乳腺导管原位癌与导管原位癌伴微浸润的临床比较

目的 分析乳腺导管原位癌(DCIS)及原位癌伴微浸润(DCIS-MI)患者治疗模式变化、临床特征、治疗结果及预后因素。方法 回顾性分析中国医学科学院肿瘤医院1999-2013年收治的866例女性患者资料。DCIS患者631例,DCIS-MI患者235例。用Kaplan-Meier法计算局控(LC)、无瘤生存(DFS)、总生存(OS)率,并Logrank检验和单因素预后分析。结果 DCIS及DCIS-MI两组之间OS、LC及DFS相近(P>0.05)。单因素分析显示Her-2阳性为OS及DFS影响因素,保乳未放疗患者LC和DFS劣于全乳切除术患者。结论 导管原位癌和导管原位癌伴微浸润总体生存结果类似,Her-2阳性为OS及DFS预后不良因素,保乳未放疗患者的LC和DFS劣于全乳切除术。     

乳腺导管原位癌与导管原位癌伴微浸润的临床比较

目的 分析乳腺导管原位癌(DCIS)及原位癌伴微浸润(DCIS-MI)患者治疗模式变化、临床特征、治疗结果及预后因素。方法 回顾性分析中国医学科学院肿瘤医院1999-2013年收治的866例女性患者资料。DCIS患者631例,DCIS-MI患者235例。用Kaplan-Meier法计算局控(LC)、无瘤生存(DFS)、总生存(OS)率,并Logrank检验和单因素预后分析。结果 DCIS及DCIS-MI两组之间OS、LC及DFS相近(P>0.05)。单因素分析显示Her-2阳性为OS及DFS影响因素,保乳未放疗患者LC和DFS劣于全乳切除术患者。结论 导管原位癌和导管原位癌伴微浸润总体生存结果类似,Her-2阳性为OS及DFS预后不良因素,保乳未放疗患者的LC和DFS劣于全乳切除术。     

乳腺导管原位癌伴微浸润与浸润癌患者的临床特征对比分析

目的:分析乳腺导管原位癌伴微浸润（ductal carcinoma in situ with microinvasion,DCIS-MI）与乳腺浸润性导管癌（invasive ductal carcinoma,IDC）患者的临床特征、治疗方式等。方法:回顾性分析55例乳腺导管原位癌伴微浸润及508例乳腺浸润性导管癌患者的临床资料,包括两组患者的年龄、月经情况、雌激素受体（estrogen receptor,ER）、孕激素受体（progestrone receptor,PR）、人表皮生长因子受体（human epidermal growth factor,HER-2）、肿瘤细胞增殖活性标志物（Ki67）的表达情况、分子分型、治疗方式及预后。结果:DCIS-MI组和IDC组患者在年龄上的差异不具有统计学意义（P＞0.05）,DCIS-MI组在已绝经及淋巴结转移阳性比例均低于IDC组（P＜0.05）;DCIS-MI组Ki67阳性表达率显著低于IDC组（P＜0.05）,ER、PR及HER-2阳性表达率与IDC组比较差异无统计学意义（P＞0.05）。DCIS-MI组Luminal A型比例高于IDC组,而Luminal B(HER-2-)型比例低于IDC组,且差异均具有统计学意义（P＜0.05）。其余分子分型差异不具有统计学意义。DCIS-MI组患者单纯乳房切除术比例（10.9%）显著高于IDC组（0.8%）（P＜0.05）。DCIS-MI患者主要采用的手术方式为乳腺癌改良根治术和全乳切除+腋窝淋巴结清扫,其比例分别为60.0%、16.4%,与IDC组患者采用相同手术方式的比例（67.3%、19.9%）无显著差异。DCIS-MI组化疗比例、放疗比例均低于IDC组（P＜0.05）,而两组患者在内分泌治疗、靶向治疗及中药治疗方面差异不具有统计学意义（P＞0.05）。DCIS-MI组和IDC组患者的5年无病生存（disease-free survival,DFS）率分别为97.0%和81.0%,差异具有统计学意义（Log-rank,χ2=4.962,P=0.026）。结论:与IDC患者相比,DCIS-MI组患者绝经前状态比例高、淋巴结转移阳性率及Ki67阳性率更低,Luminal A型比例更高而Luminal B(HER-2-)型比例更低;DCIS-MI组患者行单纯乳房切除术比例更高,放疗及化疗比例更低,其预后更好。     

Radiation therapy for ductal carcinoma in situ: a decision analysis

BACKGROUND:

The benefit of adding radiation therapy after excision of ductal carcinoma in situ (DCIS) is widely debated. Randomized clinical trials are underpowered to delineate long‐term outcomes after radiation.

METHODS:

The authors of this report constructed a Markov decision model to simulate the clinical course of DCIS in a woman aged 60 years who received treatment with either of 2 breast‐conserving strategies: excision alone or excision plus radiation therapy. Sensitivity analyses were used to study the influence of risk of local recurrence, likelihood of invasive disease at recurrence, surgical choice at recurrence, and patient age at diagnosis on treatment outcomes.

RESULTS:

The addition of radiation therapy was associated with slight improvements in invasive disease‐free and overall survival. However, radiation therapy decreased the chance of having both breasts intact over a patient's lifetime. Radiation therapy improved survival by 2.1 months for women who were diagnosed with DCIS at age 60 years but decreased the chance of having both breasts by 8.6% relative to excision alone. The differences in outcomes between the treatment strategies became smaller with increasing age at diagnosis. Sensitivity analyses revealed a greater benefit for radiation with an increased likelihood of invasive recurrence. The decrement in breast preservation with radiation therapy was mitigated by an increased likelihood of mastectomy at the time of recurrence or new breast cancer diagnosis.

CONCLUSIONS:

The current analysis quantified the benefits of radiation after excision of DCIS but also revealed that radiation therapy may increase the likelihood of eventual mastectomy. Therefore, the authors concluded that patient age and preferences should be considered when making the decision to add or forgo radiation for DCIS. Cancer 2012;. © 2011 American Cancer Society.     

Telomerase activity in ductal carcinoma in situ of the breast

Telomerase plays an important role in maintaining the stability of the chromosomes. Activity of telomerase has been detected in proliferating and immortalized cell lines and in a number of malignant tumors including invasive breast cancer. The aim of the study was to examine telomerase activity in ductal carcinoma in situ (DCIS), which is considered to be a precursor lesion of infiltrating breast carcinoma, using a PCR-based telomerase activity protocol (TRAP). We examined 35 samples obtained from histologically confirmed breast biopsies, including 13 normal breast tissues, 11 infiltrating ductal carcinoma (IDC), nine DCIS, and two DCIS with microinvasion. Telomerase activity was demonstrated in 8/9 samples of DCIS, both samples of DCIS with microinvasion, and all but one sample of IDC. Normal breast tissue had no demonstrable telomerase activity. Our results indicate that telomerase is activated frequently in early breast carcinogenesis, although its utilization as a biomarker in DCIS is questionable.     

Effect of radiotherapy boost and hypofractionation on outcomes in ductal carcinoma in situ

BACKGROUND:

Boost radiotherapy (RT) improves outcomes for patients with invasive breast cancer, but whether this is applicable to patients with pure ductal carcinoma in situ (DCIS) is unclear. This study examined outcomes from whole breast RT, with or without a boost, and the impact of different dose‐fractionation schedules in a population‐based cohort of women with pure DCIS treated with breast‐conserving surgery (BCS).

METHODS:

Data was analyzed for 957 subjects diagnosed between 1985 and 1999. RT use was analyzed over time. Ten‐year Kaplan‐Meier local control (LC), breast cancer specific survival (BCSS), and overall survival (OS) were compared using the log‐rank test. Cox regression modeling of LC was performed.

RESULTS:

Median follow‐up was 9.3 years. Of the patient cohort 475 (50%) had no RT (NoRT) after BCS, 338 (35%) had RT without a partial breast boost (RTNoB), and 144 (15%) had RT with boost (RT + B). Subjects with risk factors of local recurrence were more likely to receive RT. Subjects receiving adjuvant RT had a trend toward improved LC (15‐year LC: NoRT 87%; RTNoB 94%; RT + B 91%; P = .065). Multivariable analysis showed that RT with or without a boost was significantly associated with improved LC (HR, 0.29 and 0.38, respectively, compared with NoRT, P = .025), with no difference associated with a boost or different dose‐fractionation schedules.

CONCLUSIONS:

Adjuvant RT improves local control in patients with DCIS treated with BCS. Hypofractionation is as effective as standard fractionation schedules. Boost RT was not associated with improved LC compared with whole breast RT alone. Cancer 2011. © 2010 American Cancer Society.     

乳腺导管原位癌与浸润性导管癌染色体微卫星杂合性缺失的比较

目的:研究乳腺导管原位癌与浸润性导管癌染色体3p区域微卫星杂合性缺失(loss of heterozygosity,LOH)的发生情况.方法:选取本院2005年9月至2009年2月手术切除石蜡包埋的乳腺癌组织切块43例,应用激光显微切割技术留取组织中乳腺浸润性导管癌(invasive ductal type carci...     

An attempt to independently verify the utility of the Van Nuys Prognostic Index for ductal carcinoma in situ

BACKGROUND: The Van Nuys Prognostic Index (VNPI) purports to predict the risk of ipsilateral breast tumor recurrence (IBTR) after excision of ductal carcinoma in situ (DCIS). It is a simple scoring scheme based on a retrospective evaluation of data from a single group of investigators. Various versions of VNPI have been proposed using clinical and pathologic features including tumor size, tumor grade, margin width, and patient age. Despite common use of VNPI in the clinical management of patients with DCIS, independent validation is lacking. METHODS: A total of 222 patients were retrospectively analyzed with mammographically detected DCIS who were treated with surgical excision alone. Wire-localized excisional biopsy was performed and surgical specimens were measured and inked to assist in margin assessment. Multiple sections of each specimen were evaluated for histopathologic subtype, histologic and nuclear grade, presence of necrosis, maximum dimension of the lesion, and margin width. Each patient was prospectively evaluated by a multidisciplinary management team and presented with adjuvant treatment options including whole breast radiotherapy and/or tamoxifen. All patients in this cohort declined radiotherapy. Thirty-one percent of patients received tamoxifen. Patients were followed clinically every 3 to 6 months, and mammographically every 6 to 12 months. IBTR was confirmed by biopsy. Wilcoxon regression analysis was used to evaluate risk groups according to 3 proposed VNPI classification schemes: VNPI Group 1 (margin, grade, and size), VNPI Group 2 (margin, grade, size, and patient age), and VNPI Group 3 (margin only). RESULTS: With a median follow-up of 4.6 years, the crude rate of IBTR was 8.6% for the entire cohort. Of the patients who developed an IBTR, 73.7% had a lesion with a maximum dimension of < or =15 mm, 47.4% had a margin > or =10 mm, and 36.8% had grade 1 histology. At 5 years, IBTR was statistically indistinguishable for the 3 VNPI models. The 5-year freedom from IBTR for low-risk, intermediate-risk, and high-risk groups according to VNPI Group 1 was 96%, 84%, and 100%, respectively (P = .20). Similarly, the 5-year freedom from IBTR for low-risk, intermediate-risk, and high-risk groups according to VNPI Group 2 was 95%, 83%, and 100%, respectively (P = .19). Taking into account margin status only (VNPI Group 3) the 5-year freedom from IBTR for low-risk, intermediate-risk, and high-risk groups was 92%, 91%, and 91%, respectively (P = .98). Tamoxifen use did not appear to affect the 5-year rate of IBTR (95% vs 94%; P = 1.0). CONCLUSIONS: The results of the current study suggest that VNPI or margin width alone is not a valid tool with which to assist in the stratification of patients after excision alone for their risk of IBTR at 5 years. Further follow-up may strengthen the predictive utility of the various VNPI classification schemes.     

Compliance with guidelines is related to better local recurrence-free survival in ductal carcinoma in situ

The aim was to study the effect of compliance with guidelines on local recurrence (LR)-free survival in patients treated for ductal carcinoma in situ (DCIS). From January 1992 to December 2003, 251 consecutive patients had been treated for DCIS in two hospitals in the North Netherlands. Every case in this two-hospital sample was reviewed in retrospect for its clinical and pathological parameters. It was determined whether treatment had been carried out according to clinical guidelines, and outcomes in follow-up were assessed. In addition, all patients treated for DCIS in this region (n=1389) were studied regarding clinical parameters, in order to determine whether the two-hospital sample was representative of the entire region. In the two-hospital sample, 31.4% (n=79) of the patients had not been treated according to the guidelines. Positive margins were associated with LR (hazard ratio (HR)=4.790, 95% confidence interval (CI) 1.696-13.531). Breast-conserving surgery and deviation from the guidelines were independent predictors of LR (HR=7.842, 95% CI 2.126-28.926; HR=2.778, 95% CI 0.982-6.781, respectively). Although the guidelines changed over time, time was not a significant factor in predicting LRs (HR=1.254, 95% CI 0.272-5.776 for time period 1992-1995 and HR=1.976, 95% CI 0.526-7.421 for time period 1996-1999). Clinical guidelines for the treatment of patients with DCIS have been developed and updated from existing literature and best evidence. Compliance with the guidelines was an independent predictor of disease-free survival. These findings support the application of guidelines in the treatment of DCIS.     

乳腺导管原位癌的间质微浸润危险因素分析

目的：分析乳腺导管原位癌（ductal carcinoma in situ,DCIS）间质微浸润的危险因素,探讨导管原位癌伴微浸润（ductal carcinoma in situ with microinvasion,DCIS-MI）患者的腋窝淋巴结术式。方法：回顾性分析2013年2 月至2016年2 月南京大学医学院附属金陵医院经手术后病理证实为DCIS、DCIS-MI 共45例患者临床资料,依据是否伴微浸润分为DCIS与DCIS-MI 组,对患者年龄、就诊时是否绝经、肿瘤大小等因素行统计学分析。结果：就诊时未绝经（P = 0.006）、肿物直径≥ 3.15cm（P = 0.006）、有恶性肿瘤家族史（P = 0.002）的患者更易发生肿瘤间质微浸润。结论：具有可触及腋窝肿物、未绝经、乳腺巨大肿物、有恶性肿瘤家族史危险因素,同时术前行穿刺或术中冰冻提示DCIS、DCIS伴可疑微浸润的患者存在微浸润可能性大,应予前哨淋巴结活检。触及腋窝肿物为首要症状患者,腋窝淋巴结清扫术应作为首选方式。     

Histological type and marker expression of the primary tumour compared with its local recurrence after breast-conserving therapy for ductal carcinoma in situ

We have investigated primary ductal carcinomas in situ (DCIS) of the breast and their local recurrences after breast-conserving therapy (BCT) for histological characteristics and marker expression. Patients who were randomized in the EORTC trial 10853 (wide local excision versus excision plus radiotherapy) and who developed a local recurrence were identified. Histology was reviewed for 116 cases; oestrogen and progesterone receptor status, and HER2/ neu and p53 overexpression were assessed for 71 cases. Comparing the primary DCIS and the invasive or non-invasive recurrence, concordant histology was found in 62%, and identical marker expression in 63%. Although 11% of the recurrences developed at a distance from the primary DCIS, nearly all these showed the same histological and immunohistochemical profile. 5 patients developed well-differentiated DCIS or grade I invasive carcinoma after poorly differentiated DCIS. Although these recurrences occurred in the same quadrant as the primary DCIS, they may be considered as second primary tumours. Only 4 patients developed poorly differentiated DCIS or grade III invasive carcinoma after well differentiated DCIS. We conclude that in most cases the primary DCIS and its local recurrence are related histologically or by marker expression, suggesting that local recurrence usually reflects outgrowth of residual DCIS; progression of well differentiated DCIS towards poorly differentiated DCIS or grade III invasive carcinoma is a non-frequent event.     

乳腺导管原位癌伴微小浸润的临床分析

目的 随着乳腺X射线摄影技术的进步及普及,使得乳腺导管原位癌伴微小浸润(ductal carcinoma in situ with microinvasion,DCIS-MI)在乳腺癌中比例增高,但所占比例＜1.0％.由于DCIS-MI术前确诊困难,病理和预后不同,同时缺乏大规模的循证医学证据指导治疗方案的选择,并存在着诸多争议,现已成为临床医师及病理医师普遍关注的热点.本研究总结和分析DCIS-MI的临床病理特征,加深对DCIS-MI的认识并探讨其合理的治疗方式.方法 回顾性分析2004-01-01-2014-12-31新疆医科大学附属肿瘤医院收治的318例患者的临床病理资料,其中乳腺导管原位癌(ductal carcinoma in situ,DCIS)患者239例,DCIS-MI患者79例.结果 DCIS与DCIS-MI在核分级(x2=29.699,P＜0.001)、粉刺型(x2=26.242,P＜0.001)、ER(x2=11.807,P=0.001)、PR(x2=7.623,P=0.006)、Ki-67阳性表这率(x2 =5.185,P=0.023)、分子分型(x2=16.570,P＜0.001)和手术方式(x2 =29.713,P＜0.001)方面均不同,差异均有统计学意义.在年龄(x2 =4.563,P=0.102)、民族(x2=2.102,P=0.147)、月经情况(x2=0.455,P=0.500)、肿块位置(x2 =0.267,P=0.605)、临床表现[包括乳房肿决(x2=1.393,P=0.238)、乳头改变(x2=1.345,P=0.246)、无症状(x2 =3.077,P=0.079)]、钙化(x2=0.010,P=0.920)、肿块的大小(x2=3.370,P=0.066)和HER-2阳性表达率(x2=0.317,P=0.574)方面差异均无统计学意义.中位随访时间为66个月,共有4例患者复发,其中DCIS组有2例胸壁复发,复发率为0.8％ (2/239);DCIS-MI组有2例胸壁复发,复发率为2.5％(2/79).DCIS组和DCIS-MI组复发率(x2=1.373,P=0.241)和总生存率(x2=1.397,P=0.237)相比,差异无统计学意义.DCIS与DCIS-MI的复发与手术方式、核分级、微浸润和腋窝淋巴结清除差异均无统计学意义,P＞0.05.结论 DCIS-MI预后较好,是一种少见的乳腺癌亚型.DCIS-MI与DCIS的腋窝淋巴结转移率和预后无差别,提示对DCIS-MI的处理应该按照DCIS的治疗方式进行处理.     

超声及钼靶X线对乳腺导管内癌与乳腺浸润性导管癌的诊断价值

目的:探讨乳腺导管内癌（ductal caicinoma in situ,DCIS）与乳腺浸润性导管癌（invasive ductal carcinoma,IDC）的超声及钼靶X线影像特征差异。方法:回顾性分析160例患者（包括62例DCIS患者及98例IDC患者）的超声及钼靶X线资料。结果:161个乳腺病灶中,有62个DCIS病灶（DCIS组）及99个IDC病灶（IDC组）。超声对IDC组病灶的检出率明显高于DCIS组,两组间的检出率有统计学意义（P＜0.05）;两组间病灶超声表现中形状、边界、边缘特征及血流信号差异有统计学意义（P＜0.05）。钼靶X线在两组病灶检出率差异有统计学意义（P＜0.05）;两组间病灶钼靶X线表现形状及边缘特征的例数差异有统计学意义（P＜0.05）。对于DCIS组,超声及钼靶X线病灶的检出率差异有统计学意义（P＜0.05）;在病灶边缘及乳腺腺体内钙化检出率这些方面,两种方法有统计学意义（P＜0.05）。结论:乳腺钼靶X线对DCIS腺体内钙化灶诊断率较高,乳腺超声对DCIS病灶检出、病灶边缘特征显示具有诊断优势。     

Pathologic and technical considerations in the treatment of ductal carcinoma in situ of the breast with lumpectomy and radiation therapy

Background: Lumpectomy and radiation therapy is considered a standard treatment option for ductal carcinoma in situ (DCIS) of the breast. The incidence of locally recurrent carcinoma using this therapeutic approach ranges from 6%–19%. Multiple studies have attempted to identify factors associated with the development of local recurrences in these patients. Despite extensive reports examining this issue, no factor(s) has consistently been correlated with outcome.Methods: This review examines the criteria that various authors have proposed as being associated with recurrence, including DCIS grade, size, histologic subtype, status of surgical margins, and technical factors to help clarify their roles in optimizing treatment outcome. The issue of the definition of the type of recurrence is also addressed.Results: Though multiple studies have examined the impact of grade, histologic subtype, necrosis, and DCIS size on outcome, no consistent results have been observed to suggest that these factors can be routinely used to guide therapy. The adequacy of excision appears to correlate with local control but is imprecisely defined by margin status alone. Based upon recent data, it appears that atypical ductal hyperplasia and cancerization of lobules in the context of coexistent DCIS, may need to be considered as part of the DCIS lesion that should be excised. This issue may account for someof the disparate results of different studies of DCIS. For statistical purposes, recent studies also suggest that only recurrences developing within or adjacent to the bed of the initial DCIS lesion should be considered when analyzing factors associated with outcome. Recurrences developing elsewhere in the breast may include new DCIS and invasive lesions that bear no biologic relationship with the initial DCIS lesion. Finally, since it is impossible to insure that all DCIS has been removed, it may be more appropriate to consider DCIS lesions as adequately or inadequately excised instead of completely or incompletely excised. Since DCIS is essentially a microscopic disease, pathologists should have a primary role in helping to define the adequacy of excision.Conclusions: Additional studies with complete pathology review and longer follow-up are needed to reach a consensus on which prognostic factors are consistently associated with recurrence for patients with DCIS treated with lumpectomy and radiation therapy. At the present time, adequacy of excision appears to correlate with outcome. However, more precise and consistent methods need to be developed to assist in the determination of adequate DCIS extirpation.     

Prognostic markers and long-term outcomes in ductal carcinoma in situ of the breast treated with excision alone

BACKGROUND:

Increased use of breast cancer screening has led to an increase in the number of diagnosed cases of ductal carcinoma in situ (DCIS). However, there is no definite way to predict progression or recurrence of DCIS. We analyzed the significance of biological markers and tumor characteristics in predicting recurrence in a large series of DCIS patients with long‐term follow‐up treated with breast conservation surgery (BCS) alone.

METHODS:

Clinical and pathological data were analyzed for 141 patients who underwent BCS for DCIS. All had negative surgical margins. Using local disease recurrence as an endpoint, we sought to determine the prognostic significance of several histopathological characteristics (tumor size, presence of necrosis, and subtype) and biological markers (estrogen receptor, progesterone receptor, and Her‐2/neu.)

RESULTS:

At a median follow‐up of 122 months (maximum follow‐up, 294 months), 60 recurrences occurred, with a median time to recurrence of 191 months. On multivariate analysis, Her‐2 positivity (3+) was found to be significantly associated with reduced time to tumor recurrence (P = .028). Tumor size and higher grade were marginally statistically significant (P = .099, P = .070). Neither necrosis nor tumor pathological characteristics were found to be significantly related to time to disease recurrence.

CONCLUSIONS:

Our results suggested that status of Her‐2/neu, larger tumor size, and higher nuclear grade were significantly correlated with time to tumor recurrence in patients treated with BCS alone. Using logistical analyses, no significant correlation was found between tumor pathological characteristics and disease recurrence. Cancer 2011. © 2011 American Cancer Society.