Introduction Of Mammographic Screening Research Articles

Ductal Carcinoma In Situ - Quo Vadis?

The introduction of mammographic screening in the early 1980's was associated, in the three following decades, with a dramatic increase in the detection of ductal carcinoma in situ (DCIS), pathology rarely detected before, on surgical specimen, at the periphery of an invasive cancer (1,2,3). It is estimated that in the United States the incidence of DCIS, each year, varies between 18 to 25% of the total number of newly diagnosed breast cancers (4,5). Ductal carcinoma in situ belongs, genetically and pathomorphologically, to a heterogenous group of preinvasive neoplastic lesions characterized by clonal proliferation of malignant cells limited to the lumen of breast ducts. It has not a known natural history and its phenotypical spectrum is wide, varying from a slowly evolving disease to a fast growing one, invading the surrounding stroma and even metastasizing to distant sites (6). In the absence of reliable prognostic markers, most of patients are submitted to invasive treatments consisting mainly in surgery, alone or associated with radiation and endocrine therapy (7). Molecular subtyping has improved the understanding of breast cancer biology and its possibilities for evolution and have provided the tools to design a more personalized treatment (8). In the absence of reliable molecular markers clinical management of patients with DCIS is based on patient's option and tumor characteristics. Based on the knowledge of today, DCIS could be used to exemplify the notions of overdiagnosis and overtreatment. The final goal of the treatment of DCIS is to prevent invasive breast cancer recurrence. Mortality rate associated with DCIS is very low, being estimated at 1-2 % at 10 years, while patients with DCIS treated by wide local excision with or without radiation may have a local recurrence rate of 5 to 30% and half of these present as an invasive cancer. Today's clinicians are not able to predict the risk of progression for a DCIS diagnosed by biopsy, but neither the risk of local recurrence, as an invasive cancer, of DCIS treated by conservative surgery with or without radiation (9). Progression to invasive cancer is difficult to be predicted as the disease is highly heterogenous. Because of these uncertainties, it is highly important to carefully inform the patient and engage her in the treatment decision process (10). There is a trend for de-escalation of treatment for DCIS. A study comparing two groups of patients with pure DCIS was conducted: one with standard care and the other under active surveillance (11). The main outcome was the probability to die from breast cancer at 10 years after the diagnosis. The mortality risk from breast cancer is higher for younger women, than the older ones, under active surveillance. Women over the age of 70 years, have many comorbidities that could induce the risk of dying, regardless of DCIS treatment decision. This study suggested that active surveillance could be a reasonable option for certain category of patients. This attitude is not without risks. A patient with DCIS on core needle biopsy could hide an invasive cancer in 25% of cases (12). Today, there are four randomized control trials of active surveillance offered to patients with low-grade DCIS: LORD (LOw Risk DCIS), COMET (Comparison of Operative to Monitoring and Endocrine Therapy), LORIS (LOw RISk DCIS) and LORETTA (10,13-16). Non-surgical approaches are of two types: active surveillance alone or associated with hormone therapy. There are some differences between the trials. While in LORD and LORIS trials the study arms are represented by active surveillance only, hormone therapy is an option in COMET trial and mandatory in the single arm trial LORETTA. The aim of these studies is to examine the safety and the effectiveness of active surveillance compared with surgical management for low-risk DCIS. The results of these trials are awaited with great interest. Patients with ductal carcinoma in situ need special counseling. To talk about "a good" cancer or even no cancer and to recommend as treatment a mastectomy is highly confusing. The language used by all members of the team must be unitary, removing the anxiety and helping patients to make the best decision. This special issue is a great opportunity to have the opinions of highly respected international specialists in the field for a comprehensive review of DCIS of the breast.

Cancer Progress and Priorities: Breast Cancer.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

Histopatološke karakteristike raka dojke od 2005 do 2019 u jednom centru u Hrvatskoj pregled promjena nakon uvođenja mammografskog probira

Histopatološke karakteristike raka dojke od 2005 do 2019 u jednom centru u Hrvatskoj pregled promjena nakon uvođenja mammografskog probira

Modeling the natural history of ductal carcinoma in situ based on population data

BackgroundThe incidence of ductal carcinoma in situ (DCIS) has increased substantially since the introduction of mammography screening. Nevertheless, little is known about the natural history of preclinical DCIS in the absence of biopsy or complete excision.MethodsTwo well-established population models evaluated six possible DCIS natural history submodels. The submodels assumed 30%, 50%, or 80% of breast lesions progress from undetectable DCIS to preclinical screen-detectable DCIS; each model additionally allowed or prohibited DCIS regression. Preclinical screen-detectable DCIS could also progress to clinical DCIS or invasive breast cancer (IBC). Applying US population screening dissemination patterns, the models projected age-specific DCIS and IBC incidence that were compared to Surveillance, Epidemiology, and End Results data. Models estimated mean sojourn time (MST) in the preclinical screen-detectable DCIS state, overdiagnosis, and the risk of progression from preclinical screen-detectable DCIS.ResultsWithout biopsy and surgical excision, the majority of DCIS (64–100%) in the preclinical screen-detectable state progressed to IBC in submodels assuming no DCIS regression (36–100% in submodels allowing for DCIS regression). DCIS overdiagnosis differed substantially between models and submodels, 3.1–65.8%. IBC overdiagnosis ranged 1.3–2.4%. Submodels assuming DCIS regression resulted in a higher DCIS overdiagnosis than submodels without DCIS regression. MST for progressive DCIS varied between 0.2 and 2.5 years.ConclusionsOur findings suggest that the majority of screen-detectable but unbiopsied preclinical DCIS lesions progress to IBC and that the MST is relatively short. Nevertheless, due to the heterogeneity of DCIS, more research is needed to understand the progression of DCIS by grades and molecular subtypes.

Dose and spatial resolution analysis of grating-based phase-contrast mammography using an inverse Compton x-ray source.

Purpose: Although the mortality rate of breast cancer was reduced with the introduction of screening mammography, many women undergo unnecessary subsequent examinations due to inconclusive diagnoses. Superposition of anatomical structures especially within dense breasts in conjunction with the inherently low soft tissue contrast of absorption images compromises image quality. This can be overcome by phase-contrast imaging.Approach: We analyze the spatial resolution of grating-based multimodal mammography using a mammographic phantom and one freshly dissected mastectomy specimen at an inverse Compton x-ray source. Here, the focus was on estimating the spatial resolution with the sample in the beam path and discussing benefits and drawbacks of the method used and the estimation of the mean glandular dose. Finally, the possibility of improving the spatial resolution is investigated by comparing monochromatic grating-based mammography with the standard one.Results: The spatial resolution is constant or also higher for the image acquired with monochromatic radiation and the contrast-to-noise ratio (CNR) is higher in our approach while the dose can be reduced by up to 20%.Conclusions: In summary, phase-contrast imaging helps to improve tumor detection by advanced diagnostic image quality. We demonstrate a higher spatial resolution for one mastectomy specimen and increased CNR at an equal or lower dose for the monochromatic measurements.

Abstract P6-15-07: Impact of increased mammary adiposity on DCIS progression

Abstract Background: The incidence of ductal carcinoma in situ (DCIS) has greatly increased since the introduction of mammographic screening. However, so far, it is still not possible to predict which patient with DCIS will further develop invasive breast cancer. Adipocyte hypertrophy and adipocyte inflammation has been associated with increased risk of developing breast cancer in postmenopausal women and with worse prognosis in breast cancer patients. In this study, we aimed 1) at evaluating the association between mammary adiposity, as assessed by digital pathology, with DCIS progression using a unique case-control series with long-term follow up and 2) study the interaction between DCIS cells and the surrounding adipocytes. Patients and methods: Mammary adipocyte size was measured in surgical specimens of 279 women with primary DCIS. These mammary adipocyte measurements were compared in 109 women with primary DCIS who subsequently developed ipsilateral invasive breast cancer (iIBC) (cases) and 170 women who did not (controls). Patients were matched for age and follow-up duration. Median follow-up time was 12.8 years. Post-menopausal patients were defined as >50 years at diagnosis and represented 220/279 (78,9%) of patients. All patients were treated with breast cancer-conserving surgery only. Intact adipocytes distant from the DCIS lesions were measured (largest diameter and area) using HALO™ image analysis software (Indica Labs, Corrales, NM) on H&E-stained whole slide images of primary DCIS. Given the specific interest in the larger adipocytes, we systematically considered the 75th percentile as unique value for each patient. An average of 4259 adipocytes (min:70, max:21107) was measured per patient. Tissue segmentation was used to measure the adipose area. Adipose triglyceride lipase (ATGL clone 2138, Cell Signaling) immunohistochemistry (IHC) was applied to study ATGL expression in DCIS cells. Her2, ER and COX-2 IHC and RNAseq of microdissected pure DCIS was already available for this series (LL. Visser et al. Clin Can Res 24 (15) 2018). Conditional logistic regression was applied to investigate differences in adipocyte hypertrophy between groups of patients (e.g., cases and controls). Results: Adipocytes were larger and the proportion of adipose tissue was higher in post-menopausal patients (both p<0.001). Mean adipocyte maximum diameter and mean adipocyte area of the 75th percentile ranged from 46.9-115.9 µm and 2016-11336 µm2 respectively. For every 1000 µm2 increase in mean adipocyte area a DCIS patient had a 1.18 increased risk for iIBC (95% CI 1.02-1.36, p= 0.028). DCIS patients with large adipocytes (above the 75th percentile) had a 2.1 increased risk for developing iIBC (95% CI: 1.18-3.72, p=0.011). This observation remained when restricting the analysis to post-menopausal patients (OR 1.19 per 1000 µm2 95% CI 1.01-1.40, p=0.038 and adipocytes above 75th percentile OR 2.2, 95% CI 1.22-3.99, p= 0.009). To further explore the potential interactions between the epithelial cells from DCIS with the adjacent adipocytes, we compared the size of the DCIS-adjacent adipocytes to those away from DCIS lesions. DCIS-adjacent adipocytes showed a reduction in size, suggesting delipidation. Adipose triglyceride lipase (ATGL) is a rate limiting lipase that can release stored free fatty acids (FFA) in DCIS cells for fatty acid ß-oxidation. In a pilot series strong ATGL expression was observed in a subset of DCIS lesions (4 of 25). Conclusion and perspective: This study is the first to demonstrate that mammary adipocyte hypertrophy is associated with an increased risk of progression for patients with DCIS. Our findings might help to distinguish potentially hazardous from harmless DCIS, enabling overtreatment of indolent DCIS. Adipocyte size will be correlated to immunohistochemical expression of ATGL, Her2, ER and COX2 in DCIS, and RNAseq data of pure microdissected DCIS. Citation Format: Mathilde Matthea Machteld Almekinders, Michael Schaapveld, Bram Thijssen, Ingrid Hofland, Marjolijn Mertz, Dennis Peters, Annegien Broeks, Lodewijk Wessels, Wilbert Zwart, Jos Jonkers, Esther Lips, Christine Desmedt, Jelle Wesseling, on behalf of the PRECISION Team. Impact of increased mammary adiposity on DCIS progression [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-15-07.

Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001–14: a case only analysis

SummaryBackgroundPolicies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis.MethodsIn this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18–89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001–14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables).FindingsWe identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001–14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53–1·70; fully adjusted OR 1·45, 95% CI 1·38–1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22–1·30; fully adjusted OR 1·18, 1·14–1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2–49·5) and lowest for women who were white with university education (29·4%, 28·2–30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%–17·2% in 1970–74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50–69 years).InterpretationThe persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease.FundingNewton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa.

Dose-compatible grating-based phase-contrast mammography on mastectomy specimens using a compact synchrotron source

With the introduction of screening mammography, the mortality rate of breast cancer has been reduced throughout the last decades. However, many women undergo unnecessary subsequent examinations due to inconclusive diagnoses from mammography. Two pathways appear especially promising to reduce the number of false-positive diagnoses. In a clinical study, mammography using synchrotron radiation was able to clarify the diagnosis in the majority of inconclusive cases. The second highly valued approach focuses on the application of phase-sensitive techniques such as grating-based phase-contrast and dark-field imaging. Feasibility studies have demonstrated a promising enhancement of diagnostic content, but suffer from dose concerns. Here we present dose-compatible grating-based phase-contrast and dark-field images as well as conventional absorption images acquired with monochromatic x-rays from a compact synchrotron source based on inverse Compton scattering. Images of freshly dissected mastectomy specimens show improved diagnostic content over ex-vivo clinical mammography images at lower or equal dose. We demonstrate increased contrast-to-noise ratio for monochromatic over clinical images for a well-defined phantom. Compact synchrotron sources could potentially serve as a clinical second level examination.

Evaluating different breast tumor progression models using screening data

BackgroundMammography screening is used to detect breast cancer at an early treatable stage, reducing breast cancer mortality. Traditionally, breast cancer has been seen as a disease with only progressive lesions, and here we examine the validity of this assumption by testing if incidence levels after introducing mammography screening can be reproduced assuming only progressive tumors.MethodsBreast cancer incidence data 1990–2009 obtained from the initially screened Norwegian counties (Akershus, Oslo, Rogaland and Hordaland) was included, covering the time-period before, during and after the introduction of mammography screening. From 1996 women aged 50–69 were invited for biennial public screening. Using estimates of tumor growth and screening sensitivity based on pre-screening and prevalence screening data (1990–1998), we simulated incidence levels during the following period (1999–2009).ResultsThe simulated incidence levels during the period with repeated screenings were markedly below the observed levels. The results were robust to changes in model parameters. Adjusting for hormone replacement therapy use, we obtained levels closer to the observed levels. However, there was still a marked gap, and only by assuming some tumors that undergo regressive changes or enter a markedly less detectable state, was our model able to reproduce the observed incidence levels.ConclusionsModels with strictly progressive tumors are only able to partly explain the changes in incidence levels observed after screening introduction in the initially screened Norwegian counties. More complex explanations than a time shift in detection of future clinical cancers seem to be needed to reproduce the incidence trends, questioning the basis for many over-diagnosis calculations. As data are not randomized, similar studies in other populations are wanted to exclude effect of unknown confounders.

Breast conservation in ductal carcinoma in situ (DCIS): what defines optimal margins?

The introduction of mammographic screening has resulted in a rise in the detection rate of ductal carcinoma in situ (DCIS), currently accounting for one-fifth of screen-detected breast cancers. Although 60-70% of DCIS are treated with breast-conserving surgery (BCS) with or without radiotherapy, the frequency of subsequent surgery to re-excise positive margins in order to reduce the probability of recurrences remains high. DCIS recurrence is associated not only with financial, health and psychological implications; approximately half these recurrences are invasive disease. An appropriate margin width for patients undergoing BCS for invasive breast cancer has been largely agreed. Although there is a perception that such recommendations may be applicable to DCIS, major differences exist which may affect this application. Importantly, DCIS patients often do not receive systemic adjuvant (endocrine) therapy and not all receive radiotherapy in routine practice. There is evidence that wide margins (i.e. >10 mm) confer better protection against recurrence than positive (i.e. 0 mm) margins; however, there remains a debate concerning the optimum margin width between 0 and 10 mm. Previous studies have demonstrated that radiation therapy may not compensate for lack of re-excision in those patients with positive or close margins, while wide margins will inevitably compromise cosmesis and patients' body image perception. This review aims to address the clinical question of the minimal margin width in DCIS treated with BCS that is associated with the lowest recurrence rate and when, therefore, further surgical intervention for re-excision can be safely avoided. A range of clinical circumstances that might affect this are considered.

Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness

BackgroundThe goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms. Effective screening should therefore lead to the detection of a greater number of small tumors, followed by fewer large tumors over time.MethodsWe used data from the Surveillance, Epidemiology, and End Results (SEER) program, 1975 through 2012, to calculate the tumor-size distribution and size-specific incidence of breast cancer among women 40 years of age or older. We then calculated the size-specific cancer case fatality rate for two time periods: a baseline period before the implementation of widespread screening mammography (1975 through 1979) and a period encompassing the most recent years for which 10 years of follow-up data were available (2000 through 2002).ResultsAfter the advent of screening mammography, the proportion of detected breast tumors that were small (invasive tumors measuring <2 cm or in situ carcinomas) increased from 36% to 68%; the proportion of detected tumors that were large (invasive tumors measuring ≥2 cm) decreased from 64% to 32%. However, this trend was less the result of a substantial decrease in the incidence of large tumors (with 30 fewer cases of cancer observed per 100,000 women in the period after the advent of screening than in the period before screening) and more the result of a substantial increase in the detection of small tumors (with 162 more cases of cancer observed per 100,000 women). Assuming that the underlying disease burden was stable, only 30 of the 162 additional small tumors per 100,000 women that were diagnosed were expected to progress to become large, which implied that the remaining 132 cases of cancer per 100,000 women were overdiagnosed (i.e., cases of cancer were detected on screening that never would have led to clinical symptoms). The potential of screening to lower breast cancer mortality is reflected in the declining incidence of larger tumors. However, with respect to only these large tumors, the decline in the size-specific case fatality rate suggests that improved treatment was responsible for at least two thirds of the reduction in breast cancer mortality.ConclusionsAlthough the rate of detection of large tumors fell after the introduction of screening mammography, the more favorable size distribution was primarily the result of the additional detection of small tumors. Women were more likely to have breast cancer that was overdiagnosed than to have earlier detection of a tumor that was destined to become large. The reduction in breast cancer mortality after the implementation of screening mammography was predominantly the result of improved systemic therapy.

Predictors for local invasive recurrence of ductal carcinoma in situ of the breast: a meta-analysis.

The introduction of mammographic screening has considerably increased the detection rate of ductal carcinoma in situ (DCIS), which has a high probability of recurrence. We carried out a meta-analysis to evaluate the predictive factors including biomarkers, tumor characteristics, and modes of detection on the risk of local invasive recurrence (LIR) following DCIS. Searches were performed in PubMed and EMBASE up to 8 July 2014. Risk estimates (hazard ratios, odds ratios, and relative risks) and their 95% confidence intervals (CIs) were extracted to calculate the strength of the associations between predictive factors and the risk of LIR after treatment of DCIS. STATA 12.0 was used to combine results in this meta-analysis. A total of 18 articles were included in the analysis. Pooled risk estimates and 95% CIs were 1.36 (1.04–1.69) for the positive margin, 1.38 (1.12–1.63) for the nonscreening detection method, 1.04 (0.84–1.24) for high nuclear grade 1, 1.32 (0.98–1.66) for intermediate nuclear grade 2, 1.18 (0.98–1.37) for comedonecrosis, 1.00 (0.92–1.08) for large tumor size, 1.34 (0.82–1.87) for multifocality, 0.74 (0.36–1.12) for estrogen receptor-positive tumors, 0.89 (0.47–1.31) for progesterone receptor-positive tumors, and 1.25 (0.7–1.81) for HER2/neu-positive tumors. Positive margin and non-screening-detected cancers were associated with a higher risk of LIR following DCIS. These predictive factors, after further validation, could be considered to tailor treatment for individual patients.

Analysis of the diagnosis and treatment of breast cancer before and after introduction of mammography screening

Analysis of the diagnosis and treatment of breast cancer before and after introduction of mammography screening

Cancer Screening Guidelines and Mortality

The effectiveness of population-level cancer screening is a salient issue in health policy that remains unresolved. This paper investigates changes in mortality after the introduction of screening guidelines for breast and prostate cancers in the United States and United Kingdom. We use differences in the timing of guideline adoption, which ages are recommended for screening, and which cancers are detectable by screening to identify the effect of guidelines. Our quadruple-differencing strategy finds a moderately sized mortality benefit from mammography and PSA screening guidelines among recommended age groups and little change in mortality rates among age groups not recommended to receive screening. Falsification tests provide additional confirmation of our results; prostate cancer rates among men did not fall after the introduction of mammography screening and breast cancer rates among women did not fall after the introduction of the PSA test.

Diagnóstico citológico en patología mamaria

The diagnosis of breast lesions is multidisciplinary, with participation by clinicians, radiologists, and pathologists. Fine-needle aspiration cytology of the breast is a technically simple and inexpensive procedure and the results can be made available immediately. This procedure can improve the management of patients with breast disease. Since the introduction of mammographic screening, more breast lesions are being detected and aspirated at a premalignant or preinvasive stage. Cytological interpretation of the findings can be very difficult and requires further investigation such as core needle biopsy. Despite these limitations, breast cytology remains the technique of choice for the study of axillary lymph nodes, recurrences, and metastatic lesions.

English

Objective: To determine if screening mammography produced the expected increase in the incidence of early-stage breast cancer and reduced the expected incidence of late-stage breast cancer in women 40 years of age or older. Design: Population-based observation study using a before and after cohort time series design. Data Sources: 1) National Health Interview Survey; 2) Surveillance, Epidemiology and End Results (SEER) data; 3) United States Census. Results: The introduction of screening mammography in the United States has been associated with a doubling in the number of cases of early-stage breast cancer detected each year from 112 to 234 cases per 100 000 women — an absolute increase of 122 cases per 100 000 women. Concomitantly, the rate at which women present with late-stage cancer has decreased from 102 to 94 cases per 100 000 women — an absolute decrease of 8 cases per 100 000 women. With the assumption of a constant underlying disease burden, it was estimated that only 8 of the 122 additional early-stage cancers diagnosed would progress to advanced disease. After excluding the transient excess incidence associated with hormone replacement therapy and adjusting for trends in the incidence of breast cancer among women younger than 40 years old, it was estimated that breast cancer was overdiagnosed (i.e., tumours were detected on screening that would never have led to clinical symptoms) in 70 000 women in 2008 and 1.3 million women in the past 30 years. Conclusion: Despite substantial increases in the number of early-stage breast cancer detected, screening mammography has only marginally reduced the rate at which women present with late-stage cancer.

Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Stromal architecture and periductal decorin are potential prognostic markers for ipsilateral locoregional recurrence in ductal carcinoma in situ of the breast

The incidence of ductal carcinoma in situ (DCIS) has increased since the introduction of screening mammography. Recurrence prediction is still not accurate, and could be improved by identifying additional prognostic markers. Periductal stroma actively participates in early breast cancer progression. Therefore, the aim of this study was to explore the prognostic potential of stromal characteristics in DCIS. Histopathological features and hormone receptor/HER2 status were analysed in a first cohort of 65 cases of DCIS with a median follow-up of 112 months. Cox regression analysis revealed that myxoid stromal architecture was significantly associated with increased ipsilateral locoregional recurrence (P = 0.015). Next, we performed immunohistochemical screening of nine stromal proteins in a second cohort of 82 DCIS cases, and correlated their expression with stromal architecture. Because reduced stromal decorin expression correlated most strongly with myxoid stroma (P < 0.001), it was selected for further analysis in the first cohort. Patients with reduced periductal decorin expression had a higher risk of recurrence (P = 0.008). Furthermore, HER2 overexpression was significantly associated with invasive but not with in situ recurrence (P = 0.007). Periductal myxoid stroma and reduced periductal decorin expression seem to be prognostic for overall ipsilateral locoregional recurrence in DCIS, whereas HER2 expression might be a more specific biomarker for invasive recurrence.

Veränderungen der Therapie des Mammakarzinoms in Bayern seit Einführung des Mammografie-Screenings. Eine Analyse bayerischer Krebsregisterdaten der Jahre 2000 bis 2008

A quality controlled mammography screening programme was initiated at the end of 2003 in Bavaria, a region with 12.5 million inhabitants, and transferred over to the national screening programme at the end of 2006. The purpose of this study was to evaluate immediate population-based consequences of mammography screening on breast cancer therapy. Data from 75 475 breast cancer cases, diagnosed between 2000 and 2008 and registered in one of the 6 Bavarian clinical cancer registries were analysed. 51.4% of these patients were between 50 and 69 years of age and therefore the target population for screening. Trends of prognostic factors and standard therapies were calculated for 3 age groups (≤49 years, 50-69 years, ≥70 years) by means of annual percentages as well as 95%-confidence intervals for the percent difference between 2000 and 2008 (year of diagnosis). For interpretation of therapy trends, logistic regression models were calculated. Therapy trends showed that the increasingly favourable stage distribution may have resulted in the reduction of more radical surgical methods such as mastectomy (2000: 32.6%; 2008: 19.6%) or axillary dissection (89.0% vs. 37.0%), especially for women aged 50-69. An increase of radiation therapies (59.7% vs. 66.6%) can be explained to some extent by the increase in breast conserving surgeries. The shift to more favourable prognostic factors led, in accordance with the guidelines, to an increase of the proportion of singular endocrine therapies (28.5% vs. 40.7%), a decrease of chemotherapies (20.4% vs. 13.1%) and therefore to more gentle systemic therapies overall. These trends strengthened in the years following the introduction of screening, with a simultaneous rise of screening participants in the target population. The introduction of mammography screening in Bavaria has already shown the expected trend towards more favourable prognostic factors. Among other things, this could be a reason for the increasing use of more gentle therapies. Whether the screening in Bavaria leads to a mortality reduction, has to be analysed on the basis of an initial comparison of participation status followed by the trends in mortality thereafter.

Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence

BackgroundTo reduce mortality, screening must detect life-threatening disease at an earlier, more curable stage. Effective cancer-screening programs therefore both increase the incidence of cancer detected at an early stage and decrease the incidence of cancer presenting at a late stage.MethodsWe used Surveillance, Epidemiology, and End Results data to examine trends from 1976 through 2008 in the incidence of early-stage breast cancer (ductal carcinoma in situ and localized disease) and late-stage breast cancer (regional and distant disease) among women 40 years of age or older.ResultsThe introduction of screening mammography in the United States has been associated with a doubling in the number of cases of early-stage breast cancer that are detected each year, from 112 to 234 cases per 100,000 women — an absolute increase of 122 cases per 100,000 women. Concomitantly, the rate at which women present with late-stage cancer has decreased by 8%, from 102 to 94 cases per 100,000 women — an absolute decrease of 8 cases per 100,000 women. With the assumption of a constant underlying disease burden, only 8 of the 122 additional early-stage cancers diagnosed were expected to progress to advanced disease. After excluding the transient excess incidence associated with hormone-replacement therapy and adjusting for trends in the incidence of breast cancer among women younger than 40 years of age, we estimated that breast cancer was overdiagnosed (i.e., tumors were detected on screening that would never have led to clinical symptoms) in 1.3 million U.S. women in the past 30 years. We estimated that in 2008, breast cancer was overdiagnosed in more than 70,000 women; this accounted for 31% of all breast cancers diagnosed.ConclusionsDespite substantial increases in the number of cases of early-stage breast cancer detected, screening mammography has only marginally reduced the rate at which women present with advanced cancer. Although it is not certain which women have been affected, the imbalance suggests that there is substantial overdiagnosis, accounting for nearly a third of all newly diagnosed breast cancers, and that screening is having, at best, only a small effect on the rate of death from breast cancer.