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OBJECTIVES To estimate rates of screen-detected and interval breast cancers, stratified by risk factor, to inform discussions of risk-stratified population screening. DESIGN Retrospective population-based cohort study; analysis of routinely collected BreastScreen WA program clinical and administrative data. SETTING, PARTICIPANTS All BreastScreen WA mammography screening episodes for women aged 40 years or more during 1 July 2007 - 30 June 2017. MAIN OUTCOME MEASURES Cancer detection rate (CDR) and interval cancer rate (ICR), by risk factor. RESULTS A total of 323 082 women were screened in 1 026 137 screening episodes (mean age, 58.5 years; SD, 8.6 years). The overall CDR was 68 (95% CI, 67-70) cancers per 10 000 screens, and the overall ICR was 9.7 (95% CI, 9.2-10.1) cancers per 10 000 women-years. Interactions between the effects on CDR of age group and five risk factors were statistically significant: personal history of breast cancer (P = 0.039), family history of breast cancer (P = 0.005), risk-relevant benign conditions (P = 0.012), hormone-replacement therapy (P = 0.002), and self-reported symptoms (P

Background In patients with triple-negative breast cancer (TNBC), oncological and survival outcomes based on locoregional treatment are poorly understood. In particular, the safety of breast-conserving surgery (BCS) for TNBC has been questioned. Methods A meta-analysis was performed to evaluate locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) rates in patients with TNBC who had breast-conserving surgery versus mastectomy. Estimates were pooled in random-effects analysis. The effect of study-level co-variables was assessed by univariable metaregression. Results Fourteen studies, including 19 819 patients operated for TNBC met the inclusion criteria; 9828 patients (49.6 per cent) underwent BCS and 9991 (50.4 per cent) had a mastectomy. Patients with smaller tumours were more likely to be selected for BCS (pooled odds ratio (OR) for T1 tumours 1.95, 95 per cent c.i. 1.64 to 2.32; P Conclusion These results should be interpreted cautiously owing to likely differences in selection for BCS or mastectomy in the included studies. Patients with TNBC selected for BCS do not, however, have a worse prognosis than those treated with mastectomy, and breast conservation can be offered when feasible clinically.

Background Previous studies have suggested improved efficiency and patient outcomes with 125I seed compared with hookwire localization (HWL) in breast-conserving surgery, but high-level evidence of superior surgical outcomes is lacking. The aim of this multicentre pragmatic RCT was to compare re-excision and positive margin rates after localization using 125I seed or hookwire in women with non-palpable breast cancer. Methods Between September 2013 and March 2018, women with non-palpable breast cancer eligible for breast-conserving surgery were assigned randomly to preoperative localization using 125I seeds or hookwires. Randomization was stratified by lesion type (pure ductal carcinoma in situ (DCIS) or other) and study site. Primary endpoints were rates of re-excision and margin positivity. Secondary endpoints were resection volumes and weights. Results A total of 690 women were randomized at eight sites; 659 women remained after withdrawal (125I seed, 327; HWL, 332). Mean age was 60.3 years in the 125I seed group and 60.7 years in the HWL group, with no difference between the groups in preoperative lesion size (mean 13.2 mm). Lesions were pure DCIS in 25.9 per cent. The most common radiological lesion types were masses (46.9 per cent) and calcifications (28.2 per cent). The localization modality was ultrasonography in 65.5 per cent and mammography in 33.7 per cent. The re-excision rate after 125I seed localization was significantly lower than for HWL (13.9 versus 18.9 per cent respectively; P = 0.019). There were no significant differences in positive margin rates, or in specimen weights and volumes. Conclusion Re-excision rates after breast-conserving surgery were significantly lower after 125I seed localization compared with HWL. Registration number: ACTRN12613000655741 (http://www.ANZCTR.org.au/).

BACKGROUND Despite extensive research on risk factors and mechanisms, the extent to which interpregnancy interval (IPI) affects hypertensive disorders of pregnancy in high-income countries remains unclear. OBJECTIVES To examine the association between IPI and hypertensive disorders of pregnancy in a high-income country setting using both within-mother and between-mother comparisons. METHODS A retrospective population-based cohort study was conducted among 103 909 women who delivered three or more consecutive singleton births (n = 358 046) between 1980 and 2015 in Western Australia. We used conditional Poisson regression with robust variance, matching intervals of the same mother and adjusted for factors that vary within-mother across pregnancies, to investigate the association between IPI categories (reference 18-23 months), and the risk of hypertensive disorders of pregnancy. For comparison with previous studies, we also applied unmatched Poisson regression (between-mother analysis). RESULTS The incidence of preeclampsia and gestational hypertension during the study period was 4%, and 2%, respectively. For the between-mother comparison, mothers with intervals of 6-11 months had lower risk of preeclampsia with adjusted relative risk (RR) 0.92 (95% confidence interval [CI] 0.85, 0.98) compared to reference category of 18-23 months. With the within-mother matched design, we estimated a larger effect of long IPI on risk of preeclampsia (RR 1.29, 95% CI 1.18, 1.42 for 60-119 months; and RR 1.30, 95% CI 1.10, 1.53 for intervals ≥120 months) compared to 18-23 months. Short IPIs were not associated with hypertensive disorders of pregnancy. CONCLUSIONS In our cohort, longer IPIs were associated with increased risk of preeclampsia. However, there was insufficient evidence to suggest that short IPIs (

Quantification of stillbirth risk has potential to support clinical decision-making. Studies that have attempted to quantify stillbirth risk have been hampered by small event rates, a limited range of predictors that typically exclude obstetric history, lack of validation, and restriction to a single classifier (logistic regression). Consequently, predictive performance remains low, and risk quantification has not been adopted into antenatal practice. The study population consisted of all births to women in Western Australia from 1980 to 2015, excluding terminations. After all exclusions there were 947,025 livebirths and 5,788 stillbirths. Predictive models for stillbirth were developed using multiple machine learning classifiers: regularised logistic regression, decision trees based on classification and regression trees, random forest, extreme gradient boosting (XGBoost), and a multilayer perceptron neural network. We applied 10-fold cross-validation using independent data not used to develop the models. Predictors included maternal socio-demographic characteristics, chronic medical conditions, obstetric complications and family history in both the current and previous pregnancy. In this cohort, 66% of stillbirths were observed for multiparous women. The best performing classifier (XGBoost) predicted 45% (95% CI: 43%, 46%) of stillbirths for all women and 45% (95% CI: 43%, 47%) of stillbirths after the inclusion of previous pregnancy history. Almost half of stillbirths could be potentially identified antenatally based on a combination of current pregnancy complications, congenital anomalies, maternal characteristics, and medical history. Greatest sensitivity is achieved with addition of current pregnancy complications. Ensemble classifiers offered marginal improvement for prediction compared to logistic regression.

OBJECTIVE To investigate the effect of interpregnancy interval (IPI) on preterm birth (PTB) according to whether the previous birth was preterm or term. DESIGN Cohort study. SETTING USA (California), Australia, Finland, Norway (1980-2017). POPULATION Women who gave birth to first and second (n = 3 213 855) singleton livebirths. METHODS Odds ratios (ORs) for PTB according to IPIs were modelled using logistic regression with prognostic score stratification for potential confounders. Within-site ORs were pooled by random effects meta-analysis. OUTCOME MEASURE PTB (gestational age

Background Breast screening programs replaced film mammography with digital mammography, and the effects of this practice shift in population screening on health outcomes can be measured through examination of cancer detection and interval cancer rates. Methods A systematic review and random effects meta-analysis were undertaken. Seven databases were searched for publications that compared film with digital mammography within the same population of asymptomatic women and reported cancer detection and/or interval cancer rates. Results The analysis included 24 studies with 16 583 743 screening examinations (10 968 843 film and 5 614 900 digital). The pooled difference in the cancer detection rate showed an increase of 0.51 per 1000 screens (95% confidence interval [CI] = 0.19 to 0.83), greater relative increase for ductal carcinoma in situ (25.2%, 95% CI = 17.4% to 33.5%) than invasive (4%, 95% CI = −3% to 13%), and a recall rate increase of 6.95 (95% CI = 3.47 to 10.42) per 1000 screens after the transition from film to digital mammography. Seven studies (80.8% of screens) reported interval cancers: the pooled difference showed no change in the interval cancer rate with −0.02 per 1000 screens (95% CI = −0.06 to 0.03). Restricting analysis to studies at low risk of bias resulted in findings consistent with the overall pooled results for all outcomes. Conclusions The increase in cancer detection following the practice shift to digital mammography did not translate into a reduction in the interval cancer rate. Recall rates were increased. These results suggest the transition from film to digital mammography did not result in health benefits for screened women. This analysis reinforces the need to carefully evaluate effects of future changes in technology, such as tomosynthesis, to ensure new technology leads to improved health outcomes and beyond technical gains.

There is no consensus on adequate negative margins in breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We systematically reviewed the evidence on margins in BCS for DCIS.A study-level meta-analysis of local recurrence (LR), microscopic margin status and threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression (frequentist) and network meta-analysis (Bayesian) that allows for multiple margin distances per study, adjusting for follow-up time.Based on 20 studies (LR: 865 of 7883), odds of LR were associated with margin status [logistic: odds ratio (OR) 0.53 for negative vs. positive/close (p 0.001); network: OR 0.45 for negative vs. positive]. In logistic meta-regression, relative to0 or 1 mm, ORs for 2 mm (0.51), 3 or 5 mm (0.42) and 10 mm (0.60) showed comparable significant reductions in the odds of LR. In the network analysis, ORs relative to positive margins for 2 (0.32), 3 (0.30) and 10 mm (0.32) showed similar reductions in the odds of LR that were greater than for0 or 1 mm (0.45). There was weak evidence of lower odds at 2 mm compared with0 or 1 mm [relative OR (ROR) 0.72, 95 % credible interval (CrI) 0.47-1.08], and no evidence of a difference between 2 and 10 mm (ROR 0.99, 95 % CrI 0.61-1.64). Adjustment for covariates, and analyses based only on studies using whole-breast radiotherapy, did not change the findings.Negative margins in BCS for DCIS reduce the odds of LR; however, minimum margin distances above 2 mm are not significantly associated with further reduced odds of LR in women receiving radiation.

Objectives Most breast screening programs worldwide have replaced screen-film mammography (SFM) with full-field digital mammography (FFDM) in expectation of technical, clinical and economic advantages. However, we are only just now able to begin to measure the effects of this practice shift in population screening on health outcomes among asymptomatic women eligible for population screening. This systematic review aims to assess the impact of digital mammography on breast cancer detection rates at screening and on interval cancer rates, as indicators of additional net benefit through early detection, or additional net harm from overdiagnosis. Method We searched Medline, Premedline, PubMed, Embase, NHSEED, DARE and Cochrane databases and identified 2139 potentially eligible papers. 31 papers were included after exclusions for relevance, duplication and other exclusion criteria. Primary outcomes are detection rates and interval cancer rates. Secondary outcomes include recall rates, false positive rates, and positive predictive values. Results are stratified by first and subsequent screening rounds. Results Preliminary results for primary outcomes are available at the present time and reveal a small increase in screen detected cancers across all studies. However, in 7 studies with data on interval cancer rates, we observed no statistically significant increase in detection rate, nor a reduction in interval cancer rates. Final data for these primary outcomes, and for secondary outcomes, are being prepared and will be presented at the conference. Conclusions Overall there has been a small increase in screen-detected cancers with the transition from film to digital mammography screening. However we observed no reduction in interval cancers, and the effect, if any, remains unclear. This observed pattern of results is consistent with a possible, small increment in cancer detection which may result in future benefit for screened women, but is also consistent with a net increase in overdiagnosis. These data reinforce the need to carefully evaluate effects of future changes in technology such as 3D mammography to ensure incremental changes to screening programs do not lead to a poorer ratio of benefit to harm from screening.

Introduction: Digital breast tomosynthesis (DBT) addresses some of the limitations of digital mammography (DM) by reducing the effect of overlapping tissue. Emerging data have shown that DBT increases breast cancer (BC) detection and reduces recall in BC screening programs. Studies have also suggested that DBT improves assessment of screen-recalled findings. Areas covered: Studies of DBT for population BC screening and those for assessment of screen-detected findings were reviewed to provide an up-to-date summary of the evidence on DBT in the screening setting. A systematic literature search was conducted for each of the topics; study-specific information and/or quantitative data on detection or accuracy were extracted and collated in tables. Expert commentary: The evidence on DBT for BC screening reinforces that DBT integrated with DM increases cancer detection rates compared to DM alone, although the extent of improved detection varied between studies. The effect of DBT on recall rates was heterogeneous with substantial reductions evident noticeably in retrospective comparative studies. The evidence on DBT for workup was sparse and those studies had limitations related to design and methods. Even though the majority showed improved specificity using DBT compared with conventional imaging, there was little evidence on how DBT impacts assessment outcomes.

Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be tailored; however, optimal response assessment methods have not been established. We estimated the accuracy of ultrasound (US) to predict pathologic complete response (pCR) using common response criteria and pCR definitions, and estimated incremental accuracy over known prognostic variables. Participants undergoing US after two cycles in the GeparTrio trial randomised to no change in NAC were eligible. US response by World Health Organisation (WHO) criteria (1D or 2D) and Response Evaluation Criteria In Solid Tumours (RECIST) was assessed. Four pCR definitions were applied. Sensitivity (correct prediction of pCR), specificity (correct prediction of no-pCR) and diagnostic odds ratios (DORs) were calculated. Areas under the curve (AUCs) were derived from logistic regression including patient variables with and without US. In 832 patients, DORs decreased as pCR definitions became less stringent (p = 0.01). For WHO-2D, DORs were as follows: 4.07 (ypT0,ypN0), 3.75 (ypT0/is,ypN0), 3.14 (ypT0/is,ypN+/-) and 2.65 (ypT0/is/1a,ypN+/-). DORs did not differ between US criteria (p = 0.60). High sensitivity and lower specificity were found for WHO-2D and RECIST; WHO-1D was highly specific with low sensitivity. Sensitivity was highest for WHO-2D predicting ypT0,ypN0 (sensitivity = 81.7%, specificity = 47.6% vs. 42.3% and 80.4% for WHO-1D). Adding US to models including patient variables (age, T-stage, histology and subtype) improved AUCs for predicting pCR by 2-3%. In conclusion, US accuracy is highest for predicting ypT0,ypN0, shown to be most prognostic of long-term survival. WHO-2D and RECIST maximise sensitivity; WHO-1D maximises specificity. US modestly improves the prediction of pCR by patient characteristics.

Background: Magnetic resonance imaging (MRI) has been proposed to guide breast cancer surgery by measuring residual tumour after neoadjuvant chemotherapy. This study-level meta-analysis examines MRI's agreement with pathology, compares MRI with alternative tests and investigates consistency between different measures of agreement. Methods: A systematic literature search was undertaken. Mean differences (MDs) in tumour size between MRI or comparator tests and pathology were pooled by assuming a fixed effect. Limits of agreement (LOA) were estimated from a pooled variance by assuming equal variance of the differences across studies. Results: Data were extracted from 19 studies (958 patients). The pooled MD between MRI and pathology from six studies was 0.1 cm (95% LOA: −4.2 to 4.4 cm). Similar overestimation for MRI (MD: 0.1 cm) and ultrasound (US) (MD: 0.1 cm) was observed, with comparable LOA (two studies). Overestimation was lower for MRI (MD: 0.1 cm) than mammography (MD: 0.4 cm; two studies). Overestimation by MRI (MD: 0.1 cm) was smaller than underestimation by clinical examination (MD: −0.3 cm). The LOA for mammography and clinical examination were wider than that for MRI. Percentage agreement between MRI and pathology was greater than that of comparator tests (six studies). The range of Pearson's/Spearman's correlations was wide (0.21–0.92; 16 studies). Inconsistencies between MDs, percentage agreement and correlations were common. Conclusion: Magnetic resonance imaging appears to slightly overestimate pathologic size, but measurement errors may be large enough to be clinically significant. Comparable performance by US was observed, but agreement with pathology was poorer for mammography and clinical examination. Percentage agreement can provide supplementary information to MDs and LOA, but Pearson's/Spearman's correlation does not provide evidence of agreement and should be avoided. Further comparisons of MRI and other tests using the recommended methods are warranted.

Pathologic complete response (pCR) is a surrogate end-point for prognosis in neoadjuvant chemotherapy (NAC) for breast cancer. We aimed to report summary estimates of the proportion of subjects achieving pCR (pCR%) by tumour subtype, and to determine whether subtype was independently associated with pCR, in a study-level meta-analysis.We systematically identified NAC studies reporting pCR data according to tumour subtype, using predefined eligibility criteria. Descriptive, qualitative and quantitative data were extracted. Random effects logistic meta-regression examined whether pCR% was associated with subtype, defined using three categories for model 1 [hormone receptor positive (HR+/HER2-), HER2 positive (HER2+), triple negative (ER-/PR-/HER2-)] and 4 categories for model 2 [HER2+ further classified as HER2+/HR+ and HER2+/HR-]. Subtype-specific odds ratios (OR) were calculated and were adjusted for covariates associated with pCR in our data.In model 1, based on 11,695 subjects from 30 eligible studies, overall pooled pCR% was 18.9% (16.6-21.5%), and in model 2 (20 studies, 8095 subjects) pooled pCR% was 18.5% (16.2-21.1%); tumour subtype was associated with pCR% (P0.0001) in both models. Subtype-specific pCR% (model 2) was: 8.3% (6.7-10.2%) in HR+/HER2- [OR 1/referent], 18.7% (15.0-23.1%) in HER2+/HR+ [OR 2.6], 38.9% (33.2-44.9%) in HER2+/HR- [OR 7.1] and 31.1% (26.5-36.1%) in triple negative [OR 5.0]; pCR% was significantly higher for the HER2+/HR- compared with the triple negative subtype, however pCR% was very similar for these subtypes (and OR=5.0 both subtypes) when studies using HER2-directed therapy with NAC were excluded from the model. Neither sensitivity analysis (excluding unknown subtypes), nor adjustment for associated covariates, substantially altered our findings.This meta-analysis provides evidence of an independent association between breast cancer subtype and pCR; odds of pCR were highest for the triple negative and HER2+/HR- subtypes, with evidence of an influential effect on achieving pCR in the latter subtype through inclusion of HER2-directed therapy with NAC.

Background Magnetic resonance imaging (MRI) may guide breast cancer surgery by measuring residual tumor size post-neoadjuvant chemotherapy (NAC). Accurate measurement may avoid overly radical surgery or reduce the need for repeat surgery. This individual patient data (IPD) meta-analysis examines MRI’s agreement with pathology in measuring the longest tumor diameter and compares MRI with alternative tests. Methods A systematic review of MEDLINE, EMBASE, PREMEDLINE, Database of Abstracts of Reviews of Effects, Heath Technology Assessment, and Cochrane databases identified eligible studies. Primary study authors supplied IPD in a template format constructed a priori. Mean differences (MDs) between tests and pathology (i.e. systematic bias) were calculated and pooled by the inverse variance method; limits of agreement (LOA) were estimated. Test measurements of 0.0 cm in the presence of pathologic residual tumor, and measurements >0.0 cm despite pathologic complete response (pCR) were described for MRI and alternative tests. Results Eight studies contributed IPD (N = 300). The pooled MD for MRI was 0.0 cm (LOA: +/−3.8 cm). Ultrasound underestimated pathologic size (MD: −0.3 cm) relative to MRI (MD: 0.1 cm), with comparable LOA. MDs were similar for MRI (0.1 cm) and mammography (0.0 cm), with wider LOA for mammography. Clinical examination underestimated size (MD: −0.8 cm) relative to MRI (MD: 0.0 cm), with wider LOA. Tumors “missed” by MRI typically measured 2.0 cm or less at pathology; tumors >2.0 cm were more commonly “missed” by clinical examination (9.3 %). MRI measurements >5.0 cm occurred in 5.3 % of patients with pCR, but were more frequent for mammography (46.2 %). Conclusions There was no systematic bias in MRI tumor measurement, but LOA are large enough to be clinically important. MRI’s performance was generally superior to ultrasound, mammography, and clinical examination, and it may be considered the most appropriate test in this setting. Test combinations should be explored in future studies. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1664-4) contains supplementary material, which is available to authorized users.

Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be tailored; however, optimal response assessment methods have not been established. We estimated the accuracy of ultrasound (US) to predict pathologic complete response (pCR) using common response criteria and pCR definitions, and estimated incremental accuracy over known prognostic variables. Participants undergoing US after two cycles in the GeparTrio trial randomised to no change in NAC were eligible. US response by World Health Organisation (WHO) criteria (1D or 2D) and Response Evaluation Criteria In Solid Tumours (RECIST) was assessed. Four pCR definitions were applied. Sensitivity (correct prediction of pCR), specificity (correct prediction of no-pCR) and diagnostic odds ratios (DORs) were calculated. Areas under the curve (AUCs) were derived from logistic regression including patient variables with and without US. In 832 patients, DORs decreased as pCR definitions became less stringent (p = 0.01). For WHO-2D, DORs were as follows: 4.07 (ypT0,ypN0), 3.75 (ypT0/is,ypN0), 3.14 (ypT0/is,ypN+/-) and 2.65 (ypT0/is/1a,ypN+/-). DORs did not differ between US criteria (p = 0.60). High sensitivity and lower specificity were found for WHO-2D and RECIST; WHO-1D was highly specific with low sensitivity. Sensitivity was highest for WHO-2D predicting ypT0,ypN0 (sensitivity = 81.7%, specificity = 47.6% vs. 42.3% and 80.4% for WHO-1D). Adding US to models including patient variables (age, T-stage, histology and subtype) improved AUCs for predicting pCR by 2-3%. In conclusion, US accuracy is highest for predicting ypT0,ypN0, shown to be most prognostic of long-term survival. WHO-2D and RECIST maximise sensitivity; WHO-1D maximises specificity. US modestly improves the prediction of pCR by patient characteristics.

Background It has been proposed that magnetic resonance imaging (MRI) be used to guide breast cancer surgery by dif ferentiating residual tumor from pathologic complete response (pCR) after neoadjuvant chemotherapy. This metaanalysis examines MRI accuracy in detecting residual tumor, investigates variables potentially affecting MRI performance, and compares MRI with other tests. Methods A systematic literature searc h was undertaken. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate (relative) diagnostic odds ratios ([R]DORs). Summary sensitivity (correct identification of residual tumor), specificity (correct identification of pCR), and areas under the SROC curves (AUCs) were derived. All statistical tests were two-sided. Results F orty-four studies (2050 patients) were included. The overall AUC of MRI was 0.88. Accuracy was lower for “standard” pCR definitions (referent category) than “less clearly described” (RDOR = 2.41, 95% confidence interval [CI] = 1.11 to 5.23) or “near-pCR” definitions (RDOR = 2.60, 95% CI = 0.73 to 9.24; P = .03.) Corresponding AUCs were 0.83, 0.90, and 0.91. Specificity was higher when negative MRI was defined as contrast enhancement less than or equal to normal tissue (0.83, 95% CI = 0.64 to 0.93) vs no enhancement (0.54, 95% CI = 0.39 to 0.69; P = .02), with comparable sensitivity (0.83, 95% CI = 0.69 to 0.91; vs 0.87, 95% CI = 0.80 to 0.92; P = .45). MRI had higher accuracy than mammography (P = .02); there was only weak evidence that MRI had higher accuracy than clinical examination (P = .10). No difference in MRI and ultrasound accuracy was found (P = .15). Conclusions MRI accurately detects residual tumor af ter neoadjuvant chemotherapy. Accuracy was lower when pCR was more rigorously defined, and specificity was lower when test negativity thresholds were more stringent; these definitions require standardization. MRI is more accurate than mammography; however, studies comparing MRI and ultrasound are required.

Magnetic resonance imaging (MRI) has been proposed to have a role in predicting final pathologic response when undertaken early during neoadjuvant chemotherapy (NAC) in breast cancer. This paper examines the evidence for MRI's accuracy in early response prediction. A systematic literature search (to February 2011) was performed to identify studies reporting the accuracy of MRI during NAC in predicting pathologic response, including searches of MEDLINE, PREMEDLINE, EMBASE, and Cochrane databases. 13 studies were eligible (total 605 subjects, range 16-188). Dynamic contrast-enhanced (DCE) MRI was typically performed after 1-2 cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared to a pre-NAC baseline scan. MRI parameters measured included changes in uni- or bidimensional tumour size, three-dimensional volume, quantitative dynamic contrast measurements (volume transfer constant [Ktrans], exchange rate constant [k(ep)], early contrast uptake [ECU]), and descriptive patterns of tumour reduction. Thresholds for identifying response varied across studies. Definitions of response included pathologic complete response (pCR), near-pCR, and residual tumour with evidence of NAC effect (range of response 0-58%). Heterogeneity across MRI parameters and the outcome definition precluded statistical meta-analysis. Based on descriptive presentation of the data, sensitivity/specificity pairs for prediction of pathologic response were highest in studies measuring reductions in Ktrans (near-pCR), ECU (pCR, but not near-pCR) and tumour volume (pCR or near-pCR), at high thresholds (typically >50%); lower sensitivity/specificity pairs were evident in studies measuring reductions in uni- or bidimensional tumour size. However, limitations in study methodology and data reporting preclude definitive conclusions. Methods proposed to address these limitations include: statistical comparison between MRI parameters, and MRI vs other tests (particularly ultrasound and clinical examination); standardising MRI thresholds and pCR definitions; and reporting changes in NAC based on test results. Further studies adopting these methods are warranted.

Background: A diagnosis of ductal carcinoma in situ (DCIS) on core needle biopsy (CNB) may represent an underestimate (or understaging) of invasive breast cancer (IBC). This is identified on excision histology in 4%-35% of CNB diagnoses of DCIS. It is of clinical significance as it may prevent informed discussion about management options for IBC and may mean that more than one surgical procedure is required. We systematically review the literature on CNB to report pooled estimates for underestimation of IBC following CNB diagnosis of DCIS and identify preoperative predictors of invasion. Methods: Studies were identified by searching MEDLINE and were evaluated against predetermined inclusion criteria: data were extracted independently by 2 authors. We calculated study-specific proportions for DCIS underestimates. Using meta-regression (random effects logistic models) we investigated the association between study-level preoperative variables and understaged IBC. Results: 47 studies met eligibility criteria reporting 6,213 cases of DCIS on CNB with excision histology as the reference standard. Table 1: Pooled underestimation rates for There were 1,482 underestimates (DCIS on CNB and IBC on excision); pooled estimate 25.9%(95% CI 22.2, 29.9). Preoperative variables associated with underestimation included ultrasound-guidance (vs stereotaxis), 14Gautomated (vs 11GVAB), high grade CNB lesion (vs nonhigh grade), size >20mm, BIRADS 4/5 (vs BIRADS3), mammographic mass (vs calc only) and palpability. Conclusion: Using available evidence we estimate that around 26% of CNB DCIS diagnoses represent understaged IBC. We identified preoperative variables associated with higher risk of understaging. This information can be used for preoperative discussion of management options, including possible sentinel node biopsy at the time of excision. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-02-01.