Small Invasive Cancers Research Articles

Overcoming the limitations of screening mammography in Japan and Korea: a paradigm shift to personalized breast cancer screening based on ultrasonography.

Screening mammography programs have been implemented in numerous Western countries with the aim of reducing breast cancer mortality. However, despite over 20 years of population-based screening mammography, the mortality rates in Japan and Korea continue to rise. This may be due to the fact that screening mammography is not as effective for Japanese and Korean women, who often have dense breasts. This density decreases the sensitivity of mammography due to a masking effect. Therefore, the early detection of small invasive cancers requires more than just mammography, particularly for women in their 40s. This review discusses the limitations and challenges of screening mammography, as well as the keys to successful population-based breast cancer screening in Japan and Korea. This includes a focus on breast ultrasonography techniques, which are based on histopathologic anatomical knowledge, and personalized screening strategies that are based on risk assessments measured by glandular tissue components.

Feasibility of Novel Technique of Flexible Cystoscopic En Bloc Snare Resection of Bladder Tumor: f-ESRBT.

Background: En bloc resection of bladder tumors (ERBT) has been used as a treatment option to improve pathologic diagnostic accuracy in non-muscle invasive bladder cancer. We report on the feasibility of a novel ERBT technique using an electrosurgical snare with flexible cystoscope: flexible cystoscopic En bloc Snare Resection of Bladder Tumor (f-ESRBT). Methods: We used the electrosurgical snare to resect a superficial bladder tumor after injection of 50% glucose in the submucosa at the tumor base. We collected each resected tumor with a basket catheter and coagulated the resected area with a coagulation electrode. A flexible cystoscope was used for all procedures. Results/Discussion: We performed 10 operations. Mean tumor size was 10.2 ± 7.3 mm and mean surgery time was 13.8 ± 6.8 minutes. All procedures were performed without complications. Results showed f-ESRBT to be simple and minimally invasive and to enable accurate pathologic diagnoses. Conclusion: f-ESRBT is a feasible treatment option for small and non-muscle invasive bladder cancer.

Abstract IA027: DCIS or cancer? Why all the confusion?

Abstract Many women diagnosed with DCIS in the United States report they are confused about their chances of developing an invasive breast cancer or metastatic cancer. They are told that DCIS is not cancer but it holds the possibility of becoming a cancer. Nevertheless, DCIS is treated in much the same way as a small invasive cancer. Surgical options include lumpectomy alone, lumpectomy with radiotherapy, unilateral or bilateral mastectomy. Much of the confusion is generated by the current paradigm that separates DCIS and invasive cancer into distinct conditions. The mortality of DCIS is 3% over 20 years and that prevention of local invasive recurrence post-DCIS does not reduce breast cancer mortality. If the invasive recurrence were the real cancer then preventing it would reduce the risk of dying but this has not been shown. Further, the risk of an invasive in-breast recurrence following DCIS is the same as the risk of an invasive in-breast recurrence following invasive breast cancer. In the Banting database, the 15-year risk of invasive local recurrence following DCIS was 15.6%, following stage I breast cancer was 15.3% and following stage II breast cancer was 15.9%. In the Banting database, the 15-year risk of ipsilateral invasive recurrence was 14% for DCIS patients who receives radiotherapy and was 29% for DCIS patients who did not received radiotherapy – a difference of 15%. In the Banting database, the 15-year risk of ipsilateral invasive recurrence was 14% for Stage I/II patients who received radiotherapy and was 27% for Stage I/II patients who did not receive radiotherapy – a difference of 13%. The benefit of radiotherapy is the same in both groups. Similarly, the benefit of unilateral mastectomy versus lumpectomy on preventing local invasive recurrence is the same for DCIS patients as it is for early-stage invasive breast cancer patients. In our SEER-based analysis of 812,851 women with breast cancer, the 25-year actuarial risk of contralateral invasive breast cancer was 10.1% for patients with DCIS and was 9.9% for patients with invasive breast cancer. Based on this finding, the benefit of performing a contralateral mastectomy at the time of diagnosis is the same for both groups. We accept lumpectomy as standard of care for invasive breast cancer even though the risk of invasive ipsilateral recurrence is much higher after lumpectomy than after mastectomy. We consider contralateral mastectomy as an option for women with invasive cancer, but as overtreatment for women with DCIS even though the risk of contralateral breast cancer is almost exactly the same. The benefit of radiotherapy is the same for patients with DCIS and stage I/II breast cancer, but we are more likely to consider it overtreatment for DCIS patients. Much of the confusion can be resolved if we consider both types of cancer to be different points on the spectrum. Breast cancer is heterogeneous; DCIS is one end of the spectrum. Accepting this fact will make the rationale behind treatment decisions easier to explain. Citation Format: Steven A. Narod. DCIS or cancer? Why all the confusion? [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA027.

Diagnostic performance of dedicated breast positron emission tomography

BackgroundDedicated breast positron emission tomography (dbPET) has been developed for detecting smaller breast cancer. We investigated the diagnostic performance of dbPET in patients with known breast cancer.MethodsEighty-two preoperative patients with breast cancer were included in the study (84 tumours: 11 ductal carcinomas in situ [DCIS], 73 invasive cancers). They underwent mammography (MMG), ultrasonography (US), and contrast-enhanced breast magnetic resonance imaging (MRI) before whole-body PET/MRI (WBPET/MRI) and dbPET. We evaluated the sensitivity of all modalities, and the association between the maximum standard uptake value (SUVmax) level and histopathological features.ResultsThe sensitivities of MMG, US, MRI, WBPET/MRI and dbPET for all tumours were 81.2% (65/80), 98.8% (83/84), 98.6% (73/74), 86.9% (73/84), and 89.2% (75/84), respectively. For 11 DCIS and 22 small invasive cancers (≤ 2 cm), the sensitivity of dbPET (84.9%) tended to be higher than that of WBPET/MRI (69.7%) (p = 0.095). Seven tumours were detected by dbPET only, but not by WBPET/MRI. Five tumours were detected by only WBPET/MRI because of the blind area of dbPET detector, requiring a wider field of view. After making the mat of dbPET detector thinner, all 22 scanned tumours were depicted. The higher SUVmax of dbPET was significantly related to the negative oestrogen receptor status, higher nuclear grade, and higher Ki67 (p < 0.001).ConclusionsThe sensitivity of dbPET for early breast cancer was higher than that of WBPET/MRI. High SUVmax was related to aggressive features of tumours. Moreover, dbPET can be used for the diagnosis and oncological evaluation of breast cancer.

Evaluating the quality and safety of the BreastScreen remote radiology assessment model of service delivery in Australia

Introduction Breast cancer is the most commonly diagnosed cancer in Australian women. Given the diverse geography and populations within Australia, the ability to offer a telemedicine-supported breast screening and assessment service may increase access. The aim of this study was to assess clinical outcomes of a telemedicine-based remote radiology assessment service delivery model for detecting breast cancer in regional Australian women compared to the traditional radiologist onsite model. Methods This study was a pre–post intervention study using de-identified administrative data. Data were collected from seven sites across three health jurisdictions within Australia. There were a total of 21,117 assessment visits, with 10,508 (49.8%) pre- and 10,609 (50.2%) post-remote model implementation. Of the 10,609 post-remote model visits, 3,904 (36.8%) were under the remote model. The main outcome was cancer detection, split into any cancer, any invasive cancer or any small invasive cancer. Timeliness of assessment was also examined. Results After adjusting for multiple factors, there were no statistically significant differences in cancer detection rates between the remote and onsite models (adjusted odds ratio (AOR) = 1.02, 95% CI 0.86–1.19, n.s.). Implementing the remote assessment model had statistically significant positive effects on the timeliness of assessment (AOR = 0.68, 95% CI 0.59–0.77, p < 0.001). Discussion This study found the remote model delivers safe and high-quality assessment services, with equivalent rates of cancer detection and improved timeliness of assessment when compared to the traditional onsite model. Careful monitoring and ongoing evaluation of any health-service model is important for ongoing safety, efficiency and acceptability.

An analysis of screen-detected invasive cancers by grade in the English breast cancer screening programme: are we failing to detect sufficient small grade 3 cancers?

ObjectiveRandomised controlled trials have shown a reduction in breast cancer mortality from mammography screening and it is the detection of high-grade invasive cancers that is responsible for much of this effect. We determined the detection rates of invasive cancers by grade, size and type of screen and estimated relative sensitivities with emphasis on grade 3 detection.MethodsThis observational study analysed data from over 11 million screening episodes (67,681 invasive cancers) from the English NHS breast screening programme over seven screening years 2009/2010 to 2015/2016 for women aged 45–70.ResultsAt prevalent (first) screens (which are unaffected by screening interval), the detection rate of small (< 15 mm) invasive cancers was 0.95 per 1000 for grade 1, but for grade 3 only 0.30 per 1000. The ratio of small (< 15 mm) to large (≥ 15 mm) cancers was 1.8:1 for grade 1 but reversed to 0.5:1 for grade 3. We estimated that the relative sensitivity for grade 3 invasive cancers was 52% of that for grade 1 and the relative sensitivity for small (< 15 mm) grade 3 only 26% of that for small (< 15 mm) grade 1 invasive cancers.ConclusionsSensitivity for small grade 3 invasive cancers is poor compared with that for grade 1 and 2 invasive cancers and larger grade 3 malignancies. This observation is likely a limitation of the current technology related to the absence of identifiable mammographic features for small high-grade cancers. Future work should focus on technologies and strategies to improve detection of these clinically most significant cancers.Key Points• The detection of small high-grade invasive cancers is vital to reduce breast cancer mortality.• We estimate the sensitivity for small grade 3 invasive cancers may be only 26% of that of small grade 1 invasive cancers. This is likely to be associated with the non-specific mammographic features for these cancers.• New technologies and appropriate strategies using current technology are required to maximise the detection of small grade 3 invasive cancers.

Precision Science on Incidence and Progression of Early-Detected Small Breast Invasive Cancers by Mammographic Features.

The aim was to evaluate how the inter-screening interval affected the performance of screening by mammographic appearances. This was a Swedish retrospective screening cohort study with information on screening history and mammography features in two periods (1977–1985 and 1996–2010). The pre-clinical incidence and the mean sojourn time (MST) for small breast cancer allowing for sensitivity by mammographic appearances were estimated. The percentage of interval cancer against background incidence (I/E ratio) was used to assess the performance of mammography screening by different inter-screening intervals. The sensitivity-adjusted MSTs (in years) were heterogeneous with mammographic features, being longer for powdery and crushed stone-like calcifications (4.26, (95% CI, 3.50–5.26)) and stellate masses (3.76, (95% CI, 3.15–4.53)) but shorter for circular masses (2.65, (95% CI, 2.06–3.55)) in 1996–2010. The similar trends, albeit longer MSTs, were also noted in 1977–1985. The I/E ratios for the stellate type were 23% and 32% for biennial and triennial screening, respectively. The corresponding figures were 32% and 43% for the circular type and 21% and 29% for powdery and crushed stone-like calcifications, respectively. Mammography-featured progressions of small invasive breast cancer provides a new insight into personalized quality assurance, surveillance, treatment and therapy of early-detected breast cancer.

Post San Antonio Breast Cancer Symposium 2018

This short review summarizes the most important facts presented at the San Antonio Breast Cancer Symposium 2018 concerning local therapy of breast cancer, including breast and lymph node surgery as well as radiotherapy. Despite the increasing use of neoadjuvant chemotherapy (nCHT) and consequently higher response and pathologic complete response (pCR) rates in the past years, breast-conserving surgery (BCS) has not increased. This is not only due to positive genetic testing, but it is mostly based on patients’ preference. On the other hand, quality of life seems to be better in young patients undergoing BCS regarding satisfaction with breasts and sexual and psychosocial well-being. Thus, surgical decision-making is crucial in young women with breast cancer and long-term quality of life aspects have to be taken into account. The safe performance of sentinel lymph node biopsy in N+ patients with or without neoadjuvant therapy is the current focus of several large randomized controlled trials. In San Antonio, new data about the impact of micro-metastases or extracapsular extension were presented. The 10-year follow-up data from the AMAROS study demonstrated similar axillary recurrence rates in patients with positive sentinel nodes undergoing complete axillary dissection or radiotherapy only. The RAPID study showed that in patients with unifocal small DCIS (Ductal carcinoma in situ) or invasive cancer <3 cm, accelerated partial breast irradiation with three-dimensional conformal radiotherapy was not inferior compared to whole breast irradiation regarding ipsilateral recurrence rate, but the regimen has to be adapted to achieve similar cosmetic results.

Minimally Invasive Intact Excision of High-Risk Breast Lesions and Small Breast Cancers: The Intact Percutaneous Excision (IPEX) Registry.

Aiming to minimize overtreatment of high-risk breast lesions (HRLs), including atypical ductal hyperplasia, and small breast cancers, including ductal carcinoma in situ (DCIS), we investigated a minimally invasive (MI) approach to definitive diagnosis and management of these conditions. In the prospective Intact Percutaneous Excision registry study, women aged 31-86years had removal of small invasive cancers, DCIS, or HRLs using image-guided 12-20mm radiofrequency basket capture (MI excision). Second-pass 20mm basket capture obtained shaved margins in cancer patients. Standard imaging (specimen, breast) and histologic criteria were applied. Patient data were registered in an Institutional Review Board approved, Health Insurance Portability and Accountability Act-compliant registry. Of 282 registered patients, 124 had DCIS (n = 52) or invasive cancer (n = 72) and 160 had HRLs. Among cancer patients, 101 (81%) had clear histologic margins [average lesion size was 11mm for both invasive cancers (4-20mm) and DCIS (1.5-20mm)]; 29 patients had re-excision (six despite clear margins). Among 160 HRLs, two were upgraded to DCIS and had MI excision. Two other HRL patients had subsequent standard surgical excision (no cancer found). For diminutive HRLs, DCIS, and invasive cancers, MI excision can achieve the same procedure goals as standard surgical excision. Because MI excision removes less tissue with small incisions, it may reduce the discomfort and expense associated with standard treatment.

Prognostic impact and possible pathogenesis of lymph node metastasis in ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS)-preinvasive breast cancer-with lymph node metastasis can clinically be treated as different stages: occult invasive cancer with true metastasis (T1N1) or pure DCIS with iatrogenic dissemination (TisN0). In this retrospective cohort study, we aimed to elucidate the prognostic impact and possible pathogenesis of nodal metastasis in DCIS to improve clinical management. Subjects were comprised of 427 patients with routine postoperative diagnosis of DCIS who underwent sentinel node (SN) biopsy using molecular whole-lymph-node analysis. Clinicopathological characteristics and prognosis were compared between SN-positive and -negative patients. Primary tumour tissues of SN-positive patients were exhaustively step-sectioned to detect occult invasions, and predictive factors for occult invasion were investigated. Median follow-up time was 73.6 months. Of the 427 patients, 19 (4.4%) were SN-positive and 408 (95.6%) were SN-negative. More SN-positive patients received adjuvant systemic therapy than SN-negative patients (84.2% vs. 5.4%). Seven-year distant disease-free survivals were favourable for both cohorts (SN-positive, 100%; SN-negative, 99.7%). By examining 1421 slides, occult invasion was identified in 9 (47.4%) of the 19 SN-positive patients. Tumour burdens in SN and incidence of non-SN metastasis were similar between patients with and without occult invasion, and no predictive factor for occult invasion was found. Node-positive DCIS has favourable prognosis with adjuvant systemic therapy. Half of the cases may be occult invasive cancer with true metastasis. In practical settings, clinicians may have to treat these tumours as node-positive small invasive cancers because it is difficult to predict the pathogenesis without exhaustive primary tumour sectioning.

Impact of microinvasion on breast cancer mortality in women with ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of epithelial cells which is confined within the basement membrane of the mammary ductal-lobular system. It is of interest to determine to what extent the potential to metastasize increases for DCIS patients when the basement membrane is breached (i.e. microinvasion is present). We retrieved the records of 525,395 women who had either first primary DCIS or small (≤2.0cm) node-negative invasive breast cancer in the Surveillance, Epidemiology and End Results (SEER) registries database (1990-2013). For each patient, we extracted information on year of diagnosis, age at diagnosis, tumour size, tumour grade, oestrogen receptor status, use of radiotherapy, type of surgery, cause of death and follow-up time. We classified patients into four groups, according to the size of the invasive component of the primary tumour. We estimated the actuarial rate of breast cancer-specific mortality at ten and 20years for women in each size category. We identified 161,394 women with pure DCIS, 13,489 women with microinvasive carcinoma (≤0.1cm of invasion), 153,856 women with invasive cancer 0.2-1.0cm in size and 196,656 women with invasive cancer 1.1-2.0cm in size. The 20-year actuarial breast cancer-specific mortality rate was 3.8% for women with pure DCIS, was 6.9% for women with microinvasive carcinoma, was 6.8% for women with invasive cancer 0.2-1.0cm in size and was 12.1% for women with invasive cancer 1.1-2.0cm in size. The adjusted hazard ratio for death associated with microinvasive carcinoma (vs. pure DCIS) was 2.00 (95% CI 1.76-2.26; p<0.0001). In terms of prognosis, microinvasive cancer more closely resembles small invasive cancer 0.2-1.0cm) than pure DCIS. For invasive cancers under 1.0cm, size has little impact on mortality.

Type B Laparoscopic Radical Trachelectomy With Pelvic Lymphadenectomy for Early Cervical Cancer

Study ObjectiveTo demonstrate the technique of laparoscopic radical trachelectomy (LRT) and laparoscopic pelvic lymphadenectomy for early cervical cancer. DesignCase report (Canadian Task Force Classification Study design III). SettingTertiary referral centre in Strasbourg, France. BackgroundOver the past 15 years, gynecologic oncologists have sought ways to preserve female fertility when treating invasive cervical cancer. Many cases of cervical cancer have been diagnosed in young women with a desire to preserve their fertility. As more women are delaying childbearing, fertility preservation has become an important consideration. Radical hysterectomy and bilateral pelvic lymphadenectomy represent the standard surgical treatment for stage IA2-IB1 cervical cancer. In some women with small localized invasive cervical cancer, there is hope for a pregnancy after treatment. Vaginal radical trachelectomy (VRT) is a fertilitypreserving surgical procedure for early-stage cervical cancers. The National Comprehensive Cancer Network has published guidelines stating that radical trachelectomy is part of the standard of care for women desiring to preserve their future fertility. VRTwas introduced in 1987 with its first reported use in 1994, and since then more than 1000 cases of VRT have been reported involving more than 250 live births. The tumor recurrence rate is between 4.2% and 5.3%, and the mortality rate is between 2.5% and 3.2%. However, VRT has several limitations despite results demonstrating the safety of the procedure. One limitation is that it is an inadequate procedure for nulliparous patients and those with history of previous conization with adverse vaginal anatomy. In addition, it is difficult to learn the techniques involved in radical vaginal surgery. PatientsA 26 year-old nulliparous women with a FIGO Stage IB1 squamous cell tumor of the cervix. A first conisation was performed with no safe resection margins. InterventionIn this video we show a type B laparoscopic radical trachelectomy with round ligament and uterine artery preservation. A laparoscopic pelvic lymphadenectomy was also performed. Our institutional review board approved this study. Measurements and Main ResultsOperative time was 240 minutes. Intraoperative blood loss was less than 100 mL. The operation was performed successfully with no intraoperative complications. Pathological findings demonstrated the presence of a cervical intraepithelial neoplasia 2 on the anterior lips from an 11 o'clock to a 1 o'clock position. Resection margins were safe. The surgical specimen did not show any residual invasive carcinoma. Twenty one lymph nodes were removed, 7 on the right side, and 14 on the left side. No metastatic adenopathy was found. The patient was discharged on day 11. After 5 months, no late complications or recurrence was detected. ConclusionsLRT appears to be a safe option for women who intend to maintain their desire for a future pregnancy.

Recurrence and Survival After Resection of Small Intraductal Papillary Mucinous Neoplasm-associated Carcinomas (≤20-mm Invasive Component): A Multi-institutional Analysis.

Early invasive carcinoma may be encountered in association with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The natural history of these early invasive lesions is unknown. Pancreatic surgical databases from 4 high-volume centers were queried for IPMNs, with invasive components measuring 20 mm or less. All cases were reviewed by GI gastrointestinal pathologists, and pathologic features were analyzed to identify predictors of recurrence and survival. A total of 70 small IPMN-associated invasive carcinomas (≤20-mm invasion) were identified, comprising 25% of resected IPMN-associated carcinomas (n = 280). Most of these small invasive cancers were multifocal (66%), less than 10 mm in size (73%), and arose in the setting of a main duct IPMN (96%). The most common adenocarcinoma subtypes were tubular (57%) and colloid (29%). Lymph node metastases were present in 19% of cases and 23% were T3 lesions. The overall recurrence rate was 24% (n = 17), and the median time to recurrence was 16 months (range: 4-132 months). Median and 5-year survival rates were 99 months and 59%. Recurrence patterns of invasive disease were local in 35%, distant in 47%, and both in 18%. Lymphatic spread and T3 stage were predictive of recurrence (univariate, P = 0.006), whereas tubular carcinoma type was the most predictive of poor overall survival (multivariate hazard ratio = 3.7, P = 0.04). This study represents the largest multi-institutional experience of resected small IPMN-associated carcinoma. Although these malignancies may frequently be cured with resection, recurrence risk is significant. Lymphatic spread, increased T stage, and tubular type carcinoma were associated with the poorest outcome.

Screen detection of ductal carcinoma in situ and subsequent incidence of invasive interval breast cancers: a retrospective population-based study

SummaryBackgroundThe value of screen detection and treatment of ductal carcinoma in situ (DCIS) is a matter of controversy. At present, the extent to which the diagnosis and treatment of DCIS could prevent the occurrence of invasive breast cancer in the future is not clear. We sought to estimate the association between detection of DCIS at screening and invasive interval cancers subsequent to the relevant screen.MethodsWe obtained aggregate data for screen-detected cancers from 84 local screening units within 11 regional Quality Assurance Reference Centres in England, Wales, and Northern Ireland from the National Health Service Breast Screening Programme. Data for DCIS diagnoses were obtained for women aged 50–64 years who were invited to and attended mammographic breast screening from April 1, 2003, to March 31, 2007 (4 screening years). Patient-level data for interval cancer arising in the 36 months after each of these were analysed by Poisson regression with invasive interval cancer screen detection rate as the outcome variable; DCIS detection frequencies were fitted first as a continuous and then as a categorical variable. We repeated this analysis after adjustment with both small size and high-grade invasive screen-detected cancers.FindingsWe analysed data for 5 243 658 women and on interval cancers occurring in the 36 months after the relevant screen. The average frequency of DCIS detected at screening was 1·60 per 1000 women screened (median 1·50 [unit range 1·54–3·56] per 1000 women). There was a significant negative association of screen-detected DCIS cases with the rate of invasive interval cancers (Poisson regression coefficient −0·084 [95% CI −0·13 to −0·03]; p=0·002). 90% of units had a DCIS detection frequency within the range of 1·00 to 2·22 per 1000 women; in these units, for every three screen-detected cases of DCIS, there was one fewer invasive interval cancer in the next 3 years. This association remained after adjustment for numbers of small screen-detected invasive cancers and for numbers of grade 3 invasive screen-detected cancers.InterpretationThe association between screen-detected DCIS and subsequent invasive interval cancers suggests that detection and treatment of DCIS is worthwhile in prevention of future invasive disease.FundingUK Department of Health Policy Research Programme and NHS Cancer Screening Programmes.

P39: Blood cell-surface-bound exosomes as a new source of tumor-specific microRNA

Background Microvesicles release by neoplastic cells were found in blood and carrying a large number of tumor distinctive molecules, like miRNA/mRNA, proteins. Considering extensive surface of blood cells we wonder if exosomesare circulated exclusively in plasma or could be associated with surface of blood cells. Materials and Methods Microvesicles circulating in blood of healthy women (HW) and breast cancer patients (BCP) were studied. Blood was fractionated into plasma and cellular fractions; in order to release cell surface bound material, blood cells were treated as it was described for cell-surface-bound (CSB) cirDNA (Tamkovich, 2005).Exosomes were pelleted at 100,000 g from 0.1 μm filtered supernatants obtained by plasma and CSB eluates centrifugation at 17,000 g, resuspended in PBS and stored in aliquots at −80 °C. Size distribution of the microparticles was characterized by TEM (Jeol, Japan), anti CD-63, CD-24, CD-9 antibodies (BD Biosciences, USA) were used as exosome markers, protein concentration was measured by NanoOrange Protein Quantitation kit (Molecular Probes, USA), total RNA and miRNA were isolated by mirVana kit, 28S rRNA were quantified by RT-qPCR after reverse transcription with 6-mer random primers, miRNA using TaqMan Small RNA Assays kit (Applied Biosystems, USA). DNA was isolated using “DNA Isolation Kit” (BioSilicaLtd, Russia) and measured by TaqMan multiplex real-time PCR for LINE1 and α-satellite repeats (Bryzgunova, 2011). Results: TEM with immunogold labeling demonstrate presence of exosomes in 30–100 nm membrane-wrapped particles isolated from both plasma and CSB eluates. TEM, NanoOrange and 28S rRNA RT-qPCR data demonstrate that CSB exosomes constitutes 2/3 of total blood exosomes. Exosomes ranged 50–70 nm prevail in blood of BCP, whereas 30–50 nm exosomes in blood of HW. Exosomal DNA is less than 0.3% of cell-free blood DNA. RNA integrity and specific quantity checked by Bioanalyzer (Agilent Technologies, USA) do not differ in cell-free and CSB exosomes. Preliminary data demonstrate overpresentation of cancer-specific miRNA (miR-103, miR-191, miR-195) in exosomes bound with erythrocyte’s as compared with exosomes bound with leukocytes or circulating in plasma. Conclusion Exosomal DNA obviously do not have any diagnostic value in contrast to RNA. CSB exosomes represent valuable source of material for small-invasive cancer diagnostics.

The Nipple-Areola Preserving Mastectomy: A Multistage Procedure Aiming to Improve Reconstructive Outcomes following Mastectomy.

Background:Ischemia of the nipple-areola complex (NAC) and periareolar tissue is commonly seen following tissue-preserving mastectomies for small invasive and noninvasive cancers. The nipple-areola preserving mastectomy is a multistage procedure in which the NAC and central mastectomy flap tissue is surgically delayed to improve the survivability in patients undergoing mastectomies followed by reconstruction.Methods:We conducted a retrospective chart review of 20 patients undergoing the 2-stage nipple-areola preserving mastectomy: the first stage comprised undermining the NAC and raising the breast skin flaps, with placement of a silicone sheet in the dissected pocket. The second stage followed 2–3 weeks after the NAC delay, with patients undergoing nipple-sparing mastectomies.Results:Mean age was 46.2 years (range, 23–59 years). Indications included breast cancer in 18 patients and BRCA gene mutation prophylaxis in 2 patients. None were actively smoking. Mean time between delay of flaps and breast reconstructions was 16 days (range, 10–35 days). One patient underwent bilateral nipple resection at the time of mastectomies due to a subareolar nipple biopsy positive for ductal carcinoma in situ. One patient underwent left nipple excision after a skin nipple biopsy was positive for metaplasia. No signs of NAC vascular compromise were observed in any of the cases.Conclusions:Our 2-stage approach benefits patients undergoing nipple-sparing mastectomy, especially those at high-risk, by safely increasing survivability of the native breast skin envelope and NAC, while improving oncologic outcomes by identification of subareolar malignancies and sentinel node status before mastectomy and reconstruction.

Does digital mammography suppose an advance in early diagnosis? Trends in performance indicators 6 years after digitalization.

PurposeTo provide a complete evaluation of the long-term impact of full-field digital mammography (FFDM) on the improvement of early diagnosis in a population-based screening program.MethodsWe included 82,961 screen-film mammograms (SFM) and 79,031 FFDM from women aged 50–69 screened biennially from 1995–2010 in Spain and followed-up to 2012. The first screening round of the program was excluded. Rates of cancer detection, interval cancer, tumoral characteristics and other quality indicators were compared between SFM and FFDM periods using the Chi-square test. Multivariate logistic regression models were fitted.ResultsDetection of ductal carcinoma in situ (DCIS) significantly increased with FFDM (0.05 % vs 0.09 %; p = 0.010), along with the proportion of small invasive cancers (<20 mm) (69.37 % vs 78.90 %; p = 0.040). The false-positive rate decreased with FFDM (4.79 % vs 3.38 %; p < 0.001) without differences in the cancer detection rate (0.42 % vs 0.43 %; p = 0.685) or in the interval cancer rate (0.14 % vs 0.14 %; p = 0.816). Adjusted models showed a significant increase in the detection of DCIS in the FFDM periods.ConclusionDigitalization has supposed an improvement in early diagnosis because DCIS and small invasive cancers increased without a change in detection rate. Moreover, false-positive reduction without an increase in the interval cancer rate was confirmed.Key Points• Cancer detection did not increase after 6 years of digital mammography • Ductal carcinoma in situ rates remained higher throughout the digital period • The proportion of small invasive cancers was higher with digital mammography • We observed an improvement in early diagnosis with digital mammography • False-positive rates remained lower throughout the digital period without interval cancer increase

A Comparison of the Risks of In-Breast Recurrence after a Diagnosis of Dcis or Early Invasive Breast Cancer

It is controversial whether ductal carcinoma in situ (dcis) is a preinvasive marker of breast cancer or if it is part of a spectrum of small cancers with malignant potential. Comparing clinical outcomes in women with invasive and noninvasive breast lesions might help to resolve the issue. From a database of 2641 patients with breast cancer, we selected women who had been treated with breast-conserving surgery for a cancer that was 2.0 cm or less in size, node-negative, and nonpalpable. No subject received chemotherapy. Cancers were categorized as noninvasive (stage 0, n = 172) or invasive (stage 1, n = 401) based on a review of the pathology records. We compared the actuarial risks of in-breast recurrence after invasive and noninvasive breast lesions before and after adjusting for tamoxifen and radiotherapy. The 18-year cumulative risk of in-breast recurrence was 35.2% for patients with dcis and 12.8% for patients with small invasive cancers (hazard ratio: 2.4; 95% confidence interval: 1.5 to 3.8; p < 0.0003). After adjustment for radiotherapy and tamoxifen treatment, the difference was small and nonsignificant (hazard ratio: 1.4; 95% confidence interval: 0.9 to 2.4; p = 0.22). For women with small, nonpalpable, node-negative breast cancers, the likelihood of experiencing an in-breast recurrence was associated with radiotherapy and with tamoxifen, but not with the presence of cancer cells invading beyond the basement membrane.

Digital Mammography Screening with Photon-counting Technique: Can a High Diagnostic Performance Be Realized at Low Mean Glandular Dose?

To assess screening performance of a direct radiography (DR) photon-counting system versus statewide screening units with different digital technologies. The local ethics board approved retrospective study of prospectively acquired data from the North Rhine-Westphalian mammography screening program (2009-2010). Informed consent was waived. Examinations in 13 312 women with a DR photon-counting system and statewide digital screening examinations in 993 822 women were included (37 computed radiography mammography systems and 55 DR systems). Diagnostic performance was assessed with cancer detection rate, recall rate, and proportion of small invasive cancers and ductal carcinoma in situ (DCIS). Mean glandular dose was calculated for DR photon counting and for a conventional DR subgroup. Differences were tested with χ(2) and t tests (P < .05). The cancer detection rate for subsequent screenings was higher for DR photon counting than statewide rates (0.76% [67 of 8842] vs 0.59% [3108 of 527 194], P = .05) at a higher recall rate (5.4% [475 of 8842] vs 3.3% [17 656 of 527 194], P = .001). Detection of invasive cancers up to 10 mm for DR photon counting was high for initial (40% [14 of 35]) and subsequent (42% [19 of 45]) screenings but not significantly different from statewide rates (initial, 31.6% [942 of 2979], P = .50; subsequent, 32.5% [765 of 2353], P = .25). The DCIS subsequent screening rate was higher for DR photon counting than statewide screening (0.23% [20 of 8842] vs 0.12% [616 of 527 194], P = .01) and the conventional DR subgroup (0.23% [20 of 8842] vs 0.12% [65 of 52 813], P = .025). Mean glandular dose for DR photon counting was significantly lower than that for conventional DR (0.60 mGy ± 0.20 vs 1.67 mGy ± 0.47 [craniocaudal views], 0.64 mGy ± 0.23 vs 1.79 mGy ± 0.53 [mediolateral oblique views], both P = .0001). Digital mammography screening with dose-efficient photon counting enables desirable detection rates of small invasive cancers and DCIS. Higher detection rates compared with statewide performance occurred with subsequent screening but had higher recall rates.

Narrow-band imaging observation of colorectal lesions using NICE classification to avoid discarding significant lesions.

To assess the risk of failing to detect diminutive and small colorectal cancers with the "resect and discard" policy. Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancers and their endoscopic features were assessed. In total, we found 681 cases of diminutive (1-5 mm) lesions in 402 patients and 197 cases of small (6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal (SM) scanty invasive carcinomas, 1 and 1 were SM-d carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically. The risk of failing to detect diminutive and small colorectal invasive cancer with the "resect and discard" strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy.