Changes in breast cancer incidence and stage distribution in Modena,Italy: the effect of a mammographic screening program

OBJECTIVE: Assessing changes in breast cancer (BC) incidence and stage distribution in the District of Modena, Italy, during the period 1992–1998, and their relationship to a mammographic screening program launched in 1995.METHODS: Demographic, clinical, and pathological data of all BC cases reported to the population-based Modena Cancer Registry between 1992 and 1998 were collected and linked to the screening database.RESULTS: A total of 3429 women were diagnosed with BC in the District of Modena between 1992 and 1998. In this period the incidence rate increased by 15.7% (from 134.3 in 1992 to 155.4 per 100,000 in 1998). The increase began in 1995 and exclusively included women aged 50–69; the incidence rose by 30.4%. Moreover, the rise was confined to early tumors, with more than half (54%) of all cases reported in 1998 diagnosed as stage 0 or I disease, compared with 42% in 1992. Screen-detected tumors were significantly smaller (13.2 mm) than other tumors diagnosed in women aged 50–69 (18.5 mm), with 46% of screen-detected tumors smaller than 10 mm. Overall, a decline in the average tumor diameter was shown (from 20.2 mm in 1992–1994 to 18 mm in 1996–1998).CONCLUSIONS: Our data confirm that mammographic screening leads to an increase in the incidence of early-stage BC cancers.     

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.     

Histopathologic indicators of breast cancer biology: insights from population mammographic screening

Histopathologic features of breast cancer such as tumour size, grade and axillary lymph node (LN) status variably reflect tumour biology and time. Recent evidence suggests that the biological character of breast cancer is established at an early stage and has a major impact on clinical course. The aim of this study was to distinguish the impact of biology on breast cancer histopathology by comparing features of breast cancers diagnosed following population mammographic screening with prevalent vs incident detection and screening interval. Central histopathology review data from 1147 cases of ductal in situ and/or invasive breast cancer were examined. Size, grade and LN status of invasive cancers were positively correlated (P < 0.001). Prevalent invasive cancers were larger (P < 0.001) and more likely to be LN positive (P = 0.02) than incident cases, but grade was not associated with screening episode (P = 0.7). Screening interval for incident cancers was positively associated with invasive cancer size (P = 0.05) and LN status (P = 0.002) but not grade (P = 0.1). Together, these data indicate that biology and time both impact on size and LN status of invasive breast cancer, but grade reflects biology alone. In view of the clinical importance of breast cancer biology, grade as its most direct indicator assumes particular significance.     

Stage-specific incidence of breast cancer before the beginning of organized screening programs in Italy

Objective: To measure stage-specific geographic and time variability of breast cancer in seven Italian areas before the onset of organized screening programs. Methods: All invasive cancers (8689 cases) arising in women aged 40–79 years during the pre-screening period 1985–1997, were considered. Multiple Poisson regression analysis was performed. Results: About 39% of the cases were classified as early, 52% as advanced, and 9% as unspecified stage. Age-adjusted incidence rates showed a significant geographic variation for early but not for advanced cancers (range: 58–103 cases/100,000 and 104–125 cases/100,000, respectively). The result was confirmed in the multiple regression analysis after adjustment for year of diagnosis and age. Early breast cancer risk adjusted for age and registry showed a significant increase over time (+ 3.9% per year for all ages, and + 6.2% per year for age category 50–79). In contrast, a decreasing time trend was observed for advanced cancer of 3 cm or over in women aged less than 60. Conclusions: In our study, early breast cancer incidence varied both by geographic area and time before the commencement of screening. The differences in early-stage incidence may well be related to differences in availability of spontaneous mammography. Late-stage incidence decreased over time in younger women and for very advanced cases, but not in the older ones, nor for cancers less than 3 cm. Early detection outside organized screening was only partially efficient in reducing advanced breast cancer incidence. The trend of incidence of advanced disease, as previously proposed, is confirmed to be a valid early indicator of effectiveness of screening.     

Change in mammographic density across birth cohorts of Dutch breast cancer screening participants

High mammographic density is a well-known risk factor for breast cancer. This study aimed to search for a possible birth cohort effect on mammographic density, which might contribute to explain the increasing breast cancer incidence. We separately analyzed left and right breast density of Dutch women from a 13-year period (2003–2016) in the breast cancer screening programme. First, we analyzed age-specific changes in average percent dense volume (PDV) across birth cohorts. A linear regression analysis (PDV vs. year of birth) indicated a small but statistically significant increase in women of: 1) age 50 and born from 1952 to 1966 (left, slope = 0.04, p = 0.003; right, slope = 0.09, p < 0.0001); 2) age 55 and born from 1948 to 1961 (right, slope = 0.04, p = 0.01); and 3) age 70 and born from 1933 to 1946 (right, slope = 0.05, p = 0.002). A decrease of total breast volume seemed to explain the increase in PDV. Second, we compared proportion of women with dense breast in women born in 1946–1953 and 1959–1966, and observed a statistical significant increase of proportion of highly dense breast in later born women, in the 51 to 55 age-groups for the left breast (around a 20% increase in each age-group), and in the 50 to 56 age-groups for the right breast (increase ranging from 27% to 48%). The study indicated a slight increase in mammography density across birth cohorts, most pronounced for women in their early 50s, and more marked for the right than for the left breast.     

从原位癌到微小浸润：乳腺肿瘤的临床病理分析及对外科治疗的影响

背景对乳腺原位癌（CIS）是否应进行前哨淋巴结活检（SLNB）目前仍处于争议中。临床诊疗中常遇到：一些在术前穿刺或术中活检被诊断为原位癌且未进行SLNB的患者,术后却经病理确诊为乳腺微小浸润性癌（MIBC）。此时,是否二次手术进行腋窝淋巴结状态评估对外科医师来说是一个困难的选择。一方面,MIBC淋巴结转移风险尚不明确;另一方面,再次手术时SLNB的准确性及可操作性往往受到质疑,多数情况下腋窝淋巴结清扫成为唯一的选择。目的识别原位癌伴发微小浸润的危险因素;比较CIS和MIBC腋窝淋巴结的转移风险;探索选择合适的病例直接进行术中前哨淋巴结活检以避免二次手术的合理性。方法对接受手术且经病理确诊的乳腺原位癌（493例）及微小浸润癌（199例）患者的临床病历资料进行回顾性的统计分析;采用Pearson卡方检验和Fisher确切概率法进行组间比对;通过单因素分析和多因素Logistic回归识别原位癌伴发微小浸润的危险因素。结果原位癌组中出现4例小叶原位癌（LCIS）,其余均为导管原位癌（DCIS）,而MIBC所伴发的原位癌均以DCIS为主。单因素分析显示,X线片BI-RADS≥4级的钙化,肿瘤﹥2.5 cm,高级别DCIS,ER（－）,PR （－）,HER-2（+++）是原位癌伴微小浸润的危险因素（P均﹤0.05）;Ki-67≥20%也可能与发生微小浸润有关（P=0.057）。使用Logistic回归将重要协变量（年龄）与上述危险因素一起进行多因素分析显示,年龄﹥50岁（P=0.034）,肿瘤﹥2.5 cm（P=0.033）,高级别DCIS（P=0.011）等是原位癌伴微小浸润的独立危险因素。此外,相对于2.0%的原位癌淋巴结转移概率,MIBC的淋巴结转移概率为5.5%,二者比较差异具有统计学意义（P=0.029）。结论 MIBC淋巴结转移风险为5.5%,多伴发于患者年龄超过50岁的较大范围的高级别DCIS中。目前来说,对合并这些高风险因素的原位癌患者直接进行SLNB是一种合理和稳妥的诊治手段,可以有效避免二次手术的发生并为下一步治疗提供依据。     

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。     

Quantification of the effect of mammographic screening on fatal breast cancers: The Florence Programme 1990-96

Breast cancer cases diagnosed in women aged 50-69 since 1990 to 1996 in the City of Florence were partitioned into those who had been invited to screening prior to diagnosis and those who had not. All cases were followed up for vital status until 31 December 1999. The cumulative number of breast cancer deaths among the cases were divided by screening and invitation status, to give the rates of cancers proving fatal within a period of 8 years of observation (incidence-based mortality). We used the incidence-based mortality rates for two periods (1985-86, 1990-96), pre and during screening. The incidence-based mortality ratio comparing 1990-96 and 1985-86 was 0.50 (95% CI : 0.38-0.66), a significant 50% reduction. For noninvited women, compared to 1985-86, there was a 41% significant mortality reduction (RR=0.59, 95% CI : 0.42-0.82). The comparable reduction in those invited was a significant 55% (RR=0.45, 95% CI : 0.32-0.61). The incidence ratio of rates of cancers stage II or worse was close to one when the noninvited in 1990-96 were compared with 1985-86 (RR=0.97, 95% CI : 0.78-1.21). Excluding prevalent cases, the rate of stage II+ breast cancer cases was 42% lower in Screened women compared with the noninvited (RR=0.58, 95% CI : 0.45-0.74). This study confirmed that new treatments and the first rounds of the screening programme contributed to reducing mortality from breast cancer.     

Risk of subsequent invasive breast carcinoma after in situ breast carcinoma in a population covered by national mammographic screening

Sweden was the first country to establish a nationwide breast cancer screening service. We used the Swedish Family-Cancer Database to evaluate the risk of invasive carcinoma after in situ carcinoma of the breast. Risk estimates for contralateral and ipsilateral invasive malignancies following age and histology specific in situ breast carcinomas were calculated using Poisson's regression analysis. The agreement between concordant and discordant morphologies of invasive and in situ breast cancer was measured using the kappa statistic. Women with in situ breast cancer showed a relative risk of 2.03 for contralateral and 3.94 for ipsilateral invasive breast cancer. The risk was higher for in situ carcinomas diagnosed before the age of 50 years and after lobular in situ breast cancers. A comparison of the risks during the past decades suggested that the risk of ipsilateral breast cancer has increased in Sweden but that of contralateral breast cancer has remained unchanged. In situ and the subsequent invasive breast cancers did not seem to share their morphologies.     

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。     

Lack of efficacy of xeromammography in preoperatively detecting lobular carcinoma in situ of the breast

Summary The medical records of fourteen patients with LCIS were reviewed to correlate the clinical, xeromammographic, and pathologic findings. The patients' xeromammograms were negative for findings associated with LCIS in 81% of the breasts that yielded biopsies positive for LCIS. Xeromammography does not appear to have improved our ability to identify patients with LCIS. Address for reprints: Don M. Morris, M.D., Department of Surgery, Louisiana State University Medical Center, 1501 Kings Highway, Shreveport, LA 71130, USA.     

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.     

Pre-operative management of Pleomorphic and florid lobular carcinoma in situ of the breast: Report of a large multi-institutional series and review of the literature

BackgroundPleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated.AimTo collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature.MethodsA multi-institutional series of P/F LCIS was retrieved. All cases were diagnosed on pre-operative biopsies, which was followed by an open surgical excision. Data on post-operative histopathology were available. A literature review was performed.ResultsA total of 117 cases were collected; invasive carcinoma and/or DCIS was present in 78/117 cases (66.7%). Seventy cases of P/F LCIS were pure on biopsy and 31 of these showed pathological upgrade in post-surgical specimens. Pre-operative biopsy accuracy was 47/78 (60.3%); pre-operative biopsy underestimation of cancer was 31/78 (39,7.%). In the literature review papers, invasive carcinoma or DCIS was associated with 274 of 418 (65.5%) cases of P/F LCIS. Pre-operative biopsy accuracy was 66% (181/274) whereas pre-operative biopsy underestimation of cancer was 33.9% (93/274).ConclusionsThe data presented here indicate that P/F LCIS is frequently associated with invasive carcinoma or high grade DCIS and that pre-operative biopsy is associated with an underestimation of malignancy. Open surgery is indicated when P/F LCIS is diagnosed pre-operatively.     

Breast density in relation to risk of ductal carcinoma in situ of the breast in women undergoing screening mammography

Objective To examine the association between breast density and risk of breast ductal carcinoma in situ (DCIS). Methods We assessed breast density in relation to DCIS risk using combined data from statewide mammography registries in NH and VT. The prospective analyses were based on 572 DCIS cases arising in 154,936 women (58,496 premenopausal and 96,440 postmenopausal). Women in the study were followed on average 4.1 years. Breast density was scored by community radiologists using BIRADS categories (fatty, scattered density, heterogeneous density, extreme density). Results In premenopausal women, based on 157 cases, the RR for DCIS risk were 0.29 (95% CI: 0.0.04, 2.24) for fatty breasts, 2.06 (95% CI: 1.39, 3.05) for heterogeneous density, and 2.40 (95% CI: 1.47, 3.91) for extreme density, relative to scattered density. In postmenopausal women, based on 369 cases, the RR for DCIS risk were 0.58 (95% CI: 0.37, 0.93) for fatty breasts, 1.41 (95% CI: 1.12, 1.78) for heterogeneous density, and 1.49 (95% CI: 0.93, 2.37) for extreme density, relative to scattered density. The possible interaction between breast density and menopausal status in relation to DCIS risk was not statistically significant. Conclusions We observed an association between breast density and DCIS risk. Although the association seemed stronger in premenopausal women, there was no evidence of an interaction involving breast density and menopausal status.     

Serum p53 autoantibodies in patients with minimal lesions of ductal carcinoma in situ of the breast

Five of 43 patients (11.6%) with ductal carcinoma in situ of the breast presented with p53 autoantibodies at diagnosis. Three seropositive patients demonstrated tumour sizes of < or = 5 mm. There was no association of p53 autoantibody status with age, clinical presentation, histological subtype, tumour size, grading, p53 immunohistochemistry or hormone receptor status.