Fracture risk in women with breast cancer: a population-based study

A positive association has been reported between greater bone density and higher breast cancer risk, suggesting that these women could be at reduced risk of fracture. To estimate fracture risk among unselected community women with breast cancer and to systematically assess associations with various risk factors including breast cancer treatments, we conducted a population‐based historical cohort study of 608 Olmsted County, MN, USA, women with invasive breast cancer first diagnosed in 1990 to 1999 (mean age 61.6 ± 14.8 years), who were followed for 5776 person‐years. Altogether, 568 fractures were observed in 270 women (98 per 1000 person‐years). Overall fracture risk was elevated 1.8‐fold, but the absolute increase in risk was only 9%, and 56% of the women did not experience a fracture during follow‐up. Excluding pathologic fractures (15%) and those found incidentally (24%), to allow for ascertainment bias, the standardized incidence ratio was 1.2 (95% confidence interval [CI] 0.99 to 1.3) for total fracture risk and 0.9 (95% CI 0.7 to 1.2) for osteoporotic fracture risk alone. Various breast cancer treatments were associated with an increased risk of fracture, but those associations were strongest for pathologic fractures, which were relatively more common among the women who were premenopausal when their breast cancer was diagnosed. Moreover, underlying clinical characteristics prompting different treatments may have been partially responsible for the associated fracture outcomes (indication bias). These data thus demonstrate that breast cancer patients in general are not at greatly increased risk of fracture but neither are they protected from fractures despite any determinants that breast cancer and high bone density may have in common. © 2012 American Society for Bone and Mineral Research.     

无淋巴结转移的乳癌的预后分析

目的　探讨辅助化疗在无淋巴结转移乳癌病人的治疗效果。方法　随访１１２ 例无淋巴结转移乳癌病人,观察其５ ,１０ 年生存率和复发转移情况。结果　辅助化疗组１０ 年转移率低于单纯手术组（ Ｐ ＜ ０ ．０５） ,１０ 年生存率高于单纯手术组（ Ｐ ＜ ０ ．０５） 。结论　对无淋巴结转移乳癌病人应常规行辅助化疗;而手术范围与生存率无关。     

乳癌的综合治疗

目的　评价乳癌综合治疗的效果。方法　回顾性分析我院１９８６ 年１０ 月～１９９３ 年１０ 月接受治疗的２４０ 例乳癌病人的临床资料。结果　综合治疗组５ 年生存率为８０ ％ ，单纯手术组５ 年生存率为５０．８ ％ （ Ｐ＜ ０ ．０１ ） 。结论　以手术治疗为主辅以化疗、放疗、免疫和内分泌治疗的综合治疗能显著改善乳癌病人的预后。     

Changes in bone biomarker concentrations and musculoskeletal symptoms among breast cancer patients initiating aromatase inhibitor therapy and women without a history of cancer

The objectives of this study were to examine: (1) changes in bone formation (osteocalcin) and bone resorption (cross-linked N-telopeptides of bone type I collagen [NTXs]) markers, as well as calcium, phosphorus, and intact parathyroid hormone, over the first 6 months of aromatase inhibitor (AI) therapy among a cohort of breast cancer patients compared with a group of unexposed women without a history of cancer; and (2) whether bone marker changes were associated with musculoskeletal pain. Eligible breast cancer patients (n = 49) and postmenopausal women without a history of cancer (n = 117) were recruited and followed for 6 months. At baseline, 3 months, and 6 months, a questionnaire was administered to assess pain and medication use, and a blood sample was drawn. Results showed that, among the breast cancer patients, calcium concentrations decreased significantly (−7.8% change; p = 0.013) and concentrations of NTXs increased significantly from baseline to 6 months (9.6% change; p = 0.012). Changes were not observed for women in the comparison group. Statistically significant differences in percent change between the breast cancer patients and the women in the comparison group were observed for calcium at 6 months (−7.8% versus 0.0%; p = 0.025), phosphorus at 6 months (−5.1% versus 16.7%; p = 0.003), NTXs at 6 months (9.6% versus −0.7%; p = 0.017), and osteocalcin at 6 months (11.5% versus −3.6%; p = 0.016). No statistically significant associations were observed between bone turnover marker changes and musculoskeletal pain among the breast cancer patients, although baseline NTXs were higher among women with onset or increase in pain compared with those reporting no pain (p = 0.08). Findings from this study suggest that AIs cause changes in bone turnover during the first 6 months of treatment; however, these changes are not associated with musculoskeletal pain. Breast cancer patients initiating AI therapy should be assessed and monitored for fracture risk using known clinical risk factors, including bone density, and managed appropriately. © 2012 American Society for Bone and Mineral Research.     

Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women

Arzoxifene is a selective estrogen receptor modulator (SERM) that has been shown to be more potent in preclinical testing than currently available agents. Its effects on clinical outcomes are not known. In a randomized, blinded trial, women aged 60 to 85 years with osteoporosis, defined as a femoral neck or lumbar spine bone mineral density T‐score of ?2.5 or less or a vertebral fracture, and women with low bone mass, defined as a bone density T‐score of ?1.0 or less and above ?2.5, were assigned to arzoxifene 20 mg or placebo daily. The primary endpoints were new vertebral fracture in those with osteoporosis and invasive breast cancer in the overall population. After 3 years, the cumulative incidence of vertebral fractures in patients with osteoporosis was 2.3% lower in the arzoxifene group than in the placebo group, a 41% relative risk reduction [95% confidence interval (CI) 0.45–0.77, p < .001]. In the overall population, the cumulative incidence of invasive breast cancer over 4 years was reduced by 1.3%, with a 56% relative reduction in risk (hazard ratio = 0.44, 95% CI 0.26–0.76, p < .001); there was no significant decrease in nonvertebral fracture risk. Arzoxifene increased the cumulative incidence of venous thromboembolic events by 0.7%, with a 2.3‐fold relative increase (95% CI 1.5–3.7). Like other SERMs, arzoxifene decreased vertebral fractures and invasive breast cancer while the risk of venous thromboembolic events increased. © 2011 American Society for Bone and Mineral Research.     

乳腺癌c-erbB2过表达与生存率、内分泌治疗效果和预后的关系

目的　研究乳腺癌c erbB 2改变与生存率、内分泌治疗效果及预后的关系 ,探讨有效反映乳腺癌c erbB2变化的简单检测方法。方法　半定量PCR检测c erbB2基因扩增 ;免疫组化检测c erbB2蛋白表达。随访 5 8例患者。结果　c erbB 2蛋白过表达 (+ + )与基因扩增有显著的一致性 (P<0 .0 1) ,一致率 93 .7%。c erbB2蛋白过表达 (+ + )患者的 5年生存率 (4 4.4% )显著低于c erbB 2阳性表达 (+ ) (66.7% )和c erbB 2阴性表达患者 (78.6% ) (P <0 .0 5 )。c erbB 2蛋白过表达患者服用三苯氧胺不能显著提高 5年生存率。结论　c erbB2蛋白过表达患者 5年生存率低、预后差 ,且对内分泌治疗不敏感。免疫组化可以简单、有效地检测乳腺癌c erbB2的改变。     

乳腺癌保乳综合治疗的疗效分析

目的　评价I ,IIa期乳腺癌保乳综合治疗的疗效。方法　将 14 1例I ,IIa期乳腺癌 (肿块距乳头≥ 3cm )前瞻性非随机分为两组 :(1)保乳治疗组 68例 ,行保留乳房的肿瘤局部广泛切除加腋窝淋巴结清扫术 ;(2 )对照组 46例 ,行乳癌改良根治术。术后均给予化疗、放疗和 /或内分泌治疗。结果　中位随访 46个月 ,两组病例均无局部复发。保乳治疗组 3a生存率为 98.0 % ,5年生存率为93 .3 % ,远隔脏器转移率为 7.4% ;改良根治组 3年生存率为 97.1% ,5年生存率为 91.3 % ,远隔脏器转移率为 8.7 ,两组各指标比较无明显差异 (P >0 .0 5 )。结论　对癌肿距乳头≥ 3cm的I ,IIa期乳腺癌采用保乳综合疗法 ,可以达到与根治术相似的治疗效果 ,可能逐渐成为治疗I ,IIa期乳腺癌患者的首选术式     

Anthropometric measurements in male breast cancer

Background: 1% of breast cancers occur in men.The etiology is obscure. An elevated BMI has been postulated to be a cause. Methods: All male breast cancer patients operated from January 1990 to May 2001 were retrospectively reviewed. Relation between BMI and male breast cancer was examined. Results: 43 males underwent breast surgery for breast cancer during this period. 3 patients were excluded from the study because of other risk factors for breast cancer.The average BMI of 40 patients was 26.54 kg/m², which is mildly above the level for normal weight. Conclusions: Excessive adipose tissue may increase risk of male breast cancer.     

Delineating breast cancer cell interactions with engineered bone microenvironments

The mechanisms leading to colonization of metastatic breast cancer cells (BCa) in the skeleton are still not fully understood. Here, we demonstrate that mineralized extracellular matrices secreted by primary human osteoblasts (hOBM) modulate cellular processes associated with BCa colonization of bone. A panel of four BCa cell lines of different bone‐metastatic potential (T47D, SUM1315, MDA‐MB‐231, and the bone‐seeking subline MDA‐MB‐231BO) was cultured on hOBM. After 3 days, the metastatic BCa cells had undergone morphological changes on hOBM and were aligned along the hOBM's collagen type I fibrils that were decorated with bone‐specific proteins. In contrast, nonmetastatic BCa cells showed a random orientation on hOBM. Atomic force microscopy‐based single‐cell force spectroscopy revealed that the metastatic cell lines adhered more strongly to hOBM compared with nonmetastatic cells. Function‐blocking experiments indicated that β₁‐integrins mediated cell adhesion to hOBM. In addition, metastatic BCa cells migrated directionally and invaded hOBM, which was accompanied by enhanced MMP‐2 and ‐9 secretion. Furthermore, we observed gene expression changes associated with osteomimickry in BCa cultured on hOBM. As such, osteopontin mRNA levels were significantly increased in SUM1315 and MDA‐MB‐231BO cells in a β₁‐integrin–dependent manner after growing for 3 days on hOBM compared with tissue culture plastic. In conclusion, our results show that extracellular matrices derived from human osteoblasts represent a powerful experimental platform to dissect mechanisms underlying critical steps in the development of bone metastases.     

In vivo tibial compression decreases osteolysis and tumor formation in a human metastatic breast cancer model

Bone metastasis, the leading cause of breast cancer‐related deaths, is characterized by bone degradation due to increased osteoclastic activity. In contrast, mechanical stimulation in healthy individuals upregulates osteoblastic activity, leading to new bone formation. However, the effect of mechanical loading on the development and progression of metastatic breast cancer in bone remains unclear. Here, we developed a new in vivo model to investigate the role of skeletal mechanical stimuli on the development and osteolytic capability of secondary breast tumors. Specifically, we applied compressive loading to the tibia following intratibial injection of metastatic breast cancer cells (MDA‐MB231) into the proximal compartment of female immunocompromised (SCID) mice. In the absence of loading, tibiae developed histologically‐detectable tumors with associated osteolysis and excessive degradation of the proximal bone tissue. In contrast, mechanical loading dramatically reduced osteolysis and tumor formation and increased tibial cancellous mass due to trabecular thickening. These loading effects were similar to the baseline response we observed in non‐injected SCID mice. In vitro mechanical loading of MDA‐MB231 in a pathologically relevant 3D culture model suggested that the observed effects were not due to loading‐induced tumor cell death, but rather mediated via decreased expression of genes interfering with bone homeostasis. Collectively, our results suggest that mechanical loading inhibits the growth and osteolytic capability of secondary breast tumors after their homing to the bone, which may inform future treatment of breast cancer patients with advanced disease. © 2013 American Society for Bone and Mineral Research     

Population prevalence of antiretroviral therapy sharing and its association with HIV viremia in rural Uganda: a cross-sectional population-based study

Introduction

Antiretroviral treatment (ART) sharing has been reported among fishermen and sex workers in Uganda and South Africa. However, no population-based studies have documented ART diversion prevalence (including sharing [giving/receiving], buying and selling) or its relationship with viremia among men and women living with HIV in Africa.

Methods

In 2018–2020, we surveyed people living with HIV aged 15–49 years in 41 communities in the Rakai Community Cohort Study, a population-based cohort in south-central Uganda. We assessed the prevalence and correlates of self-reported lifetime and past-year ART diversion, stratifying by age and gender and documenting sources of diverted drugs. We used log-binomial regression to quantify the relationship between diversion patterns and viremia (viral load >40 copies/ml), reported as unadjusted and adjusted prevalence ratios (aPR) with 95% confidence intervals (CI).

Results

Of 2852 people living with HIV and self-reporting current ART use, 266 (9.3%) reported lifetime ART diversion. Giving/receiving drugs were most common; few participants reported buying, and none reported selling. Men (12.9%) were more likely to report lifetime diversion than women (7.4%), with men aged 25–34 reporting high levels of sharing (18.9%). Friends were the most common sources of shared drugs, followed by spouses/sexual partners. Patterns of lifetime and past-year diversion were similar. Among participants with viral load results, 8.6% were viraemic. In adjusted analyses, people who reported only giving ART were nearly twice as likely to be viraemic than those who reported no diversion (aPR: 1.94, 95% CI: 1.10−3.44), and those reporting only receiving ART were less likely to exhibit viremia (aPR: 0.46, 95% CI: 0.12−1.79), although the latter was not statistically significant. Reporting both giving and receiving ART was not associated with viremia (aPR: 0.79, 95% CI: 0.43−1.46). Reporting buying ART, though rare, was also correlated with higher rates of viremia, but this relationship was not statistically significant (aPR: 1.98, 95% CI: 0.72−5.45).

Conclusions

ART sharing is common among persons reporting ART use in rural Uganda, particularly among men. Sharing ART was associated with viremia, and receiving ART may facilitate viral suppression. HIV programmes may benefit from considering ART sharing in counselling messages.     

Health‐related needs reported by adolescents living with HIV and receiving antiretroviral therapy in sub‐Saharan Africa: a systematic literature review

IntroductionAdolescents living with HIV (ALHIV) on antiretroviral therapy (ART) have specific health needs that can be challenging to deliver. Sub‐Saharan Africa (SSA) is home to 84% of the global population of ALHIV, of whom about 59% receive ART. Several studies in SSA have demonstrated health service gaps due to lack of synchronized healthcare for ALHIV receiving ART. We conducted a systematic review of health‐related needs among ALHIV on ART in SSA to inform decisions and policies on care.MethodsWe searched MEDLINE, Web of Science, EMBASE, PsycINFO, Cochrane library and grey literature for studies reporting health‐related needs among ALHIV receiving ART in SSA, between January 2003 and May 2020.Results and discussionOf the 2333 potentially eligible articles identified, 32 were eligible. Eligible studies were published between 2008 and 2019, in 11 countries: Zambia (7), Uganda (6), Tanzania (4), South Africa (4), Kenya (3), Ghana (2), Zimbabwe (2), Rwanda (1), Malawi (1), Botswana (1) and Democratic Republic of Congo (1). Seven categories of health needs among ALHIV were identified. In descending order of occurrence, these were: psychosocial needs (stigma reduction, disclosure and privacy support, and difficulty accepting diagnosis); dependency of care (need for family and provider support, and desire for autonomy); self‐management needs (desire for better coping strategies, medication adherence support and reduced ART side effects); non‐responsive health services (non‐adolescent friendly facility services and non‐compatible school system); need for food, financial and material support; inadequate information about HIV (desire for more knowledge to fight misinformation and misconception); and developmental and growth needs (desire to experience sex, parenthood and love). Ecological analysis identified different priority needs between ALHIV, their caregivers and healthcare providers, including psychosocial needs, financial challenges and non‐responsive health services, respectively.ConclusionsTo respond effectively to the health needs of ALHIV and improve ART adherence, interventions should focus on stigma reduction, disclosure challenges and innovative coping mechanisms for ART. Interventions that address the health needs of ALHIV from the perspective of carers and providers, such as financial support schemes and adolescent‐friendly healthcare strategies, should supplement efforts to improve adolescent ART adherence outcomes.     

Growth Factors, Apoptosis, and Survival of Mammary Epithelial Cells

Programmed cell death (apoptosis) occursregularly during normal growth and development of themammary gland. One of the most dramatic examples ofapoptosis is evident during the remodeling of the breast that accompanies postlactational involution.Transgenic mouse models have demonstrated thatoverexpression of polypeptides such as transforminggrowth factor alpha (TGF)³ and insulinlike growth factor I (IGF-I) can block this remodeling, suggestingthat these growth factors may be acting as survivalfactors for the mammary epithelium. In contrast,transgenic mice that overexpress the growth inhibitor transforming growth factor beta (TGF-)show increased apoptosis in the mammary epitheliumthroughout mammary development, suggestive of amechanism working to counterbalance the survivalfactors. Experiments with mammary epithelial cell lines cultured invitro have confirmed that these growth factors canindeed regulate apoptosis and survival in mammaryepithelial cells; EGF, IGF-I, and basic fibroblastgrowth factor (bFGF) act as survival factors formammary epithelial cells, while TGF- induces theirdeath. In breast cancer, cytotoxic drugs and hormoneablation increase the expression of TGF-, which may function to induce cell death by eitherparacrine or autocrine mechanisms. Lastly, although ithas very limited expression in the breast, TNFhas been shown to be effective in the rapid, direct induction of cell death in breast cancer celllines. Together, these studies describe a complexdynamic pattern of cell death-inducing and survivalfactors that promote the development of the maturemammary gland and that rapidly remodel the tissue afterlactation.     

Adjuvant therapy for older women with breast cancer

The major risk factor for breast cancer is increasing age and more than half of all breast cancers in affluent nations occur in women 65 years and older. Co-morbidity is a key consideration in offering systemic adjuvant treatment to older women since significant co-morbidity minimizes the potential value of any adjuvant therapy. Tamoxifen has clearly been shown to significantly decrease the risk of recurrence and improve survival in women of all ages who have estrogen (ER) or progesterone receptor (PR) positive invasive breast cancer, including those 70 years and older. Chemotherapy in older patients can improve survival but adds little to tamoxifen in women with node-negative, ER+ or PR+ tumors: it should be reserved for older women who have reasonable life-expectancy and larger node-negative tumors, or node-positive tumors. Ageism is still a barrier to clinical trials participation and clinical trials focusing on older women are needed.     

乳腺导管内乳头状瘤的外科治疗

目的　探讨治疗乳腺导管内乳头状瘤的有效方法。方法　采用亚甲蓝标记切除蓝染导管及腺体的方法治疗 13 2例乳腺导管内乳头状瘤 (4例伴有癌变 ) ,评价其疗效。结果　导管内乳头状瘤 91例 ,导管内乳头状瘤病 41例 ,其中 ,癌变 4例。 119例 (90 .1%)随访 3～ 46个月 ,术后原导管溢液治愈 ,无复发。结论　采用亚甲蓝标记切除蓝染导管及其腺体是治疗乳腺导管内乳头状瘤的可靠方法。     

青年乳腺癌微血管密度与其侵袭性关系

目的　探讨青年乳腺癌微血管密度与其侵袭性关系。方法　SABC免疫组化法检测 40例青年乳腺癌 (年龄≤ 3 5岁 )和 3 0例绝经期乳腺癌组织中微血管密度 (MVD )值 ,探讨其与腋窝淋巴结转移、临床病理特征之间的相互关系 ,比较两组之间的差异。结果　青年组腋窝淋巴结阳性率和MVD值 ( 70 %和 65 .2 8± 15 .0 6)均明显高于绝经组 ( 4 0 %和 5 1.91± 15 .0 6) ( P <0 .0 5和 P <0 .0 1)。MVD值与腋窝淋巴结转移和TNM临床分期有关 (P <0 .0 5和P <0 .0 1)。结论　青年乳腺癌侵袭性强与肿瘤血管生成有关。     

保乳手术加综合治疗治疗乳腺癌的临床研究

目的　探讨保乳手术加综合治疗乳腺癌的手术适应证、治疗方法和疗效。方法　对 46例I～IIb 期乳腺癌施行保乳手术加术后放疗、化疗及内分泌治疗等综合治疗 (保乳组 ) ;并与同期施行改良根治术加综合治疗的 5 0例I～IIb 期乳腺癌 (对照组 )进行对比。两组患者术后均随访 0 .5～ 14年 ,平均 4年。结果　保乳组 46例双侧乳房乳头基本对称、外形丰满 ,外观优良。保乳组、对照组的平均手术时间分别为 (14 3 .7± 2 1.6)min ,(181.9± 16.0 )min ;术中平均出血量分别为 (2 42± 73 )ml ,(3 76± 5 6)ml ,手术并发症率分别为 15 .2 %,3 4.0 %;保乳组均优于对照组 (均P <0 .0 5 )。保乳组 3 ,5 ,10年期生存率分别是 96.8%,88.9%,85 .7%,总局部复发率是 6.5 %;对照组 3 ,5 ,10年期生存率分别是 97.1%,89.5 %,87.5 %,总局部复发率是 4.0 %。两组生存率和复发率比较差异无显著性(均P >0 .0 5 )。结论　临床早期乳腺癌采用保乳手术加综合治疗可以取得满意的临床疗效 ,可作为早期乳腺癌的首选治疗方法。     

乳癌诊治的进展

目的 介绍近年来乳癌诊断和治疗的进展。方法 复习近期有关乳癌的国内外文献，并作有关乳癌诊治进展的评论。结果 NF－κB和端粒酶可能成为乳癌新抗癌靶点。核素扫描、纤维乳管镜、乳癌微转移检测、免疫细胞化学检测等均是近年对乳癌早期诊断方法的发展。乳癌治疗的进展有保留乳房手术、哨兵淋巴结勘测、新辅助化疗、生物化学修饰治疗、三苯氧胺（TAM）和1，25（OH）2D3治疗。结论 近年来，对早期乳癌的诊治概念和模式已有明显的改进。