分子分型对乳腺导管内原位癌无复发生存率的影响

目的探讨乳腺导管内原位癌(DCIS)的分子分型与无复发生存率的关系。方法选取南方医科大学附属小榄医院普外科2008年1月至2016年6月收治的DCIS患者135例,根据分子分型分为四个亚组［性激素受体(HR)+／人类表皮生长因子受体2(HER2)-组83例,HR+／HER2+组26例,HR-／HER2+组16例,三阴型(TN)组10例］,比较四组患者的病理分级、肿瘤大小、放疗等临床病理资料及生存预后情况;随访48个月,采用Cox回归分析患者预后的影响因素。结果四组的病理分级和生存状态差异有统计学意义,TN组多为低分化或未分化,未见高分化,且肿瘤复发比例较高(P<005)。四组在生存时间、年龄、肿瘤部位、肿瘤大小、手术方式、有无放疗方面差异无统计学意义;HR+／HER2-组无复发生存率为927％,HR+／HER2+组为923％,HR-／HER2+组为875％,TN组为700％。Cox回归分析结果显示TN亚型是无复发生存率的危险因素(aHR=3538,P=0005),而放疗是无复发生存率的保护因素(aHR=0325,P=0005)。结论分子分型是影响DCIS患者预后的独立危险因素之一,TN型DCIS患者预后较其他亚型差,放疗能改善DCIS患者的无复发生存率。     

Recurrence of Breast Cancer following local excision alone for ductal carcinoma in situ

OBJECTIVE: To assess recurrence of breast cancer following local excision alone for ductal carcinoma in situ. METHODS: Eighteen patients who received complete resection for noninvasive ductal carcinoma between 1982 and 1997 were investigated in this study. The mean age of the patients was 45 (29-78) years old. The initial presentation was a clinically palpable tumor in 4 patients, nipple discharge in 6, and microcalcification on mammograms in 8. Patients with palpable tumor underwent wide excision with at least a 2-cm free margin. Patients whose mammograms showed microcalcification underwent lumpectomy, and those who showed nipple discharge underwent duct-lobular segmentectomy. Five patients who underwent lymph node dissection up to level I or II had no lymph node metastasis. The mean follow-up period was 86 months. RESULTS: Local recurrence in the conserved breast was seen in five (27.8%) of 18 patients. The actuarial five-year event-free survival was 76.2%. The histological type of the recurrent tumor was ductal carcinoma in situ in three patients and invasive carcinoma in two. There was no difference in age at initial operation or histological subtype between patients with and without recurrent disease, but patients presenting with nipple discharge initially had a significantly shorter ipsilateral disease-free interval than those presenting with tumor or microcalcification on mammograms. All patients with local recurrence in the conserved breast were treated with breast-conserving surgery or subcutaneous mastectomy. CONCLUSION: Local recurrence frequently occurs in patients presenting with nipple discharge treated by duct-lobular segmentectomy for noninvasive ductal carcinoma. Either wide excision with a larger free margin or adjuvant radiation therapy following duct-lobular segmentectomy should be considered for these patients.     

Conditional relative survival of patients with endometrial cancer: a Korean National Cancer Registry study

ObjectiveThe purpose of this study was to estimate 5-year conditional relative survival (5Y CRS) rates of endometrial cancer (EC) in Korea accounting for time already survived. Subgroup-specific estimates stratified by various patient characteristics were also presented.MethodsUsing the data from the Korean Central Cancer Registry, 5Y CRS rates were calculated in patients who were diagnosed with EC between 1998 and 2017. The CRS rates were presented by year of diagnosis, age at diagnosis, histology, cancer stage, and treatment received.ResultsThe 5-year relative survival rate at the time of diagnosis was 89.0% for all cases. The probability of surviving an additional 5 years (i.e., 5Y CRS), if the patient survived 1, 2, 3, 4, and 5 years after diagnosis was 91.8%, 94.1%, 95.6%, 96.5%, and 97.3%, respectively. Patients with poor initial prognoses, i.e., those who were older, had non-endometrioid histology, and high stage, showed the largest improvements in 5Y CRS, reaching >90% for most subgroups, except those with serous histology (88.4%) and distant stage (77.7%). Patients aged ≥70 years had the highest probability of death in the 1st and 2nd years after diagnosis (13.8 and 11.0%), but the conditional probability of death in the 3rd, 4th, and 5th years declined rapidly to 7.3%, 4.5%, and 3.7%, respectively.ConclusionThe CRS rates for patients with EC improved with increased time elapsed from diagnosis. The greatest improvements in 5Y CRS were observed among patients who were older, those with non-endometrioid histology, and those with more advanced disease.     

Breast ductal carcinoma in situ with microinvasion: a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas

BACKGROUND: The significance of microinvasion is still debated and clinical management is controversial. The authors defined ductal carcinoma in situ with microinvasion (DCIS-MI) as DCIS with infiltration of the periductal stroma by a few tumor cells, singly (type 1) or in clusters (type 2). With this definition, the authors attempted to evaluate the clinical significance of microinvasion. METHODS: The authors compared the clinical, pathologic features, and survival (median follow-up, 7.3 years) of 1248 patients with, respectively, DCIS (722 patients), DCIS-MI with microinvasion type 1 and type 2 (243 patients), and invasive ductal carcinoma in situ with a predominant DCIS component greater than or equal to 80% of the tumor (IDC-DCIS, 283 patients). RESULTS: Microinvasion was associated with DCIS histologic type, grade, and extent (respectively, P < 10(-8), P < 10(-3), P < 10(-4)). Axillary lymph node metastases were observed in a few patients with DCIS and DCIS-MI type 1 (respectively, 1.4% and none), in 10.1% with DCIS-MI type 2 and in 27.6% with IDC-DCIS. Metastasis free and overall survival probabilities were significantly different between three groups in the following order from best to worst prognosis: 1) the group comprising DCIS and DCIS-MI type 1, 2) the DCIS-MI type 2 group, and 3) the IDC-DCIS group. CONCLUSIONS: The authors' results suggest there are two types of DCIS-MI: 1) type 1 that behaves like DCIS and should be managed as such; 2) type 2 that is less pejorative than IDC-DCIS but is more so than type 1.     

Breast cancer in males: a study of 15 cases of pure ductal carcinoma in situ]

Ductal carcinoma in situ of the breast is very rare in men, representing 0-7% of all male breast cancers. We analysed 15 cases from a retrospective multicentric series of 404 patients (3.7%). It occurs earlier than infiltrating carcinoma (mean age: 55 years), sometimes before 40 years of age. The main symptoms are bloody nipple discharge or retro areolar mass. Modified radical mastectomy constitutes the basic treatment. Lower axillary dissection can eventually be indicated in comedocarcinoma or in tumors larger than 25 mm. The main histologic subgroup is papillary carcinoma, pure or intracystic. As is the case in women, local recurrence, invasive or not, rarely occurs. Theoretically, the cure rate approaches 100%. However, as in all cases of breast cancer in men, an important number of deaths due to secondary cancer or intercurrent disease have been noted. Until now, no clear etiologic factors have been found.     

Clinical subtypes and prognosis of pregnancy-associated breast cancer: results from the Korean Breast Cancer Society Registry database

Purpose

We analyzed the clinicopathologic characteristics and prognosis of pregnancy-associated breast cancer (PABC) according to clinical subtypes to better understand the characteristics of PABC.

Methods

A total of 83,792 female patients between the ages of 20 and 49 were enrolled in the Korean Breast Cancer Society Registry database from January 1, 1996 to December 31, 2015. ‘PABC’ is defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. Other patients were defined as ‘non-PABC’ patients.

Results

In non-PABC patients, luminal A subtype was the most common (50.2%). In PABC patients, TNBC was the most common (40.4%) subtype, while luminal A comprised 21.2% and HER2 subtype comprised 17.3%. There was a significant difference in overall survival (OS). In non-PABC patients, TNBC had the highest HR (HR 2.3, 95% CI 2.1–2.6). In PABC patients, the luminal B subtype (HR+ HER2-high Ki67) had the highest HR at 7.0 (95% CI 1.7–29.1). In multivariate analysis of OS by subtypes, PABC patients had significantly higher HR than non-PABC patients in the HER2 subtype (HR 2.0, 95% CI 1.1–3.7) and luminal B subtype (HR+ HER2-high Ki67) (HR 4.4, 95% CI 1.6–12.3).

Conclusion

PABC showed different biologic features than non-PABC. PABC had a particularly poor prognosis in the luminal B (HR+ HER2-highKi67) and HER2 subtypes. To improve the prognosis of PABC, treatment should be considered according to subtype. Development of drugs that can be used during pregnancy is needed.

     

Different prognosis of young breast cancer patients in their 20s and 30s depending on subtype: a nationwide study from the Korean Breast Cancer Society

Purpose

Numerous studies have demonstrated that breast cancer in young women (BCY) has unfavorable prognostic features and more unfavorable subtypes. However, few studies have evaluated the effect of subtype disparities on breast cancer prognosis by age, especially for BCY. We analyzed breast cancer mortality stratified by tumor subtype according to age among patients younger than 50 years.

Methods

Data from the Korean Breast Cancer Society Registry for patients diagnosed with invasive breast cancer when aged less than 50 years between 2003 and 2010 were reviewed retrospectively.

Results

We identified 30,793 patients with breast cancer who were eligible for analysis. Of these, 793 (2.6%) were aged 20–29 and 8926 (28.8%) were aged 30–39. Median follow-up duration was 84 months. Mean age was 42.4 years. Patients in their 20s were more likely to have cancer of advanced stage and higher nuclear grade, present with lymphovascular invasion, and have unfavorable subtypes. Patients in the 20s group showed worse prognosis. In multivariate analysis for overall survival (OS), the hazard ratio (HR) for patients in the 20s group was higher than that for the 30s and 40s groups, and patients with triple-negative breast cancer (TNBC) showed higher HR than patients with HER-2 or luminal subtype (all p < 0.0001). When stratified by subtype, luminal subtype showed significantly worse prognosis in the 20s group than the 30s and 40s groups, whereas HER-2 and TNBC subtypes showed no significant difference.

Conclusion

Patients in their 20s with breast cancer had unfavorable characteristics and worse prognosis than patients in their 30s and 40s. When stratified by tumor subtype, patients in their 20s with luminal subtype of breast cancer showed worse prognosis than older patients, whereas HER-2 and TNBC subtypes showed no significant differences.

     

The Basic Facts of Korean Breast Cancer in 2011: Results of a Nationwide Survey and Breast Cancer Registry Database

Breast cancer is the second most frequent malignancy in Korean women, with a continuously increasing incidence. The Korean Breast Cancer Society has constructed a nationwide breast cancer database through an online registration program. The aim of the present study was to report the fundamental facts on Korean breast cancer in 2011, and to analyze the changing patterns in clinical characteristics and breast cancer management in Korea over the last 10 years. Data on newly diagnosed breast cancer patients, including the total number of cases, age, stage, and type of surgery, for the year 2011 were collected from 84 hospitals and clinics nationwide using a questionnaire survey. Additional data relating to the changing patterns of breast cancer in Korea were collected from the online breast cancer registry database and analyzed. According to nationwide survey data, a total of 16,967 patients were newly diagnosed with breast cancer in 2011. The crude incidence of female breast cancer, including invasive cancer and in situ cancer, was 67 cases per 100,000 women. Analysis of the survey and registry data gave equivalent results in terms of age distribution, stage, and type of surgery. The median age at diagnosis was 50 years, and the proportion of postmenopausal women (51.3%) was higher than that of premenopausal women (48.7%) with breast cancer. The incidence of stage 0 and stage I breast cancer increased continuously over the last 10 years (56.3% in 2011), and breast conserving surgery (65.7%) was performed more frequently than total mastectomy (33.8%). The total number of breast reconstruction surgeries increased approximately 8-fold. We conclude that the clinical characteristics of breast cancer have changed over the past 10 years in Korea, and surgical management has changed accordingly. Analysis of nationwide registry data will contribute to a better understanding of the characteristics of breast cancer in Korea.     

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.     

The Basic Facts of Korean Breast Cancer in 2012: Results from a Nationwide Survey and Breast Cancer Registry Database

The Korean Breast Cancer Society has constructed a nationwide breast cancer database through utilization of an online registration program. We have reported the basic facts about breast cancer in Korea in 2012, and analyzed the changing patterns in the clinical characteristics and management of breast cancer in Korea over the last 10 years. Data on patients newly diagnosed with breast cancer were collected for the year 2012 from 97 hospitals and clinics nationwide using a questionnaire survey, and from the online registry database. A total of 17,792 patients were newly diagnosed with breast cancer in 2012. The crude incidence rate of female breast cancer, including invasive cancer and in situ cancer, was 70.7 cases per 100,000 women. The median age at diagnosis was 51 years, and the proportion of postmenopausal women was higher than that of premenopausal women among those diagnosed with breast cancer. The proportion of cases of early breast cancer increased continuously, and breast-conserving surgery was performed in more cases than total mastectomy in that same year. The total number of breast reconstruction surgeries increased approximately 3-fold over last 10 years. The 5-year overall survival rate for all stages of breast cancer patients was extremely high. The clinical characteristics of breast cancer have changed in ways that resulted in high overall survival over the past 10 years in Korea, and the surgical management of the disease has changed accordingly. Analysis of nationwide registry data will contribute to a better understanding of the characteristics of breast cancer in Korea.     

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.     

Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers' experience

PURPOSE: To assess the long-term outcome for women with ductal carcinoma in situ of the breast treated in current clinical practice by conservative surgery with or without definitive breast irradiation. METHODS AND MATERIALS: We analyzed 705 cases of ductal carcinoma in situ treated between 1985 and 1995 in nine French regional cancer centers; 515 underwent conservative surgery and radiotherapy (CS+RT) and 190 CS alone. The median follow-up was 7 years. RESULTS: The 7-year crude local recurrence (LR) rate was 12.6% (95% confidence interval [CI] 9.4-15.8) and 32.4% (95% CI 25-39.7) for the CS+RT and CS groups, respectively (p <0.0001). The respective 10-year results were 18.2% (95% CI 13.3-23) and 43.8% (95% CI 30-57.7). A total of 125 LRs occurred, 66 and 59 in the CS+RT and CS groups, respectively. Invasive or microinvasive LRs occurred in 60.6% and 52% of the cases in the same respective groups. The median time to LR development was 55 and 41 months. Nine (1.7%) and 6 (3.1%) nodal recurrences occurred in the CS+RT and CS groups, respectively. Distant metastases occurred in 1.4% and 3% of the respective groups. Patient age and excision quality (final margin status) were both significantly associated with LR risk in the CS+RT group: the LR rate was 29%, 13%, and 8% among women aged < or =40, 41-60, and > or =61 years (p <0.001). Even in the case of complete excision, we observed a 24% rate of LR (6 of 25) in women <40 years. Patients with negative, positive, or uncertain margins had a 7-year crude LR rate of 9.7%, 25.2%, and 12.2%, respectively (p = 0.008). RT reduced the LR rate in all subgroups, especially in those with comedocarcinoma (17% vs. 59% in the CS+RT and CS groups, respectively, p <0.0001) and mixed cribriform/papillary tumors (9% vs. 31%, p <0.0001). In the multivariate Cox regression model, young age and positive margins remained significant in the CS+RT group (p = 0.00012 and p = 0.016). Finally, the relative LR risk in the CS+RT group compared with the CS group was 0.35 (95% CI 0.25-0.51, p = 0.0001). Subsequent contralateral breast cancer occurred in 7.1% and 7.5% of the patients in the CS+RT and CS groups, respectively. CONCLUSION: Despite the absence of randomization, our results are extremely consistent with the updated National Surgical Adjuvant Breast Project B17 and European Organization for Research and Treatment of Cancer 10853 trials. We also noted that the LR risk was very high in women <40 years and/or in the case of incomplete excision.     

Temporal patterns of childhood cancer survival 1991 to 2016: A nationwide register-study based on data from the German Childhood Cancer Registry

Childhood cancer is the leading disease-related cause of death among under 15 year olds in Europe. Since primary preventive measures are lacking, improving survival probabilities and long-term well-being remain primary goals. With this report, we provide the first long-term assessment and interpretation of patterns in childhood cancer survival in Germany, covering a period of 30 years. Using data from the German Childhood Cancer Registry, we assessed temporal patterns of cancer survival among children (0-14 years) diagnosed in Germany from 1991 to 2016, by cancer type, age at diagnosis and sex. We calculated overall survival (OS) and average annual percentage changes of the respective 5-year OS estimates. OS improved across all cancer types, age groups as well as for boys and girls over time. Five-year OS for all childhood cancers combined increased from 77.8% in 1991-1995 to 86.5% in 2011-2016, with stronger improvements during the early 1990s. The most pronounced survival improvement was seen for acute myeloid leukaemia, at 2% annually and 5-year OS recently reaching 81.5%. Survival improvements for some diagnoses such as neuroblastoma, renal tumours and bone tumours have flattened out. Tremendous enhancements in diagnostics, treatment and supportive care have affected average survival improvements for most cancer types. Recently, survival improvements have decelerated overall and for some cancer types, it plateaued at an unsatisfactory level. As not all children benefited equally from the survival improvements, personal factors (eg, socioeconomic circumstances, health literacy, access to care) likely affect individual prognosis and warrant further investigation.     

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.     

A proposal for the histopathological diagnosis of ductal carcinoma in situ of the Breast

BACKGROUND: As the incidence of ductal carcinoma in situ (DCIS) is increasing, it is necessary to make a guideline for the pathological examination and diagnosis of DCIS, by creating criteria based on clinical and biological aspects of the disease. METHOD: We collected biopsy specimens originally diagnosed as benign lesions, from patients who subsequently developed invasive carcinoma in the ipsilateral breast. The histology of the biopsy specimens was re-evaluated principally according to the 1995 Philadelphia Consensus on DCIS. Histopathological agreement on each biopsy specimen was made by the JBCS Study Group members under a multiviewer microscope. In the course of making conclusive agreements among the pathologists, we developed a consensus for the histopathological diagnosis of DCIS, especially non-comedo types. RESULTS: DCIS is defined as a carcinoma of ductal epithelial origin, without any evidence of stromal invasion. It is necessary to note the methods of pathologic examination required to diagnose DCIS. Stromal invasion is an important prognostic factor, and should be diagnosed with caution. Classification of proliferative ductal lesions as benign or malignant (DCIS), the subtype of DCIS (nuclear grade, architecture, and necrosis), and the histological grading of DCIS are proposed and recommended. CONCLUSION: Although we have made a new proposal according to current concepts, there are still several unresolved problems. Thus further examination and modification will be necessary in the future.     

Cancer survival in parents who lost a child: a nationwide study in Denmark

Psychological stress has been suggested to shorten cancer survival, but few studies have examined the effect of parental bereavement, and the results have been inconsistent. We identified all 21 062 parents who lost a child in Denmark from 1980 to 1996 and among them, 1630 parents with subsequent incident cancer formed the exposed cohort. We recruited 6237 incident cancer patients from a group of 293 745 randomly selected unexposed parents matched on family structure at the same time as the bereaved parents. All incident cancers in the two cohorts were followed to the end of 1997, or until they died. Cox proportional-hazards regression models were used to evaluate the hazard ratio (HR) of dying in exposed parents with cancer. The overall HR of dying from an incident cancer in exposed parents was 1.23 (95% confidence interval 1.03-1.47) compared to parents with cancer who did not lose a child. The HRs were nearly identical to those in the unexposed parents for site-specific cancers like lung cancer, breast cancer, and other groups of cancers like cancers in all digestive organs, smoking-related cancers, alcohol-related cancers, hormone-related cancers, virus/immune-related cancers, and lymphatic/haematopoietic cancers. Death of a child is not a strong prognostic factor for cancer survival among parents diagnosed with cancer after the bereavement. However, a small impairment in overall cancer survival cannot be ruled out.