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Background: Rates of contralateral prophylactic mastectomy (CPM) are increasing among women with unilateral breast cancer despite low rates of contralateral recurrence and lack of survival benefit. We aimed to investigate the decisional needs and supports required to ensure adequate and quality decision-making by patients with breast cancer facing the decision regarding CPM.Methods: In this qualitative study, we used semistructured interviews developed with the use of the Ottawa Decision Support Framework to investigate the decisional needs and supports of women (aged > 18 yr) with nonhereditary breast cancer who had previously discussed CPM with their care provider. Patients were recruited from 2 academic cancer centres in Toronto, Ontario. Interviews were conducted between June 2016 and October 2017. We analyzed responses to the open-ended questions iteratively and inductively to establish major themes within the results.Results: Ten patients were recruited. Eight patients reported having initiated the discussion about CPM. Although most patients reported feeling supported, 6 mentioned some degree of decisional conflict. Cancer risk reduction was the most commonly reported perceived benefit of CPM (9 patients), followed by improved psychologic well-being (7). Most patients (8) did not mention the lack of survival benefit of CPM as a disadvantage of the procedure. Patients indicated that information resources (in 8 cases) and improved counselling from their health care team (in 7) would assist in decision-making.Conclusion: Our findings illustrate the disconnect between true and perceived risks (i.e., surgical risk) and benefits (potential recurrence and survival benefit) of CPM, which is not being managed adequately despite support from the health care team. A decision aid may address unmet patient need by providing a reliable resource regarding the benefits and risks of this procedure, while helping patients understand their values and realign their expectations. [ABSTRACT FROM AUTHOR]

Increasing numbers of women are seeking evaluation of screen-detected breast abnormalities, and more women with breast cancer are living with the consequences of treatment. Improved technologies have helped to individualize diagnostic evaluation and treatment, improve efficacy and minimize morbidity. This article highlights some of these technologies. Superior imaging techniques have improved breast cancer screening and show promise for intraoperative surgical guidance and postoperative specimen evaluation. Digital mammography improves the sensitivity of mammography for women younger than 50 years with dense breasts, and tomosynthesis may improve specificity. Magnetic resonance imaging provides sensitive delineation of the extent of the disease and superior screening for women with a greater than 25% lifetime risk of breast cancer Minimally invasive techniques have been developed for the assessment of intraductal lesions, biopsy of imaging abnormalities, staging of the axilla and breast radiotherapy. Ductoscopy facilitates intraductal biopsy and localization of lesions for excision, sentinel lymph node biopsy is becoming standard for axillary staging, and intraoperative radiotherapy has the potential to reduce treatment time and morbidity. Three-dimensional imaging allows correlation of final histology with preoperative imaging for superior margin assessment. Related techniques show promise for translation to the intraoperative setting for surgical guidance. New classifications of breast cancers based on gene expression, rather than morphology, describe subtypes with different prognoses and treatment implications, and new targeted therapies are emerging. Genetic fingerprints that predict treatment response and outcomes are being developed to assign targeted treatments to individual patients likely to benefit. Surgeons play a vital role in the successful integration of new technologies into practice. [ABSTRACT FROM AUTHOR]

Background: We sought to identify criteria for the intraoperative assessment of sentinel lymph node (SLN) involvement in women with early breast cancer. We also sought to determine whether the SLN nomogram developed by the Memorial Sloan-Kettering Cancer Center (MSKCC) to predict nonsentinel lymph node (NSLN) involvement when the SLN is positive would accurately predict NSLN involvement in our patient population.Methods: We performed 405 SLN biopsies in 397 women between January 1998 and June 2005. We determined factors associated with SLN metastases using univariate and multivariate logistic regression. Ninety women who had 1 positive SLN or more and underwent axillary lymph node dissection (ALND) had complete data for analysis. We applied the MSKCC nomogram retrospectively to this subset of women, and we calculated the probability of NSLN involvement and compared it with the observed rate.Results: Multifocality and the presence of lymphovascular invasion were predictive of SLN involvement. Ductal carcinoma in situ was negatively associated with SLN involvement. Intraoperative evaluation identified 57 (63%) of the 90 women with involved SLN, of which 26 (29%) had involved NSLN. Application of the MSKCC nomogram to our data set produced an area under the receiver operator characteristic curve of 0.71. The nomogram tended to overestimate the probability of NSLN involvement in our population.Conclusion: Lymphovascular invasion and multifocality were associated with SLN involvement. Women with small low-grade tumours may not require routine intraoperative evaluation of SLNs. The MSKCC nomogram appears to be most useful as a decision aid in selecting those women with an involved SLN in whom ALND may be omitted. [ABSTRACT FROM AUTHOR]

The article focuses on the results of research which was conducted in an effort to determine the factors associated with the use of percutaneous needle biopsy to diagnose breast cancer in Ontario. Researchers found that geographic variation exists across Ontario in the use of percutaneous biopsy, particularly image guided biopsy, for the diagnosis of breast cancer.

Purpose: Women with breast cancer often require an extensive diagnostic work-up. We sought to determine the overall wait time, from the patient's perspective, from identification of an imaging abnormality to definitive treatment. The objective was to identify which factors contribute to overall wait time in women with breast cancer. Methods: A retrospective chart review in a tertiary care center was performed to identify all women who had breast surgery for invasive carcinoma and ductal carcinoma in situ. We recorded the dates of first imaging abnormality, first biopsy, subsequent imaging and biopsy, first consultation with any physician at the cancer center, first surgical consultation, and date of surgery. Clinical data that might influence these dates were then extracted. Wait times were calculated and factors associated with wait times were described. Results: Eligible consecutive women with a cancer diagnosis (n = 264) were identified. The median time between first imaging abnormality and definitive surgery was 79 days. The median time from first surgical consultation to surgery was significantly longer in women who underwent magnetic resonance imaging and in women who underwent initial imaging outside of our tertiary care center (P < .05). On multivariable analysis, the modifiable factors associated with prolonged wait times included number of preoperative clinic visits, number of visits to radiology, and initial imaging outside of our center (P < .05). Conclusion: Extensive diagnostic work-up is an important factor that affects the time to definitive surgery. A more integrated approach using a rapid diagnostic clinic for tissue diagnosis initially, followed by facilitated preoperative evaluation, may potentially decrease wait times in breast evaluation. [ABSTRACT FROM AUTHOR]

Introduction: Older adults with cancer may not receive the same opportunities for treatment as younger patients. In this retrospective population-based cohort study, we explored whether age was an independent predictor of receiving specialist consultation and treatment., Methods: Patients age 45-99 were identified from the Ontario Cancer Registry having a primary solid tumor diagnosed between 01/Jan/2010 and 31/Dec/2019. We used logistic regression adjusted sociodemographic and clinical characteristics to compare the likelihood of consultation or receipt of treatment using linear splines at critical ages of 65, 80, and 90 years., Results: A total 168,232 (42%), 165,205 (41%), 57,360 (14%), and 7810 (2%) patients were diagnosed age 45-64, 65-79, 80-89, and 90-99, respectively. The likelihood of surgical consultation decreased as patients reached 65 years [adjusted odds ratio (aOR) 0.86 (0.84-0.89)], which decreased further among octogenarians [aOR 0.63 (0.59-0.67)]. Similar results were observed for consultation with a medical oncologist and radiation oncologist. Receipt of surgery also decreased with age. Three-month post-operative mortality was higher among older patients [aRR 1.38 (1.26-1.50) per 10 years, p < 0.0001], an effect that remained similar as patients reached age 65 + years of age (p = 0.09 for change). For stage I patients, 3-month post-operative survival was high across all age groups, ranging from 99.8% in 45-64 year-olds, 99.4% in 65-79 year-olds, and 98.1% among octogenarians and nonagenarians (lung, colorectal, breast, cervical cancer patients)., Conclusion: Older patients were less likely to have specialist consultations. More comprehensive data collection on clinical factors and referral patterns is needed to improve care for elderly cancer patients., Competing Interests: Conflicts of interest Dr. Ines B. Menjak has some consultancy/honoraria for companies related to lung cancer: Amgen, Astrazeneca. Honoraria for speaking from BMS and Astrazeneca. Education funding from Takeda, Astrazeneca, BMS. All other coauthors have no conflicts to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: In Ontario, patients with breast cancer typically receive their diagnoses through the Ontario Breast Screening Program (OBSP) after an abnormal screen, through screening initiated by a primary care provider or other referring physician, or through follow-up of symptoms by patients' primary care providers. We sought to explore the association of the route to diagnosis (screening within or outside the OBSP or via symptomatic presentation) with use of OBSP-affiliated breast assessment sites (O-BAS), wait times until diagnosis or treatment, health care use and overall survival for patients with breast cancer., Methods: In this retrospective cohort study, we used the Ontario Cancer Registry to identify adults (aged 18-105 yr) who received a diagnosis of breast cancer from 2013 to 2017. We excluded patients if they were not Ontario residents or had missing age or sex, or who died before diagnosis. We used logistic regression to evaluate factors associated with categorical variables (whether patients were or were not referred to an OBAS, whether patients were screened or symptomatic) and Cox proportional hazards regression to identify factors associated with all-cause mortality., Results: Of 51 460 patients with breast cancer, 42 598 (83%) received their diagnoses at an O-BAS. Patients whose cancer was first detected through the OBSP were more likely than symptomatic patients to be given a diagnosis at an O-BAS (adjusted odds ratio 1.68, 95% confidence interval [CI] 1.57 to 1.80). Patients screened by the OBSP were given their diagnoses 1 month earlier than symptomatic patients, but diagnosis at an O-BAS did not affect the time until either diagnosis or treatment. Patients referred to an O-BAS had significantly better overall survival than those who were not referred (adjusted hazard ratio 0.73, 95% CI 0.66 to 0.80)., Interpretation: Patients screened through the OBSP were given their diagnoses earlier than symptomatic patients and were more likely to be referred to an O-BAS, which was associated with better survival. Our findings suggest that individuals with signs and symptoms of breast cancer would benefit from similar referral processes, oversight and standards to those used by the OBSP., Competing Interests: Competing interests: Steven Habbous, Esha Homenauth, Andriana Barisic, Sharmilaa Kandasamy, Vicky Majpruz, Katharina Forster, Marta Yurcan, Anna Chiarelli, Claire Holloway and Andrea Eisen are employees or consultants of Ontario Health (Cancer Care Ontario), which funds the Ontario Breast Screening Program. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Introduction: Diagnostic assessment programs (DAPs) were implemented in Ontario, Canada, to improve the efficiency of the lung cancer care continuum. We compared the efficiency and effectiveness of care provided to patients in DAPs relative to usual care (non-DAPs)., Methods: Lung cancer patients diagnosed between 2014 and 2016 were identified from the Ontario Cancer Registry. Using administrative databases, we identified various health-care encounters 6 months before diagnosis until the start of treatment and compared utilization patterns, timing, and overall survival between DAP and non-DAP patients., Results: DAP patients were younger ( P < 0.0001), had fewer comorbidities ( P = 0.0006), and were more likely to have early-stage disease (36% vs. 25%) than non-DAP patients. Although DAP patients had a similar time until diagnosis as non-DAP patients, the time until treatment was 8.5 days shorter for DAP patients. DAP patients were more likely to receive diagnostic tests and specialist consultations and less likely to have duplicate chest imaging. DAP patients were more likely to receive brain imaging. Among early-stage lung cancers, brain imaging was high (74% for DAP and 67% for non-DAP), exceeding guideline recommendations. After adjustment for clinical and demographic factors, DAP patients had better overall survival than non-DAP patients (hazard ratio [HR]: 0.79 [0.76-0.82]), but this benefit was lost after adjusting for emergency presentation (HR: 0.96 [0.92-1.00]). A longer time until treatment was associated with better overall survival., Conclusion: DAPs provided earlier treatment and better access to care, potentially improving survival. Quality improvement opportunities include reducing unnecessary or duplicate testing and characterizing patients who are diagnosed emergently., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Annals of Thoracic Medicine.)

There is a large and growing population of women who have a personal history of breast cancer (PHBC). This systematic review was undertaken to explore the outcomes of surveillance mammography in breast cancer survivors, and to examine the evidence for screening these women within an organized population-based screening program. We searched Cochrane Central Register of Controlled Trials (CENTRAL Issue 6, 2015), OVID MEDLINE and EMBASE (January 2012 to June 22, 2015) for English-language studies of surveillance of the target population. A study author extracted study outcomes, which were audited by a research assistant. One systematic review and 5 primary studies were included. These showed that surveillance mammography may reduce breast cancer-specific mortality through early/asymptomatic detection (Hazard Ratio for those without compared to with symptoms:HR: 0.64, 95% CI 0.55 - 0.74). Three studies showed that semi-annual mammography is likely not of greater benefit than annual mammography. No evidence was found to suggest that surveillance mammography for women with a PHBC should not be conducted within an organized screening program. The small evidence-base had a high level of heterogeneity in populations, interventions and outcomes. Based on this review, organized screening programs should reassess their guidelines on surveillance mammography and consider including women with a PHBC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Our aim was to conduct a Phase I clinical trial to determine the feasibility of intraoperative detection of tumor margins in HER2 positive breast carcinoma using a hand-held γ-probe following administration of (111)In-DTPA-trastuzumab Fab fragments. Accurate delineation of tumor margins is important for preventing local recurrence., Methods: Six patients with HER2-positive in situ or invasive ductal carcinoma were administered 74MBq (0.5mg) of (111)In-DTPA-trastuzumab Fab fragments and counts in the tumor, surgical cavity wall and en face margins were measured intraoperatively at 72h post-injection using the Navigator or C-Trak γ-probes. Margins were evaluated histologically. Quantitative whole body planar imaging was performed to estimate radiation absorbed doses using OLINDA/EXM software. SPECT imaging of the thorax was performed to evaluate tumor uptake. The pharmacokinetics of elimination from the blood and plasma were determined over 72h., Results: There were no acute adverse reactions from (111)In-DTPA-trastuzumab Fab fragments and no changes in hematological or biochemical indices were found over a 3month period. (111)In-DTPA-trastuzumab Fab fragments exhibited a biphasic elimination from the blood and plasma with t1/2α=11.9h and 7.5h, respectively, and t1/2β=26.6 and 20.7h, respectively. The radiopharmaceutical accumulated in the liver, spleen and kidneys. SPECT imaging did not reveal tumor in any patient. The mean effective dose was 0.146mSv/MBq (10.8mSv for 74MBq). Counts in excised tumors were low but were higher than in margins. Margins in two patients harboured tumor but this was not correlated with counts obtained using the γ-probes. Surgical cavity counts were high and likely due to detection of γ-photons outside the surgical field., Conclusion: We conclude that it was not feasible, at least at the administered amount of radioactivity used in this study, to reliably detect the margins of disease in patients with in situ or invasive ductal carcinoma intraoperatively using a hand-held γ-probe and (111)In-DTPA-trastuzumab Fab fragments due to low uptake in the tumor and involved margins., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To achieve high-quality unilateral supine breast magnetic resonance imaging (MRI) as a step to facilitate image aiding of clinical applications, which are often performed in the supine position. Contrast-enhanced breast MRI is a powerful tool for the diagnosis of cancer. However, prone patient positioning typically used for breast MRI hinders its use for image aiding., Materials and Methods: A fixture and a flexible four-element receive coil were designed for patient-specific shaping and placement of the coil in close conformity to the supine breast. A 3D spoiled gradient sequence was modified to incorporate compensation of respiratory motion. The entire setup was tested in volunteer experiments and in a pilot patient study., Results: The flexible coil design and the motion compensation produced supine breast MR images of high diagnostic value. Variations in breast shape and in tissue morphology within the breast were observed between a supine and a diagnostic prone MRI of a patient., Conclusion: The presented supine breast MRI achieved an image quality comparable to diagnostic breast MRI. Since supine positioning is common in many clinical applications such as ultrasound-guided breast biopsy or breast-conserving surgery, the registration of the supine images will aid these applications., (Copyright © 2011 Wiley Periodicals, Inc.)

Introduction: The human epidermal growth factor receptor-2 (HER2) gene is amplified in 25% of invasive breast cancers, and receptor overexpression has been noted in up to 60% of early stages of the disease [ductal carcinoma in situ (DCIS)]. Preclinical studies have revealed high tumor/blood ratios (>27:1) for (111)In-labeled Fab fragments of the HER2 monoclonal antibody, trastuzumab (Herceptin) ((111)In-DTPA-trastuzumab Fab) at 72 h pi in athymic mice bearing subcutaneous human breast cancer xenografts. Our aim in this study was to formulate a kit for preparation of (111)In-DTPA-trastuzumab Fab injection under good manufacturing practice (GMP) conditions suitable for human administration in a Phase I clinical trial of imaging and radioimmunoguided surgery (RIGS) of HER2-positive breast cancer., Methods: Fab fragments were produced by digestion of trastuzumab IgG (Herceptin) with immobilized papain for 20 h at 37°C. Fab fragments were purified by ultrafiltration, then reacted with a 10-fold molar excess of diethylenetriaminepentaacetic acid (DTPA) dianhydride. DTPA-Fab fragments were purified, then sterilized by filtration into unit dose glass vials (kits). Kits were tested against specifications for volume (0.9-1.1 ml), protein concentration (0.45-0.55 mg/ml), pH (5.5-6.5), DTPA substitution (0.5-4.0 mol DTPA/mol Fab), appearance (clear, colorless and particle free), labeling efficiency (≥ 85%), and sterility and apyrogenicity (USP XXXII). Immunoreactivity of (111)In-DTPA-trastuzumab Fab towards HER2 was measured by saturation radioligand binding assays using SKBR-3 human breast cancer cells (specifications: K(a) = 0.6-9.6 × 10(7) L/mol; B(max) = 0.6-10.4 × 10(6) sites/cell). (111)In-DTPA-trastuzumab Fab injection was prepared by adding 80-100 MBq of (111)InCl(3) to a single kit vial and incubating for 30 min at room temperature. (111)In-DTPA-trastuzumab Fab was assayed for the amount of radioactivity and tested for pH, radiochemical purity (RCP), appearance and sterility., Results: Pure and homogeneous Fab fragments were produced. Eleven lots of kits met established quality specifications. The labeling efficiency with (111)In was 90.6 ± 2.2%. (111)In-DTPA-trastuzumab Fab bound specifically to HER2 on SKBR-3 cells (K(a) = 4.8 ± 2.5 × 10(7) L/mol and B(max) = 1.6 ± 0.8 × 10(6) sites/cell). Thirteen lots of (111)In-DTPA-trastuzumab injection met all established specifications. Kits were stable for 90 days and (111)In-DTPA-trastuzumab Fab injection was stable for 24 h stored at 4 °C., Conclusions: A kit was formulated under GMP conditions for the preparation of (111)In-DTPA-trastuzumab Fab injection suitable for human administration. The kits were approved by Health Canada., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Rationale and Objectives: An in vivo evaluation of a new trimodality breast localization marker was performed with magnetic resonance imaging (MRI), ultrasound (US), x-ray, and histopathology. The evaluation of the marker in animal tests should help define its utility for surgical biopsy localization in humans., Materials and Methods: Five rabbits were used and sacrificed at 2 days, 1 week, 2 weeks, 4 weeks, and 7 weeks after marker implantation. The marker placement and tissue biopsies were performed under US guidance. MRI, US, and x-ray imaging were performed to monitor the contrast of the marker, track marker migration. The biologic compatibility of the marker was demonstrated by histopathologic analysis., Results: The contrast of the marker was clear and stable on each imaging modality over the 7-week study period. Acute inflammation was visible by 2 days after marker injection, with evidence of granulation tissue and angiogenesis at 2 weeks after implantation. A modest degree of chronic inflammation and angiogenesis remained evident at 4 weeks after procedure, and fibrosis persisted 7 weeks after procedure with no further tissue changes. These results suggest that the new marker is biocompatible and can remain interstitial for up to 7 weeks. Furthermore, very little marker migration was observed. On removal, the marker was found to be mechanically stable., Conclusion: This in vivo animal study demonstrates that the new marker may be appropriate for in vivo human testing and as an alternative to traditional wire localization currently used for breast surgery.