Long-term survival of women with basal-like ductal carcinoma in situ of the breast: a population-based cohort study

Background  

Microarray gene-profiling of invasive breast cancer has identified different subtypes including luminal A, luminal B, HER2-overexpressing and basal-like groups. Basal-like invasive breast cancer is associated with a worse prognosis. However, the prognosis of basal-like ductal carcinoma in situ (DCIS) is still unknown. Our aim was to study the prognosis of basal-like DCIS in a large population-based cohort.     

Second cancers following in situ carcinoma of the breast

Carcinoma in situ (CIS) of the breast has increased manyfold in incidence rates and as a proportion of new breast cancers following the introduction of mammographic breast screening. To provide population-based estimates of invasive breast cancer risk following CIS, we linked data on 249 incident primary CIS (median age 53 years) to the Cancer Registry of the Swiss Canton of Vaud (about 600,000 inhabitants) over the period 1977–1994. Women with concurrent invasive cancers of the breast were not included. Standardized incidence ratios (SIR) were determined according to the exact Poisson distribution, with stratification for age and year of diagnosis. A total of 24 cases of breast cancer vs. 3.4 expected [SIR = 7.2, 95% confidence interval (CI): 4.6–10.6], and 7 cases of other neoplasms (except non-melanomatous skin cancer) vs. 6.9 expected (SIR = 1.0, 95% CI: 0.4–2.1) were observed. The SIR was 10.4 during the first year, 5.6 between 1 and 4 years, and 7.7 after ≥5 years after CIS diagnosis. SIRs were consistent in women below and above age 55 years, but somewhat higher for ductal (SIR = 8.6) than lobular (SIR = 4.2) CIS. Six deaths from breast cancer were observed vs. 1.5 expected (standardized mortality ratio = 4.0, 95% CI: 1.5–8.7). In 13/19 ductal CIS, but in 2/4 lobular CIS, invasive cancer occurred in the same breast. In most women, CIS and subsequent invasive cancer showed the same morphological (i.e., ductal or lobular) features. The cumulative risk of breast cancer was 16% 10 years after CIS diagnosis, emphasizing the importance of adequate surveillance of women after CIS of the breast. Int. J. Cancer 77:392–395, 1998. © 1998 Wiley-Liss, Inc.     

Invasive breast cancer following ductal and lobular carcinoma in situ of the breast

We considered the risk of subsequent invasive breast cancer in a population-based series of 579 carcinomas in situ (CIS) of the breast (482 ductal, 88 lobular) registered between 1977 and 2002 in the Swiss Canton of Vaud. A total of 55 cases of invasive breast cancer were observed vs. 12.3 expected, corresponding to a standardized incidence ratio (SIR) of 4.5 (95% confidence interval [CI], 3.4-5.8). The SIR was 4.6 after ductal and 4.2 after lobular CIS, was similar with passing time since CIS diagnosis, but was higher (SIR = 5.5) for women aged <55 years. At 20 years following CIS, the cumulative risk of invasive breast cancer was 26%, similar for lobular and for ductal CIS. The incidence of invasive breast cancer following CIS showed no consistent pattern of trends with age, all rates in subsequent age groups ranging between 10 and 18 in 1,000. This is compatible with the occurrence of a single mutational event in a population of susceptible women.     

Factors influencing the quality of local management of ductal carcinoma in situ: a cohort study

Background

Guidelines recommend radiotherapy (rt) after breast-conserving surgery (bcs) for optimal control of ductal carcinoma in situ (dcis). The aim of the present study was to characterize the rates of rt consideration and administration, and to identify factors influencing those rates in a cohort of women diagnosed between 1998 and 2005 in Quebec.

Methods

Quebec’s medical service claims and discharge abstract database were used. Using consultation for rt as an indicator for rt consideration, odds ratios (ors) and 95% confidence intervals (cis) were estimated using a generalized estimating equations regression model.

Results

Of 4139 women analyzed (mean age: 58 years), 3435 (83%) received a consultation for rt, and 3057 of them (89%) proceeded with treatment. The rate of rt consideration increased by 7.1% over the study period, with notable differences in the various age groups. Relative to women 50–69 years of age, the ors for being considered for rt were, respectively, 0.89 (95% ci: 0.71 to 1.12), 0.71 (95% ci: 0.55 to 0.92), and 0.20 (95% ci: 0.14 to 0.31) for women younger than 50, 70–79, and 80 years of age and older. Distance to a designated breast care centre lowered the probability of rt consideration, but the presence of comorbidities did not. A surgeon’s volume of bcss increased the probability of being considered for rt by 7% for every 10 such procedures performed (or: 1.07; 95% ci: 1.04 to 1.11).

Conclusions

Consideration for rt has increased over time. However, older women (despite being in good health) and those living far from a designated breast care centre or having a low-case-volume surgeon were less likely to be considered for rt.     

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.     

Pure ductal carcinoma in situ and in situ component of ductal invasive carcinoma of the breast. A preliminary morphometric study

Nuclear pleomorphism is a fundamental feature in evaluating the aggressiveness of ductal carcinoma in situ (DCIS) of the breast. In this study, pure DCIS and the in situ component (IS-comp) of invasive duct carcinoma (IDC) are compared in order to verify if these are two different entities or the same process observed at different times during its evolution. Five cases of pure DCIS and nine of IDC with extensive in situ component were selected. They were moderately and poorly differentiated. 30 nuclei for each DCIS, and 30 nuclei for both the in situ and invasive component of each IDC were studied; thus, a total of 720 nuclei were submitted to the SAM (Shape Analytical Morphometry) analysis, which enables a numerical expression not only of dimensions (area, perimeter, diameter) but also of nuclear contour irregularities and nuclear shape distortions. Univariate statistical comparisons were carried out between the nuclei of: (1) DCIS and in situ component of invasive duct carcinoma, (2) DCIS and the invasive component of infiltrating carcinoma and (3) between the in situ and invasive component of infiltrating carcinoma. Multivariate analysis was utilized to compare nuclei of DCIS with the in situ component of IDC. The in situ features of each tumor were also evaluated with the mitotic index (MI). Nuclei of pure DCIS resulted significantly larger (p < 0.001) and with a more regular shape (p < 0.001) than those of the in situ component of IDC. No differences were observed between the nuclei of the in situ and the invasive component of infiltrating carcinomas. Multivariate statistical analysis discriminated 77% of nuclei of in situ proliferation when both G2 and G3 tumors were considered, and 80% when only G3 tumors were considered. In conclusions morphological differences exist between pure DCIS and the in situ component of IDC, which may be an expression of their biological behavior; moreover, these morphological differences seem to have a better discriminating power within the same histological grade.     

Grade of recurrent in situ and invasive carcinoma following treatment of pure ductal carcinoma in situ of the breast

The grade of recurrent in situ and invasive carcinoma occurring after treatment of pure ductal carcinoma in situ (DCIS) has been compared with the grade of the original DCIS in 122 patients from four different centres (The Royal Marsden Hospitals, London and Sutton, 57 patients; Guy's Hospital, London, 19 patients; Nottingham City Hospital, 31 patients and The Royal Liverpool Hospital, 15 patients). The recurrent carcinoma was pure DCIS in 70 women (57%) and in 52 women (43%) invasive carcinoma was present, which was associated with an in situ element in 43. In all, 19 patients developed a second recurrence (pure DCIS in 11 and invasive with or without an in situ element in eight). The majority of invasive carcinomas followed high-grade DCIS. There was strong agreement between the grade of the original DCIS and that of the recurrent DCIS (kappa=0.679), which was the same in 95 of 113 patients (84%). The grade of the original DCIS showed only fair agreement with the grade of recurrent invasive carcinoma (kappa=0.241), although agreement was stronger with the pleomorphism score of the recurrent carcinoma (kappa=0.396). There was moderate agreement, in recurrent invasive lesions, between the grade of the DCIS and that of the associated invasive element (kappa=0.515). Other features that showed moderate or strong agreement between the original and recurrent DCIS were necrosis and periductal inflammation. The similarity between the histological findings of the original and subsequent DCIS is consistent with the concept that recurrent lesions represent regrowth of residual carcinoma. In addition, although agreement between the grade of the original DCIS and that of any subsequent invasive carcinoma was only fair, there is no suggestion that low-grade DCIS lesions progress to higher grade lesions or to the development of higher grade invasive carcinoma. This is in agreement with immunohistochemical and molecular data indicating that low-grade and high-grade mammary carcinomas are quite different lesions.     

乳腺导管原位癌及其微浸润的临床病理研究

目的 探讨乳腺导管原位癌（DCIS）患者微浸润（MI）与其他临床病理参数的关系.方法 回顾性分析2006年10月至2012年10月本院收治的131例乳腺DCIS患者的临床资料,采用Spearman相关性分析检验DCIS-MI、淋巴结转移与其病理分级之间是否具有相关性,采用Fisher确切概率法分析DCIS-MI是否影响其淋巴结转移,比较DCIS手术方式、病理级别、微浸润、腋窝淋巴结清扫是否影响其复发.结果 （1）在131例DCIS的病理分级中,低级别60例（45.8%）,中级别60例（45.8%）,高级别11例（8.4%）,各组DCIS-MI分别有12例、31例、8例,与病理分级之间具有相关性（r=0.375,P=0.000）.（2）共计76例行前哨淋巴结活组织检查,3例转移;56例行腋窝淋巴结清扫,5例转移.腋窝淋巴结转移与微浸润有关（P=0.015）,与病理分级之间无相关性（r=0.154,P=0.107）.（3）本组DCIS患者随访3月至6年,1例中风死亡,3例局部复发,无乳腺癌死亡.DCIS复发与手术方式、病理分级、微浸润、腋窝淋巴结清扫均无关（P=0.359、1.000、1.000、0.260）.结论 DCIS病理分级高易发生DCIS-MI;DCIS-MI易发生腋窝淋巴结转移.     

Management of women with ductal carcinoma in situ of the breast: a population-based study.

BACKGROUND: Increasing incidence of ductal carcinoma in situ (DCIS) confronts patients and clinicians with optimal treatment decisions. This multidisciplinary study investigates therapeutic modalities of DCIS in daily practice and provides recommendations on how to increase quality of care. PATIENTS AND METHODS: All women (n = 116) with unilateral DCIS recorded in the Geneva Cancer Registry from 1995 to 1999 were considered. Information concerned patient and tumor characteristics, treatment and outcome. Factors linked to therapy were determined using a case-control approach. Cases were women with treatment of interest and controls other women on the study. RESULTS: Most DCIS cases (62%) were discovered by mammography screening. Ninety (78%) women had breast-conserving surgery (BCS), 18 (16%) mastectomy and seven (6%) bilateral mastectomy. Eight (7%) patients had tumor-positive margins, 18 (16%) lymph node dissection and two (1.7%) chemotherapy. Twenty-five per cent of women with BCS had no radiotherapy, three had radiotherapy after mastectomy. Less than 50% underwent breast reconstruction after mastectomy. Method of discovery, multifocality, tumor localization, size and differentiation were linked to the use of BCS or lymph node dissection. CONCLUSIONS: Because of important disparities in DCIS management, recommendations are made to increase quality of care, in particular to prevent axillary dissection or bilateral mastectomy and to increase the use of radiotherapy after BCS.     

乳腺导管原位癌和乳腺导管原位癌伴微浸润的分子分型差异性研究

背景与目的：乳腺导管原位癌伴微浸润（ductal carcinoma in situ with microinvasion,DCISMI）是乳腺导管原位癌（ductal carcinoma in situ,DCIS）发展到浸润性乳腺癌（invasive breast cancer,IDC）的中间阶段,该研究旨在分析乳腺DCIS和DCIS-MI这两类早期乳腺癌不同临床病理学特征和各个分子分型间的差异。方法：本回顾性研究纳入了317例DCIS患者,其中227例（71.6%）为纯DCIS患者,90例（28.4%）为DCIS-MI患者。所有患者根据其DCIS成分而非微浸润成分的免疫组织化学检查结果分成腔面A型［雌激素受体（estrogen receptor,ER）和（或）孕激素受体（progesterone receptor,PR）阳性,人类表皮生长因子受体2（human epidermal growth factor receptor 2,HER-2）阴性］、腔面B型［ER和（或）PR阳性,HER-2阳性］、HER-2过表达型（ER和PR阴性,HER-2阳性）和基底样型（ER和PR阴性,HER-2阴性）。结果：DCIS-MI患者的肿瘤大小倾向更大（P=0.059）,病理核分级显著更高（P=0.002）。和DCIS患者相比,乳腺DCIS-MI患者中腔面A型比例较低而基底样型比例较高（P=0.001）。结论：乳腺DCIS和DCIS-MI间分子分型分布不同,临床病理特征迥异,提示DCIS-MI是DCIS发展的新阶段,有了“质”的改变,本结论有待后续更大样本量的研究进行验证。     

Breast cancer and ductal carcinoma in situ among women with prior squamous or glandular precancer in the cervix: a register-based study

Background:

Human papillomavirus and hormonal contraceptives may be risk factors for cervical precancer and malignant breast tumours.

Methods:

Standardised incidence ratios (SIRs) of malignant breast tumours during 1970–2008 were estimated separately for women with prior squamous and glandular cervical precancer.

Results:

Women with squamous precancer and women with glandular precancer in the cervix had a significantly higher risk of malignant breast tumours than the general female population (SIR, 95% confidence interval: 1.10, 1.05–1.14 and 1.52, 1.11–2.08, respectively).

Interpretation:

Shared risk factors or screening attendance may explain the excess risk of malignant breast tumours among women with a history of cervical precancer.     

Surgery and outcomes of ductal carcinoma in situ of the breast: a population-based study in Australia

We examined surgery and outcome in a population-based series of 2109 women newly diagnosed with ductal carcinoma in situ (DCIS) in 1995-2000 in New South Wales (NSW), Australia. The sole data source for the study was pathology records in the NSW Cancer Registry. Most DCIS was treated with breast-conserving surgery (BCS); use of breast conservation increased throughout the 6 years of the study. Women who were younger, had higher grade DCIS or had larger lesions were significantly and independently less likely to have BCS than other women. Eighteen percent of women had lymph nodes removed, most often with mastectomy. The NSW Cancer Registry does not collect information about radiotherapy. Based on cancer registrations alone, 97.7% of women were free of ipsilateral invasive cancer after three years; more women who had mastectomy were cancer-free (100%) than women who had breast-conserving surgery (97.2%; P=0.05).     

Proteomics of human breast ductal carcinoma in situ

We report the first proteomic analysis of matched normal ductal/lobular units and ductal carcinoma in situ (DCIS) of the human breast. An understanding of the transition from normal epithelium to the first definable stage of cancer at the functional level of protein expression is hypothesized to contribute to improved detection, prevention, and treatment. Ten sets of two-dimensional gels were evaluated, containing either matched normal ductal/lobular units or DCIS from either whole tissue sections or up to 100,000 laser capture microdissected epithelial cells. Differential protein expression was confirmed by image analysis. Protein spots (315) were excised and subjected to mass spectrometry sequencing. Fifty-seven proteins were differentially expressed between normal ductal/lobular units and DCIS. Differences in overall protein expression levels and posttranslational processing were evident. Ten differentially expressed proteins were validated in independent DCIS specimens, and 14 of 15 proteomic trends from two-dimensional gel analyses were confirmed by standard immunohistochemical analysis using a limited independent tumor cohort. Many of the proteins identified were previously unconnected with breast cancer, including proteins regulating the intracellular trafficking of membranes, vesicles, cancer preventative agents, proteins, ions, and fatty acids. Other proteomic identifications related to cytoskeletal architecture, chaperone function, the microenvironment, apoptosis, and genomic instability. Proteomic analysis of DCIS revealed differential expression patterns distinct from previous nucleic acid-based studies and identified new facets of the earliest stage of breast cancer progression.     

乳腺导管增生及原位癌的形态学定量分析

目的对比分析乳腺导管增生及导管原位癌的形态学定量参数。方法细胞涂片经常规巴氏染色,组织学切片经HE染色; 带有数码摄像机的彩色病理图像采集系统及半自动图像定量分析系统; 定量指标包括：细胞核直径、周长、面积、圆形度及核质比例; 结果乳腺导管增生及导管原位癌所分析的各项参数均有差异,具有统计学意义（P〈0.001,P〈0.05）; 乳腺导管增生及导管原位癌各组内部,细胞涂片和组织切片对比所分析的各项参数均无差异。结论细胞核直径、周长、面积、核质比及圆形度可作为形态学特征性定量参数,区分乳腺导管增生及导管原位癌。     

Cost-effectiveness of radiation therapy following conservative surgery for ductal carcinoma in situ of the breast

PURPOSE: To assess the cost-effectiveness of radiation therapy (RT) in patients with ductal carcinoma in situ (DCIS) after breast-conserving surgery (BCS). METHODS AND MATERIALS: A Markov model was constructed for a theoretical cohort of 55-year-old women with DCIS over a life-time horizon. Probability estimates for local noninvasive (N-INV), local invasive (INV), and distant recurrences were obtained from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17. Utilities for eight nonmetastatic health states were collected from both healthy women and DCIS patients. Direct medical (2002 Medicare fee schedule) and nonmedical costs (time and transportation) of RT were ascertained. RESULTS: For BCS + RT vs. BCS alone, the estimated N-INV and INV rates at 12 years were 9% and 8% vs. 16% and 18%, respectively. The incremental cost of adding RT was 3300 US dollars despite an initial RT cost of 8700 US dollars due to higher local recurrence-related salvage costs incurred with the BCS alone strategy. An increase of 0.09 quality-adjusted life-years (QALYs) primarily reflected the lower risk of INV with RT, resulting in an incremental cost-effectiveness ratio (ICER) of 36,700 US dollars/QALY. Sensitivity analyses revealed the ICER to be affected by baseline probability of a local recurrence, relative efficacy of RT in preventing INV, negative impact of an INV on quality of life, and cost of initial RT. Cost of salvage BCS + RT and source of utilities (healthy women vs. DCIS patients) influenced the ICER albeit to a lesser degree. CONCLUSIONS: Addition of RT following BCS for patients with DCIS should not be withheld because of concerns regarding its cost-effectiveness.     

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.