women with breast cancer. These AAAs include anastrozole, letrozole, and exemestane, and all are superior to tamoxifen in both efficacy and safety. In particular, they reduce the incidence of serious adverse events such as thromboembolism and endometrial cancer that are associated with tamoxifen treatment. On the other hand, the AAAs lead to profound estrogen depletion and appear to have a pronounced effect on bone mineral density (BMD), and a significantly higher incidence of osteoporosis/osteopenia and bone fracture has been reported in some trials. Bisphosphonate therapies, including zoledronic acid (ZA), have emerged as a promising means of reducing bone loss associated with antiaromatase therapy. Several large, randomized, multicenter trials are underway to determine whether upfront or delayed ZA therapy can decrease BMD losses in patients undergoing treatment with the antiaromatase agent letrozole (Z-FAST; ZO-FAST, and E-ZO-FAST), and early results from the Zometa-Femara adjuvant synergy trial (Z-FAST) trial indicate a significant benefit of upfront ZA therapy compared with delayed ZA therapy. Forthcoming results from all these trials should determine whether ZA could be used to improve bone heath in women undergoing adjuvant therapy with AAAs for breast cancer.     

Effects of zoledronic acid on bone mineral density in premenopausal women receiving neoadjuvant or adjuvant therapies for HR+ breast cancer: the ProBONE II study

Summary

The effects of bisphosphonates on altered bone turnover marker (BTM) levels associated with adjuvant endocrine or chemotherapy in early breast cancer have not been systematically investigated. In ProBONE II, zoledronic acid decreased these elevated BTM levels and increased bone mineral density (BMD) during adjuvant therapy, consistent with its antiresorptive effects.

Introduction

Adjuvant chemotherapy or endocrine therapy for early hormone receptor-positive breast cancer (HR⁺ BC) is associated with rapid BMD loss and altered BTM levels. Adjuvant bisphosphonate studies demonstrated BMD increases, but did not investigate BTM effects. The randomized, double-blind, ProBONE II study investigated the effect of adjuvant zoledronic acid (ZOL) on BMD and BTM in premenopausal women with early HR⁺ BC.

Methods

Seventy premenopausal women with early HR⁺ BC received adjuvant chemotherapy and/or endocrine therapy plus ZOL (4 mg IV every 3 months) or placebo for 24 months. Primary endpoint was change in lumbar spine BMD at 24 months versus baseline. Secondary endpoints included femoral neck and total femoral BMD changes, changes in BTM, and safety.

Results

Lumbar spine BMD increased 3.14 % from baseline to 24 months in ZOL-treated participants versus a 6.43 % decrease in placebo-treated participants (P?<?0.0001). Mean changes in T- and Z-scores, and femoral neck and total femoral BMD, showed similar results. Bone resorption marker levels decreased ～55 % in ZOL-treated participants versus increases up to 65 % in placebo-treated participants (P?<?0.0001 for between-group differences). Bone formation marker (procollagen I N-terminal propeptide) levels decreased ～57 % in ZOL-treated participants versus increases up to 45 % in placebo-treated participants (P?<?0.0001 for between-group differences). Adverse events were consistent with the established ZOL safety profile and included one case of osteonecrosis of the jaw after a tooth extraction.

Conclusions

Adding ZOL to adjuvant therapy improved BMD, reduced BTM levels, and was well tolerated in premenopausal women with early HR⁺ BC receiving adjuvant chemotherapy and/or endocrine therapy.     

乳腺癌患者CK19mRNA表达的意义及辅助化疗对骨髓微转移的影响

目的探讨乳腺癌患者外周血、淋巴结和骨髓的微转移情况,以及辅助化疗对骨髓微转移的影响。方法采用RT-PCR技术同时检测可手术的69例乳腺癌患者的外周血、淋巴结和骨髓中CK19 mRNA的表达,并观察辅助化疗对骨髓微转移的影响。结果骨髓微转移24例(34.8%),外周血CK19mRNA阳性11例(15.9%)。淋巴结微转移阳性40例(58.0%),其中淋巴结病理学检查阳性的35例中,32例(91.4%)淋巴结微转移阳性,在淋巴结病理学检查阴性的34例中,8例(23.5%)淋巴结微转移阳性。淋巴结微转移阳性的40例中,18例(45.0%)骨髓微转移阳性。24例骨髓微转移阳性的患者在接受6个周期的CAF方案辅助化疗后,有7例骨髓微转移转阴(29.2%)。结论CK19 mRNA的表达可作为评价乳腺癌微转移的指标。外周血微转移的检测,其敏感性和特异性较骨髓差;骨髓微转移的检测可作为评价辅助化疗敏感性的指标之一。     

Bone marrow micrometastases and adjuvant treatment of breast cancer

The immunohistochemical detection of epithelially derived cells in the bone marrow of patients with primary breast cancer has been shown to be associated with increased risk of distant relapse as well as higher rates of cancer-related death. Despite the correlation between bone marrow micrometastases and poor outcome in breast cancer patients, bone marrow status does not yet have an established role in patient management. In this prospective study, adjuvant therapy recommendations for 43 patients with stage I, II, or III breast cancer treated with lumpectomy or mastectomy, sentinel lymph node biopsy and/or axillary dissection, and intraoperative bone marrow aspiration were recorded. Recommendations were made by a multidisciplinary tumor board both blinded and unblinded to the results of the bone marrow aspiration. In our study, 10 of the 43 breast cancer patients were found to have bone marrow micrometastases. Four of these patients (40%) had axillary lymph node metastases. When blinded to the results of the bone marrow aspiration, the tumor board recommended adjuvant chemotherapy for these four node-positive patients, as well as two node-negative patients. When unblinded to the results of the bone marrow aspiration, the tumor board did not change its recommendations for any of these six patients. The remaining four node-negative, bone marrow-positive patients were not advised to have adjuvant chemotherapy by the tumor board when blinded to bone marrow status. However, once the tumor board was informed of the presence of bone marrow micrometastases, adjuvant chemotherapy was recommended for all of these patients. The results of this pilot study indicate that the presence of bone marrow micrometastases in breast cancer patients with stage I, II, or III disease does influence recommendations for adjuvant chemotherapy, particularly in patients with node-negative disease.     

Dietary patterns in Canadian men and women ages 25 and older: relationship to demographics,body mass index,and bone mineral density

Background  

Previous research has shown that underlying dietary patterns are related to the risk of many different adverse health outcomes, but the relationship of these underlying patterns to skeletal fragility is not well understood. The objective of the study was to determine whether dietary patterns in men (ages 25-49, 50+) and women (pre-menopause, post-menopause) are related to femoral neck bone mineral density (BMD) independently of other lifestyle variables, and whether this relationship is mediated by body mass index.     

Incidence and prognostic factors of Japanese breast cancer patients with bone metastasis

Background Few previous studies have analyzed the incidence of bone metastases in a defined population of Japanese breast cancer patients and their prognosis after chemotherapy. Methods This is a retrospective cohort study. We investigated 695 patients who underwent surgery for breast cancer. The strategy of adjuvant therapy was as follows. Patients with both estrogen receptors (ERs) and progesterone receptors (PgRs) had endocrine therapy as initial adjuvant therapy (n = 239). Patients with neither ERs nor PgRs had chemotherapy. When metastasis to other organs, including bone, was identified, patients received chemotherapy. The survival rates after surgery and after the onset of bone metastasis, as well as the incidence of bone metastasis, were calculated. We also evaluated the prognostic and predictive factors. Results Bone metastases developed in 148 of 695 patients. All 148 received chemotherapy, and 121 of them developed spinal metastases. The 5-year survival rate after bone metastases was 26.1%. Prognostic factors for bone metastases were visceral metastases and PgR status. Cord compression was observed in 17 of the 148 patients, with the thoracic spine being the most common. The 1-year survival rate for patients with bone metastases who received chemotherapy was 66.3%, whereas that of patients with paralysis after spinal metastases was 17.6%. Within 6 months of the development of spinal cord compression, 70.6% of the patients died. Conclusions We reported the incidence and prognostic factors for a defined population of Japanese breast cancer patients with bone and spinal metastases. Our results suggest that the expected survival time for patients with paralysis who received adequate endocrine therapy or chemotherapy is generally poor. However, to detect a predictive factor of long survival after paralysis and establish the indications for surgery, a comparative study among large groups of patients with paralysis and with different backgrounds is necessary.