Breast Magnetic Resonance Imaging for Preoperative Evaluation of Breast Cancer: A Systematic Review and Meta-Analysis.

Purpose: Preoperative breast magnetic resonance imaging (MRI) is known to detect additional cancers that are occult on mammography and ultrasound. There is debate as to whether these additional lesions affect clinical outcomes. The objective of this systematic review was to summarize the evidence on whether additional information on disease extent obtained with preoperative breast MRI in patients with newly diagnosed breast cancer affects surgical management, rates of recurrence, survival, re-excision, and early detection of bilateral cancer. Methods: Embase, MEDLINE, and Cochrane Central Register of Controlled Trials were searched until January 2021 (partial update July 2022) for studies comparing outcomes with versus without pre-operative MRI. Included were both randomized controlled trials and other comparative studies provided MRI and control groups had equivalent disease and patient characteristics or methods such as multivariable analysis or propensity score matching were used to control potential confounders. Results: The search resulted in 26,399 citations, of which 8 randomized control trials, 1 prospective cohort study, and 42 retrospective studies met the inclusion criteria. Use of MRI resulted in decreased rates of reoperations (OR = 0.73, 95% CI = 0.63 to 0.85), re-excisions (OR = 0.63, 95% CI = 0.45 to 0.89), and recurrence (HR = 0.77, 95% CI = 0.65 to 0.90). Increased detection of synchronous contralateral breast cancers led to a reduction in metachronous contralateral breast cancer (HR = 0.71, 95% CI = 0.59 to 0.85). Hazard ratios for recurrence-free and overall survival were 0.77 (95% CI = 0.53 to 1.12) and 0.89 (95% CI = 0.74 to 1.07). Conclusion: This systematic review indicates substantial benefits of pre-operative breast MRI in decreasing reoperations and recurrence.

Estimating the incidence of breast cancer recurrence using administrative data.

BACKGROUND: Breast cancer is the most common cancer among women, but most cancer registries do not capture recurrences. We estimated the incidence of local, regional, and distant recurrences using administrative data. METHODS: Patients diagnosed with stage I-III primary breast cancer in Ontario, Canada from 2013 to 2017 were included. Patients were followed until 31/Dec/2021, death, or a new primary cancer diagnosis. We used hospital administrative data (diagnostic and intervention codes) to identify local recurrence, regional recurrence, and distant metastasis after primary diagnosis. We used logistic regression to explore factors associated with developing a distant metastasis. RESULTS: With a median follow-up 67 months, 5,431/45,857 (11.8%) of patients developed a distant metastasis a median 23 (9, 42) months after diagnosis of the primary tumor. 1086 (2.4%) and 1069 (2.3%) patients developed an isolated regional or a local recurrence, respectively. Patients with distant metastatic disease had a median overall survival of 15.4 months (95% CI 14.4-16.4 months) from the time recurrence/metastasis was identified. In contrast, the median survival for all other patients was not reached. Patients were more likely to develop a distant metastasis if they had more advanced stage, greater comorbidity, and presented with symptoms (p < 0.0001). Trastuzumab halved the risk of recurrence [OR 0.53 (0.45-0.63), p < 0.0001]. CONCLUSION: Distant metastasis is not a rare outcome for patients diagnosed with breast cancer, translating to an annual incidence of 2132 new cases (17.8% of all breast cancer diagnoses). Overall survival remains high for patients with locoregional recurrences, but was poor following a diagnosis of a distant metastasis.

Associations between clinical pathway concordance, cost, and survival outcomes for stage II colon cancer: a population-based study.

This study measures patient's concordance between clinical reference pathways with survival or cost among a population-based cohort of colon cancer patients applying a continuous measure of concordance. The primary hypothesis is that a higher concordance score with the clinical pathway is significantly associated with longer survival or lower cost. The study informs whether patient's adherence to a defined clinical pathway is beneficial to patients' outcomes or health system. An externally determined clinical pathway for colon cancer was used to identify treatment nodes in colon cancer care. Using observational data up to 2019, the study generated a continuous measure of pathway concordance. The study measured whether incremental improvements in pathway concordance were associated with survival and treatment costs. Concordance between patients' reference pathways and their observed trajectories of care was highly statistically associated with survivorship [hazard ratio: 0.95 (95% confidence interval, CI, 0.95-0.96)], showing that adherence to the clinical pathway was associated with a lower mortality rate. An increase in concordance was statistically significantly associated with a decrease in health system cost. When patients' care followed the clinical pathway, survival outcomes were better and total health system costs were lower in this cohort. This finding creates a compelling case for further research into understanding the barriers to pathway concordance and developing interventions to improve outcomes and help providers implement best practice care where appropriate.

Development of population-level colon cancer pathway concordance measures and association with survival.

Clinical cancer pathways help standardize healthcare delivery to optimize patient outcomes and health system costs. However, population-level measurement of concordance between standardized pathways and actual care received is lacking. Two measures of pathway concordance were developed for a simplified colon cancer pathway map for Stage II-III colon cancer patients in Ontario, Canada: a cumulative count of concordant events (CCCE) and the Levenshtein algorithm. Associations of concordance with patient survival were estimated using Cox proportional hazards models adjusted for patient characteristics and time-dependent cancer-related activities. Models were compared and the impact of including concordance scores was quantified using the likelihood ratio chi-squared test. The ability of the measures to discriminate between survivors and decedents was compared using the C-index. Normalized concordance scores were significantly associated with patient survival in models for cancer stage-a 10% increase in concordance for Stage II patients resulted in a CCCE score adjusted hazard ratio (aHR) of death of 0.93, 95% CI 0.88-0.98 and a Levenshtein score aHR of 0.64, 95% CI 0.60-0.67. A similar relationship was found for Stage III patients-a 10% increase in concordance resulted in a CCCE aHR of 0.85, 95% CI 0.81-0.88 and a Levenshtein aHR of 0.78, 95% CI, 0.74-0.81. Pathway concordance can be used as a tool for health systems to monitor deviations from established clinical pathways. The Levenshtein score better characterized differences between actual care and clinical pathways in a population, was more strongly associated with survival and demonstrated better patient discrimination.

Inverse optimization on hierarchical networks: an application to breast cancer clinical pathways.

Clinical pathways are standardized processes that outline the steps required for managing a specific disease. However, patient pathways often deviate from clinical pathways. Measuring the concordance of patient pathways to clinical pathways is important for health system monitoring and informing quality improvement initiatives. In this paper, we develop an inverse optimization-based approach to measuring pathway concordance in breast cancer, a complex disease. We capture this complexity in a hierarchical network that models the patient's journey through the health system. A novel inverse shortest path model is formulated and solved on this hierarchical network to estimate arc costs, which are used to form a concordance metric to measure the distance between patient pathways and shortest paths (i.e., clinical pathways). Using real breast cancer patient data from Ontario, Canada, we demonstrate that our concordance metric has a statistically significant association with survival for all breast cancer patient subgroups. We also use it to quantify the extent of patient pathway discordances across all subgroups, finding that patients undertaking additional clinical activities constitute the primary driver of discordance in the population.

Patient opinions on contralateral prophylactic mastectomy: A patient-driven discussion in need of tuning?

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.

Factors associated with waiting time to breast cancer diagnosis among symptomatic breast cancer patients: a population-based study from Ontario, Canada.

PURPOSE: A prolonged time from first presentation to cancer diagnosis has been associated with worse disease-related outcomes. This study evaluated potential determinants of a long diagnostic interval among symptomatic breast cancer patients. METHODS: This was a population-based, cross-sectional study of symptomatic breast cancer patients diagnosed in Ontario, Canada from 2007 to 2015 using administrative health data. The diagnostic interval was defined as the time from the earliest breast cancer-related healthcare encounter before diagnosis to the diagnosis date. Potential determinants of the diagnostic interval included patient, disease and usual healthcare utilization characteristics. We used multivariable quantile regression to evaluate their relationship with the diagnostic interval. We also examined differences in diagnostic interval by the frequency of encounters within the interval. RESULTS: Among 45,967 symptomatic breast cancer patients, the median diagnostic interval was 41 days (interquartile range 20-92). Longer diagnostic intervals were observed in younger patients, patients with higher burden of comorbid disease, recent immigrants to Canada, and patients with higher healthcare utilization prior to their diagnostic interval. Shorter intervals were observed in patients residing in long-term care facilities, patients with late stage disease, and patients who initially presented in an emergency department. Longer diagnostic intervals were characterized by an increased number of physician visits and breast procedures. CONCLUSIONS: The identification of groups at risk of longer diagnostic intervals provides direction for future research aimed at better understanding and improving breast cancer diagnostic pathways. Ensuring that all women receive a timely breast cancer diagnosis could improve breast cancer outcomes.

Patient-reported symptoms following mastectomy alone or lumpectomy plus radiation for early stage breast cancer: a cohort study.

PURPOSE: Studies examining symptom differences between surgeries for breast cancer patients rarely incorporate the effects of adjuvant treatment choice. We sought to understand differences in patient-reported symptoms between lumpectomy plus radiation and mastectomy in the year following surgery. METHODS: This cohort study used linked administrative datasets. The exposure was defined as lumpectomy plus radiation or mastectomy. The outcomes of moderate-to-severe (score ≥ 4) patient-reported symptoms were obtained using the Edmonton symptom assessment system (ESAS). Line plots were created to determine symptom trajectories in the 12 months following surgery, and the relationships between surgery and each of the nine symptoms were assessed using multivariable analyses. Clinical significance was determined as a difference of 10%. RESULTS: Of 13,865 Stage I-II breast cancer patients diagnosed 2007-2015, 11,497 underwent lumpectomy plus radiation and 2368 underwent mastectomy. Symptom trajectories were similar for all nine symptoms until approximately 5 months postoperatively when they diverged and mastectomy symptoms started becoming more severe. On multivariable analyses, patients undergoing mastectomy were at an increased risk of reporting moderate-to-severe depression (RR 1.19, 95% CI 1.09-1.30), lack of appetite (RR 1.11, 95% CI 1.03-1.20), and shortness of breath (RR 1.16, 95% CI 1.04-1.15) compared to those undergoing lumpectomy plus radiation. CONCLUSIONS: Even with the addition of adjuvant radiation, patients who are treated with lumpectomy fare better in three of nine patient-reported symptoms. Further examination of these differences will assist in better shared decision-making regarding surgical treatments.

Practitioner Opinion on Contralateral Prophylactic Mastectomy: How Do We Steer a Patient-Driven Discussion?

BACKGROUND: Contralateral prophylactic mastectomy (CPM) is increasing despite a recent statement from The American Society of Breast Surgeons discouraging average-risk women with unilateral breast cancer (BC) from undergoing CPM. The objective of our study was to conduct a needs assessment of BC health practitioners to gather information about their opinions, attitudes, and experiences surrounding CPM. METHODS: The Ottawa Decision Support Framework was the theoretical framework for the development of the interview guide. Semistructured interviews were conducted until data saturation with a convenience sample of 16 BC practitioners (Ontario, Canada), including oncologic and reconstructive surgeons, medical oncologists, and nurse navigators. RESULTS: Nearly all practitioners identified the discussion regarding CPM as patient-initiated. The majority of practitioners (13/16) described their role as supporting the patient in the decision-making process. Practitioners described educating patients on the lack of survival benefit and in general discouraging CPM. Practitioners agreed that most patients demonstrate decisional conflict (11/16) as a barrier to decision-making, and it is a challenge to realign patients' understanding and expectations. Almost all practitioners (15/16) identified a need for information materials to help educate patients on the risks and benefits of CPM and to help realign expectations. CONCLUSIONS: Practitioners have identified CPM in average-risk women with unilateral BC as a patient-driven phenomenon that is on the rise, despite highlighting the increased risk of complications and lack of survival benefit. Our practitioner needs assessment identifies the need for a dynamic decision aid to help guide the shared decision-making process for practitioners and patients.

Axillary Lymph Node Ultrasound Following Neoadjuvant Chemotherapy in Biopsy-Proven Node-Positive Breast Cancer: Results from the SN FNAC Study.

BACKGROUND: The sentinel node biopsy following neoadjuvant chemotherapy (SN FNAC) study has shown that in node-positive (N+) breast cancer, sentinel node biopsy (SNB) can be performed following neoadjuvant chemotherapy (NAC), with a low false negative rate (FNR = 8.4%). A secondary endpoint of the SN FNAC study was to determine whether axillary ultrasound (AxUS) could predict axillary pathological complete response (ypN0) and increase the accuracy of SNB. METHODS: The SN FNAC trial is a study of patients with biopsy-proven N+ breast cancer who underwent SNB followed by completion node dissection. All patients had AxUS following NAC and the axillary nodes were classified as either positive (AxUS+) or negative (AxUS-). AxUS was compared with the final axillary pathology results. RESULTS: There was no statistical difference in the baseline characteristics of patients with AxUS+ versus those with AxUS-. Overall, 82.5% (47/57) of AxUS+ patients had residual positive lymph nodes (ypN+) at surgery and 53.8% (42/78) of AxUS- patients had ypN+. Post NAC AxUS sensitivity was 52.8%, specificity 78.3%, and negative predictive value 46.2%. AxUS FNR was 47.2%, versus 8.4% for SNB. If post-NAC AxUS- was used to select patients for SNB, FNR would decrease from 8.4 to 2.7%. However, using post-NAC AxUS in addition to SNB as an indication for ALND would have led to unnecessary ALND in 7.8% of all patients. CONCLUSION: AxUS is not appropriate as a standalone staging procedure, and SNB itself is sufficient to assess the axilla post NAC in patients who present with N+ breast cancer.

Evaluating wait times from screening to breast cancer diagnosis among women undergoing organised assessment vs usual care.

BACKGROUND: Timely coordinated diagnostic assessment following an abnormal screening mammogram reduces patient anxiety and may optimise breast cancer prognosis. Since 1998, the Ontario Breast Screening Program (OBSP) has offered organised assessment through Breast Assessment Centres (BACs). For OBSP women seen at a BAC, an abnormal mammogram is followed by coordinated referrals through the use of navigators for further imaging, biopsy, and surgical consultation as indicated. For OBSP women seen through usual care (UC), further diagnostic imaging is arranged directly from the screening centre and/or through their physician; results must be communicated to the physician who is then responsible for arranging any necessary biopsy and/or surgical consultation. This study aims to evaluate factors associated with diagnostic wait times for women undergoing assessment through BAC and UC. METHODS: Of the 2 147 257 women aged 50-69 years screened in the OBSP between 1 January 2002 and 31 December 2009, 155 866 (7.3%) had an abnormal mammogram. A retrospective design identified two concurrent cohorts of women diagnosed with screen-detected breast cancer at a BAC (n=4217; 47%) and UC (n=4827; 53%). Multivariable logistic regression analyses examined associations between wait times and assessment and prognostic characteristics by pathway. A two-sided 5% significance level was used. RESULTS: Screened women with breast cancer were two times more likely to be diagnosed within 7 weeks when assessed through a BAC vs UC (OR=1.91, 95% CI=1.73-2.10). In addition, compared with UC, women assessed through a BAC were significantly more likely to have their first assessment procedure within 3 weeks of their abnormal mammogram (OR=1.25, 95% CI=1.12-1.39), ⩽3 assessment procedures (OR=1.54, 95% CI=1.41-1.69), ⩽2 assessment visits (OR=1.86, 95% CI=1.70-2.05), and ⩾2 procedures per visit (OR=1.41, 95% CI=1.28-1.55). Women diagnosed through a BAC were also more likely than those in UC to have imaging (OR=1.99, 95% CI=1.44-2.75) or a biopsy (OR=3.69, 95% CI=2.64-5.15) vs consultation only at their first assessment visit, and two times more likely to have a core or FNA biopsy than a surgical biopsy (OR=2.08, 95% CI=1.81-2.40). Having ⩽2 assessment visits was more likely to reduce time to diagnosis for women assessed through a BAC compared with UC (BAC OR=10.58, 95% CI=8.96-12.50; UC OR=4.47, 95% CI=3.94-5.07), as was having ⩽3 assessment procedures (BAC OR=4.97, 95% CI=4.26-5.79; UC OR=2.95, 95% CI=2.61-3.33). Income quintile affected wait times only in women diagnosed in UC, with those in the two highest quintiles more likely to receive a diagnosis in 7 weeks. CONCLUSIONS: Women with screen-detected breast cancer in OBSP were more likely to have shorter wait times if they were diagnosed through organised assessment. This might be as a result of women diagnosed through a BAC having more procedures per visit, procedures scheduled in shorter intervals, and imaging or biopsy on their first visit. Given the significant improvement in timeliness to diagnosis, women with abnormal mammograms should be managed through organised assessment.

Breast screening for survivors of breast cancer: A systematic review.

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.

Whole-mount pathology of breast lumpectomy specimens improves detection of tumour margins and focality.

AIMS: Technical limitations in conventional pathological evaluation of breast lumpectomy specimens may reduce diagnostic accuracy in the assessment of margin and focality. A novel technique based on whole-mount serial sections enhances sampling while preserving specimen conformation and orientation. The aim of this study was to investigate assessment of focality and margin status by the use of whole-mount serial sections versus simulated conventional sections in lumpectomies. METHODS AND RESULTS: Two pathologists interpreted whole-mount serial sections and simulated conventional sections for 58 lumpectomy specimens by reporting the closest margin and focality. Measurements were compared by the use of McNemar's chi-squared test. Statistically significant differences were observed in the assignment of both margin positivity (P = 0.014) and multifocality (P = 0.021). A positive margin or multifocal disease was identified by the use of whole-mount serial sections but missed in the simulated conventional assessment in 10.3% and 17.2% of all cases, respectively. There was no case in which a positive margin was detected only in the simulated conventional assessment. CONCLUSIONS: The whole-mount technique is more sensitive than conventional assessment for identifying a positive margin or multifocal disease in breast lumpectomy specimens. Undersampling in conventional sections was implicated in almost all cases of discordance. The majority of positive margins or secondary foci identified only in whole-mount serial sections concerned in-situ disease.

Utilization of Percutaneous Needle Biopsy for Breast Diagnosis in a Comprehensive Breast Center: Implications for Development of Quality Indicators.

INTRODUCTION: Percutaneous needle biopsy (PNB) is the standard of care for diagnosis of breast lesions. Rates of excisional biopsy for breast diagnosis in North America have been reported at approximately 35 %, although significant regional variation exists. A target rate of PNB for diagnosis of breast abnormalities is needed to facilitate quality improvement. We sought to describe the use of PNB in a referral practice, the clinical scenarios prompting PNB or surgical biopsy (SB), and the accuracy and rate of PNB to inform the ultimate development of a benchmark rate of PNB in breast diagnosis. MATERIALS AND METHODS: Female patients age 18-90 years, referred to Sunnybrook Health Sciences Centre, a large teaching hospital affiliated with the University of Toronto, with a breast lesion prompting tissue diagnosis with SB and/or PNB between 2002 and 2009 were studied. Each biopsied lesion was characterized by method of biopsy: PNB, SB, or PNB followed by SB. For each lesion, we collected data on patient demographics and breast cancer risk, reason for referral, imaging characteristics (breast imaging-reporting and data system classification, full description, final impression before biopsy), and pathology from each biopsy method. We report concordance between the final impression pre-biopsy and the PNB diagnosis with final surgical diagnosis where applicable. RESULTS: One thousand and twenty-six lesions were biopsied, 987 (96 %) with PNB. The benign:malignant ratio for the entire cohort was 1.2:1. Final impression was concordant with final pathology in 674/862 (78 %) and PNB diagnosis was concordant with SB pathology in 487/556 (88 %). The reasons for SB without PNB were required pathologic evaluation of the entire lesion (n = 19), patient choice (n = 5), other biopsy technique used (n = 6), technical (n = 4), planned mastectomy (n = 3), and enlarging mass (n = 2). 155/559 (28 %) of lesions without evidence of malignancy on PNB ultimately underwent SB. Papillary lesions and radial scars were more likely to undergo SB with or without prior PNB. Lesions deemed to be suspicious or malignant on final impression were more likely to be excised after a benign diagnosis at PNB. CONCLUSION: The vast majority of lesions requiring tissue diagnosis can be accurately diagnosed with PNB. Benchmarks for rates of PNB of 90 % or greater may be considered for performance measurement in appropriate populations.

A Patient-Centered Approach to Wait Times in the Surgical Management of Breast Cancer in the Province of Ontario.

BACKGROUND: Wait time for breast cancer is an important contributor to cancer outcomes and patient satisfaction. This study sought to define a patient-centered wait time by measuring the time from the first abnormal imaging to definitive surgery. The authors hypothesized that multiple preoperative investigations significantly increase the patient-centered wait time. METHODS: A retrospective analysis of prospectively maintained databases at the Institute for Clinical and Evaluative Sciences in Ontario, Canada was performed. Women undergoing primary surgery for invasive breast cancer from 2003 to 2011 were evaluated. The median wait time between the first abnormal imaging and definitive surgery was calculated. Uni- and multivariable analyses were performed to identify characteristics of the patients, treating institution, and diagnostic pathway that contribute significantly to the patient-centered wait time. RESULTS: Our final cohort consisted of 42,179 patients: 31,837 (75 %) who had breast conserving surgery and 10,342 (25 %) who underwent mastectomy. The median wait time from the first abnormal imaging to definitive surgery was 52 days (intraquartile range 35-76 days). In adjusted analysis, older patient age, later year of surgery, additional preoperative imaging, and biopsies beyond those required for diagnosis significantly and independently extended the surgical wait time. Preoperative consultations and institutional factors such as volume of breast surgery performed and geographic location also independently had an impact on surgical wait time. CONCLUSIONS: This study defined a novel patient-centered measure of surgical wait time that more fully embraces the wait experienced by the patient. Many common preoperative interventions had a significant impact on overall wait time experienced by the patient. Evidence-based quality initiatives to coordinate appropriate investigations are needed to reduce wait times.

A prospective study of mastectomy patients with and without delayed breast reconstruction: long-term psychosocial functioning in the breast cancer survivorship period.

INTRODUCTION: For women who have mastectomy, breast reconstruction is an option which may improve psychosocial functioning. The purpose of this study was to evaluate changes in psychosocial functioning over a long follow-up period after mastectomy, specifically examining the differences between those with mastectomy alone and those who underwent postmastectomy delayed breast reconstruction (DBR). METHODS: This was a prospective longitudinal survey study of women with mastectomy in which a repeated measures design was used to compare psychosocial function scores over 3 timepoints: 1) pre-mastectomy; 2) one year post-mastectomy; and 3) long-term post-mastectomy (mean 6.3 years). In addition, psychosocial functioning was compared between the mastectomy alone group and the group who elected for DBR. RESULTS: 67 women who completed questionnaires at all three time points were included. The long-term follow-up time post-mastectomy was 75.2 months (6.3 years). Twenty-eight women (41.8%) underwent DBR in the study period. For the entire cohort, between one-year and long-term post-mastectomy, there were significant improvements in scores for body concerns (P = 0.03), cancer-related distress (P = 0.01), and total distress (P = 0.04). At long-term follow-up, women with DBR had significantly higher levels of total distress (P = 0.01), obsessiveness (P = 0.03), and cancer-related distress (P = 0.02) compared to those with mastectomy alone. There were no differences in quality of life between the two groups at any time point. CONCLUSIONS: Psychosocial functioning improves over time in patients treated with mastectomy in the long-term breast cancer survivorship period, which may be related to the effect of time post-treatment, rather than an effect of choice for or against DBR.

Digital compared to screen-film mammography: breast cancer prognostic features in an organized screening program.

Our previous study found cancer detection rates were equivalent for direct radiography compared to screen-film mammography, while rates for computed radiography were significantly lower. This study compares prognostic features of invasive breast cancers by type of mammography. Approved by the University of Toronto Research Ethics Board, this study identified invasive breast cancers diagnosed among concurrent cohorts of women aged 50-74 screened by direct radiography, computed radiography, or screen-film mammography from January 1, 2008 to December 31, 2009. During the study period, 816,232 mammograms were performed on 668,418 women, and 3,323 invasive breast cancers were diagnosed. Of 2,642 eligible women contacted, 2,041 participated (77.3 %). The final sample size for analysis included 1,405 screen-detected and 418 interval cancers (diagnosed within 24 months of a negative screening mammogram). Polytomous logistic regression was performed to evaluate the association between tumour characteristics and type of mammography, and between tumour characteristics and detection method. Odds ratios (OR) and 95 % confidence intervals (CI) were recorded. Cancers detected by computed radiography compared to screen-film mammography were significantly more likely to be lymph node positive (OR 1.94, 95 %CI 1.01-3.73) and have higher stage (II:I, OR 2.14, 95 %CI 1.11-4.13 and III/IV:I, OR 2.97, 95 %CI 1.02-8.59). Compared to screen-film mammography, significantly more cancers detected by direct radiography (OR 1.64, 95 %CI 1.12-2.38) were lymph node positive. Interval cancers had worse prognostic features compared to screen-detected cancers, irrespective of mammography type. Screening with computed radiography may lead to the detection of cancers with a less favourable stage distribution compared to screen-film mammography that may reflect a delayed diagnosis. Screening programs should re-evaluate their use of computed radiography for breast screening.

Surgical resident experience in breast disease: a national study.

BACKGROUND: Management of breast disease is an integral component of general surgery. This study was performed to describe the exposure to breast disease by residents in Canadian general surgery programs. METHODS: This study involved a 20-item survey and pilot semistructured interviews. Surgical trainees at 12 training programs in Canada participated in the survey. Results were used to characterize resident experience with breast surgery and clinics. RESULTS: Residents across all post-graduate training years and from 12 Canadian medical schools responded (n = 162, 44 %). Residents had the most breast surgery experience in PGY2 and PGY3 years. One third of trainees performed ≤ 1 breast procedure per month. Only 25 % had attended more than one breast clinic per month. Lumpectomies were the most common procedure (20.7/year) and 94 % of residents performed sentinel lymph node biopsy. Four pilot semistructured interviews were performed. The greatest stated barriers to breast training were "lack of time" and the impression that these were "lower priority cases." CONCLUSIONS: Achieving competence in breast disease management is a key requirement for general surgery trainees. Surgical educators must ensure that the quality and quantity of residency training in breast diseases is sufficient for future surgeons to provide optimal patient care.

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways.

Insulin-like growth factor binding protein 7 (IGFBP7) has been shown to be a tumor suppressor in a variety of cancers. We previously have shown that IGFBP7 expression is inversely correlated with disease progression and poor outcome in breast cancer. Overexpression of IGFBP7 in MDA-MB-468, a triple-negative breast cancer (TNBC) cell line, resulted in inhibition of growth and migration. Xenografted tumors bearing ectopic IGFBP7 expression were significantly growth-impaired compared to IGFBP7-negative controls, which suggested that IGFBP7 treatment could inhibit breast cancer cell growth. To confirm this notion, 14 human patient primary breast tumors were analyzed by qRTPCR for IGFBP7 expression. The TNBC tumors expressed the lowest levels of IGFBP7 expression, which also correlated with higher tumorigenicity in mice. Furthermore, when breast cancer cell lines were treated with IGFBP7, only the TNBC cell lines were growth inhibited. Treatment of NOD/SCID mice harboring xenografts of TNBC cells with IGFBP7 systemically every 3-4 days inhibited tumorigenesis, with associated anti-angiogenic effects, together with increased apoptosis. Upon examining the mechanism of IGFBP7-mediated growth inhibition in TNBC cells, we found that cells not only were arrested in G1 phase of the cell cycle but also underwent senescence as a result of treatment with IGFBP7. Interestingly, IGFBP7 treatment was also associated with strong activation of the stress-associated p38 MAPK pathway, together with upregulation of p53 and the cyclin-dependent protein kinase (CDK) inhibitor, p21(cip1). Prolonged treatment of cells with IGFBP7 resulted in increased cell death, marked by an increase in apoptotic cells and associated cleaved PARP. This is the first study showing that exogenous IGFBP7 inhibits TNBC cell growth both in vitro and in vivo. Taken together, these results suggest IGFBP7 treatment might have therapeutic potential for TNBC.

Changes in psychosocial functioning 1 year after mastectomy alone, delayed breast reconstruction, or immediate breast reconstruction.

BACKGROUND: In this study, we report on the changes in psychosocial functioning over 1 year following breast cancer surgery in 3 groups of women, including those with mastectomy alone, those with mastectomy and immediate reconstruction, and those with delayed reconstruction. METHODS: Women with breast cancer at 2 teaching hospitals in Ontario who were undergoing mastectomy alone, mastectomy with immediate reconstruction, or delayed reconstruction were asked to complete a battery of psychosocial questionnaires at their preoperative appointment and 1 year following surgery. RESULTS: A total of 190 women consented to participate in the study and completed the presurgical questionnaires. There were no presurgical differences between the 3 groups in quality of life, anxiety, depression, or sexual functioning. However, women who were undergoing delayed breast reconstruction (i.e., already had a mastectomy) had higher levels of body stigma (P = 0.01), body concerns (P = 0.002), and transparency (P = 0.002) than women who were undergoing mastectomy alone or mastectomy with immediate reconstruction. Of these women, 158 (83.2%) completed the 1-year follow-up. There were no significant differences in any of the psychosocial functioning scores between the 3 groups. DISCUSSION: Contrary to the assumed psychological benefits of breast reconstruction, psychological distress was evident among women regardless of reconstruction or timing of reconstruction. Further, psychosocial functioning (including quality of life, sexual functioning, cancer-related distress, body image, depression, and anxiety) was not different at 1-year postsurgery between women with mastectomy alone, mastectomy with immediate reconstruction, and delayed reconstruction. These results suggest that women need psychosocial support after breast cancer diagnosis, even if they have breast reconstruction.