Mucinous cancers have fewer genomic alterations than more common classes of breast cancer

Mucinous cancers of the breast are distinguished histologically by their abundant pools of mucin and low degree of nuclear pleomorphism. Relative to the more common breast cancers of no distinctive type (ductal carcinoma), mucinous cancers have a relatively favorable prognosis. In a study of chromosomal changes in mucinous cancers, we evaluated the extent of loss of heterozygosity (LOH) at chromosomal regions commonly deleted in usual infiltrating ductal carcinoma, including markers on chromosomal arms 1p, 1q, 3p, 6q, 8p, 9p, 11p, 11q, 13q, 16q, 17p, and 17q. Remarkably, we found an average frequency of LOH of only 1.9 of these 12 chromosomal arms in 18 cases of mucinous carcinoma, compared to an average frequency of LOH of 6.4 of these same chromosomal arms in cases of infiltrating ductal cancer. In three of the 18 cases of mucinous carcinoma studied, including one case with regional lymph node metastases, no LOH was seen at any of the 12 chromosomal regions studied. We considered the possibility of other chromosomal loci being more commonly affected in mucinous cancers and conducted comparative genomic hybridization on six of the cases. These studies demonstrated a low overall frequency of genomic copy number changes (mean of 3.1 changes per case) and failed to reveal any other chromosomal locus with frequent losses that had not been evaluated by microsatellite analysis. Together, these data indicate that mucinous cancers of the breast do not have the extensive genomic alterations that are typically found in more common variants of breast cancer. Thus, mucinous cancers most likely have less genetic instability than most other forms of breast cancer and the molecular pathogenesis of this form of breast cancer is likely to be substantially different than that of usual ductal breast cancer.     

特殊类型乳腺恶性病变与常见浸润性导管癌超声声像图的对比分析

目的 探讨少见的特殊类型乳腺恶性病变与常见乳腺浸润性导管癌的超声声像特征差异.方法 选取经术后病理证实的乳腺乳头状癌34例,乳腺黏液癌39例,同期诊断的乳腺浸润性导管癌100例,对3组患者的术前超声声像进行分析对比,探讨乳腺乳头状癌、乳腺黏液癌与乳腺浸润性导管癌的声像特征差异.结果 乳腺乳头状癌的病灶直径≥2 cm(76.47％)、边界清晰(52.94％)、边缘无毛刺(73.53％)、后方回声不衰减或增强(82.35％)、病灶内部等回声(35.29％)、无微小钙化灶(55.88％)的比例均高于乳腺浸润性导管癌,差异均有统计学意义(P﹤0.05);乳腺黏液癌的病灶边缘无强回声晕(79.49％)、后方回声不衰减或增强(84.62％)、病灶内部混杂回声(64.10％)、病灶内部等回声(25.64％)、无微小钙化灶(74.36％)的比例均高于乳腺浸润性导管癌,差异均有统计学意义(P﹤0.05).结论 乳腺乳头状癌、乳腺黏液癌与乳腺浸润性导管癌的声像特征存在差异,可以作为术前鉴别诊断的一种辅助手段应用.     

Carcinome colloïde pur du sein : étude anatomoclinique de sept cas

PurposeBreast mucinous carcinoma is a particular histological form characterized by the extracellular production of mucus. The pure form is rarely reported and its prognostic is better than the other types of the breast cancer. The aim of the present study was to discuss the various anatomoclinical, therapeutic aspects and the prognostic factors of the pure mucinous carcinoma of the breast.Patients and methodsWe report seven cases diagnosed over a period of 11 years (1993-2003) in the laboratory of anatomy and pathological cytology of the university hospital of Sfax. A review of the clinical files with immunohistochemistry study (hormonal receptor, synaptophysine, chromogranine, Bcl2, Ki67, P53 and Her-2/neu (C-erbB-2)) were carried out for all the cases.Resultspure colloid carcinoma of the breast accounted for 0,5% of the whole of the breast cancers. The average age of patients was 69 years. At the time of the diagnosis, four tumours were classified T4, one T3, two T2, two N1 and one N3; no patient had presented metastasis (M0) according to pTNM classification. The echomammography showed regular contours mass in four cases. The anatomopathological study showed that the neuroendocrine differentiation was found in two cases, all the tumours had presented positivity for the hormonal receptors (oestrogen and progesterone) and negativity for the other antibodies, two cases exhibited the Bcl2 positivity and negativity for the other antibodies. An adjuvant radiotherapy was carried out for all the patients. The average duration of follow-up was of 33 months; the evolution was marked by the occurrence of metastases in two cases.ConclusionThe pure colloid carcinoma of the breast constitutes a particular morphological entity which deserves to be individualized; neuroendocrine differentiation of these tumours must be required. Their forecast is relatively favourable.     

Mucinous carcinoma of the breast in Japan. A prognostic analysis based on morphologic features

In 175 women with mucinous carcinoma (MC) of the breast, the morphologic features, the clinicopathological features (age, tumor size, and nodal status) and prognoses were investigated. They were divided into two types, those with "unmixed type" (n = 140) showing no component of invasive ductal carcinoma (IDC) and "mixed type" (n = 35) including an IDC component. The unmixed type showed less frequent (P less than 0.01) nodal involvement and a higher degree (P less than 0.005) of extracellular mucus production than the mixed type. The presence of nodal metastases showed no correlation with the degree of mucus production. The 10-year survival rate of the unmixed type (90.4%) was better (P less than 0.001) than in the mixed type (66.0%). In the unmixed type, a higher level of mucus production showed trends toward a better prognosis, younger age and smaller tumor size (P less than 0.01). In the mixed type, the degree of mucus production showed no significant correlation with either the age, tumor size, or prognosis. It is more important for the prognosis of patients with MC to have no IDC component than to show abundant mucus within the tumor.     

可手术年轻乳腺癌92例临床分析

[目的]探讨可手术年轻乳腺癌的临床病理特点及诊治策略。[方法]回顾分析92例年龄≤40岁的可手术乳腺癌患者（年轻组）的临床资料,随机抽取年龄在41—69岁的年长乳腺癌患者（年长组）92例与年轻组作临床病理特点分析比较。[结果]年轻组肿块长径0．8～6．5cm,平均2．8era。浸润性导管癌82例,导管内癌、导管内癌微浸润、髓样癌各2例,导管内乳头状瘤原位癌、黏液腺癌、浸润性导管癌伴灶区黏液腺癌、混合性癌各1例。淋巴结分期Nn19例,N1 51例,N2及以上22例。浸润癌组织学分级Ⅰ-Ⅱ级47例,Ⅲ级42例。免疫组化：ER／PR阳性57例,Her-2阳性30例;三阴性乳腺癌22例;有癌栓者33例。病理分期0期3例,Ⅰ期28例,Ⅱ期35例,Ⅲ期26例。与年长组比较,年轻组在高组织学分级、Her-2阳性、伴有癌栓三者比例较高,差异有统计学意义（P值分别为0．048、0．044、0．022）;而在肿瘤大小、是否为浸润性癌、淋巴结分期、激素受体阳性比例、是否三阴性乳腺癌及病理分期上与年长组均无明显差异（P〉0．05）。[结论]年轻乳腺癌有独特的病理学特点,恶性程度更高,应早诊断、早治疗。     

Risk of subsequent contralateral breast carcinoma in a population of patients with in-situ breast carcinoma

One hundred ninety-one cases of unilateral noninvasive breast carcinoma were studied with regard to the development of subsequent cancers in the contralateral breast. The majority of patients were treated by mastectomy and have been followed for an average of nine years. Their overall survival did not differ significantly from that of age-specific population survival figures for U. S. women. Among all cases, 13 or 6.8% subsequently developed contralateral carcinoma; 3.1% of these contralateral tumors were invasive. The authors found only one histological type, namely lobular carcinoma in-situ for which the development of subsequent contralateral carcinomas was statistically significant. Seven of the 68 women with this type developed second breast cancers (10.3%; 4.4% of these were invasive). These data suggest that the occurrence of clinically apparent subsequent cancers developing in the opposite breast following the diagnosis of in-situ carcinoma is relatively small.     

A case of mucinous carcinoma of the breast that demonstrated a good pathological response to neoadjuvant chemotherapy despite a poor clinical response

A 30-year-old woman presented with a right breast tumor. Mucinous carcinoma was diagnosed by core needle biopsy (T2: 5 cm N1 M0). Despite receiving a neoadjuvant anthracycline and taxane regimen, the patient demonstrated no clinical response (NC). Based on the patient's strong preference, we performed breast-conserving surgery. On histological examination, we observed widespread mucus and a few viable malignant cells, a Grade 2 therapeutic response. Neither optimal management procedures nor guidelines for chemotherapy for primary mucinous carcinoma of the breast have been established. It is a reasonable assumption, however, that discordance between the clinical response and therapeutic response to neoadjuvant chemotherapy may occur in cases of mucinous carcinoma.     

Massive mucinous carcinoma of the breast untreated for 6 years

 We report a patient with a massive mucinous carcinoma of the breast that had been untreated for 6 years. A 47-year-old premenopausal woman presented with a large right-breast mass. Although she had noticed a lump in the right breast 6 years previously, she had not sought treatment. The tumor had enlarged gradually and become ulcerated. With a diagnosis of advanced breast cancer with skin invasion, she underwent right mastectomy with a free skin graft. No lymph node metastases or distant metastases were detected. The histologic diagnosis of the tumor was pure mucinous carcinoma of the breast with no component of ordinary invasive ductal cancer. She has been well without evidence of tumor recurrence for 7 years after the surgery. The prognosis for mucinous carcinoma of the breast has been recognized as relatively good. The results in our patient are consistent with the biological behavior of this carcinoma. Received: August 29, 2002 / Accepted: December 12, 2002 Correspondence to:F. Yoneyama     

Carcinome mucineux du sein : profil clinique,biologique et évolutif

PurposeMucinous carcinoma of the breast accounts for 1 to 4% of all breast cancer. There are two histological subtypes: mixed mucinous carcinoma, where the ductal carcinoma is associated with the colloid component, and pure mucinous carcinoma, with a favorable prognosis, where the mucus surrounds the tumour tissue and constitutes a mechanical barrier limiting cell invasion and making this form less aggressive. Our study aimed to determine retrospectively the main epidemiological, clinical, biological, and therapeutic features, as well as the prognosis of this rare form of breast carcinoma.Materials and methodsThe authors report 32 cases of mucinous carcinoma of the breast diagnosed in Mohammed-VI centre for cancer treatment in Casablanca.ResultsThe average tumour size was 4.5 cm (0.5–7 cm). We found ten positive lymph node dissections, seven of them were of mixed mucinous carcinoma with a tumour size ranging between 4 and 7 cm. Mucinous carcinoma was pure in 16 cases, mixed in 14 and a neuroendocrine differentiation was found in two cases. Most tumours were of an intermediate histological grade (n = 19) with positive hormonal receptors (68%). After a mean follow-up of 30 months, complete remission was maintained in 92% of evaluable patients.ConclusionMucinous carcinoma is a rare type of breast cancer, with a favourable prognosis for the pure form.     

Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance

Metastases to axillary lymph nodes is an important factor in predicting prognosis and survival in primary operable carcinoma of the breast. A series of post mastectomy lymph nodes (150 cases) was selected in this retrospective study, in which the initial diagnosis had been no metastases by light microscopy and in which a long follow-up was available (average 10 years). The original H&E sections from these cases were immunostained to detect metastases which might not have been previously appreciated. The study was performed using a cocktail of 5 monoclonal antibodies directed against epithelial antigens. The object was to explore the possibility of detection of occult micrometastases by immunohistochemistry and to evaluate their prognostic significance. Micrometastases with individual cells and cell clusters were readily detected by this technique in 14% of all cases. It also became apparent towards the end of the study that micrometastases could be detected with equal sensitivity by any one of the 5 monoclonal antibodies. Positive staining of malignant cells was found to be more frequent in invasive lobular carcinoma (ILC) than in invasive ductal carcinoma (IDC). However, for the IDC group a striking association was found between micrometastases and both recurrence and survival rate. The ILC sample was considered too small for meaningful interpretation. We recommend the use of immunohistochemical techniques using monoclonal antibodies for the detection of occult metastases in lymph nodes to improve the prediction of recurrence and survival in invasive ductal carcinoma of the breast.     

Multinucleated mammary stromal giant cells: a benign lesion that simulates invasive carcinoma.

Multinucleated stromal giant cells were found in breast tissue from 14 patients treated by mastectomy for carcinoma over 3 decades (1950s to 1970s). Nine cases were found in a review of 200 consecutive mastectomies (4.5%) performed in 1978. The average age was 51 years with nine patients in their 40s. Other than the age distribution, no association with marital status, family history of breast carcinoma, hormone usage, tumor type, or stage of disease was observed. This benign lesion of undetermined significance should not be misinterpreted as invasive carcinoma. Multinucleated stromal giant cells have been observed in breast specimens from patients not known to have carcinoma at the time of biopsy. These patients had a similar age distribution as those with concurrent carcinoma. Follow-up will be required to determine if the association with carcinoma is significant or merely a coincidence reflecting age or some other yet to be identified factor.     

Diagnosis of T0 carcinoma of the breast

From 1978 through 1986, 74 cases (77 lesions) of T₀ carcinoma of the breast were studied. All of these cases were treated with mastectomy. Pathologically, 52 cases (67.5%) were early carcinoma, including noninvasive (30), early invasive (19) and specific type (3). Axillary lymph node metastasis was present in 12.9% of the cases. Follow-up study revealed that 46 patients have been living and in good health for 3–5 years. For successful detection, the following prerequisites are indispensable: (1) physicians concerned must be aware of the new concept that most early breast carcinoma may not be palpable; (2) physicians must be well familiarized with the clinical manifestations of nonpalpable carcinoma of the breast; (3) any abnormalities of the breast must be thoroughly investigated until proven otherwise; and (4) combined diagnostic procedures must be used.     

产生基质的化生性乳腺癌六例临床病理分析

目的 产生基质的化生性乳腺癌(matrix-producing metaplastic carcinoma of the breast,MPMC)较罕见,病理形态非常特殊,容易导致误诊.本研究探讨MPMC临床病理学特征、诊断要点及鉴别诊断.方法 收集2010-01-01-2016-01-01北京大学人民医院MPMC患者6例.患者均为女性,年龄42~73岁,中位年龄49岁.分析6例MPMC的临床特点,观察其组织病理学表现并进行免疫组化染色,同时复习相关文献资料.结果 肿瘤呈结节状生长,部分区域呈浸润性生长方式.结节周围为大片上皮样巢团,中央为黏液软骨样基质,可见坏死.6例上皮样细胞团均为乳腺浸润性导管癌,4例组织学分级呈Ⅲ级改变,2例为Ⅱ级.免疫组化6例患者中有4例ER、PR和C-erbB-2阴性,1例ER阳性,1例C-erbB-2为+,6例CK5/6、S100、CK和Vimentin、EGFR阳性.另做组织化学染色AB-PAS,6例均为阳性.结论 MPMC一种非常罕见的恶性肿瘤,诊断时需与叶状肿瘤等鉴别,免疫组化有助于鉴别诊断.     

Breast cancer in women thirty years old or less]

PURPOSE: Breast cancer rarely occurs in very young women, its diagnosis and management could sometimes be difficult. Our aim is to analyse the epidemiological and clinicopathological features of a group of very young women and especially to evaluate the results of therapeutic strategy. METHODS: We report a retrospective study conducted at the department of radiotherapy in Alexis-Vautrin Centre, concerning 30 patients aged < or = 30 years in whom a diagnosis of invasive breast carcinoma was made between 1986 and 2001. RESULTS: Six patients had familial history of breast cancer. Palpable tumor was found in 90% of cases, the average size was 3.5 cm. Eleven patients presented with stage I, 11 presented with stage II, 6 presented with stage III and 2 presented with stage IV. Five cancers were diagnosed after pregnancy (average tumor size = 5.8 cm). Eleven patients received neoadjuvant chemotherapy and 23 (82%) of 28 operable cases of invasive malignancy underwent breast conservative surgery (BCS). We found an invasive ductal carcinoma with grade III in 13/27 cases and a nodal involvement in a half of cases, 11 patients of 26 had no expression of oestrogen receptor. The average follow-up was 5 years: six patients (20%) recurred locally (all of them were initially treated by BCS), four patients developed a contralateral breast cancer and three developed a second malignancy. Ten patients died of their metastatic disease. The 5-year overall survival rate was 78%. CONCLUSION: Our results are consistent with those of the published reports and suggest that very young women with breast cancer have a poorer prognosis compared with the older ones. They should receive, according to their prognostic factors, an appropriate regional, systemic and hormonal therapy.     

A case of multiple breast mucinous carcinomas

A case was a 46-year-old woman who presented with the left breast lump confirmed about 30 years ago. In August 2006, the patient came to our hospital for consultation due to her breast lump was enlarged. Mammography revealed a frequent occurrence of the mass shadow of marginal irregularity and we diagnosed it with category 4. Breast echography showed a lot of irregular lesions. Even breast MRI presented a multiple mass-related lesion. The malignancy was possible, and a needle biopsy diagnosed them to be mucinous carcinoma. Pectoralis muscle preservation mastectomy and sentinel lymph node biopsy technique were used for surgery. Histopathology also diagnosed it to be mucinous carcinoma, T2N0 M0, stage IIA, ER (+), PgR (+), HER2 score 0. It has been 4 years since the operation but no sign of recurrence/metastasis was observed at present. There have been few reports of breast cancer with multiple cases, mucinous carcinoma as a case in point. Therefore, we report the invaluable case in addition to some paper consideration with it.     

Colloid cancers of the breast. Value of radiotherapy. A series of 138 cases treated at the Curie Institute

A series of 138 mucinous breast carcinomas was treated at the Institut Curie from 1970 to 1980: 107 were diagnosed as "pure" mucinous carcinoma and 31 as "mixed" mucinous carcinomas. Fifty per cent of the cases were stage T2 and 78% N0-N1a. Treatment methods were radical mastectomy in 113 cases (82%) with pre-operative irradiation for 37 patients and post-operative irradiation for 14 patients. A conservative treatment was used for 25 patients, consisting either of lumpectomy followed by radiotherapy (in 15 cases) or radiotherapy alone (in 10 cases). The five-year actuarial survival rate was 81% for the "pure" group and 87% for the "mixed" group; it was 70 and 75%, respectively, at ten years follow-up. In this series, survival was not influenced by the type of treatment. The efficacy of radiotherapy was evaluated from the local recurrence rate: only four local failures among the 25 conservative treatments were noted. Our conclusion is that radiotherapy, with or without lumpectomy, is efficient in mucinous breast carcinoma and could be useful in selected cases.     

乳腺肿瘤中nm23基因蛋白的表达及意义

目的 探讨转移抑制基因nm23蛋白在乳腺肿瘤中的表达情况及临床意义。方法 应用免疫组化S-P法，对131例乳腺良、恶性肿瘤进行nm23基因蛋白检测，对其中102例乳腺癌者雌激素受体（ER）和孕激素受体（PR）检测。结果 nm23蛋白在浸润性小叶癌、导管内癌及粘液腺癌中呈高表达，而在髓样癌中呈低表达。nm23蛋白表达与乳腺癌患者的年龄、组织学分级、淋巴结转移及ER有密切相关性。结论 nm23蛋白表达可作为判断乳腺癌预后的一项独立指标，其高表达显示乳腺癌预后较好。     

The signaling adapter protein PINCH is up-regulated in the stroma of common cancers,notably at invasive edges

BACKGROUND: PINCH is an LIM (double zinc finger domain) protein that functions as an adapter at a key convergence point for integrin and growth factor signal transduction. Because no information is available regarding its expression in vivo in human tissues, this study evaluated the distribution and abundance of PINCH in patients with breast, prostate, lung, colon, and skin carcinomas. METHODS: A polyclonal antibody was raised to a purified 6-histidine PINCH fusion protein and used to evaluate 74 cases comprising 33 breast carcinomas (21 ductal carcinomas, 6 lobular carcinomas, 4 ductal carcinomas in situ, 2 lobular carcinomas in situ), 22 prostate carcinomas, 5 colon carcinomas, 6 lung carcinomas (3 adenocarcinomas and 3 squamous carcinomas), and 8 skin carcinomas (4 basal cell carcinomas and 4 squamous cell carcinomas) by immunoperoxidase histochemistry of formalin-fixed, paraffin-embedded tissues. Lysates of frozen tissue from the epithelium of two normal breasts and six breast carcinomas were evaluated by immunoblotting. RESULTS: Immunostaining for PINCH was increased in the cytoplasm of fibroblastoid cells in areas of the tumor-associated stroma in all carcinomatous tissues evaluated. The most intense stromal immunostaining for PINCH was noted at invasive edges, particularly in breast carcinomatous tissue. Immunoblotting of lysates from normal breast and breast carcinomatous tissue confirmed that PINCH protein expression was markedly increased in breast carcinomatous tissues. CONCLUSIONS: PINCH is up-regulated in tumor-associated stromal cells, particularly at invasive edges, and may be a marker for stroma manifesting the ability to facilitate invasion. Because of this and because PINCH functions as a "molecular switch" in signal transduction, PINCH may be a new target for drug discovery aimed at the tumor-associated stroma.     

A comparison of the results of long-term follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast

Follow-up information was obtained on 199 women with breast biopsy specimens containing intraductal epithelial proliferation. The proliferations were divided into regular or ordinary intraductal hyperplasia (IDH) (117 cases) and atypical intraductal hyperplasia (AIDH) (82 cases). The average length of follow-up was 14 years for the patients with IDH and 12.4 years for the patients with AIDH. Of the 117 patients with ordinary IDH, carcinoma subsequently developed in six (5%); three of these were invasive carcinomas (2.6%). All three invasive carcinomas were in the ipsilateral breast, but of the three intraductal carcinomas (IDCa), two were in the contralateral breast. Of the 82 patients with AIDH, invasive carcinoma subsequently developed in eight (9.8%); six of these were located in the ipsilateral breast and two in the contralateral breast. One of these six patients died of disseminated carcinoma. The average interval to the subsequent carcinoma (intraductal and invasive carcinoma) was about the same in the two groups (8.3 years for AIDH and 8.8 years for IDH lacking atypia). When considering only subsequent invasive carcinomas, the interval was 8.3 years for the AIDH and 14.3 years for the IDH lacking atypia. Of the 14 patients with IDH and a family history of breast carcinoma, invasive carcinoma subsequently developed in one (7%) as compared with two (2%) of the 91 with a negative family history. Among patients with AIDH, invasive carcinoma subsequently developed in two of the 13 (15%) of those with a family history of breast carcinoma as compared with one of 57 (1.8%) of the women with a negative family history. The presence of atypia in epithelial hyperplasia is a significant factor in increasing the likelihood of the development of subsequent invasive carcinoma (P = 0.03; two-tailed test). Of women with AIDH, invasive carcinoma subsequently developed in 17% of those with sclerosing adenosis (SA) as compared with 4.2% of those without it. Therefore, SA may be a contributing factor to increased risk. A positive family history also appears to increase the likelihood of the subsequent development of invasive carcinoma, particularly in patients with AIDH.     

保留乳房天然结构的乳腺癌改良根治术后即刻乳房成形术的临床应用

目的探讨保留乳房天然结构的乳腺癌改良根治术后即刻自体组织乳房成形术在临床中的运用价值。方法乳腺癌患者12例,其中DCIS 6例,浸润性导管癌3例,小管癌1例,髓样癌1例,黏液癌1例;保留乳房皮肤的乳腺癌改良根治术9例,保留乳头乳晕复合体的乳腺癌改良根治术3例。全组均保留或重建乳房下皱襞,切除乳腺组织和腋窝淋巴结,应用下腹部横行腹直肌肌皮瓣或背阔肌肌皮瓣即刻乳房成形。结果横行腹直肌肌皮瓣乳房成形术3例,背阔肌肌皮瓣乳房成形术9例,术后皮瓣均存活,皮瓣血管通畅,成形乳房外观良好。结论对早期乳腺癌患者行保留乳房天然结构的乳腺癌改良根治术后即刻自体组织乳房成形,切口隐蔽,成形乳房形态效果良好,可以获得较好的美容效果。