Breast cancer diagnosis and treatment wait times in specialized diagnostic units compared with usual care: a population-based study.

Background: Breast assessment sites (bass) were developed to provide expedited and coordinated care for patients being evaluated for breast cancer (bca) in Ontario. We compared the diagnostic and treatment intervals for patients diagnosed at a bas and for those diagnosed through a usual care (uc) route. Methods: This population-based, cross-sectional study of patients diagnosed with bca in Ontario during 2007-2015 used linked administrative data. "Diagnostic interval" was the time from the earliest cancer-related health care encounter before diagnosis to diagnosis; "treatment interval" was the time from diagnosis to treatment. Diagnosis at a bas was determined from the patient's biopsy and mammography institutions. Interval lengths for the bas and uc groups were compared using multivariable quantile regression, stratified by detection method. Results: The diagnostic interval was shorter for patients who were bas-diagnosed than for those who were uc-diagnosed, with adjusted median differences of -4.0 days [95% confidence interval (ci): -3.2 days to -4.9 days] for symptomatic patients and -5.4 days (95% ci: -4.7 days to -6.1 days) for screen-detected patients. That association was modified by stage at diagnosis, with larger differences in patients with early-stage cancers. In contrast, the treatment interval was longer in patients who were bas-diagnosed than in those who were uc-diagnosed, with adjusted median differences of 4.2 days (95% ci: 3.8 days to 4.7 days) for symptomatic patients and 4.2 days (95% ci: 3.7 days to 4.8 days) for screen-detected patients. Conclusions: Diagnosis of bca through a bas was associated with a shorter diagnostic interval, but a longer treatment interval. Although efficiencies in the diagnostic interval might help to reduce distress experienced by patients, the longer treatment intervals for patients who are bas-diagnosed remain a cause for concern.

Can concordance between actual care received and a pathway map be measured on a population level in Ontario? A pilot study.

Background: Clinical pathways are associated with improved adherence to clinical guidelines; however, most studies have evaluated pathways for a single intervention at a single institution. The objective of the present study was to develop and evaluate a method of measuring concordance with a population-based clinical pathway map to determine if that method could be feasible for assessing overall health system performance. Methods: Patients with stage ii or iii colon cancer diagnosed in 2010 were identified, and clinical data were obtained through linkages to administrative databases. Pathway concordance was defined a priori based on receipt of key elements of the Ontario Health (Cancer Care Ontario) colorectal pathway maps. For stages ii and iii colon cancer alike, concordance was reported as the proportion of patients receiving care that followed the predefined key elements of the pathway map. Regression analysis was used to identify predictors of concordant care. Results: Our study identified 816 patients with stage ii and 800 patients with stage iii colon cancer. Of the patients with stage ii disease, 70% (n = 571) received concordant care. Of the patients with stage iii disease, results showed high concordance for all key elements except receipt of chemotherapy, leading to an overall concordance rate of 39% for that cohort. Conclusions: Our method of measuring concordance was feasible on a population-based level, but future studies to validate it and to develop more sophisticated methods to measure concordance in larger cohorts and various disease sites are necessary. Measurement of clinical pathway concordance on a population-based level has the potential to be a useful tool for assessing system performance.

Three-dimensional tumor visualization of invasive breast carcinomas using whole-mount serial section histopathology: implications for tumor size assessment.

PURPOSE: Linear tumor size (T-size) estimated with conventional histology informs breast cancer management. Previously we demonstrated significant differences in margin and focality estimates using conventional histology versus digital whole-mount serial sections (WMSS). Using WMSS we can measure T-size or volume. Here, we compare WMSS T-size with volume, and with T-size measured conventionally. We also compare the ellipsoid model for calculating tumor volume to direct, WMSS measurement. METHODS: Two pathologists contoured regions of invasive carcinoma and measured T-size from both WMSS and (simulated) conventional sections in 55 consecutive lumpectomy specimens. Volume was measured directly from the contours. Measurements were compared using the paired t-test or Spearman's rank-order correlation. A five-point 'border index' was devised and assigned to each case to parametrize tumor shape considering 'compactness' or cellularity. Tumor volumes calculated assuming ellipsoid geometry were compared with direct, WMSS measurements. RESULTS: WMSS reported significantly larger T-size than conventional histology in the majority of cases [61.8%, 34/55; means = (2.34 cm; 1.99 cm), p < 0.001], with a 16.4% (9/55) rate of 'upstaging'. The majority of discordances were due to undersampling. T-size and volume were strongly correlated (r = 0.838, p < 0.001). Significantly lower volume was obtained with WMSS versus ellipsoid modeling [means = (1.18 cm3; 1.45 cm3), p < 0.001]. CONCLUSIONS: Significantly larger T-size is measured with WMSS than conventionally, due primarily to undersampling in the latter. Volume and linear size are highly correlated. Diffuse tumors interspersed with normal or non-invasive elements may be sampled less extensively than more localized masses. The ellipsoid model overestimates tumor volume.

Improving patient flow and timeliness in the diagnosis and management of breast abnormalities: the impact of a rapid diagnostic unit.

BACKGROUND: Efforts to streamline the diagnosis and treatment of breast abnormalities are necessary to limit patient anxiety and expedite care. In the present study, we examined the effect of a rapid diagnostic unit (rdu) on wait times to clinical investigations and definitive treatment. METHODS: A retrospective before-after series, each considering a 1-year period, examined consecutive patients with suspicious breast lesions before and after initiation of the rdu. Patient consultations, clinical investigations, and lesion characteristics were captured from time of patient referral to initiation of definitive treatment. Outcomes included time (days) to clinical investigations, to delivery of diagnosis, and to management. Groups were compared using the Fisher exact test or Student t-test. RESULTS: The non-rdu group included 287 patients with 164 invasive breast carcinomas. The rdu group included 260 patients with 154 invasive carcinomas. The rdu patients had more single visits for biopsy (92% rdu vs. 78% non-rdu, p < 0.0001). The rdu group also had a significantly shorter wait time from initial consultation to delivery of diagnosis (mean: 2.1 days vs. 16.7 days, p = 0.0001) and a greater chance of receiving neoadjuvant chemotherapy (37% vs. 24%, p = 0.0106). Overall time from referral to management remained statistically unchanged (mean: 53 days with the rdu vs. 50 days without the rdu, p = 0.3806). CONCLUSIONS: Introduction of a rdu appears to reduce wait times to definitive diagnosis, but not to treatment initiation, suggesting that obstacles to care delivery can occur at several points along the diagnostic trajectory. Multipronged efforts to reduce system-related delays to definitive treatment are needed.

Cost-effectiveness analysis of whole-mount pathology processing for patients with early breast cancer undergoing breast conservation.

BACKGROUND: Obtaining accurate histopathologic detail for breast lumpectomy specimens is challenging because of sampling and loss of three-dimensional conformational features with conventional processing. The whole-mount (wm) technique is a novel method of serial pathologic sectioning designed to optimize cross-sectional visualization of resected specimens and determination of margin status. METHODS: Using a Markov chain cohort simulation cost-effectiveness model, we compared conventional processing with wm technique for breast lumpectomies. Cost-effectiveness was evaluated from the perspective of the Canadian health care system and compared using incremental cost-effectiveness ratios (icers) for cost per quality-adjusted life-year (qaly) over a 10-year time horizon. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model with willingness-to-pay (wtp) thresholds of $0-$100,000. Costs are reported in adjusted 2014 Canadian dollars, discounted at a rate of 3%. RESULTS: Compared with conventional processing, wm processing is more costly ($19,989 vs. $18,427) but generates 0.03 more qalys over 10 years. The icer is $45,414, indicating that this additional amount is required for each additional qaly obtained. The model was robust to all variance in parameters, with the prevalence of positive margins accounting for most of the model's variability. CONCLUSIONS: After a wtp threshold of $45,414, wm processing becomes cost-effective and ultimately generates fewer recurrences and marginally more qalys over time. Excellent baseline outcomes for the current treatment of breast cancer mean that incremental differences in survival are small. However, the overall benefit of the wm technique should be considered in the context of achieving improved accuracy and not just enhancements in clinical effectiveness.

An International Multicenter Review of the Malignancy Rate of Excised Papillomatous Breast Lesions.

BACKGROUND: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. METHODS: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. RESULTS: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology (p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. CONCLUSIONS: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients.

3D Pathology Volumetric Technique: A Method for Calculating Breast Tumour Volume from Whole-Mount Serial Section Images.

Tumour size, most commonly measured by maximum linear extent, remains a strong predictor of survival in breast cancer. Tumour volume, proportional to the number of tumour cells, may be a more accurate surrogate for size. We describe a novel "3D pathology volumetric technique" for lumpectomies and compare it with 2D measurements. Volume renderings and total tumour volume are computed from digitized whole-mount serial sections using custom software tools. Results are presented for two lumpectomy specimens selected for tumour features which may challenge accurate measurement of tumour burden with conventional, sampling-based pathology: (1) an infiltrative pattern admixed with normal breast elements; (2) a localized invasive mass separated from the in situ component by benign tissue. Spatial relationships between key features (tumour foci, close or involved margins) are clearly visualized in volume renderings. Invasive tumour burden can be underestimated using conventional pathology, compared to the volumetric technique (infiltrative pattern: 30% underestimation; localized mass: 3% underestimation for invasive tumour, 44% for in situ component). Tumour volume approximated from 2D measurements (i.e., maximum linear extent), assuming elliptical geometry, was seen to overestimate volume compared to the 3D volumetric calculation (by a factor of 7x for the infiltrative pattern; 1.5x for the localized invasive mass).

Imaging technologies in breast diagnosis and surgical treatment.

The diagnostic and surgical management of breast cancer has changed dramatically over the past 2 decades. All facets in the multidisciplinary management of breast cancer are rapidly evolving and being driven forward by technological advances. Conventional imaging techniques are now being augmented with advances in molecular imaging that probe biological properties of tissue to create images, and optical imaging which reflects physical properties of normal and diseased tissues. Automated computer assisted biopsy techniques are being developed to sample breast tissue with a higher degree of accuracy and patient comfort. As the trend toward minimally invasive breast surgery continues ablative techniques such as radiofrequency ablation, cryoablation, interstitial laser ablation and focused ultrasound ablation are being explored to potentially avoid the need for surgery all together. New intraoperative lesion localization techniques such as 3-dimensional ultrasonographic tumor models, magnetic resonance imaging (MRI)-guided projection and reproduction, radioguided occult lesion localization and optical imaging techniques are being developed to improve surgical guidance. Evaluation of advanced imaging and intraoperative guidance techniques requires more comprehensive histopathological examination of surgical specimens, prompting the development of techniques aimed at to improving upon the current limitations in breast pathology. This review will describe the development of new technologies in breast imaging, tumor ablation, intraoperative surgical guidance and tissue processing aimed at advancing minimally invasive diagnosis and treatment of breast cancer.

Factors affecting axillary lymph node retrieval and assessment in breast cancer patients.

BACKGROUND: Breast cancer is the most common female cancer in North America. Axillary lymph node dissection (ALND) is important for staging, prognosis, and adjuvant treatment decisions. The purpose of this study was to identify factors that affect the number of lymph nodes (LN) retrieved in ALND for breast cancer. METHODS: All patients who underwent ALND for breast cancer at Sunnybrook Health Sciences Centre and Women's College Hospital between July 1999 and June 2006 were included. The number of LN retrieved was identified from pathology reports. Univariate and multivariate analysis was undertaken to identify variables influencing this outcome. RESULTS: 1084 patients were identified with a mean number of LN of 14.5. In multivariate analyses, significant covariates included sentinel LN biopsy (P = 0.011), degree of extranodal extension (P = 0.005), tumor grade (P = 0.058), and age (P = 0.043). Thirteen percent of the variation in LN yield was accounted for by institutional, provider, patient, and tumor related factors, leaving 87% attributable to inherent biological or other differences between patients. CONCLUSION: The yield of ALND may be influenced by multiple factors, often not related to the surgery. In settings where >10 LNs are routinely retrieved at ALND, biological variation between patients should be recognized as major a contributor to the LN yield. Adjuvant treatment decisions based on this outcome should take this into consideration.