Male ductal carcinoma in situ: diagnosis and management of a rare disease in men.

Ductal carcinoma in situ is very rare in male patients, accounting for approximately 5%-7% of all male breast cancers. We present a case of a man in his early 70s who presented with bloody nipple discharge and gynaecomastia and was subsequently diagnosed with ductal carcinoma in situ (DCIS). We discuss his management with surgical resection and the consideration of adjuvant treatment. We also review the existing literature on the presentation, diagnosis and management of DCIS in men.

Granulomatous lobular mastitis co-existing with ductal carcinoma in situ: Report of three cases and review of the literature.

Granulomatous lobular mastitis (GLM) is a benign and infrequent chronic breast ailment. Although this lesion can be clinically and radiographically mistaken for early-onset breast cancer, it is a rare occurrence for the two to coexist. This report describes three such cases. In all three patients, the primary signs and symptoms were related to the formation of diffuse breast masses or abscesses. Breast ultrasound and MRI revealed glandular edema and dilated breast ducts. The biopsies of all lesions exhibited both granulomatous inflammation confined to the lobules of the breast, abundant interstitial inflammatory cell infiltrates, and apparently cancerous cells located in dilated ducts with intact basement membranes. The surgically excised specimens confirmed the diagnosis of GLM and ductal carcinoma in situ (DCIS) in all three patients who underwent breast mass resection. By clinical imaging and clinical manifestations, GLM may obscure a concurrent DCIS, as highlighted by the cases reported herein.

Atypical ductal hyperplasia on vacuum-assisted breast biopsy: a scoring system to predict the risk of upgrade to malignancy.

RATIONALE AND OBJECTIVES: Our multicentric study analysed clinical, radiologic and pathologic features in patients with atypical ductal hyperplasia (ADH) diagnosed with vacuum-assisted biopsy (VAB), to identify factors associated with the risk of upgrade, to develop a scoring system to support decision making. MATERIALS AND METHODS: Patients with ADH on VAB under stereotactic/tomosynthesis guidance (2012-2022) were eligible. Inclusion criteria were availability of surgical histopathological examination of the entire lesion or radiologic follow-up (FUP) ≥ 24 months. VAB results were compared with surgical pathological results or with imaging FUP evolution to assess upgrade. A backward stepwise linear regression was used to identify predictors of upgrade. The discriminatory power of the model was calculated through the area under the receiver operating curve (ROC-AUC); the Hosmer-Lemeshow test was used to assess model calibration. The points system was developed based on the selected risk factors, and the probability of upgrade associated with each point total was determined. RESULTS: 112 ADH lesions were included: 91 (91/112, 81.3%) underwent surgical excision with 20 diagnosis of malignancy, while 21 (21/112, 18.7%) underwent imaging FUP with one interval change (mean FUP time 48 months). Overall upgrade rate was 18.7% (21/112). Age, menopausal status, concurrent breast cancer, BIRADS classification and number of foci of ADH were identified as risk factors for upgrade. Our model showed an AUC = 0.85 (95% CI 0.76-0.94). The points system showed that the risk of upgrade is < 2% when the total score is ≤ 1. CONCLUSION: Our scoring system seemed a promising easy-to-use decision support tool for management of ADH, decreasing unnecessary surgeries, reducing patients' overtreatment and healthcare costs.

Recent insights on the clinical, pathological, and molecular features of intraductal carcinoma of the prostate.

Intraductal carcinoma of the prostate, a unique histopathologic entity that is often observed (especially in advanced prostate cancer), is characterized by the proliferation of malignant cells within normal acini or ducts surrounded by a basement membrane. Intraductal carcinoma of the prostate is almost invariably associated with an adjacent high-grade carcinoma and is occasionally observed as an isolated subtype. Intraductal carcinoma of the prostate has been demonstrated to be an independent poor prognostic factor for all stages of cancer, whether localized, de novo metastatic, or castration-resistant. It also has a characteristic genetic profile, including high genomic instability. Recognizing and differentiating it from other pathologies is therefore important in patient management, and morphological diagnostic criteria for intraductal carcinoma of the prostate have been established. This review summarizes and outlines the clinical and pathological features, differential diagnosis, molecular aspects, and management of intraductal carcinoma of the prostate, as described in previous studies. We also present a discussion and future perspectives regarding intraductal carcinoma of the prostate.

Superparamagnetic iron oxide (SPIO) for axillary mapping in patients with ductal carcinoma in situ undergoing mastectomy: single-institution experience.

PURPOSE: Unnecessary axillary surgery can potentially be avoided in patients with DCIS undergoing mastectomy. Current guidelines recommend upfront sentinel lymph node biopsy during the index operation due to the potential of upstaging to invasive cancer. This study reviews a single institution's experience with de-escalating axillary surgery using superparamagnetic iron oxide dye for axillary mapping in patients undergoing mastectomy for DCIS. METHODS: This is a retrospective single-institution cross-sectional study. All medical records of patients who underwent mastectomy for a diagnosis of DCIS from August 2021 to January 2023 were reviewed and patients who had SPIO injected at the time of the index mastectomy were included in the study. Descriptive statistics of demographics, clinical information, pathology results, and interval sentinel lymph node biopsy were performed. RESULTS: A total of 41 participants underwent 45 mastectomies for DCIS. The median age of the participants was 58 years (IQR = 17; range 25 to 76 years), and the majority of participants were female (97.8%). The most common indication for mastectomy was diffuse extent of disease (31.7%). On final pathology, 75.6% (34/45) of mastectomy specimens had DCIS without any type of invasion and 15.6% (7/45) had invasive cancer. Of the 7 cases with upgrade to invasive disease, 2 (28.6%) of them underwent interval sentinel lymph node biopsy. All sentinel lymph nodes biopsied were negative for cancer. CONCLUSION: The use of superparamagnetic iron oxide dye can prevent unnecessary axillary surgery in patients with DCIS undergoing mastectomy.

Cytomorphological Assessment in Aspirates of Ductal Carcinoma in situ: Correlations with Histopathologic Grade, Architectural Pattern, and Invasion.

INTRODUCTION: Fine-needle aspiration biopsy (FNAB) of the breast is an effective and widely adopted diagnostic technique. Histopathologic grading of ductal carcinoma in situ (DCIS) has prognostic significance. In this current study, FNAB of DCIS was reviewed to identify parameters that predict grading, histopathologic architecture, and presence of invasion in DCIS. METHODS: Aspirates from histopathology-proven cases of DCIS were retrieved and reviewed for cytomorphologic parameters including cellularity, composition, epithelial fragment architecture cellular/nuclear features. RESULTS: In total 104 aspirates were reviewed. Cytopathologic cellular features - large nuclear size (p = 0.005), prominent nucleoli (p = 0.011), increased nuclear membrane irregularity (p = 0.043), high variation in nuclear size (p = 0.025), and presence of apoptotic figures in epithelial structures (p < 0.001); and background debris (p = 0.033) correlated with a high-grade diagnosis. Cytoplasmic vacuolation (p = 0.034) was seen exclusively in non-high-grade aspirates. Epithelial fragment architecture did not correlate with grading. A predominance (≥50%) of solid aggregates and papillary fragments on FNAB correlated with histopathologically solid (p = 0.039, p = 0.005) and papillary (p = 0.029, < p = 0.001) patterns. No parameter showed correlation with invasion. CONCLUSION: FNAB is effective in predicting DCIS grading. Epithelial fragment architecture assessment is limited to papillary or solid types, and FNAB cannot predict focal invasion in DCIS.

Outcomes of High-Risk Breast MRI Screening in Women Without Prior History of Breast Cancer: Effectiveness Data from a Tertiary Care Center.

OBJECTIVE: To evaluate the diagnostic performance outcomes of a breast MRI screening program in high-risk women without prior history of breast cancer. METHODS: Retrospective cohort study of 1 405 consecutive screening breast MRI examinations in 681 asymptomatic women with high risk of breast cancer without prior history of breast cancer from January 1, 2015, to December 31, 2019. Outcomes (sensitivity, specificity, positive predictive value, negative predictive value, false-negative rate [FNR], cancer detection rate [CDR]) and characteristics of cancers were determined based on histopathology or 12-month follow-up. MRI examinations performed, BI-RADS assessments, pathology outcomes, and CDRs were analyzed overall and by age decade. Results in incidence screening round (MRI in last 18 months) and nonincidence round were compared. RESULTS: Breast MRI achieved CDR 20/1000, sensitivity 93.3% (28/30), and specificity 83.4% (1 147/1375). Twenty-eight (28/1 405, CDR 20/1000) screen-detected cancers were identified: 18 (64.3%, 18/28) invasive and 10 (35.7%, 10/28) ductal carcinoma in situ. Overall, 92.9% (26/28) of all cancers were stage 0 or 1 and 89.3% (25/28) were node negative. All 14 incidence screening round malignancies were stage 0 or 1 with N0 disease. Median size for invasive carcinoma was 8.0 mm and for ductal carcinoma in situ was 9.0 mm. There were two false-negative exams for an FNR 0.1% (2/1 405). CONCLUSION: High-risk screening breast MRI was effective at detecting early breast cancer and associated with favorable outcomes.

Mode of Detection of Second Breast Cancers in Patients Undergoing Surveillance After Treatment of Ductal Carcinoma in Situ.

BACKGROUND: For patients undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS), the NCCN Guidelines for Breast Cancer recommend annual breast imaging and physical examination every 6 to 12 months for 5 years, and then annually. The aim of our study was to evaluate the modes of detection (imaging, patient reported, or physical examination) of second cancers in a cohort of patients undergoing surveillance after primary DCIS treatment to better inform surveillance recommendations. METHODS: We performed a retrospective cohort study of patients with DCIS treated between January 1, 2008, and December 31, 2011, within a large integrated health care system. Information on patient demographics, index DCIS treatment, tumor characteristics, and mode of detection of second breast cancer was obtained from the electronic health record or chart review. RESULTS: Our study cohort consisted of 1,550 women, with a median age of 59 years at diagnosis. Surgical treatment of DCIS included lumpectomy (75.0%; n=1,162), unilateral mastectomy (21.1%; n=327), or bilateral mastectomy (3.9%; n=61), with or without sentinel lymph node biopsy. Additionally, 44.4% (n=688) and 28.3% (n=438) received radiation and endocrine therapies, respectively. Median follow-up was 10 years, during which 179 (11.5%) women were diagnosed with a second breast cancer. Of the second cancers, 43.0% (n=77) were ipsilateral and 54.8% (n=98) contralateral, and 2.2% (n=4) presented with distant metastases; 61.5% (n=110) were invasive, 36.3% (n=65) were DCIS, and 2.2% (n=4) were Paget's disease. Second breast cancers were imaging-detected in 74.3% (n=133) of cases, patient-detected in 20.1% (n=36), physician-detected in 2.2% (n=4), and detected incidentally on imaging or pathology from procedures unrelated to oncologic care in 3.4% (n=6). CONCLUSIONS: In our cohort of patients undergoing surveillance following diagnosis and treatment of DCIS, 2% of second breast cancers were detected by a clinical breast examination. This suggests that survivorship care should prioritize mammography and patient education regarding breast self-examination and symptoms that warrant evaluation to detect second breast cancers.

Clinical presentations and outcomes of young women aged <40 yrs with Ductal carcinoma in situ.

INTRODUCTION: Ductal carcinoma in situ (DCIS) in young women is rare and not well studied. Since they do not qualify for mammographic screening, they are more likely to present with symptoms. Young women have also been associated with poorer outcomes, but it is unknown whether presentation mode affects outcome. We aimed to compare characteristics of DCIS patients <40 years of age presenting with symptoms versus those without, and determine whether presentation mode affects recurrence. METHODS: Pure DCIS patients aged <40 years were retrospectively analyzed. Clinical presentation, pathology and recurrence data were collected. Statistical analysis was performed to investigate the correlation of presentation mode with outcomes. RESULTS: 40 patients with 41 cases were included. The mean age at diagnosis was 32.3 years (range 17-39). 73.2% and 26.8% presented with symptoms or abnormal imaging respectively. Of the cases who presented with symptoms, 86.7%, 10.0% and 3.3% had palpable lump, nipple discharge or breast pain, respectively. The average tumor size was 22.0 mm (range 2.0-86.9) and 12.2 mm (range 3-25) for patients who presented with symptoms and non-symptomatic group, respectively. Cases presenting with symptoms were statistically associated with higher grade (p = 0.0090). On median follow-up of 85 months, there were 3 (7.3%) recurrences, which were not statistically associated with presentation mode. CONCLUSION: Young women with DCIS tend to present with symptoms, with breast lump as the commonest symptom. Symptomatic patients tend to be associated with grade III tumours, compared to non-symptomatic patients. On long-term follow-up, mode of presentation was not statistically associated with recurrence.

KRT15 in early breast cancer screening and correlation with HER2 positivity, pathological grade and N stage.

Objective: This study was designed to explore KRT15 dysregulation and its correlation with clinical characteristics among ductal carcinoma in situ (DCIS), DCIS with microinvasion (DCIS-MI) and invasive breast cancer (IBC) patients. Methods: KRT15 from lesion samples of 50 DCIS patients, 48 DCIS-MI patients and 50 IBC patients was detected by immunohistochemistry. Results: KRT15 discriminated IBC patients from DCIS patients (area under the curve [AUC] = 0.895; 95% CI = 0.836-0.954) and DCIS-MI patients (AUC = 0.707; 95% CI = 0.606-0.808). In DCIS patients, KRT15 was negatively correlated with pathological grade (p = 0.015). In DCIS-MI patients, KRT15 was positively related to estrogen receptor positivity but negatively associated with Ki-67 (both p < 0.05). In IBC patients, KRT15 was negatively linked to HER2 positivity, histological grade, N stage and tumor node metastasis stage (all p < 0.05). Conclusion: KRT15 assessment may help with early breast cancer screening.

Recruiting women with ductal carcinoma in situ to a randomised controlled trial: lessons from the LORIS study.

BACKGROUND: The LOw RISk DCIS (LORIS) study was set up to compare conventional surgical treatment with active monitoring in women with ductal carcinoma in situ (DCIS). Recruitment to trials with a surveillance arm is known to be challenging, so strategies to maximise patient recruitment, aimed at both patients and recruiting centres, were implemented. METHODS: Women aged ≥ 46 years with a histologically confirmed diagnosis of non-high-grade DCIS were eligible for 1:1 randomisation to either surgery or active monitoring. Prior to randomisation, all eligible women were invited to complete: (1) the Clinical Trials Questionnaire (CTQ) examining reasons for or against participation, and (2) interviews exploring in depth opinions about the study information sheets and film. Women agreeing to randomisation completed validated questionnaires assessing health status, physical and mental health, and anxiety levels. Hospital site staff were invited to communication workshops and refresher site initiation visits to support recruitment. Their perspectives on LORIS recruitment were collected via surveys and interviews. RESULTS: Eighty percent (181/227) of eligible women agreed to be randomised. Over 40% of participants had high anxiety levels at baseline. On the CTQ, the most frequent most important reasons for accepting randomisation were altruism and belief that the trial offered the best treatment, whilst worries about randomisation and the influences of others were the most frequent most important reasons for declining. Most women found the study information provided clear and useful. Communication workshops for site staff improved knowledge and confidence but only about half said they themselves would join LORIS if eligible. The most common recruitment barriers identified by staff were low numbers of eligible patients and patient preference. CONCLUSIONS: Recruitment to LORIS was challenging despite strategies aimed at both patients and site staff. Ensuring that recruiting staff support the study could improve recruitment in similar future trials. TRIAL REGISTRATION: ISRCTN27544579, prospectively registered on 22 May 2014.

Incidental DCIS within a fibroadenoma.

A female in her early 20s was referred to the breast-endocrine surgeons with a self-detected tender left breast lump on the background of a family history of breast cancer. A physical examination revealed a rubbery and mobile mass in the left upper breast. Ultrasound demonstrated a solid hypoechoic mass with a likely differential diagnosis of fibroadenoma, with a subsequent core needle biopsy (CNB) confirming a fibroadenoma. Given the size and tenderness of the lump, an excisional biopsy was performed. Histology revealed a fibroadenoma with components of low-grade ductal carcinoma in situ, contained within the fibroadenoma and excised with clear margins.Following surgical excision, a multidisciplinary review determined that no further local therapy was required and recommended a genetics referral. This case was interesting as it raised important questions, including what the best surveillance strategies are for female patients with breast cancer within fibroadenoma and determining the risk and probability of missing epithelial atypia via CNB.

Frozen Sections in Decision-Making Regarding the Axillary Procedures in Breast Conserving Surgery for Intraductal Carcinoma at Preoperative Diagnosis.

BACKGROUND: Axillary evaluation is unnecessary for pure ductal carcinoma in situ (DCIS); however, it is performed because of the risk of upstaging to invasive cancer. We assessed the role of intraoperative frozen section (IOF) biopsy in reducing invasive cancer upstaging and axillary evaluation in preoperative DCIS patients. METHODS: We reviewed patients with preoperative DCIS who underwent breast-conserving surgery (BCS) with IOF biopsy. Positive IOF biopsy findings were defined as the presence of invasive or micro-invasive cancer. The IOF biopsy and permanent pathology findings were compared. RESULTS: Seventy-eight patients underwent BCS with IOF biopsy. Six patients showed positive IOF biopsy findings; five of these patients showed concordant permanent pathology findings. Sentinel lymph node biopsy (SLNB) was positive in one patient. Thirteen patients with invasive breast cancer were missed by IOF biopsy; they underwent SLNB during the second surgery. None of them had metastatic lymph nodes. The sensitivity and specificity of IOF biopsy were 27.7% and 98.3%, respectively, with 82.1% accuracy. None of the other factors showed statistically significant relationships with the permanent pathology findings, except for the IOF biopsy findings. CONCLUSION: IOF evaluation can aid in detecting the invasiveness of tumors in patients with preoperative DCIS.

Diagnostic Pitfalls in Breast Cancer Pathology With an Emphasis on Core Needle Biopsy Specimens.

CONTEXT.­: Breast pathology has many mimics and diagnostic pitfalls. Evaluation of malignant breast lesions, particularly in the biopsy setting, can be especially challenging, with diagnostic errors having significant management implications. OBJECTIVE.­: To discuss the pitfalls encountered when evaluating ductal carcinoma in situ and invasive breast carcinomas, providing histologic clues and guidance for appropriate use and interpretation of immunohistochemistry to aid in the correct diagnosis. DATA SOURCES.­: Data were obtained from review of pertinent literature of ductal carcinoma in situ and invasive breast carcinomas and from the experience of the authors as practicing breast pathologists. CONCLUSIONS.­: Awareness of the pitfalls in diagnosing breast cancers is important when creating a differential diagnosis for each breast lesion evaluated. This review will cover some of these scenarios to aid in the diagnostic process.

Ipsilateral tumor recurrence risk in women with ductal carcinoma in situ: application of the Van Nuys Prognostic Index and the Memorial Sloan Kettering Cancer Center nomogram.

PURPOSE: To apply the Van Nuys Prognostic Index (VNPI) and the Memorial Sloan Kettering Cancer Center (MSKCC) ductal carcinoma in situ (DCIS) nomogram to DCIS patients with known long-term outcomes. METHODS: A retrospective review was performed of consecutive patients diagnosed with DCIS from 2007 to 2014. Included patients underwent breast-conserving surgery (BCS) and were followed with imaging for at least five years. For each patient, the VNPI and MSKCC nomogram risk estimates were determined. In addition, variables used in both models were compared between women with and without recurrences using the Wilcoxon signed-rank test and the Pearson's chi-squared test. RESULTS: Over the eight-year period, 456 women (average age 57 years, range 30-87) underwent BCS for DCIS. Thirty-one (6.8%) experienced an ipsilateral recurrence. The average VNPI scores were 7 (range 5-9) and 7 (range 4-10) for women with and without a recurrence (p = 0.14), respectively, with 4-6, 7-9, and 10-12 being the low, moderate, and high-risk groups, respectively. Per the MSKCC nomogram, the average five-year recurrence risks were 5% (range 1-12%) and 4% (range 1-38%) for women with and without a recurrence (p = 0.09), respectively. The recurrence risk-related variables were younger patient age, need for one or more re-excision surgeries, and use of endocrine therapy for 0 to less than five years after surgery. CONCLUSION: Ipsilateral tumor recurrence risk estimates based on the VNPI and MSKCC nomogram are similar between women with DCIS who did and did not have a recurrence, suggesting that more robust prognostic models are needed.

Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?

Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS-Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one-the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial-incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research.

The long-term psychosocial consequences of screen-detected ductal carcinoma in situ and invasive breast cancer.

OBJECTIVE: Ductal carcinoma in situ (DCIS) is a risk factor for invasive breast cancer (IBC). The prognosis of DCIS is considerably better than for IBC, yet women do not distinguish between the threat. We aimed to compare the psychosocial consequences of screen-detected DCIS and IBC, and to examine this comparison over time. METHODS: We surveyed a Danish mammography-screening cohort from 2004 to 2018. We assessed outcomes at six-time points: baseline, 1, 6, 18, 36 months, and 14 years after the screening. We measured psychosocial consequences with the Consequences Of Screening - Breast Cancer (COS-BC): a condition-specific questionnaire that is psychometrically validated and encompasses 14 psychosocial dimensions. We used weighted linear models with generalized estimating equations to compare responses between groups. We used a 1% level of significance. RESULTS: 170 out of 1309 women were diagnosed with breast cancer (13.0%). 23 were diagnosed with DCIS (13.5%) and 147 with IBC (86.5%). From baseline to six months after diagnosis, there were no significant differences between women with DCIS and IBC. However, mean scores indicated that IBC generally was more affected than DCIS. After six months, we observed that women with DCIS and IBC might be affected differently in the long term; mean scores and mean differences showed that IBC were more affected on some scales, while DCIS were on others. CONCLUSION: Overall, the DCIS and IBC experienced similar levels of psychosocial consequences. Women might benefit from renaming DCIS to exclude cancer nomenclature.

Should low-risk DCIS lose the cancer label? An evidence review.

BACKGROUND: Population mammographic screening for breast cancer has led to large increases in the diagnosis and treatment of ductal carcinoma in situ (DCIS). Active surveillance has been proposed as a management strategy for low-risk DCIS to mitigate against potential overdiagnosis and overtreatment. However, clinicians and patients remain reluctant to choose active surveillance, even within a trial setting. Re-calibration of the diagnostic threshold for low-risk DCIS and/or use of a label that does not include the word 'cancer' might encourage the uptake of active surveillance and other conservative treatment options. We aimed to identify and collate relevant epidemiological evidence to inform further discussion on these ideas. METHODS: We searched PubMed and EMBASE databases for low-risk DCIS studies in four categories: (1) natural history; (2) subclinical cancer found at autopsy; (3) diagnostic reproducibility (two or more pathologist interpretations at a single time point); and (4) diagnostic drift (two or more pathologist interpretations at different time points). Where we identified a pre-existing systematic review, the search was restricted to studies published after the inclusion period of the review. Two authors screened records, extracted data, and performed risk of bias assessment. We undertook a narrative synthesis of the included evidence within each category. RESULTS: Natural History (n = 11): one systematic review and nine primary studies were included, but only five provided evidence on the prognosis of women with low-risk DCIS. These studies reported that women with low-risk DCIS had comparable outcomes whether or not they had surgery. The risk of invasive breast cancer in patients with low-risk DCIS ranged from 6.5% (7.5 years) to 10.8% (10 years). The risk of dying from breast cancer in patients with low-risk DCIS ranged from 1.2 to 2.2% (10 years). Subclinical cancer at autopsy (n = 1): one systematic review of 13 studies estimated the mean prevalence of subclinical in situ breast cancer to be 8.9%. Diagnostic reproducibility (n = 13): two systematic reviews and 11 primary studies found at most moderate agreement in differentiating low-grade DCIS from other diagnoses. Diagnostic drift: no studies found. CONCLUSION: Epidemiological evidence supports consideration of relabelling and/or recalibrating diagnostic thresholds for low-risk DCIS. Such diagnostic changes would need agreement on the definition of low-risk DCIS and improved diagnostic reproducibility.