乳腺癌CD44和nm23基因表达与侵袭转移的关系

目的：探讨粘附分子CD44和抑癌基因nm23与乳腺癌侵袭转移的关系。方法：采用逆转录聚合酶链反应（RT－PCR）方法对30例乳腺癌及10例乳腺良性肿瘤组织中CD44V6和nm23-H1基因的表达进行检测,结果：乳腺癌组织中CD44V6及nm23-H1的表达明显高于乳腺良性肿瘤;CD44V6和nm23-H1的阳性表达与乳腺癌的临床分期和是否有淋巴结转移密切相关,而与乳腺癌的病理类型无关。结论：CD44V6和nm23-H1异常表达是乳腺癌发生发展,浸润转移的重要分子学改变。同时检测两者可更好地预测其进展程度和对淋巴结转移的判断。     

血管内皮生长因子在乳腺癌中的表达及其与腋窝淋巴结转移的关系

目的：探讨血管内皮生长因子（ＶＥＧＦ）和微血管密度（ＭＶＤ）与乳腺浸润性导管癌腋窝淋巴结转移的关系。方法：采用ＬＳＡＢ法对６５例浸润性导管癌术后根治标本,进行ＶＥＧＦ的表达和微血管密度的测定。结果：６５例乳腺癌的 ＭＶＤ为（４７．６±２２．４）个,ＶＥＧＦ总阳性率为 ８０．００％;ＶＥＧＦ、ＭＶＤ与淋巴结转移有关,在腋窝淋巴结转移的乳腺癌组织中,ＶＥＧＦ的阳性率 ８８．８９％（３２／３６）,ＭＶＤ（５６．６±２０．５）,均明显高于无腋窝淋巴结转移者ＶＥＧＦ的阳性率 ６８．９６％（２０／２９）,ＭＶＤ（３１．３±１８．９）．差异有显著性（Ｐ＜０．０５）;ＶＥＧＦ和 ＭＶＤ在乳腺浸润性导管癌中的表达具有显著的正相关（ｒ＝８.２１３,Ｐ＜０．０５）。结论：ＶＥＧＦ与乳腺癌血管生成密切相关;ＶＥＧＦ表达的增高及 ＭＶＤ的增加对乳腺癌腋窝淋巴结转移可能有促进作用。     

血管影像在乳腺癌诊断中的重要作用(附100例乳腺癌及200例良性乳腺增生对照分析)

[目的 ]提高对乳腺病血管像的认识 ,进而提高对乳腺良恶性病的诊断率。 [方法 ]选取经手术病理证实为乳腺癌的病例 1 0 0例 ,从乳腺体检中发现或经追踪观察为乳腺轻度增生的病例 2 0 0例乳腺 X线影像进行对照分析。 [结果 ]乳腺恶性与良性病变在血管像上有一定区别 :1血管像增粗。血管像横径大于2 .0 mm为增粗 ,乳腺恶性病变有 76例 ( 76.0 % ) ,良性病变有 40例 ( 2 0 .0 % ) ;2血管像增多。血管像条数多于 3条为增多 ,乳腺恶性病变有 61例 ( 61 .0 % ) ,乳腺良性病变有 46例 ( 2 3.0 % ) ;3血管像增大。弯曲度小于 1 5 0°血管像迂曲明显 ,乳腺恶性病变有 83例 ( 83.0 % ) ,乳腺良性病变有 42例 ( 2 1 .0 % ) ;4血管像走行特点。呈花瓣状 ,恶性病变有 33例 ( 33.0 % ) ,良性病变有 2例 ( 1 .0 % ) ;呈残端状 ,恶性病变有 34例 ( 34.0 % ) ,良性病变有 3例 ( 1 .5 % ) ;呈放射状 ,恶性病变有 1 3例 ( 1 3.0 % ) ,良性病变有 1例( 0 .5 % )。 [结论 ]掌握乳腺病血管像的特征 ,可以帮助确定乳腺病病变性质 ,提高对隐性癌和微小癌的诊断率和治愈率 ,从而延长生存期     

不饱和脂肪酸逆转乳腺癌细胞株耐药性研究

目的　探讨不饱和脂肪酸二十二碳六烯酸 (DHA)是否能够逆转人乳腺癌细胞的多药耐药性(MDR)。方法　采用MTT法对DHA和阿霉素合用时肿瘤细胞的半数抑制率 (IC50 )进行检测。结果　DHA(10 μg/ml)组能提高MCF 7/R细胞株对阿霉素敏感性 3.2倍 ,DHA(2 0 μg/ml)组提高 5 .1倍 ,均有非常显著性差异 (P <0 .0 1)。结论　DHA能部分逆转乳腺癌耐药细胞对阿霉素的耐药性     

Should oncoplastic breast conserving surgery be used for the treatment of early stage breast cancer? Using the GRADE approach for development of clinical recommendations

IntroductionThe potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice.MethodsA panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach.ResultsAccording to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence).DiscussionThis review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients’ values.Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.     

Do hospital type or caseload make a difference in chemotherapy treatment patterns for early breast cancer? Results from 104 German institutions, 2008–2017

BackgroundOver the past decade, chemotherapy has been used more selectively in early breast cancer (EBC) due to better risk stratification. Neoadjuvant chemotherapy (NACT) has evolved to the primary treatment option. The type and size of hospitals is known to have a substantial influence on the kinds of treatment they provide, and therefore on patient outcomes (e.g. rates for pathological complete response, pCR), but it is not yet known how this has affected delivery of chemotherapy for EBC in Germany.MethodsThis study analyzed chemotherapy use and pCR rates after NACT for EBC patients treated at 104 German institutions 2008–2017. Institutions were separated into associated hospital type (university hospital; teaching hospital; community hospital) and annual caseload (≤100; 101–250; >250 cases/year).ResultsOverall, 124,084 patients were included, of whom 11.6% were treated at university hospitals, 63.1% at teaching hospitals, and 25.3% at community hospitals. In total, 46,274 (37.3%) received chemotherapy, of whom 44,765 had information available about systemic treatment and surgery. From 2008 to 2017, chemotherapy use declined from 48.3% to 36.4% for university hospitals, from 40.7% to 30.3% for teaching hospitals, and from 42.4% to 33.7% for community hospitals. Furthermore, the proportion of NACT increased the most in university hospitals (from 32.0% to 68.1%); whereas, the rate of pCR (defined as ypT0 ypN0) increased irrespective of institutional type. Analyses regarding annual caseload did not show any differences.ConclusionsThe results from this large, nationwide cohort reflect a more selective use of chemotherapy in Germany, irrespective of institutional type or case load.     

The role of CDK4/6 inhibitors in early breast cancer

The use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) has proven to be a successful strategy in the treatment of advanced hormone receptor-positive (HR⁺) and human epidermal growth factor receptor 2-negative (HER2^-) breast cancer (BC), leading to a strong interest in their possible role in the treatment of early luminal BC. In this review we collect the most relevant and recent information on the use of CDK4/6i for the treatment of early BC in the neoadjuvant and adjuvant settings. Specifically, we evaluate the results of the large phase 3 adjuvant trials recently released, which have yielded apparently divergent results. We also examine the relevance of biomarkers as response predictive factors for CDI4/6i, the combination between radiotherapy and CDK4/6i, and provide a critical discussion on the evidence that we have so far and future directions of the role of these drugs in the treatment of early BC.     

First-line bevacizumab-containing therapy for HER2-negative locally advanced/metastatic breast cancer: Real-world experience from >2000 patients treated in the multicentre AVANTI study

AimThe multicentre non-interventional AVANTI study assessed safety, effectiveness and patient-reported outcomes with approved first-line bevacizumab-containing regimens for HER2-negative locally recurrent/metastatic breast cancer (LR/MBC) in German routine oncology practice.MethodsEligible patients had HER2-negative LR/MBC, no bevacizumab contraindications and no prior chemotherapy for LR/MBC. Chemotherapy schedule, diagnostics and follow-up were at physicians’ discretion. Data were collected for 1 year after starting bevacizumab, then every 6 months for 1.5 years (maximum follow-up: 2.5 years). Patients and physicians rated treatment satisfaction. Subgroup analyses were prespecified in clinically relevant populations, including triple-negative breast cancer (TNBC).ResultsBetween November 1, 2009 and April 30, 2016, 2065 eligible patients at 346 centres received bevacizumab with paclitaxel or capecitabine. Patients receiving bevacizumab–capecitabine were less likely to have de novo disease and more likely to have TNBC, age ≥60 years and prior anthracycline/taxane and/or endocrine therapy. Median PFS was 12.6 (95% CI 11.9–13.2) months (12.8 with bevacizumab–paclitaxel, 10.5 with bevacizumab–capecitabine); median OS was 23.9 (95% CI 22.2–25.1) months. Outcomes were worse in patients with TNBC, prior anthracycline/taxane or prior endocrine therapy. Grade ≥3 adverse events occurred in 27% of patients. Treatment was discontinued for adverse events in 15%. Treatment satisfaction was rated as good or better by 304/394 responding patients (77%) at week 54 and in 1393/2065 patients (67%) by physicians overall.ConclusionsIn routine clinical practice, effectiveness and safety of first-line bevacizumab-containing therapy for LR/MBC were consistent with experience from phase III trials. Patient and physician treatment satisfaction showed high concordance.     

Unique challenges and outcomes of young women with breast cancers from a tertiary care cancer centre in India

BackgroundYoung (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying.MethodsThe YBC treated with a curative intent between 2015 and 2016 at our institute were analysed.ResultsThere were 1228 patients with a median age of 36 (12–40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) –III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0–131) months, 5-year overall and disease-free survival was 79.6% (76.8–82.5) and 59.1% (55.8–62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8–90.6), 77.3% (73.4–81.2), 69.7% (52.5–86.9) and disease-free survival was 94% (85.9–100), 65.9% (60.3–71.5), 55% (50.5–59.5), and 29.6% (14–45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6–86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients.ConclusionMore than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus.     

Safety of cyclin-dependent kinase4/6 inhibitor combined with palliative radiotherapy in patients with metastatic breast cancer

IntroductionCyclin-dependent kinase (CDK)4/6 inhibitor is a first-line therapy for metastatic ER+/HER2-breast cancer. However, there are limited data on safety of combined radiotherapy (RT) and CDK4/6 inhibition.MethodsWe conducted a retrospective study of women with metastatic breast cancer who received palliative RT within 14 days of CDK4/6 inhibitor use. The primary endpoint was toxicity per Common Terminology Criteria for Adverse Events v5. Secondary endpoints were pain response and local control based on clinical assessment and imaging.ResultsThirty patients underwent 36 RT courses with palbociclib (n = 34 courses, 94.4%) or abemaciclib (n = 2, 5.6%). RT was delivered before, concurrently or after CDK4/6 inhibitors in 7 (19.4%), 8 (22.2%), and 21 (58.3%) of cases with median 3.5 days from RT to closest CDK4/6 inhibitor administration. Median RT dose was 30Gy (range 8–40.05Gy). Treated sites included brain (n = 5, 11.6%), spine (n = 19, 44.2%), pelvis (n = 9, 20.9%), other bony sites (n = 6, 14.0%) and others (n = 4, 9.3%). No acute grade ≥3 non-hematologic toxicity occurred. No increased hematologic toxicity was attributable to RT with grade 3 hematologic toxicities rates 16.7%, 0%, and 6.7% before, during, and 2 weeks after RT completion. All but one patient (29/30) achieved symptom relief. Local control rates were 94.4%, 91.7% at 6 and 12 months.ConclusionsThe use of RT within 2 weeks of CDK4/6 inhibitors had low acceptable toxicity and high efficacy, suggesting that it is safe for palliation of metastatic breast cancer.