绝经后Luminal B型乳腺癌的内分泌治疗

目的 探讨芳香化酶抑制剂和三苯氧胺对绝经后Luminal B型乳腺癌患者的疗效.方法 收集天津市肿瘤医院2002年7月至2005年3月间733例术后接受辅助内分泌治疗的原发性乳腺癌患者资料,肿瘤性质均经手术切除病理组织学证实.患者均为绝经后且ER阳性,其中501例接受三苯氧胺治疗,232例接受芳香化酶抑制剂治疗.采用免疫组化SP法进行ER、PR、HER2检测.随访时间36～90个月,中位随访时间46个月.结果 芳香化酶抑制剂治疗组Luminal B型乳腺癌患者三年无瘤生存率高于三苯氧胺组(90.6% vs.88.6%,P=0.038).三苯氧胺组亚组分析显示:LN+/HER2+患者三年无瘤生存率低于LN+/HER2-患者(88.2% vs 90.4%,P=0.037);HER2+/PR+患者高于HER2+/PR-患者(90.8% vs.89.5%,P=0.032).芳香化酶抑制剂组内LN(+)和LN(-)亚组中,HER2(+)患者与HER2(-)患者的三年无瘤生存率差异均无统计学意义(P>0.05);而HER2+/PR+组高于HER2+/PR-组(91.9% vs.90.5%,P=0.029).芳香化酶抑制剂组潮热、阴道出血、静脉血栓形成的发生率低,肌肉骨骼疼痛、骨折的发生率则高于三苯氧胺组(P<0.05).结论 芳香化酶抑制剂对绝经后Luminal B型患者疗效好于三苯氧胺,此效果不受患者腋窝淋巴结状态的影响,且耐受性和安全性较好.     

绝经后Luminal B型乳腺癌的内分泌治疗

目的 探讨芳香化酶抑制剂和三苯氧胺对绝经后Luminal B型乳腺癌患者的疗效.方法 收集天津市肿瘤医院2002年7月至2005年3月间733例术后接受辅助内分泌治疗的原发性乳腺癌患者资料,肿瘤性质均经手术切除病理组织学证实.患者均为绝经后且ER阳性,其中501例接受三苯氧胺治疗,232例接受芳香化酶抑制剂治疗.采用免疫组化SP法进行ER、PR、HER2检测.随访时间36～90个月,中位随访时间46个月.结果 芳香化酶抑制剂治疗组Luminal B型乳腺癌患者三年无瘤生存率高于三苯氧胺组(90.6% vs.88.6%,P=0.038).三苯氧胺组亚组分析显示:LN+/HER2+患者三年无瘤生存率低于LN+/HER2-患者(88.2% vs 90.4%,P=0.037);HER2+/PR+患者高于HER2+/PR-患者(90.8% vs.89.5%,P=0.032).芳香化酶抑制剂组内LN(+)和LN(-)亚组中,HER2(+)患者与HER2(-)患者的三年无瘤生存率差异均无统计学意义(P>0.05);而HER2+/PR+组高于HER2+/PR-组(91.9% vs.90.5%,P=0.029).芳香化酶抑制剂组潮热、阴道出血、静脉血栓形成的发生率低,肌肉骨骼疼痛、骨折的发生率则高于三苯氧胺组(P<0.05).结论 芳香化酶抑制剂对绝经后Luminal B型患者疗效好于三苯氧胺,此效果不受患者腋窝淋巴结状态的影响,且耐受性和安全性较好.     

芳香化酶抑制剂新辅助内分泌治疗三苯氧胺耐药的老年性局部晚期乳腺癌的研究

目的探讨芳香抑制剂新辅助内分泌治疗三苯氧胺耐药的老年性局部晚期乳腺癌的临床疗效。方法回顾性分析既往接受三苯氧胺新辅助内分泌治疗失败,后改用芳香化酶抑制剂,且能够评估疗效和记录疾病进展时间的41例老年性局部晚期乳腺癌患者,主要观察终点为临床获益率（Clinical benefit rate,CBR）。结果分别接受阿那曲唑（n=16）、伊西美坦（n=14）和来曲唑（n=11）新辅助内分泌治疗的三组乳腺癌患者的临床病理特征相似（χ2=1.579,P=0.547）,不同的芳香化酶抑制剂均能获得明显改善三苯氧胺治疗失败的老年性局部晚期乳腺癌的治疗效果,其CBR分别为阿那曲唑62.5%,伊西美坦78.57%和来曲唑72.73%,治疗效果相似（χ2=3.787,P=0.327）。结论芳香化酶抑制剂新辅助内分泌治疗三苯氧胺耐药的老年性局部晚期乳腺癌,仍可以获得明显的临床缓解,且不同的芳香化酶抑制剂的CBR相似。     

雌、孕激素受体和表皮生长因子受体2在乳腺癌分型中的应用

目的 研究乳腺癌分子亚型的临床病理特征及预后.方法 SP法检测509例手术切除的乳腺癌雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、表皮生长因子受体2(erbB-2,Her-2)表达并对其分型,Her-2-、ER/PR+为腔上皮样A亚型(Luminal A),Her-2+、ER/PR+为腔上皮样B亚型(Luminal B),Her-2-、ER-、PR-为三阴性型(Tripie-negative)、Her-2+、ER-、PR-为ERBB2+亚型(ERBB2+).χ~2检验比较亚型的临床病理特征,Kaplan-Meier法分析5年无瘤生存率(DFS),单因素和Cox多因素分析与复发和转移相关的因素.结果 Luminal A占所有病例40.5%(206/509),Luminal B占18.5%(94/509),Tripie-negative占21.4%(109/509),ERBB2+19.6%(100/509).三阴性型乳腺癌中髓样癌的比例高于其他类型乳腺癌(P<0.05),4种亚型复发转移率差异有统计学意义(P=0.029).多因素分析发现淋巴结状态和l临床分期是独立的预后影响因素(P=0.000).ERBB2+和Triple-negative的DFS分别为81%、78.9%,低于Luminal A和Luminal B的DFS(88.8%、90.4%)(P=0.025).结论 在本组乳腺癌患者中,Luminal A亚型所占比例最高,Triple-negative和ERBB2+复发转移率高,预后较Luminal A和Luminal B亚型差.     

芳香化酶抑制剂在乳腺癌治疗中的应用

芳香化酶抑制剂通过抑制肾上腺、脂肪及乳腺癌等组织中的芳香化酶,阻止雄烯二酮及睾酮转化为雌激素,使血液中雌激素水平下降,抑制雌激素依赖性癌细胞生长。内分泌治疗是乳腺癌的一种重要治疗手段[1]。绝经后妇女的雌激素主要来源于雄激素前体物质在外周组织的芳香化,因此芳香化酶抑制剂特别适用于绝经后雌激素受体(ER)和(或)孕激素受体(PR)阳性的乳腺癌患者,使复发、转移的危险性减少,5年、10年生存率明显提高。1非特异性芳香化酶抑制剂代表药物如氨鲁米特(Aminoglutethi mide,AG)为第1代芳香化酶抑制剂,对绝经后晚期乳腺癌有效率为30%,…     

三苯氧胺治疗时女性血清雌激素水平的变化

三本氧胺是一非类固醇族抗雌激素制剂，已广泛应用于乳腺癌的辅助治疗，其确切机制仍未完全阐明。三苯氧胺具有双重作用，即抗雌激素和雌激素作用。作者以往曾报道绝经后乳腺癌妇女应用三苯氧胶后的脱氧雄甾酮（DHEA）、雌附（E）和雌二醇（E2）的变化。停用三苯氧胺后，DHEA、E1和E2值下降，去势手术后更进一步下降，再用三苯氧胺后又见上升，初步认为三苯氧胺可刺激肾上腺产生DHEA在周围组织再芳香化成E1和E2。为了进一步阐明长期三苯氧胺治疗对绝经前后病人的雌激素和DHEA血清值，作者选47例乳腺癌妇女进行观察，平均60岁（30～…     

三苯氧胺治疗乳腺增生病102例分析

作者对102例乳腺增生病用针穿细胞洲定ER、PR同时作细胞学检查,排除乳腺癌.ER、PR阳性76例(74.5%),阴性26例(25.5%).全部病例均用三苯氧胺治疗,显效84例(82.4%),有效2例(1.96%).受体阳性的76例全部(100%)显效;受体阴性的26例中显效8例(30.8%),有效2例(7.7%).三苯氧胺治疗乳腺增生病,副作用少,疗效好,是目前较为理想的药物,值得推广应用.     

分子分型对可手术浸润性乳腺癌预后的影响

目的研究分子分型对可手术浸润性乳腺癌预后的影响。方法收集2015—2018年在河南省肿瘤医院确诊的接受手术治疗的7 869例浸润性乳腺癌病例, 依据激素受体(HR)和HER2状态将患者分为HR+/HER2-、HR+/HER2+、HR-/HER2+和HR-/HER2- 4组, 分别用Kaplan-Meier曲线法和COX回归分析各组患者无病生存(DFS)和总生存(OS)的差异。结果在7 869例乳腺癌患者中, HR+/HER2-、HR+/HER2+、HR-/HER2+和HR-/HER2-组患者分别占52.9%、17.5%、14.1%和15.5%。总人群的5年DFS和OS分别为86.30%和94.29%。HR+/HER2-组的5年DFS(88.12%)高于HR+/HER2+组(84.67%)(P=0.026)、HR-/HER2+组(84.19%)(P<0.001)和HR-/HER2-组(83.70%)(P<0.001)。HR+/HER2-组和HR+/HER2+组的5年OS差异无统计学意义(95.38%比95.17%, P=0.187), 高于HR-/HER2+组(92.26%)...     

183例三阴性乳腺癌临床病理特征及生存分析

目的 研究三阴性乳腺癌的临床病理特征和预后.方法 回顾性分析南京医科大学第一附属医院2003年1月至2009年12月收治的1042例原发乳腺癌患者的临床资料.所有患者通过免疫组化分为3组:ERBB2+,HR +/ERBB -和三阴性乳腺癌. 结果 183例为三阴性乳腺癌.三阴性乳腺癌患者其肿块直径超过2 cm的比例和组织学分级三级发生率比ERBB2+和HR+/ERBB2-患者高(P＜0.01).而ERBB2+患者的P53阳性率比三阴性乳腺癌患者和HR +/ERBB2 -患者高(P＜0.01).HR +/ERBB2 -患者与ERBB2+患者、三阴性乳腺癌患者相比骨转移比例更高(P=0.006).3组患者间内脏远处转移差异无统计学意义.随访期间,3组5年无复发生存率差异有统计学意义(P =0.029),ERBB2+患者最低,为80.3％.结论 本组三阴性乳腺癌患者肿块直径超过2 cm比例较高,组织学分级三级发生率较高,但其5年无复发生存率高于ERBB2+患者.     

芳香化酶抑制剂对绝经后乳腺癌患者的骨密度影响

目的评估芳香化酶抑制剂(aromatase inhibitors,AIs)对绝经后乳腺癌患者骨密度(bonemineral density,BMD)的影响。方法利用双能X线骨密度仪对203例绝经后乳腺癌妇女进行腰椎正位(L1-L4)、左侧股骨颈以及左侧全髋的BMD测定,其中103例患者接受了AIs治疗,对照组为100例同年龄段未接受AIs治疗的乳腺癌患者。结果接受AIs治疗患者的腰椎、左股骨颈和左侧全髋三个部位的BMD均显著低于对照组(P<0.05)。病例组中有67例(65.0%)被诊断为骨量减少,24例(23.3%)被诊断为骨质疏松;对照组中有60例(60.0%)被诊断为骨量减少,19例(19.0%)被诊断为骨质疏松。病例组患者中骨质疏松加骨量减少的总发生率高于对照组,两组间有统计学差异(P<0.05)。结论绝经后乳腺癌患者存在不同程度的骨量减少和骨质疏松,芳香化酶抑制剂对乳腺癌患者的骨密度具有负面影响,对接受芳香化酶抑制剂治疗的绝经后乳腺癌患者,应当定期监测其骨密度和采取适当的预防性骨质疏松治疗,以减少骨质疏松和骨折的风险。     

HER2 positivity is not associated with adverse prognosis in high-risk estrogen receptor-positive early breast cancer patients treated with chemotherapy and trastuzumab

Co-expression of human epidermal growth factor receptor-2 (HER2) and hormone receptor (HR) predicted worse prognosis in early breast cancer before trastuzumab was developed. We aimed to investigate whether HER2 positivity was still associated with worse outcome in high-risk estrogen receptor (ER) positive patients treated with trastuzumab and chemotherapy. In the present study, 227 ER+/HER2+ patients treated with trastuzumab and chemotherapy (HER2-pos-T group) and 1097 ER+/HER2-patients treated with chemotherapy alone (HER2-neg group) during 2009 and 2015 were retrospectively enrolled for the comparison of disease-free survival (DFS) and overall survival (OS). At a median follow-up of 59 months, 174 DFS events and 69 deaths were observed. The estimated 5-year DFS rate was 94.2% in the HER2-pos-T group and 87.4% in the HER2-neg group (Log-rank P = 0.014). HER2-pos-T group was associated with significantly better DFS in multivariate analysis (HR 0.38, 95% CI: 0.22–0.67, Log-rank P = 0.001). The estimated 5-year OS rates for the two groups were 97.2% and 95.7%, respectively (Log-rank P = 0.183). In multivariable analysis, patients in the HER2-pos-T group had significantly better OS compared with those in the HER2-neg group (HR 0.40, 95% CI: 0.17–0.95, Log-rank P = 0.037). We concluded that high-risk ER+/HER2+ breast cancer patients treated with chemotherapy and trastuzumab had superior prognosis compared with ER+/HER2-patients. Therefore, HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab.     

Prognostic and predictive value of TFF1 for adjuvant endocrine therapy in Chinese women with early ER positive breast cancer: Comparing aromatase inhibitors with tamoxifen

Factors that predict in favor of an aromatase inhibitors (AIs) over tamoxifen (TAM) in estrogen receptor (ER) breast cancer remains to be identified. We compared progesterone receptor (PR) and trefoil factor 1 (TTF1) status (+ve versus −ve) as predictive of superior effect of AI’s over tamoxifen among a total of 1973 Chinese women with early ER+ breast cancer. The expression of TFF1 was independently associated with ER and PR. However, there was no correlation with TFF1 and HER-2 expression. Treatment effect was more pronounced in the ER+/TFF1+ postmenopausal patients with a hazard ratio favoring AIs (HR = 0.397, 95%CI 0.183-0.860), but not in the PR positive cohorts (HR = 0.466, 95%CI 0.186-1.164). We suggested that AIs was better than TAM especially in the postmenopausal patients with ER+/TFF1+ breast cancer; however the clinical application of this observation still requires further prospective studies.     

Addition of adjuvant tamoxifen to cyclophosphamide,methotrexate and 5-fluorouracil for premenopausal women with oestrogen receptor-positive breast cancer

OBJECTIVE: To study the value of adjuvant tamoxifen (TAM) in premenopausal women with oestrogen receptor (ER)-positive breast cancer who received adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) polychemotherapy. METHODS: Four hundred and two premenopausal ER-positive breast cancer patients who received CMF chemotherapy between January 1990 and December 1999 were retrospectively studied. Disease-free survival (DFS) and overall survival (OS) were used to evaluate the clinical value of TAM therapy. The relationships between nodal status and TAM were also analysed. RESULTS: After a mean of 41 months of follow-up, 43 (13.7%) patients died of breast cancer and 68 (19.9%) patients suffered recurrence. There was a significant difference between TAM and non-TAM treatment groups for DFS (p=0.0058), but no significant difference for OS. For node-negative patients, there was no significant difference between the TAM and non-TAM treatment groups for either DFS or OS. For node-positive patients, the difference between TAM and non-TAM treatment groups was significant for both DFS and OS (p=0.0497 and p=0.0285, respectively). CONCLUSION: TAM resulted in additional benefit to premenopausal patients with node-positive ER-positive breast cancer who received the CMF polychemotherapy regimen.     

Progesterone receptor status provides predictive value for adjuvant endocrine therapy in older estrogen receptor-positive breast cancer patients

Estrogen receptor (ER) status can predict the efficacy of endocrine therapy. However, the predictive significance of the progesterone receptor (PgR) is controversial in an adjuvant setting. Records of 758 ER+ breast cancer patients who received adjuvant tamoxifen (TAM) for 3-5 years were reviewed to evaluate the predictive value of PgR for TAM treatment in ER+/PgR+ and ER+/PgR- groups. By a median of 40 months' follow-up, there was no significant difference between the two groups with regard to disease-free-survival (DFS). On the basis of STEPP analysis showing the tendency of age effect on DFS in both the ER+/PgR- and ER+/PgR+ groups, we classified the ER+ patients into three strata by age (<45, 45-60, and >or=60 years). There was no significant difference in DFS and overall survival (OS) between the two groups in the <45 stratum and the 45-60 stratum. In contrast, the ER+/PgR- group had a worse prognosis in the >or=60 stratum with regard to both DFS (P=0.0484) and OS (P=0.0009). The results suggest that PgR status might be a predictive factor of benefit to be gained from adjuvant TAM for older ER+ patients with regard to DFS and OS. This should take into account older ER+/PgR- patients who tend to be resistant to TAM.     

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??Effect of non-sentinel lymph node status on prognosis of Luminal B (HER2 negative) early breast cancer with positive sentinel lymph nodes YE Jing-ming*, XU Ling, LIU Qian, et al. *Breast Disease Center, Peking University First Hospital, Beijing100034, China
Corresponding author: LIU Yin-hua, E-mail??liuyinhua@medmail.com.cn
Abstract Objective To evaluate the effect of non-sentinel lymph node status on prognosis of Luminal B ??HER2 negative?? early breast cancer. Methods Luminal B ??HER2 negative?? early breast cancer with positive sentinel lymph node treated from January 2008 to December 2014 in Peking University First Hospital entered the retrospective study. The clinicopathological features and their relationship with non-sentinel lymph nodes status were analyzed statistically. The effect of non-sentinel lymph nodes status on prognosis of Luminal B ??HER2 negative?? early breast cancer with positive sentinel lymph nodes were also analyzed. Results In the group of 142 patients with positive sentinel lymph nodes ??SLN???? the average number of SLNs detected in each patient were 2.06±1.26. The number of positive SLNs was associated with the status of non-sentinel lymph nodes?? but not the age?? BMI?? menopause?? T stage?? histological grade?? lympho-vascular invasion. Non-SLN axillary lymph node non-metastasis occurred in 78 patients (54.9%), DFS 93%, OS 93.1%; non-SLN axillary lymph node metastasis occurred in 64 patients (45.1%), DFS 95.2%, OS 91.9%. Based on Log-rank (Mantel-Cox) test, There was no significant difference between two groups in DFS (χ2=0.011, P=0.918) and OS (χ2=0.348, P=0.555) . Conclusion The number of positive sentinel lymph nodes in Luminal B ??HER2 negative?? early breast cancer patients with sentinel lymph nodes metastasis were associated with the status of non-sentinel lymph nodes. There were no statistical differences betweennon-sentinel lymph nodes metastasis group and non-metastasis group in disease free survival and over-roll survival.     

Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry

To investigate the significance of immunohistochemical molecular subtyping, we evaluated outcomes of subtypes based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Using tissue microarrays, 1006 breast cancer patients between November 1999 and August 2005 were categorized into four subtypes: luminal A (ER+ and/or PR+, HER2-, Ki-67 < 14%), luminal B (ER+ and/or PR+, HER2-, Ki-67 ≥ 14% or ER+ and/or PR+, HER2+), HER2-enriched (ER-, PR-, HER2+), and triple-negative breast cancer (TNBC) (ER-, PR-, HER2-). Demographics, recurrence patterns, and survival were retrospectively analyzed using uni-/multivariate analyses. Luminal A, luminal B, HER2-enriched, and TNBC accounted for 53.1%, 21.7%, 9.0%, and 16.2% of cases, respectively. Luminal A presented well-differentiation and more co-expression of hormone receptors comparing to luminal B. HER2-enriched showed larger size and higher nodal metastasis. TNBC demonstrated younger age at diagnosis, larger size, undifferentiation, higher proliferation, and frequent visceral metastases. The peak of recurrence for luminal A was at 36 months postoperatively, while that for HER2-enriched and TNBC peaked at 12 months. The relapse risk of luminal B was mixed. Luminal A showed the best survival, but no difference was observed between the other three subtypes. When matched by nodal status, however, TNBC showed the worst outcomes in node-positive patients. In multivariate analyses, luminal A remained a positive prognostic significance. Immunohistochemically-defined subtypes showed different features, recurrence patterns, and survival. Therefore, molecular subtypes using four biomarkers could provide clinically useful information of tumor biology and clinical behaviors, and could be used for determining treatment and surveillance strategies.     

HER2/neu表达对乳腺癌术后应用CMF化疗病人预后的影响

目的：研究HER2/neu癌基因在乳腺癌组织中的表达，探讨其对接受手术及CMF（环磷酰胺、氨甲碟呤和氟脲嘧啶）辅助化疗病人预后的影响。方法：选择1995年至2001年间112例接受手术和术后行CMF化疗的乳腺癌病人的组织标本，用免疫组织化学方法检测原发肿瘤HER2/neu蛋白及雌孕激素受体的表达，结合临床病理资料并分析其与5年生存率的关系。结果：本组乳腺癌组织中HER2/neu的过度表达率为21．4％（n=24）。经随访13～104月，整体病人的5年无病生存率为85．3％，5年总体生存率为91．1％。HER2／neu过度表达者的5年无病生存率为43．2％，而HER2/neu表达缺失者为71％（P=0．01）。HER2/neu过度表达者的5年总体生存率为49．2％，而HER2/neu表达缺失者为83.3％（P=0．02）。同时，生存率亦与肿瘤大小和孕激素受体密切相关。结论：乳腺癌组织中HER2/neu蛋白的过度表达与接受手术及术后CMF化疗病人的预后密切相关，可以作为预测其复发及转移的重要指标。