男性乳腺癌的治疗及预后因素分析:附37例报告

目的　探讨男性乳腺癌 (MBC )的治疗和预后因素。方法　回顾性分析 3 7例男性乳腺癌的临床资料。手术方式包括经典根治术 (10例 ) ,改良根治术 (19例 ) ,单纯乳房切除术 同侧腋窝淋巴结摘除术 (4例 ) ,单纯乳房切除术 (4例 )等。结果　上述手术方式的患者 5年生存率依次为 80 .0 %,78.9%,2 5 .0 %,2 5 .0 %;腋窝淋巴结有转移和无转移的患者 5年生存率分别为 5 0 .0 %和 93 .3 %;雌激素受体 (ER)阳性和阴性的患者 5年生存率分别是 80 .0 %和 42 .8%(P <0 .0 5 ) ;结论　改良根治术是MBC的首选术式 ,术后可根据情况辅以其他治疗 ;腋窝淋巴结转移、病理类型及肿瘤分期等因素影响预后 ,其中手术方式和腋窝淋巴结状况为影响预后的主要因素。     

男性乳腺癌的研究进展

目的总结男性乳腺癌(male breast cancer,MBC)的病因、治疗等方面的研究进展。方法通过阅读文献的方法,对MBC的病因、治疗等进行综述。结果家族史、乳腺癌易感蛋白1/2(BRCA1/2)基因突变、雌雄激素水平不平衡等众多因素是导致MBC发生的危险因素。前哨淋巴结活检(sentinel lymph node biopsy,SLNB)在MBC患者中具有可行性。放疗可以控制MBC的局部复发,化疗可能对远期生存率有益。MBC的内分泌治疗原则不能完全等同于女性乳腺癌(female breast cancer,FBC)。结论 MBC的危险因素众多,放化疗及内分泌治疗均可使MBC患者获益,但仍需大样本、高质量的临床研究论证。     

男性乳腺癌的诊治进展

男性乳腺癌（male breast cancer，MBC）是一种少见的恶性肿瘤，发病年龄往往较大，预后较女性乳腺癌差。近年来随着发病率的增加而越来越被重视。由于本病的特殊性，早期常因被忽视而导致延误诊治。本文就MBC的发病情况、分子生物学特征、诊断及治疗等方面的进展作一综述。     

生物分子学在甲状腺肿瘤中的应用

随着免疫组织化学和分子生物学等高新技术的发展，诸如肿瘤细胞ＤＮＡ含量的测定、增殖细胞核抗原（ＰＣＮＡ）、雌激素受体、癌基因、抑癌基因的研究已应用于胃癌、结肠直肠癌、胰腺癌和乳腺癌的诊治以及预后检测，但有关在甲状腺肿瘤中的研究和应用报道较少，本文就重点对生物分子学在甲状腺肿瘤中的应用加以综合介绍。     

不同HER-2表达水平乳腺癌患者新辅助化疗疗效与生存分析

背景与目的 新辅助化疗是早期高危或局部晚期乳腺癌降期保乳和提高整体治愈率重要的治疗策略,新辅助化疗人群的选择和方案的制订依赖于分子分型。然而目前尚缺乏不同人表皮生长因子受体2（HER-2）表达水平的乳腺癌新辅助化疗疗效及生存预后差异的研究。本研究通过比较不同HER-2表达水平的乳腺癌患者新辅助化疗疗效及生存预后的差异,旨在明确其新辅助化疗疗效及生存预后的影响因素,为临床新辅助化疗人群选择和方案制订提供参考。方法 回顾性分析2018年1月—2022年5月于中南大学湘雅医院乳腺外科接受新辅助化疗且行根治性手术的乳腺癌患者资料。比较不同HER-2表达水平（0表达、低表达、过表达）患者临床病理特征的差异,用Logistic回归分析筛选病理完全缓解（pCR）的独立影响因素,用Kaplan-Meier方法估计患者的生存曲线,用Log-rank检验比较生存率的差异,通过Cox回归分析筛选预后的独立影响因素。结果 共纳入601例患者,其中HER-2 0表达231例（38.4%）、HER-2低表达137例（22.8%）、HER-2过表达233例（38.8%）。与HER-2 0表达患者和HER-2过表达患者比较,HER-2低表达患者具有更高的BMI,合并肿瘤家族史更少见,组织学分级更低,激素受体（HR）阳性比例更高;HER-2过表达患者的肿瘤纤维化程度明显低于HER-2 0表达和HER-2低表达患者（均P<0.05）。HER-2低表达患者中,HR阴性亚组患者较HR阳性亚组患者肿块更大,组织学分级更高,Ki-67水平更高（均P<0.05）。全组患者中,HER-2表达水平、pCR、临床淋巴结分期（cN）是患者无病生存（DFS）的独立影响因素（均P<0.05）。HER-2过表达患者的新辅助化疗pCR率及DFS率明显高于HER-2低表达和HER-2 0表达患者（均P<0.05）,但HER-2低表达和HER-2 0表达患者的新辅助化疗pCR率及DFS率无明显差异（均P>0.05）。肿瘤纤维化程度和雌激素受体（ER）状态是HER-2 0表达乳腺癌pCR的独立影响因素,间质肿瘤浸润淋巴细胞（sTILs）水平是HER-2低表达乳腺癌pCR的独立影响因素,肿瘤纤维化程度和ER状态是HER-2过表达乳腺癌pCR的独立影响因素（均P<0.05）。结论 新辅助化疗对HER-2过表达乳腺癌患者的疗效优于HER-2 0表达和HER-2低表达乳腺癌患者。ER状态和纤维化程度、sTILs水平分别是HER-2 0表达与低表达患者pCR的独立影响因素,而ER状态与纤维化程度是HER-2过表达患者pCR的独立影响因素。     

男性乳腺癌：附17例报告

目的:探讨男性乳腺癌的诊断、治疗及预后。方法:回顾性分析17例男性乳腺癌患者的临床资料。结果:17例患者平均年龄为59.6岁。其中Ⅰ期3例，Ⅱ期5例，Ⅲ期7例，Ⅳ期2例。以典型浸润性导管癌为主，乳腺癌的雌、孕激素受体阳性率分别为82.4 %和72.5 %。均行根治性手术治疗，术后辅以放疗、内分泌治疗和（或）化疗。其中1例失访，2例术后8个月~3年死于其它疾病，余14例术后已生存1～12年。结论:男性乳腺癌发病率低，发病年龄偏大,易误诊;内分泌治疗首选他莫昔芬;影响其预后的因素很多，其中最重要的是诊断时肿瘤的分期和淋巴结受累情况。     

c-myb、bcl-2和ER在乳腺癌组织中的表达与临床病理特征及预后的关系

目的：探讨c-myb、bcl-2与ER基因在乳腺癌组织中的表达及其与乳腺癌临床特征及预后的关系,以及它们之间的相关性。方法：采用RT-PCR、免疫组织化学技术检测乳腺癌及良性病变组织中c-myb、bcl-2和ER基因表达情况,分析比较表达组和未表达组生存资料的差异。结果：乳腺癌组织中存在c-myb、bcl-2基因的表达,乳腺良恶性组织之间表达的差异具有统计学意义（P〈0.01）。乳腺癌c-myb基因表达组和未表达组生存率的差异有统计学意义（P〈0.01）,乳腺癌bcl-2基因表达组和未表达组生存率的差异也有统计学意义（P〈0.01）。多因素回归发现c-myb不是乳腺癌的独立预后因素。Pearson相关性分析发现c-myb与bcl-2和ER都有相关性。结论：乳腺癌组织中存在c-myb基因的高表达,而且c-myb与bcl-2、ER受体都有相关性。c-myb可能成为评价乳腺癌预后的重要分子生物学标记,并有望成为乳腺癌治疗的一个靶点。     

血清肿瘤标志物YKL-40与乳腺癌预后关系的研究

目的：探讨血清YKL-40水平与乳腺癌预后相关因素的关系。方法：采用酶联免疫吸附试验测定乳腺癌患者（实验组）及健康者（对照组）各40例的血清YKL-40水平,比较YKL-40水平在不同年龄、肿瘤直径、淋巴结转移、病理类型及TNM分期患者间的差异。结果：乳腺癌患者血清YKL-40水平明显高于健康对照组（P〈0.05）。肿瘤直径〉2 cm患者YKL-40水平明显高于直径≤2 cm组患者（P〈0.01）。淋巴结转移阳性患者血清YKL-40水平明显高于淋巴结转移阴性患者（P〈0.05）。随着肿瘤TNM分期进展,血清YKL-40水平逐渐升高（P〈0.01）。不同年龄及病理类型患者间血清YKL-40水平无明显差异。结论：血清YKL-40水平与乳腺癌预后相关,可望成为乳腺癌新的肿瘤标志物及治疗靶点。     

乳腺癌患者术后预后相关因素分析

目的探讨影响乳腺癌患者术后预后的相关因素。方法对101例乳腺癌患者，进行回顾性研究。本组病例采用Log—rank单因素分析和COX多因素模型的分析方法分析乳腺癌预后的相关指标。结果Log-rank单因素分析结果提示肿瘤大小（直径〉5em）、病理分级、淋巴结转移、HER-2／neu和CD44五个因素是乳腺癌的预后因素（P均〈0．05），ER和PR不能作为乳腺癌的预后指标；进一步采用COX多因素分析结果提示，仅有HER-2／neu、肿瘤大小、淋巴结转移和病理分级是乳腺癌预后的独立预测指标。结论肿瘤大小、病理分级、淋巴结转移、HER-2／neu是临床判断乳腺癌预后有价值的指标。     

老年男性乳腺癌

男性乳腺癌(male breast cancer,MBC)的最早文字记载可追朔到5000年前的古埃及,但由于该病罕见,对其临床和病原学等方面了解不多.近年来对MBC回顾性研究及分子生物学方面的探讨丰富了对MBC的认识.现回顾近年文献,综述如下.1 MBC的流行病学和病因学     

Men and women show similar survival outcome in stage IV breast cancer

PurposeTo evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC).MethodsPatients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS).ResultsA total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50–69 years and with estrogen receptor–positive disease.ConclusionsThere was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders.     

The biology of male breast cancer

Important differences have begun to emerge concerning the molecular profile of female and male breast cancer which may prove to be of therapeutic value. This review examined all the available data on the genomics of MBC. Most male cancers are ER+ve but without a corresponding increase in PR positivity and only a weaker association with estrogen-controlled markers such as PS2, HSP27 and Cathepsin-D. HER2 +ve cancers are rare in males and the role of androgen receptor is controversial. Although the Luminal A phenotype was the most frequent in both MBC and FBC, no Luminal B or HER2 phenotypes were found in males and the basal phenotype was very rare. Using hierarchical clustering in FBC, ERα clustered with PR, whereas in MBC, ERα associated with ERβ and AR. Based on limited data it appears that Oncotype DX is effective in determining recurrence risk in selected MBC. In future, tailored therapies based on genomics will probably yield the most promising approach for both MBC and FBC.     

Therapeutic strategies in male breast cancer: Clinical implications of chromosome 17 gene alterations and molecular subtypes

Male breast cancer (MBC) is a rare disease. To date, therapy is mainly based on studies and clinical experiences with breast cancer in women. Only little is known about molecular typing of MBC, particularly with regard to potential biological predictors for adjuvant therapy. In female breast cancer tumors with chromosome 17 centromere (CEP17) duplication, HER2 and/or Topoisomerase II alpha (Topo II-α) gene alterations have been suggested to be associated with poor prognosis and increased sensitivity to anthracycline-containing regimens.In a well characterized cohort of 96 primary invasive MBC, we studied CEP17, HER2 and Topo II-α alterations by fluorescence in-situ hybridization (FISH), and expression of hormone receptors (HR), HER2 and Ki67 by immunohistochemistry to define molecular subtypes. Tumor characteristics and follow-up data were available and correlated with molecular findings.HER2 amplification and Topo II-α amplification/deletion were exceptionally rare in MBC (6.3% and 3.1%, respectively). CEP17 polysomy were found in 9.4% of tumors. HER2, Topo II-α and CEP17 gene alterations were not correlated to patients outcome. 96.9% of our cases were HR positive. Triple negative tumors were found in only 3.1% of the cases. In nodal negative tumors luminal A subtypes were significantly associated with better overall survival.Our results provide evidence for a predominant male breast cancer phenotype, characterized by HR expression and a lack of HER2/Topo II-α alterations and CEP17 duplicates. Therefore, the impact of anthracycline sensitivity linked to HER2/Topo II-α alterations as found in female breast cancer has low clinical significance for this specific male breast cancer phenotype.     

Current and emerging therapies of HER2-positive metastatic breast cancer

The HER2 receptor as measured by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) is overexpressed in 15–20% of all breast cancers and traditionally represents adverse biology and a guarded prognosis, particularly in HER2 positive metastatic breast cancer (MBC). Trastuzumab and newer anti-HER2 targeting agents have significantly improved the clinical outcomes of patients with HER2 positive MBC. The development of new techniques has led to discovery of promising biomarkers that can lead to more precise selection of patients for anti-HER2 therapies. This paper summarizes these new biomarkers, useful in selecting patients for treatment with new and emerging therapies for HER2 positive MBC. Emerging next generation sequencing techniques have truly changed the landscape of HER2 positive MBC. Deployment of multiple anti-HER2 therapies in combination is a strategy which has yielded additive or even synergistic effects and has led to markedly improved patient outcomes in HER2+ MBC. In the future, in order to further improve the treatment of these patients and to reduce toxicities, we need to improve our understanding of HER2-dependent pathways and their function, and to develop further treatment combinations while optimizing selection of patients by identifying new biomarkers. The results of prospective studies using CTCs, cDNA and other promising new biomarkers are awaited with great interest.     

乳腺髓样癌的治疗

目的探讨乳腺髓样癌临床特征、治疗和预后。方法回顾性分析1995年1月至1999年12月收治的乳腺髓样癌的临床资料。结果26例乳腺髓样癌占同期治疗女性乳腺癌616例的4.2%,年龄31~66(45.8±10.6)岁,肿瘤大小1~5 CM,腋淋巴结阳性率23.1%,腋淋巴结转移的发生与乳腺肿瘤的大小无关,免疫组化检测雌激素(ER)、孕激素(PR)和HER-2/NEU的阳性率分别为26.3%、21.1%和5.3%。全组进行手术和辅助化疗(环磷酰胺、甲氨蝶呤和氟尿嘧啶)。5例服用三苯氧胺,3例进行放射性治疗。随访时间5~9年,平均7.5年,总的5年生存率为88.4%。结论乳腺髓样癌的预后较好,手术加辅助性化疗是治疗的重要手段,分子生物学指标在乳腺髓样癌预后中的作用应该受到足够的重视。     

The prognostic significance of molecular subtype for male breast cancer: A 10-year retrospective study

BackgroundMale breast cancer (MBC) is rare. Molecular subtype has been utilized widely in female breast cancer. But the relationship between subtype and prognosis in MBC patients is still unknown. We aim to study the impact of molecular subtype on the prognosis of MBC.MethodsWe identified MBC cases from 1990 to 2011 retrospectively; molecular subtype was assigned by immunohistochemistry. We compared overall survival in different subtypes by Kaplan–Meier method and COX proportional hazard regression model.Results68 patients with MBC were included in analysis with 115 months of a median follow-up time. Comparing to non-luminal A (subtypes of Luminal B, HER2 over-express and Basal-like) group, patients with luminal A had a lower recurrent rate and better overall survival (10-year survival rate was 78.0% vs 67.0%, mean survival time 197.46 ± 12.22 months vs 146.51 ± 16.88 months, p < 0.05).ConclusionMolecular subtype may have prognosis-predicting value for MBC.     

Breast conservation for male breast cancer: Case report of intraoperative radiation

Male breast cancer (MBC) comprises <1% of all breast cancers in the United States. MBC is typically treated with total mastectomy while the majority of female breast cancer is treated with breast conservation therapy combined with various forms of radiation. One method that has developed over the last two decades is the use of intraoperative radiation therapy (IORT) as a type of accelerated partial breast irradiation to direct the treatment field to the tumor bed. Since overall prognosis and systemic therapy recommendations for MBC are similar to breast cancer in women, we describe the first case of MBC treated with BCS and IORT. Our patient is a 62‐year‐old male who was found to have a right breast 1.6 cm palpable mass at the 10:00 position 1 cm radially from the nipple. Core biopsy demonstrated invasive ductal carcinoma, moderately differentiated, estrogen and progesterone receptor positive, and Her 2 Negative. The patient had a strong desire for breast conservation, and needed to minimize daily radiation treatments due to his work schedule. After discussion among our multidisciplinary tumor board, we felt this patient to be suitable for BCS and IORT given his age, favorable tumor subtype, size, and clinically early stage breast cancer. A right axillary sentinel lymph node biopsy and central lumpectomy was performed. The INTRABEAM device (Carl Zeiss Meditec, Oberkochen, Germany) was utilized for radiation delivery. The patient had negative margins on his final pathology. The postoperative course was uneventful and at the 6 month follow‐up visit there were no issues and he had an excellent cosmetic outcome. BCS and IORT is an option in appropriately selected male patients with favorable subtype early stage breast cancer.     

Hereditary breast cancer: part II. Management of hereditary breast cancer: implications of molecular genetics and pathology

Abstract:  Management of patients at high risk for hereditary breast cancer (HBC) must critically assess its phenotypic and genotypic heterogeneity, particularly evidenced by the varying spectra of cancer sites that are integral to the respective HBC syndromes. Targeted management must consider their biology, pathology, and molecular genetics, all in concert with their respective carcinogenic pathways, as they may differ significantly from one breast cancer syndrome to the next. A striking example of management differences pertains to BRCA1 and BRCA2 mutation-positive breast cancers wherein those with BRCA1 mutations are frequently estrogen receptor (ER)-negative in contrast to BRCA2 mutations which are more frequently ER-positive; therein, significant differences exist with respect to anti-estrogen therapy which will be more amenable to BRCA2 versus BRCA1 mutation carriers manifesting breast cancer. In turn, tumors that are negative for ER, PR, and Her2-neu, often referred to as "triple negative" tumors, may also harbor a unique basal-like gene expression profile and are characterized by poor prognosis wherein endocrine and/or Her2-neu-targeted therapies are not effective treatment options. A further confounder pertains to the lifetime risk for ovarian cancer, which differs strikingly between BRCA1 mutation carriers, who show a 40–60% lifetime risk, and their BRCA2 counterparts, who carry a lifetime risk of approximately 12–15% for ovarian cancer. It is clear that as we learn more about the biology and the molecular aspects of hereditary forms of breast cancer, it will be compelling for the clinician to integrate this knowledge with pharmacologic, radiologic, and surgical treatment options for these high-risk patients.     

The influence of reduction mammaplasty techniques in synchronous breast cancer diagnosis and metachronous breast cancer prevention

BACKGROUND: Although reduction mammaplasty (RM) is a well-described technique for cosmetic objectives, there are few reports regarding its bilateral application combined with oncologic breast surgery in patients with breast cancer. The purpose of this study is to analyze the role of RM in the contralateral breast (CB) synchronous cancer (SBC) incidence, the impact in risk reduction for metachronous breast cancer (MBC), the disease-free period, and overall survival METHODS: Patients were divided into 2 groups; group I: 114 pts submitted to oncologic surgery associated with immediate CB RM. Group II: 135 pts without CB RM. Mean time of follow-up was 51.5 months for both groups. Data regarding age, tumor size, histologic type and grade, clinical stage, and adjuvant therapy were collected RESULTS: Except for the CB RM, no differences were observed between the groups. In group I, the diagnosis of an occult, synchronic, and invasive carcinoma was noted in 1.8%, in situ in 2.6%, and MBC in 1.8%. In group II, MBC was observed in 6.7%. No difference was observed between the 2 groups (P = 0.062). The initiation of adjuvant therapy, the disease-free period, and overall survival were not influenced by the CB RM. CONCLUSION: CB RM is a reliable technique providing an opportunity for diagnosis of an occult SBC. There is evidence of reduction of MBC; however, a larger number of patients are necessary for significant conclusions. The technique should be considered in combination with immediate breast reconstruction. Success depends on patient selection and careful intraoperative management.     

Metaplastic breast carcinoma: Current therapeutic approaches and novel targeted therapies

Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer consisting of various combinations of malignant epithelial and mesenchymal cells. Its aggressive growth pattern combined with its histological heterogeneity account for MBC's characteristic resistance to systemic therapies, which subsequently leads to increased risk of recurrence and breast cancer mortality compared with other invasive mammary carcinomas. The aim of this review is to discuss the current therapeutic approaches, both in loco‐regional as well as in systemic management of MBC. With the accumulation of knowledge from histopathologic assessment and the increasing identification of underlying molecular aberrations, emerging, novel targeted therapies will enable physicians to implement a more individualized and efficacious therapeutic strategy, leading hopefully to an improvement in the poor prognosis of MBC.