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Journal ArticleDOI

Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project

TL;DR: Ipsilateral DCIS events lessened after 5 years, while the risk of ipsilateral invasive cancer remained consistent to beyond 10 years, highlighting the need for prolonged follow-up of screen-detected DCIS.
Abstract: The Sloane audit compares screen-detected ductal carcinoma in situ (DCIS) pathology with subsequent management and outcomes. This was a national, prospective cohort study of DCIS diagnosed during 2003–2012. Among 11,337 patients, 7204 (64%) had high-grade DCIS. Over time, the proportion of high-grade disease increased (from 60 to 65%), low-grade DCIS decreased (from 10 to 6%) and mean size increased (from 21.4 to 24.1 mm). Mastectomy was more common for high-grade (36%) than for low-grade DCIS (15%). Few (6%) patients treated with breast-conserving surgery (BCS) had a surgical margin <1 mm. Of the 9191 women diagnosed in England (median follow-up 9.4 years), 7% developed DCIS or invasive malignancy in the ipsilateral and 5% in the contralateral breast. The commonest ipsilateral event was invasive carcinoma (n = 413), median time 62 months, followed by DCIS (n = 225), at median 37 months. Radiotherapy (RT) was most protective against recurrence for high-grade DCIS (3.2% for high-grade DCIS with RT compared to 6.9% without, compared with 2.3 and 3.0%, respectively, for low/intermediate-grade DCIS). Ipsilateral DCIS events lessened after 5 years, while the risk of ipsilateral invasive cancer remained consistent to beyond 10 years. DCIS pathology informs patient management and highlights the need for prolonged follow-up of screen-detected DCIS.

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TL;DR: In this article , the authors performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases.
Abstract: Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.

20 citations

Journal ArticleDOI
TL;DR: The aim of this review is to highlight the pharmacological actions of medicinal plants and their bioactive compounds on breast cancer and the role of these substances in breast cancer chemoprevention.

17 citations

Journal ArticleDOI
TL;DR: In this paper , the outcomes of patients with DCIS with and without micro-invasion diagnosed between 2003 and 2012 within the Sloane project were analyzed, with a considerable variation in reported incidence among screening units (0-25%), with microinvasion associated with high grade DCIS, larger DCIS size, comedo necrosis and solid, cribriform architecture.
Abstract: The diagnosis, management and prognosis of microinvasive breast carcinoma remain controversial.We analysed the outcomes of patients with DCIS with and without microinvasion diagnosed between 2003 and 2012 within the Sloane project.Microinvasion was recorded in 521 of 11,285 patients (4.6%), with considerable variation in reported incidence among screening units (0-25%). Microinvasion was associated with high-grade DCIS, larger DCIS size, comedo necrosis and solid, cribriform architecture (all P < 0.001). Microinvasion was more frequent in patients who underwent mastectomy compared with breast-conserving surgery (BCS) (6.9% vs 3.6%, P < 0.001), and in those undergoing axillary nodal surgery (60.4% vs 30.3%, P < 0.001) including the subset undergoing BCS (43.4% vs 8.5%, P < 0.001). Nodal metastasis rate was low and not statistically significant difference from the DCIS only group (P = 0.68). Following median follow-up of 110 months, 3% of patients had recurrent ipsilateral high-grade DCIS, and 4.2% developed invasive carcinoma. The subsequent ipsilateral invasion was of Grade 3 in 71.4% of patients with microinvasion vs 30.4% in DCIS without microinvasion (P = 0.02). Distant metastasis and breast cancer mortality were higher with microinvasion compared with DCIS only (1.2% vs 0.3%, P = 0.01 and 2.1% vs 0.8%; P = 0.005).The higher breast cancer mortality with microinvasion indicates a more aggressive disease.

8 citations

Journal ArticleDOI
TL;DR: The authors in this paper determined the outcomes of women who had no surgery for screen-detected ductal carcinoma in situ (DCIS) in the 6 months following diagnosis.

7 citations

Journal ArticleDOI
08 Mar 2022-BJS open
TL;DR: In this article , a systematic review was performed as per the PRISMA guidelines to establish the likelihood of having positive sentinel lymph node biopsy (SLNB+) for Ductal carcinoma in situ (DCIS) and to establish parameters predictive of SLNB+.
Abstract: Axillary lymph node status remains the most powerful prognostic indicator in invasive breast cancer. Ductal carcinoma in situ (DCIS) is a non-invasive disease and does not spread to axillary lymph nodes. The presence of an invasive component to DCIS mandates nodal evaluation through sentinel lymph node biopsy (SLNB). Quantification of the necessity of upfront SLNB for DCIS requires investigation. The aim was to establish the likelihood of having a positive SLNB (SLNB+) for DCIS and to establish parameters predictive of SLNB+.A systematic review was performed as per the PRISMA guidelines. Prospective studies only were included. Characteristics predictive of SLNB+ were expressed as dichotomous variables and pooled as odds ratios (o.r.) and associated 95 per cent confidence intervals (c.i.) using the Mantel-Haenszel method.Overall, 16 studies including 4388 patients were included (mean patient age 54.8 (range 24 to 92) years). Of these, 72.5 per cent of patients underwent SLNB (3156 of 4356 patients) and 4.9 per cent had SLNB+ (153 of 3153 patients). The likelihood of having SLNB+ for DCIS was less than 1 per cent (o.r. <0.01, 95 per cent c.i. 0.00 to 0.01; P < 0.001, I2 = 93 per cent). Palpable DCIS (o.r. 2.01, 95 per cent c.i. 0.64 to 6.24; P = 0.230, I2 = 0 per cent), tumour necrosis (o.r. 3.84, 95 per cent c.i. 0.85 to 17.44; P = 0.080, I2 = 83 per cent), and grade 3 DCIS (o.r. 1.34, 95 per cent c.i. 0.80 to 2.23; P = 0.270, I2 = 0 per cent) all trended towards significance in predicting SLNB+.While aggressive clinicopathological parameters may guide SLNB for patients with DCIS, the absolute and relative risk of SLNB+ for DCIS is less than 5 per cent and 1 per cent, respectively. Well-designed randomized controlled trials are required to establish fully the necessity of SLNB for patients diagnosed with DCIS.CRD42021284194 (https://www.crd.york.ac.uk/prospero/).

7 citations

References
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Journal ArticleDOI
TL;DR: The artificial synthesis of a number of the components of the vitamin B complex has made available pure crystalline material in large amounts for clinical research, and thus a milestone in the history of these affections has been passed.
Abstract: AFFECTIONS of the nervous system which result from inadequate nutrition have assumed an increasingly important position through the rapid accumulation of clinical, experimental, and pathological data. The artificial synthesis of a number of the components of the vitamin B complex has made available pure crystalline material in large amounts for clinical research, and thus a milestone in the history of these affections has been passed. It now seems appropriate to review and summarize the knowledge of these important substances. To evaluate the status of a nutritional deficiency in man is difficult. As a rule the patient induces his own disease and provides a deficiency that is not quantitatively measurable, but frequently clinical and laboratory evaluations are attempted. Both the laboratory method and the clinical method have certain advantages. Mice are not yet men and until they are the work coming -from the study of human beings is essential. Since the experience of investigators working with animals may often point the way for clinical research, we have interspersed in this review a few of the pertinent studies on the effect of nutritional deficiency on the nervous system of animals. A scheme for illustrating the multiple factors of the vitamin B complex is given in Fig. 1. To date the following portions of the vitamin B complex have been isolated and synthesized in amounts sufficient to allow for clinical trial: thiamin hydrochloride, nicotinic acid, riboflavin, and 2-methyl, 3-hydroxy, 4, 5-di (hydroxymethyl) pyridine. The deficiencies of these substances as they apply to the nervous system of man will be discussed briefly.

4,261 citations

Journal ArticleDOI
TL;DR: It is concluded that screening reduces breast cancer mortality but that some overdiagnosis occurs, and results from observational studies support the occurrence of over Diagnosis, but estimates of its magnitude are unreliable.

1,451 citations

Journal ArticleDOI
TL;DR: Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% and was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size.
Abstract: Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2 P <.00001), and it was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size. The proportional reduction in ipsilateral breast events was greater in older than in younger women (2P < .0004 for difference between proportional reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years, 10.8% vs 27.8% at ages ≥ 50 years) but did not differ significantly according to any other available factor. Even for women with negative margins and small low-grade tumors, the absolute reduction in the 10-year risk of ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002). After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality.

574 citations

Journal ArticleDOI
TL;DR: To assess the potential of breast-conserving treatment for ductal carcinoma in situ (DCIS), 82 mastectomy specimens were studied by Egan's serial subgross method and found adequate excision of many DCIS will require a wide excision involving up to a whole quadrant.

561 citations

Journal ArticleDOI
TL;DR: This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision.
Abstract: Summary Background Initial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial. Methods Women with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870. Findings Between May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9–14·7), 376 (163 invasive [122 ipsilateral vs 39 contralateral], 197 DCIS [174 ipsilateral vs 17 contralateral], and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio [HR] 0·41, 95% CI 0·30–0·56; p Interpretation This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision. Funding Cancer Research UK and the Australian National Health and Medical Research Council.

479 citations