Breast cancer risk of lobular-based hyperplasia after biopsy: "ductal" pattern lesions

Three thousand three hundred three women were followed an average of 17 years following benign breast biopsy. These women comprise 84.4% of those originally targeted for follow-up. Risk of invasive breast cancer development was analyzed in relation to the hyperplasia classification scheme of Wellings et al (JNCI 1975; 55:231-73) that is based on terminal ductal-lobular units (ALA). Cancer risk was also assessed with respect to family history of breast cancer in first-degree relatives (FHBC), as well as atypical features of hyperplasia recognized by resemblance to carcinoma in situ of ductal type (ADH). There was a trend of increasing cancer risk with increasing degree of ALA lesion, reaching 1.9 with ALA-IV lesions having both qualitative and quantitative features of advanced atypical hyperplasia. When ADH lesions are removed from the analysis, any predictive power of ALA lesions is lost. ADH recognizes histologic lesions with a four- to fivefold increased risk of breast cancer. FHBC interacts with any hyperplastic lesion so as to approximately double the cancer risk.     

乳腺腺体局限性增厚区段切除在乳腺癌早期检出价值的探讨

目的：探讨乳腺腺体局限性增厚与乳腺癌的关系,以及合理的处理对策。方法：１９９８ 年２ 月～１９９８ 年１０ 月连续对山东省济宁市乳腺病医院就诊的４０ 例乳腺腺体局限性增厚的患者施行了区段切除术。结果：检出早期癌２ 例,癌组织大小均＜ １０ｃｍ ;囊性增生１５ 例;乳头状瘤病１２ 例。所检出的癌及增生性病变占病例总数的７３ ％ 。结论：对乳腺腺体局限性增厚应予以高度重视,以期早期检出乳腺癌、限制癌前病变进一步发展。     

Cell-mediated immunity to mouse mammary tumor virus antigens by patients with hyperplastic benign breast disease

Peripheral blood leukocytes of patients with preoperative breast cancer, benign breast disease, and benign gynecologic disorders and normal healthy females were tested, as blind coded specimens, with murine mammary tumor virus (MuMTV) antigens in the direct and indirect leukocyte migration inhibition (LMI) assays. The incidence of reactivity by patients with breast cancer was low. (From 5 to 35% breast cancer patients reacted, depending on which group of control individuals they were compared to and what antigen was used.) Nonparametric analyses showed no differences between control groups (normal donors and patients with gynecologic disorders) and breast cancer patients with either assay. However, there was a significant difference between benign breast disease patients with hyperplasia and 1) benign breast disease patients without hyperplasia (P less than 0.03) and 2) patients with gynecologic disorders (P less than 0.04) in the direct assay when it was performed blindly with the gp52 antigen. Patients with hyperplasia (benign breast disease as well as breast cancer) had a higher incidence of enhanced migration in the indirect test than breast disease patients without hyperplasia. The enhanced migration to the MuMTV was correlated to enhanced migration to a 3-M KCI extract of the breast cancer cell line MCF-7 in simultaneous tests. Thus the LMI assays with MuMTV antigens do not appear valuable in breast cancer diagnosis, but they may help to identify a small group of benign breast disease patients whose breast pathology is thought to be associated with a high risk for developing breast cancer.     

CD44~+/CD24~-、CD44~-/CD24~+在乳腺良恶性病变中的分布特点和临床病理意义

[目的]探讨CD44+/CD24-细胞、CD44-/CD24+细胞在乳腺癌发生不同阶段中(乳腺良性增生、乳腺不典型增生、乳腺原位癌、乳腺癌)分布规律,及其与乳腺癌临床病理因素之间的关系。[方法]采用免疫组化双染色方法检测45例正常乳腺组织、41例良性增生乳腺组织、39例不典型增生乳腺组织、51例乳腺原位癌组织、121例乳腺癌组织中CD44、CD24的表达情况,分析CD44+/CD24-细胞、CD44-/CD24+细胞在乳腺癌发生不同阶段中的数量和分布特点。[结果]CD44+/CD24-细胞存在于20.0%(9/45)的正常乳腺组织中,在29.3%(12/41)的乳腺良性增生组织、35.9%(14/39)的乳腺不典型增生组织、43.1%(22/51)的乳腺原位癌组织、52.9%(64/121)的浸润性乳腺癌组织中检测到CD44+/CD24-细胞,随着病变的进展,CD44+/CD24-细胞的数量也增加,差异具有显著统计学意义。此外,在33.3%(15/45)的正常乳腺组织中有CD44-/CD24+表达,43.9%(18/41)的乳腺良性增生组织、46.2%(18/39)的乳腺不典型增生组织、68.6%(35/51)的乳腺原位癌组织、86.0%(104/121)的浸润性乳腺癌组织检测到CD44-/CD24+细胞,且阳性细胞百分率随病变程度升高。在浸润性乳腺癌组织中CD44+/CD24-的表达与肿瘤有无淋巴结转移相关(P<0.05),但与病人年龄、月经状态、肿瘤的组织学类型、病理分级、肿瘤大小、ER、PR及Her-2的表达无显著相关(P>0.05),CD44-/CD24+的表达率与乳腺癌患者的各项临床病理特征均无统计学意义(P>0.05)。[结论]CD44+/CD24-、CD44-/CD24+细胞在乳腺增生和癌变过程中可能起重要作用。     

良恶性乳腺疾病的DNA倍性及细胞周期分析

 本文用流式细胞仪检测了111份乳腺肿块和95份肿块周围组织的DNA含量和细胞周期，对良恶性乳腺疾病的DNA倍性及细胞增殖活性进行比较，以探讨其在肿瘤诊断上的价值。结果表明，乳腺癌的异倍体率高达78％，且以多倍体为主，占89．74％；18例乳腺增生症中有2例异倍体（11．11％），43例乳腺纤维腺瘤中有11例异倍体（25．58％），但乳腺良性疾病和其周围组织以及癌周组织中均未见多倍体。细胞周期分析发现，乳腺癌及其癌周组织的增殖活性（S期百分比或增殖指数PI）明显高于乳腺良性疾病及其周围组织。结果提示，多倍体或高增殖活性在乳腺良恶性肿瘤的鉴别诊断中具有很重要的意义。     

不可触及的乳腺病灶行钼靶下导丝定位活检的临床应用

目的:探讨应用乳腺钼靶下导丝定位穿刺活检技术对不可触及的乳腺病变(NPBL)定性诊断上的价值。方法:本组24例不可触及,而钼靶上显示的乳腺微小病变,通过钼靶立体定位穿刺,放入导引钢丝定位后引导手术切除,进行组织病理学检查。结果:24例乳腺病变,乳腺癌5例,其中Tis期3例,T1期2例;小叶增生12例,纤维腺瘤3例,导管内乳头状瘤1例,慢性炎症3例。结论:钼靶引导下导丝定位穿刺活检对不可触及的乳腺病变的定位定性诊断以及对早期乳腺癌的诊断有重要价值。     

Evaluation of a breast cancer risk prediction model expanded to include category of prior benign breast disease lesion

BACKGROUND:

Benign breast diseases (BBD) encompass several histologic subtypes with various risks of subsequent breast cancer. Information on previous benign breast disease biopsies has been incorporated into breast cancer risk prediction models; however, the type of histologic lesion has not been taken into account. Given the substantial heterogeneity in breast cancer risk dependent on the type of benign lesion, the authors evaluated whether incorporating this level of detail would improve the discriminatory power of risk classification models.

METHODS:

By using data from the Nurses' Health Study, a breast cancer nested case‐control study (240 cases; 1036 controls), the authors determined predictors of categories of BBD lesions and developed imputation models. The type of BBD, imputed for each cohort member who reported a diagnosis, was added to a modified version of the Rosner‐Colditz breast cancer risk prediction model.

RESULTS:

Compared with the model that included only previous BBD (yes/no), the model that included categories of BBD was significantly improved (P < .0001). Overall, including the category of BBD increased the concordance statistic from 0.628 to 0.635. By using risk reclassification, inclusion of the type of BBD resulted in a 17% increase in incidence per increase of 1 risk decile, holding the model without BBD type risk decile constant.

CONCLUSIONS:

Although the current data suggested that the inclusion of BBD category may improve breast cancer risk classification, the clinical utility of such a model will depend on the consistency of histologic classification of benign breast disease lesions. Cancer 2010. © 2010 American Cancer Society.     

乳腺癌前病变与乳腺癌相关的多指标病理学研究

目的：探讨各种乳腺癌前病变与乳腺癌发生的关系。方法：应用全乳腺大切片技术结合ＣＥＡ、ｃ－ｅｒｂＢ－２癌基因产物免疫组化检测及流式细胞术（ＦＣＭ）测定ＤＮＡ含量、Ｓ期细胞比率（ＳＰＦ）和细胞增殖指数（ＰＩ）,对３９３例乳腺癌标本进行癌旁和癌前病变与乳腺癌相关性的多指标综合研究。结果：乳腺癌最多见的癌旁病变是导管上皮增生（５５．２％）,其次为囊性增生病（５３．４％）和乳头状瘤病（２２．２％）。其中与乳     

乳晕双环切口治疗乳腺囊性增生症伴乳房下垂

目的探讨沿乳晕双环法在肿块型乳腺囊性增生症伴乳房下垂治疗中的应用及其意义。方法患者取直立位设计切口：先确定新乳头的位置,画出外环,再以原乳头为中心,画出直径为3．5～4．0cm的内环。之后,去除内外环之间的表皮,广泛分离乳房皮下组织,切除囊性增生病变,并将剩余乳腺组织塑形、悬吊。结果本方法治疗轻、中度乳房下垂的乳腺囊性增生症患者共45例,术后乳房外形满意,乳头、乳晕血供和感觉良好,瘢痕不明显,效果良好。结论对于有需要手术的乳腺良性病变且伴有轻、中度乳房下垂的患者,采用沿乳晕的双环切口既可切除病变,又可悬吊乳房。其操作简便,效果满意。     

Endoscopic classification of intraductal lesions and histological diagnosis

BACKGROUND: To diagnose intraductal lesions endoscopically the Japanese Association of Mammary Ductoscopy classified the endoscopical appearance of lesions into three types. We investigated the correlation between endoscopic classification and histological diagnosis. METHODS: From April 1998 to February 2001, we enrolled 129 female patients who were diagnosed histologically and whose intraductal lesions were detected by mammary ductoscopy. The endoscopic classification consists of three types. The polypoid type is a localized expansive lesion. This type is divided into two subtypes, the solitary subtype (solitary polypoid lesion) and the multiple subtype (multiple polypoid lesions). The combined type is polypoid lesion(s)coexisting with a superficial type. The superficial type is a superficial spreading lesion such as a continuous luminal irregularity accompanied by no obvious elevations. RESULTS: There were 65 cases of breast cancer and 64 cases of benign papillary lesions. Fifty-four cases of benign papillary lesions and 7 cases of breast cancer were classified as the polypoid-solitary type. Seven benign cases and 13 cases of cancer were classified as the polypoid-multiple type. Two benign cases and 16 cases of cancer were classified as the combined type. Only one benign case and 29 cases of cancer were classified as the superficial type. There is significant correlation between endoscopical types and the histological diagnosis (p<0.0001). CONCLUSIONS: Endoscopic classification is useful to diagnose intraductal lesions.     

Sclerosing adenosis and risk of breast cancer

Over one million American women have a benign breast biopsy annually. Sclerosing adenosis (SA) is a common, but poorly understood benign breast lesion demonstrating increased numbers of distorted lobules accompanied by stromal fibrosis. Few studies of its association with breast cancer have been conducted, with contradictory results. We studied SA in the Mayo Benign Breast Disease (BBD) Cohort, which includes women who had benign biopsies at Mayo-Rochester 1967–2001. Breast cancer risk in defined subsets was assessed using standardized incidence ratios (SIRs), relative to the Iowa Surveillance, Epidemiology, and End Results registry. This BBD cohort of 13,434 women was followed for a median of 15.7 years. SA was present in 3,733 women (27.8 %) who demonstrated an SIR for breast cancer of 2.10 (95 % CI 1.91–2.30) versus an SIR of 1.52 (95 % CI 1.42–1.63) for the 9,701 women without SA. SA was present in 62.4 % of biopsies with proliferative disease without atypia and 55.1 % of biopsies with atypical hyperplasia. The presence of SA stratified risk in subsets of women defined by age, involution status, and family history. However, SA does not further stratify risk in women diagnosed with other forms of proliferative breast disease, either with or without atypia. SA is a common proliferative lesion of the breast which, as a single feature, conveys an approximate doubling of breast cancer risk. Its role in breast carcinogenesis remains undefined; its presence may aid in risk prediction for women after a breast biopsy.     

Benign breast lesions at risk of developing cancer—A challenging problem in breast cancer screening programs

BACKGROUND:

Cytology and core‐needle biopsies are not always sufficient to exclude malignancy in benign breast lesions (BBL) that are at risk of developing cancer, and open biopsy often is mandatory. In screening programs, open biopsies performed for lesions that are at risk of developing malignancy are considered benign. The authors of this report evaluated the impact of the screen‐detected BBL at risk of developing cancer that were counted in the quota of benign breast open biopsies in the Breast Cancer Screening Program of Verona.

METHODS:

Benign open biopsies were subdivided into 4 groups according to their risk of developing cancer: Histo1, normal histology; Histo2, ‘pure’ BBL (fibroadenoma, fibrocystic disease, mastitis, adenosis); Histo3, BBL with a low risk of developing cancer (radial scar, papilloma, papillomatosis, phyllodes tumor, mucocele‐like lesion); and Histo4, BBL with a high risk of developing cancer (atypical columnar cell hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia).

RESULTS:

Of 510 open biopsies, 83 biopsies were benign, and the ratio of benign to malignant biopsies was 1:5. Histo1 was observed in 4.8% of all benign open biopsies, Histo2 was observed in 37.4%, Histo3 was observed in 31.3%, and Histo4 was observed 26.5%.

CONCLUSIONS:

BBL at risk of developing cancer may be numerous in screening programs. It is inappropriate to include BBL at risk of developing cancer in the overall benign open biopsy rate. The authors propose separating pure BBL from lesions at higher risk of developing cancer. To date, there is no evidence to support the premise that detecting high‐risk proliferative lesions leads to benefits in terms of reduced mortality; however, these lesions need to be counted separately for future evaluations. Cancer 2009. © 2008 American Cancer Society.     

Histologic associations and long-term cancer risk in columnar cell lesions of the breast: a retrospective cohort and a nested case-control study

BACKGROUND: Mammary columnar cell lesions with atypia have been receiving increased scrutiny in view of their association with atypical hyperplasia (AH) and carcinoma. However, the few retrospective outcome studies performed have failed to establish an increased risk for recurrence or carcinoma on long-term follow-up. METHODS: The authors evaluated the overall cancer risk for 1261 biopsies with columnar cell lesions (CCL) in 4569 women from the Nashville Breast Cohort who were biopsied between 1969 and 1988. On the basis of Schnitt and Vincent-Salomon's classification, they also classified 229 biopsies with CCL into 3 categories: without hyperplasia or atypia, with hyperplasia lacking atypia, and with atypia. By using a nested case-control design, they compared the risks of invasive cancer associated with these 3 categories. RESULTS: A 2- to 3-fold increase in the occurrence of AH in the presence of CCL versus in their absence (P< .005) was observed. Relative risk of invasive breast cancer for women with both AH and CCL compared with those with AH alone did not differ significantly (risk ratio [RR]=1.55; P= .29). The presence of CCL alone was associated with a mild increase in the overall cancer risk (RR=1.47; P= .05). In the nested case-control study, no significant risk difference was observed among the 3 categories of CCL. CONCLUSIONS: The authors observed a positive association between CCL and AH. The possibility that CCL by themselves significantly elevate breast cancer risk is not well supported. However, a finding of CCL on benign breast biopsy may indicate the presence of AH, a more worrisome lesion.     

乳腺良性病变和乳腺癌临床病理特征及相关性分析

目的：探讨乳腺良性病变和乳腺癌的临床病理特征及相互关系.方法：对2 222例乳腺良性病变和乳腺癌的临床病理资料进行回顾性分析,免疫组化检测ER在癌旁组织中的表达.结果：乳腺增生性病变占乳腺良性病变的94.8%,乳腺浸润性癌在恶性肿瘤中占95.8%;乳腺癌平均发病年龄为47.1岁,显著高于乳腺增生性病变的34.98岁（Wilcoxon秩和检验,P＜0.000 1）;有恶性肿瘤家族史的乳腺疾病患者,发生乳腺癌的概率（6.5%）大于发生乳腺良性病变的概率（1.9%）,P＜0.001;72%的乳腺增生性病变存在＞3种病理成分;乳腺癌旁组织中不典型增生的发生率（23.5%）显著高于良性乳腺增生性病变中不典型增生的发生率（2.49%）,P＜0.01;乳腺癌旁不同良性病变与癌一样,对ER均有高表达.结论：乳腺增生性病变是女性最常见的病变成分复杂的良性疾病,其演变过程与乳腺癌有关.     

不伴肿物乳头溢液124例分析

 目的　深讨不伴肿物乳头溢液对检出早期乳腺癌及癌前病变的临床价值。方法　对124例不伴肿物乳头溢液患者(其中浆液性溢液47例,血性溢液74例,脓性3例),行手术治疗,先行病变导管切除,如为恶性,则行乳腺癌改良根治术。结果　本组病例良性者115例,占92.7%,其中乳腺导管内乳头状瘤和乳腺囊性增生病占79%;乳头状瘤(病)伴瘤细胞或导管上皮增生活跃(癌前病变)14例,占11.3%;乳腺癌9例,占7.3%,9例患者均为血性乳头溢液,占血性溢液之12.2%,均为临床早期癌(T0期乳腺癌)。结论　不伴肿物乳头溢液对检出早期乳腺癌及癌前病变有重要的临床价值。     

大炎肽与乳腺肿瘤恶化的关系

 目的 检测大炎肽在各类乳腺肿瘤组织中的分布,并验证它是否和乳腺肿瘤恶化相关。方法采用免疫组化辣根过氧化物酶染色检测。结果 乳腺癌的阳性染色率为90%,良性肿瘤的阳性率为20.5%。和其他肿瘤相比,乳腺癌着色差异显著（P〈0.005）。淋巴结转移癌中也有大炎肽分布。而良性组织中基本不表达。在乳腺癌样本中,大炎肽免疫着色强度随着组织增生、不典型增生和癌变的恶化而加深。结论 大炎肽可能在乳腺肿瘤的恶化过程中起到了一定的作用。     

乳腺良恶性病变GSTP1 基因的突变和多态性分析*

目的:检测谷胱甘肽S-转移酶P1（glutathione S-transferase P 1，GSTP1）基因各外显子的突变和多态性，探讨其与乳腺癌发生的关系。方法:选取乳腺癌及其相应癌旁增生组织标本各50例，良性增生组织标本50例，正常乳腺组织50例和正常人（志愿者）血液淋巴细胞15例为研究对象，运用PCR-SSCP 技术和DNA测序的方法检测GSTP1 基因外显子突变和多态性。结果:1）在3/50例（6%）乳腺癌组织中检测到GSTP1 基因外显子3 的11个位点发生突变，其中8 个突变位点是错义突变（MS），均可导致氨基酸的改变；2 个突变位点是同义突变（SS），氨基酸未发生改变；1 个突变位点发生移码突变（FS），造成氨基酸读码框顺序的改变，并产生新的终止密码子，使蛋白发生截短，造成功能缺失。在5/50例（10%）乳腺癌组织中检测到外显子4 的12个位点发生突变，其中6 个为错义突变（MS），均可导致氨基酸的改变；6 个移码突变（FS），突变热点在221 位碱基，发生率最高（33%）。 外显子6、7 和剪接点未见突变。在正常人外周血淋巴细胞、正常乳腺组织、癌旁和非癌旁乳腺增生组织中均未检测到该基因突变。2）在12/50例（24%）乳腺癌，5/50例（10%）乳腺癌旁增生，3/50例（6%）乳腺良性增生，3/50例（6%）正常乳腺组织和1/15例（6.7%）正常人淋巴细胞检测到GSTP1 基因外显子5 第313 核苷酸多态性（A→G，导致Ile105Val）。 结论:研究结果提示:1）GSTP1 基因外显子突变可能与部分乳腺癌的发生有关；2）GSTP1 第5 外显子的多态性与乳腺癌易感性可能有关。      

1883例乳腺肿块回顾性分析

目的总结我国最南端三亚热带地区乳腺疾病的发病情况.方法回顾性统计分析1 883例乳腺疾病的临床病理资料.结果非肿瘤性病变694例(36.9%),其中乳腺增生病602例(32.0%).肿瘤性病变1 189例(63.1%),良性肿瘤857例(45.5%),其中乳腺腺纤维瘤833例(44.2%);恶性肿瘤332例(17.6%),其中乳腺癌327例(17.3%).50岁以上181例,占恶性肿瘤发病人数的54.5%.结论乳腺癌总的发病率低于国内其他地区,而50岁以上年龄组高发.     

乳腺不同类型病变与乳腺癌细胞DNA含量分析

目的：探讨乳腺不同类型病变与乳腺癌发生的关系。方法：应用流式细胞术（ＦＣＭ）测定细胞核ＤＮＡ指数（ＤＩ）、Ｓ期细胞比率（ＳＰＦ）和细胞增殖指数（ＰＩ）,对１２０例乳腺不同类型病变进行分析。结果：ＤＩ、ＳＰＦ及ＰＩ均随正常上皮→轻度增生→中度增生→重度增生→非浸润癌→浸润而信次增加,重芳增生是与乳腺癌最密切相关的癌前病变。结论：对癌前病变特别是重度增生进行ＦＣＭ分析,有利于发现早期乳腺癌。     

Monoclonal antibody 44-3A6 as a marker for breast carcinoma.

The monoclonal antibody (MAb) 44-3A6 detects a 40-kD cell surface protein on adenocarcinomas and may serve as an effective marker for glandular differentiation. Immunohistochemical analysis of 123 paraffin-embedded malignant breast tissue specimens, 27 normal or benign breast disease specimens and 10 atypical hyperplasia specimens from patients without breast cancer was performed with MAb 44-3A6. The antigen was identified in 76% of breast cancer specimens, 0% of normal or benign breast disease specimens and 88% of the atypical hyperplasia specimens. MAb 44-3A6 also detected this antigen on adjacent normal breast ductal cells in 88% of the breast cancer specimens. There was no statistically significant correlation between immunoreactivity and histological mitotic or nuclear grade, recurrence or overall survival. This study suggests that the cell surface antigen detected by the MAb 44-3A6 may serve as an important marker in the differentiation of normal breast epithelium into an atypical or malignant lesion.