Widespread Use Of Mammography Research Articles

Changing trends in the management of ductal carcinoma in situ in Republic of Korea: a comprehensive analysis using Health Insurance Review and Assessment data [2009-2020

Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.

Learning from the wastage: histomorphology of columnar cell lesions and other changes in surgical pathology breast specimens

Introduction: In recent few decades, widespread use of mammography has resulted in increased detection of precursor and preinvasive breast lesions such as atypical ductal hyperplasia, ductal carcinoma in situ and, a type of breast lesion termed, ‘Flat epithelial atypia” which belongs to the group of columnar cell lesions with atypia. Although in India, invasive breast cancer is still most common presentation than early preinvasive lesions, with advanced diagnostic set up and increased awareness, early detection of preinvasive lesions is bound to be increased in future. For their accurate diagnosis, it is very necessary to be aware and alert about the morphology of these lesions. Objectives: Present study was undertaken to study the morphology of Columnar Cell Lesion and other changes in Surgical Biopsy specimens received in Histopathology laboratory of a tertiary health care centre. Materials and Methods: Excessive sections were taken from breast tissue surrounding the primary lesion in mastectomy or wide local excision specimens received over two-year duration and were examined for various changes in the epithelium and in the stroma especially columnar cell lesions and other precursor lesions. Results: A spectrum of precursor lesions including columnar cell lesions could be commonly seen in most of the specimens. Their morphology and differential diagnosis could be studied in details in these sections which otherwise are wasted usually. Conclusion: The tissue surrounding primary lesion in surgical pathology breast specimens is a good source to study the detailed morphology of columnar cell lesions and other lesions to get familiar with them for their accurate detection and early diagnosis in future. Keywords: Precursor breast lesions, Columnar cell lesions, Flat epithelial atypia, Ductal hyperplasia.

Impact of Overdiagnosis on Long-Term Breast Cancer Survival.

Elucidating whether and how long-term survival of breast cancer is mainly due to cure after early detection and effective treatment and therapy or overdiagnosis resulting from the widespread use of mammography provides a new insight into the role mammography plays in screening, surveillance, and treatment of breast cancer. Given information on detection modes, the impact of overdiagnosis due to mammography screening on long-term breast cancer survival was quantitatively assessed by applying a zero (cured or overdiagnosis)-inflated model design and analysis to a 15-year follow-up breast cancer cohort in Dalarna, Sweden. The probability for non-progressive breast cancer (the zero part) was 56.14% including the 44.34% complete cure after early detection and initial treatment and a small 11.80% overdiagnosis resulting from mammography screening program (8.94%) and high awareness (2.86%). The 15-year adjusted cumulative survival of breast cancer was dropped from 88.25% to 74.80% after correcting for the zero-inflated part of overdiagnosis. The present findings reveal that the majority of survivors among women diagnosed with breast cancer could be attributed to the cure resulting from mammography screening and accompanying effective treatment and therapy and only a small fraction of those were due to overdiagnosis.

Using tumor phenotype, histological tumor distribution, and mammographic appearance to explain the survival differences between screen-detected and clinically detected breast cancers.

In the era of mass screening for breast cancer with mammography, it has been noted that conventional tumor attributes and mammographic appearance are insufficient to account for the better prognosis of screen-detected tumors. Such prognostication may require additional updated pathological information regarding tumor phenotype (e.g., basal status) and histological tumor distribution (focality). We investigated this hypothesis using a Bayesian approach to analyze breast cancer data from Dalarna County, Sweden. We used data for tumors diagnosed in the Swedish Two-County Trial and early service screening period, 1977-1995, and from the mature service screening period, 1996-1998. In the early period of mammographic screening (1977-1995), the crude hazard ratio (HR) of breast cancer death for screen-detected cases compared with symptomatic ones was 0.22 (95% CI: 0.17-0.29) compared with 0.53 (95% CI: 0.34-0.76) when adjusted for conventional tumor attributes only. Using the data from the mature service screening period, 1996-1998, the HR was 0.23 (95% CI: 0.08-0.44) unadjusted and 0.71 (95% CI: 0.26-1.47) after adjustment for tumor phenotype, mammographic appearance, histological tumor distribution, and conventional tumor attributes. The area under the ROC curve (AUC) for the prediction of breast cancer deaths using these variables without the detection mode was 0.82, only slightly less than that observed when additionally including the detection mode (AUC=0.83). Using Freedman statistics, conventional tumor attributes and mammographic appearances explained 58% (95% CI: 57.5-58.6%) of the difference of breast cancer survival between the screen-detected and the clinically detected breast cancers, whereas the corresponding figure was increased to 77% (95% CI: 75.6-77.6%) when adding the two information on tumor phenotype and histological tumor distribution. The results indicated that conventional tumor attributes and mammographic appearance are not sufficient to be interim markers for explaining the survival difference between screen-detected and clinically detected cancers in the era marked by the widespread use of mammography. Additional information on tumor phenotype and histological distribution may be added as effective interim markers for explaining the benefit of the early detection of breast cancer with mammography.

RNA-Seq of Human Breast Ductal Carcinoma In Situ Models Reveals Aldehyde Dehydrogenase Isoform 5A1 as a Novel Potential Target

Breast ductal carcinoma in situ (DCIS) is being found in great numbers of women due to the widespread use of mammography. To increase knowledge of DCIS, we determined the expression changes that are common among three DCIS models (MCF10.DCIS, SUM102 and SUM225) compared to the MCF10A model of non-tumorigenic mammary epithelial cells in three dimensional (3D) overlay culture with reconstituted basement membrane (rBM). Extracted mRNA was subjected to 76 cycles of deep sequencing (RNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of RNA-Seq results showed 295 consistently differentially expressed transcripts in the DCIS models. These differentially expressed genes encode proteins that are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFβ signaling, show association with cell-cell signaling, cell-cell adhesion and cell proliferation, and have a notable bias toward localization in the extracellular and plasma membrane compartments. RNA-Seq data was validated by quantitative real-time PCR of selected differentially expressed genes. Aldehyde dehydrogenase 5A1 (ALDH5A1) which is an enzyme that is involved in mitochondrial glutamate metabolism, was over-expressed in all three DCIS models at both the mRNA and protein levels. Disulfiram and valproic acid are known to inhibit ALDH5A1 and are safe for chronic use in humans for other disorders. Both of these drugs significantly inhibited net proliferation of the DCIS 3D rBM overlay models, but had minimal effect on MCF10A 3D rBM overlay models. These results suggest that ALDH5A1 may play an important role in DCIS and potentially serve as a novel molecular therapeutic target.

Biomarkers in the Diagnosis of Primary and Recurrent Breast Cancer

Despite the widespread use of mammography for breast cancer screening, breast cancer remains the most common cause of cancer-related mortality among women worldwide. The identification of biomarkers that identify cancers when they are small, localized and most treatable is an important aim of current breast cancer research. Biomarkers need to be sensitive, specific, reproducible and easily collected from patients from readily accessible tissue or body fluids. While conventional biomarker research has focused on soluble proteins, cell markers, proteomics and DNA methylation, much progress has also been made in the field of immunobiomarkers and multiparameter gene arrays. Currently, no one biomarker has demonstrated sufficient sensitivity and reproducibility for independent clinical and commercial use. This review summarizes the current state of breast cancer biomarker research and anticipated future directions.

Discovery and Validation of Breast Cancer Early Detection Biomarkers in Preclinical Samples

Despite the widespread use of mammography for breast cancer screening, breast cancer remains the most common cause of cancer-related mortality among women worldwide. The identification of blood-based biomarkers useful for the early detection of breast cancer could have a major impact on reducing breast cancer disease burden by identifying cancers early when they are most treatable. We conducted a series of large-scale proteomic discovery and validation studies using preclinical samples from the Women's Health Initiative Observational Study prospective cohort. Of the 503 proteins quantified in experiments conducted on samples from ER(+) breast cancer patients and matched controls, 57 differentiated cases from controls. The seven candidates were assessed in an independent validation set with a commercially available ELISA assay. We confirmed that one of these candidates, epidermal growth factor receptor (EGFR), was elevated in cases versus controls. Compared to women in the lowest EGFR quartile, those in the highest quartile has a 2.90-fold (p = 0.0005) increased risk of developing breast cancer. An interaction with use of menopausal hormone therapy was observed such that among current estrogen plus progestin users, those in the highest EGFR quartile had a 9.04-fold (p = 0.0004) increased risk of developing breast cancer. While the performance of EGFR in terms of sensitivity and specificity is insufficient for it to be used on its own clinically, the formal validation of EGFR suggests that there may indeed be changes in the plasma proteome prior to the clinical diagnosis of breast cancer that are detectable and of potential clinical utility.

Abstract A30: The ZNF217 breast cancer oncogene, found amplified at 20q13, is a potential biomarker for aggressive disease

Abstract Background: ZNF217 is found amplified at the 20q13.2 locus in 20% of breast tumors. Recent work suggests that ZNF217 may encourage neoplastic transformation by promoting cell survival through aberrant transcriptional regulation of genes upstream of the PI3K pathway. An unbiased, functional genomics approach was used to identify potential ZNF217 gene targets, among them the ErbB3 receptor tyrosine kinase.) Our work demonstrates a strong positive correlation between ZNF217 and ErbB3 expression in breast tumors supported by gain and loss of function cell culture studies (manuscript in press). This suggests a novel mechanism for ErbB3 overexpression. Importantly, ErbB3 potently activates the PI3K pathway, driving tumor cell survival and invasion. Preliminary results, modeling ZNF217 amplification in MCF10A 3D matrigel culture suggest an aggressive phenotype. The concept that ZNF217 positively regulates ErbB3 expression, contributing to survival and invasiveness of tumors with 20q13 amplification, is innovative. Knowledge that a significant number of breast tumors are amplified at the 20q13 locus containing ZNF217, suggests utility as an early biomarker for invasive disease. Hypothesis: The 20q13.2 locus is associated with aggressive features (high histological grade, DNA aneuploidy, high S-phase fraction, axillary nodal involvement). We will explore ZNF217 overexpression as a surrogate marker for 20q13 amplification and a potential biomarker for prediction of invasive potential and metastatic disease. Preliminary array Comparative Genomic Hybridization (aCGH) identified a significant number of 20q13-amplified breast tissue samples with increased ZNF217 copy numbers. We hypothesize that breast tissue samples taken at the time of biopsy could be assayed for amplified ZNF217 and will predict cancers with trajectory towards aggressive disease. This comprehensive study will report the association between 20q13 amplification, ZNF217 copy number, and ZNF217 nuclear expression. Employing ZNF217 immunohistochemistry (IHC), as a clinical test similar to the HercepTest, could simultaneously screen for 20q13-positive and ZNF217-positve breast tumors providing valuable prognostic information. Study: To examine overlap for ZNF217 amplification at 20q13 and ZNF217 overexpression, paraffin-embedded breast tissue samples (with 10 years follow-up data) will be screened using aCGH to identify 100 samples that are 20q13-amplified and 50 specimens with no extra copies. The ZNF217 copy number will be determined using aCGH analysis software. To determine ZNF217 protein levels in the 20q13-amplified or nonamplified samples, IHC will be performed and nuclei scored for positivity by blinded pathologists. Statistical analysis will determine the significant correlation and potential for ZNF217 as a surrogate marker for amplified 20q13. ZNF217 positivity will be correlated with poor patient prognosis including progression to IDC or development of distant metastases as well as disease-free and overall survival. In addition, we will correlate ZNF217 levels with other prognostic factors; PR, ER, HER2, and lymph node status. Impact on breast cancer: We propose that ZNF217, amplified at 20q13, may provide prognostic value and stratification of tumors, predicting aggressive lesions at early stages of breast tumor development. Widespread use of mammography in breast cancer screening has led to earlier detection, identifying patients with preinvasive disease. Biomarkers that will accurately predict the propensity of a tumor to progress to invasive disease are needed to provide opportunities for early and aggressive therapy when warranted; avoiding drastic measures when unnecessary. Our study will determine if ZNF217 will be a useful biomarker that can be immediately introduced into the clinic with routine, inexpensive IHC assay at the time of biopsy. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A30.

A Very Favourable Mammographic Screening Impact on Breast Cancer Characteristics and Treatment Modalities in France. Analysis of 2806 Cases.

Abstract Introduction In 2005, 49800 new breast cancers (BC) occurred in France, representing the first (36%) female cancer. The new national screening program was displayed in all regions in 2003-2004, including women from 50 to 74 years old.Material and methods In 2001-2002, a first National Survey (NS1) was conducted, including 1159 new BC in France. In 2007-2008, we performed a second national survey (NS2) including 1647 BC in order to compare all epidemiological clinico-pathological features and treatment modalities. Both studies were multicentric, prospective and non selective. There were respectively 124 and 130 involved physicians working in cancer centres, general or teaching hospitals and private clinics.Results The main results are shown in table 1. Median age remained constant (58 years), but with increased rates in women under 40 (from 5.6% to 7%) and older than 70 (from 20.4% to 22.4%). A three-fold increase (+ 15.8%) of T0 lesion (screening detected) was observed in NS2, with a concomitant T2 decrease (- 8.7%) and a stable rate of T3T4 and metastatic forms (3.6%). Concomitant pT1a-b rate increased (+ 9.4%) and pN+ rate dramatically decreased (- 12.1%), especially pN>3 (- 6%).Hormone receptors positivity and SBR grade distribution were similar. Her2 over-expression decreased from 20.6% to 12.4%, but dosages were performed in 31% (NS1) and 91% (NS2) of BC, respectively. The mastectomy rate was identical but axillary dissection decreased from 80% to 42.6%, whereas SLNB increased from 2.7% to 41%.Radiotherapy rates were identical, both after mastectomy and conservative surgery, but with a decrease in nodal volumes treatment. A 7.7% decrease in chemotherapy (CT) and a 6% increase in hormonotherapy (HT) were observed.A detailed analysis of age and HRT influence will be presented, as well as modifications in CT and HT prescriptions.Conclusion In the last decade, the widespread use of mammography strongly modified the clinico-pathological features of BC (e.g. pN+ and Her 2+++ rates) with resulting reduction treatment heaviness, especially in post-menopausal women. Thus, we can assume that in the coming years, increasing survival rates will be observed.Clinical pathological features and treatment comparison in both national surveysCLINICALNS1 (2001-2002)NS2 (2007-2008)pMedian age57 y58 yNST08.6%24.4%<0.001T149.5%42.3%NST232.5%23.8%<0.001T3T47.6%8.8%<0.001Tx1.8%0.7%<0.005N076.7%81.2%<0.001M+3.5%3.6%NSHISTOPATHOLOGICAL Median size (mm)1815<0.001pT1a2.44NSpT1b16.522.3<0.001pT1c43.442.5NSpT234.227<0.001pT3T43.33.2NSpN+44.432.3<0.001pN1-329.522.6<0.001pN>314.98.9>0.001ER+79.783.7<0.001PgR+69.772.5NSHR+ (Total)83.985.3NSHer2+++20.612.4<0.01TREATMENT Surgery Mastectomy77.5%77.3%NSCon. surgery22.5%22.7%NSAxillary dissection80%42.6%<0.001Sentinel L.N.B.2.7%41%<0.001SLNB+AD15.4%16.4%NSRadiotherapy After BCS98%97.4%NSAfter mastectomy89%89.5%NSChemotherapy (adj.)58.7%51%<0.001Hormonal treatment (adj.)76.5%82.5%<0.001 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4006.

Breast carcinoma grading, estimation of tumor size, axillary lymph node status, staging, and nottingham prognostic index scoring on mastectomy specimens

Breast carcinoma is the most common malignant tumor and the leading cause of cancer death in women. In western countries, a sharp increase in the detection of breast carcinoma, largely due to widespread use of mammography, has recently led to a fall in breast cancer mortality. This, however, is not true for less developed countries, in which mortality continues to rise. The aim of this study was to acquire information about the extent and spread of breast carcinoma in our patients by grading the tumors, determining the tumor size, and axillary lymph node status, staging of the tumors and Nottingham Prognostic Index (NPI) scoring on the available material. One hundred and twenty consecutive mastectomy specimens with axillary lymph node sampling removed for breast carcinoma and received in the section of histopathology, Aga Khan University, in the year 2005, were included in the study. Standard protocols were used for the processing of the specimens, and reporting was done using a standard format incorporating all relevant tumor parameters. NPI was applied to the cases. Out of the 120 cases, 5 (4.17) were grade 1, 91 (75.83) were grade 2, and 24 (20%) were grade 3. Also, 9 cases (7.5%) were T1 (4 were T1b, and 5 were T1c); 53 (44.16%) were T2; 50 (41.66%) were T3; and 8 (6.66%) were T4. Axillary lymph nodes were available in 107 cases. In 13 cases, no lymph nodes were recovered. Out of 107 cases 27 (25.23%) lymph nodes were negative for metastases pN0; 29 (27.10%) cases were pN1; 26 (24.30) were pN2; and 25 cases (23.36%) were pN3. Extranodal spread was present in 56 (70%) out of the 80 cases in which lymph nodes were positive. The average microscopic size of nodal metastasis was 1.7 cms. Significant statistical association was found between the number of positive nodes and perinodal extension (P = 0.001). Tumor necrosis was present in 76 out of 120 cases (63.33%). Vascular invasion was present in 43 out of 120 cases (35.83%). NPI scores were greater than 5.4 in 60 out of 107 cases (56.1%) indicating poor prognosis. The large majority of the cases were grade 2 tumors. Most cases (all grades) were T2 or T3, and were axillary lymph node positive. Large majority of cases with nodel metastases showed extra nodal spread. The majority of patients had NPI scores greater than 5.4 indicating poor prognosis. Significant statistical association was found between the number of positive nodes and perinodal extension (P = 0.001). The findings show extensive and advanced disease trends in our patients.

Digital versus screen film mammography: a clinical comparison.

Breast carcinoma is the most common malignancy among women in developed countries, and its incidence is on the rise in developing countries. In Malaysia, it accounts for about 30% of newly-diagnosed female cancers [1]. Imaging of the breast can be traced to its earliest origins in 1913 when a surgeon, Albert Salomon, used radiography images of mastectomy specimens to demonstrate the spread of breast carcinoma to the axillary lymph nodes. However it was not until 1960 that the widespread use of mammography became possible. This was attributed to Robert L. Egan who described a mammography technique that was reproducible. The first x-ray unit dedicated to breast imaging was available by 1965. By the 1970s, mammography as a screening device became standard practice [2]. This was because mammography by then had been proven to be the most effective method of detecting early breast carcinoma. The use of mammography in screening of breast carcinoma has been found to significantly reduce the mortality of this disease [3]. The transfer of imaging to the digital format began two decades ago with the introduction of digital radiography. By natural progression, other imaging modalities then adopted the digital technology. The transition from conventional mammography to its digital counterpart, however, was delayed due to the difficulty of producing a full-field digital detector [4]. The first full-field digital mammography unit was approved for sale by the Food and Drug Administration in 2000 [5]. Since then numerous hospitals and medical centres worldwide have installed digital mammography systems.

Giant fat containing breast masses: report of six cases

Six patients with giant fat containing breast masses encountered over a 20 year period are presented including a brief review of the literature. These benign tumours especially the giant varieties are rare but are likely to be increasingly diagnosed because of the widespread use of mammography.

Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases.

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.

Accuracy of the “Triple Test” in the Diagnosis of Palpable Breast Masses in Saudi Females

For patients who present to clinicians with palpable breast lesions, the triple test: (physical examination, mammography and fine-needle aspiration cytology) can be employed to provide accurate diagnosis. In this study, the sensitivity, specificity and predictive values of triple test components were studied separately and in combination. During the study period (from January 1998 to December 1999), 140 patients with palpable breast masses were subjected to all components of the triple test followed by confirmatory open biopsy. Physical examination showed 82.6% sensitivity, 97.3% specificity and 86.4% positive predictive value. Mammography showed 87.5% sensitivity, 97.3% specificity and 87.5% positive predictive value and fine-needle aspiration cytology (FNAC) showed 91.7% sensitivity, 100% specificity and 100% positive predictive value in concordant cases (elements had either all malignant or all benign results). The triple test was 100% accurate in the diagnosis of palpable breast lesions when all three elements were concordant. Based on these results, we recommend elimination of the confirmatory open biopsy, which will result in reduced expenses and morbidity compared with open biopsy.

Tratamiento conservador del carcinoma ductal in situ de la mama

Since the widespread use of mammography, the incidence of ductal carcinoma in situ of the breast has increased. Until few years ago the standard treatment was mastectomy, however, from the analysis of conservative treatment trials for invasive carcinoma, it was evident that ductal carcinoma in situ could also be treated conservatively. This was confirmed later by randomized trials. To analyze the experience of our Institution with conservative treatment of ductal carcinoma in situ of the breast. A search through the data base of our Institution found 69 patients treated with lumpectomy and radiotherapy between the years 1976 and 1997. Twenty three of 69 patients (33%) were diagnosed because of a palpable mass. Eleven of twelve were diagnosed prior to 1990 and 12 of 57 after 1990. With a median follow-up of 48 months local control and overall survival is 97%. None of the patients underwent mastectomy. Conservative treatment of ductal carcinoma in situ of the breast is a reasonable alternative, mainly if we realize that with increasing frequency--the diagnosis is made through mammography and with non-palpable lesions. The results reported in this study are similar to those reported by other centers.

Lymph node metastasis from ductal carcinoma in situ with microinvasion.

Widespread use of mammography has increased the detection of ductal carcinoma in situ with microinvasion (DCISM) in pathology specimens. Currently there is disagreement regarding the incidence of axillary metastasis from DCISM. The controversy centers on whether complete lymphadenectomy is indicated for axillary staging, given its morbidity and the reportedly minimal rate of axillary involvement in these patients. Intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) may obviate complete axillary lymph node dissection in selected breast carcinoma patients. In intraoperative lymphatic mapping, isosulfan blue dye is used to demonstrate the course of lymphatic flow from the breast tumor to the first draining or sentinel lymph node. This blue-stained lymph node is selectively excised for pathologic examination; its tumor status is used to predict the tumor status of the other axillary lymph nodes. The authors examined whether SLND would be suitable for staging DCISM. From February 1992 to January 1997, 14 patients with DCISM underwent intraoperative lymphatic mapping and SLND at the John Wayne Cancer Institute in Santa Monica, California. Clinical and pathologic data were prospectively collected. Primary DCISM tumors ranged in size from 0.9 to 6.5 cm. Nine patients presented with mammographic abnormalities, two patients presented with Paget's disease and a palpable lesion, and three patients presented with palpable lesions. Two patients (14.3%) had tumor-involved sentinel lymph nodes. One of these patients had two sentinel lymph nodes, both of which contained single cancer cells identified by immunohistochemistry. The other patient had 1 sentinel lymph node, in which a 0.3-cm metastasis was revealed by light microscopy. Completion axillary dissection was performed on both patients and revealed no further tumor positive lymph node metastases. SLND can detect lymph node micrometastases (tumor deposits <2 mm) in patients with DCISM. The clinical relevance of these micrometastases is unknown, but their existence shows that DCISM can involve the lymph nodes.

Prognostic factors for patients with breast cancers 1cm and smaller.

The widespread use of mammography has resulted in the detection of an increasing number of small invasive breast cancers, i.e. those that are 1cm and smaller. Patients with these small cancers generally have a low incidence of axillary lymph node metastases, and this has led some to question the routine use of axillary dissection in these patients. In addition, the prognosis of these patients is generally favorable, and the routine use of adjuvant systemic therapy is difficult to justify. Nonetheless, some patients with these small invasive cancers will have axillary nodal involvement and/or develop metastatic disease. The identification of this prognostically unfavorable subset of patients within this otherwise favorable group is an important goal of clinical research. In this article, we review the available literature on prognostic factors for patients with breast cancers 1cm and smaller to help determine which of these features might be of value in the identification of patients at risk for axillary lymph node involvement and/or metastatic disease.

Systemic Treatment for Stage I and Stage II Breast Cancer

Breast cancer presents as two interrelated problems. The first is disease in the breast and axillary lymph nodes and the second is metastatic spread to distant sites. Local diseases can be controlled with less morbidity than in the past because of advances in surgery and radiotherapy. In addition, heightened public awareness and the more widespread use of mammography have increased the detection of smaller cancers that have a better prognosis and are easier to treat. The problem of late relapse leading to death, however, motivates continued intensive study of systemic therapy as treatment for the undetectable micrometastatic disease remaining after surgery. Currently, hormonal therapy and chemotherapy are known to prolong disease-free and overall survival in nearly all groups of patients, although the relative and absolute influences of drug therapies are modest and vary among patient subgroups, and the proper application of these treatments to the hundreds of thousands of patients diagnosed worldwide per year could have a major impact on public health. For the future, clinical trials and laboratory advances indicate that novel dosing and scheduling of chemotherapy agents combined with newer modalities may provide even greater impact against occult disseminated disease.

Management of in situ and minimally invasive breast carcinoma.

In situ breast carcinoma represents an early localized stage in the transition to invasive breast carcinoma and has an especially favorable prognosis with appropriate management. The widespread use of mammography has contributed to its increased rate of diagnosis. The two histologic forms of this entity have distinct pathologic and biologic characteristics, with different therapeutic implications. Lobular carcinoma in situ is considered a marker of increased risk for subsequent invasive carcinoma and is most commonly managed by nonoperative surveillance. Ductal carcinoma in situ behaves more as a true anatomic precursor of invasive disease and has the same therapeutic options as invasive breast carcinoma. Minimally invasive breast carcinoma should be considered a fundamentally different entity, primarily because of its potential for systemic metastasis that in situ lesions do not theoretically have. There are still many outstanding issues and dilemmas to be resolved by scientific investigation before the intriguing potential of these early forms of breast malignancy are fully understood.

Losing the "war against cancer": a need for public policy reforms.

Editorial note: On February 4, 1992, at a press conference sponsored by a public interest group, Food and Water, Inc., a group of scientists, including Dr. Samuel S. Epstein, presented a statement at the National Press Club in Washington, D.C., criticizing the cancer policies of the National Cancer Institute (NCI), the American Cancer Society, and some 20 cancer centers. A few days earlier, a commentary on breast cancer by Dr. Epstein questioning the widespread use of mammography was published in the Los Angeles Times. We are pleased to present these statements in the Journal, along with a response from the NCI, a response from the American College of Radiology (ACR), and a rebuttal to these NCI and ACR responses from Dr. Epstein.