The Association between Mutational Signatures and Clinical Outcomes among Patients with Early-Onset Breast Cancer.

Early-onset breast cancer (EoBC), defined by a diagnosis <40 years of age, is associated with poor prognosis. This study investigated the mutational landscape of non-metastatic EoBC and the prognostic relevance of mutational signatures using 100 tumour samples from Alberta, Canada. The MutationalPatterns package in R/Bioconductor was used to extract de novo single-base substitution (SBS) and insertion-deletion (indel) mutational signatures and to fit COSMIC SBS and indel signatures. We assessed associations between these signatures and clinical characteristics of disease, in addition to recurrence-free (RFS) and overall survival (OS). Five SBS and two indel signatures were extracted. The SBS13-like signature had higher relative contributions in the HER2-enriched subtype. Patients with higher than median contribution tended to have better RFS after adjustment for other prognostic factors (HR = 0.29; 95% CI: 0.08-1.06). An unsupervised clustering algorithm based on absolute contribution revealed three clusters of fitted COSMIC SBS signatures, but cluster membership was not associated with clinical variables or survival outcomes. The results of this exploratory study reveal various SBS and indel signatures may be associated with clinical features of disease and prognosis. Future studies with larger samples are required to better understand the mechanistic underpinnings of disease progression and treatment response in EoBC.

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

The Canadian Breast Cancer Symposium 2023 Meeting Report.

On 15-16 June 2023, healthcare professionals and breast cancer patients and advocates from across Canada met in Toronto, Ontario, for the 2023 Canadian Breast Cancer Symposium (CBSC.). The CBSC. is a national, multidisciplinary event that occurs every 2 years with the goal of developing a personalized approach to the management of breast cancer in Canada. Experts provided state-of-the-art information to help optimally manage breast cancer patients, including etiology, prevention, diagnosis, experimental biology, and therapy of breast cancer and premalignant breast disease. The symposium also had the objectives of increasing communication and collaboration among breast cancer healthcare providers nationwide and providing a comprehensive and real-life review of the many facets of breast cancer. The sessions covered the patient voice, the top breast cancer papers from different disciplines in 2022, artificial intelligence in breast cancer, systemic therapy updates, the management of central nervous system metastases, multidisciplinary management of ductal carcinoma in situ, special populations, optimization-based individual prognostic factors, toxicity management of novel therapeutics, survivorship, and updates in surgical oncology. The key takeaways of these sessions have been summarized in this conference report.

Adjuvant Ovarian Function Suppression in Premenopausal Hormone Receptor-Positive Breast Cancer.

Importance: Few oncology studies have assessed the effectiveness of adjuvant ovarian function suppression (OFS) in observational settings for premenopausal hormone receptor-positive breast cancer. Target trial emulation is increasingly used for estimating treatment outcomes in observational cohorts. Objectives: To describe hormone therapy and OFS treatment patterns (aim 1), examine the association between adding OFS to tamoxifen (TAM) or aromatase inhibitor (AI) and survival (aim 2), and examine the association between duration of hormone treatment (TAM or AI) plus OFS (H-OFS) and survival (aim 3). Design, Setting, and Participants: This population-based cohort study included all premenopausal, early-stage breast cancer diagnoses between 2010 and 2020 in Alberta, Canada. Target trial emulation was conducted. Eligibility criteria were directly modeled after the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT). Participants were followed up for a maximum of 5 years. Data were analyzed from July 2022 through March 2023. Exposures: For aim 2, exposures were receiving the following baseline treatments for 2 years: AI + OFS (AI-OFS), TAM + OFS (T-OFS), and TAM alone. For aim 3, exposures were a 2-year or greater and a less than 2-year duration of H-OFS. Main Outcomes and Measures: Recurrence-free survival was the primary outcome of interest. Marginal structural Cox models with inverse probability treatment and censoring weights were used to estimate hazard ratios (HRs), adjusted for baseline and time-varying confounding variables. Results: Among 3434 female patients with premenopausal, early-stage breast cancer diagnoses (median [IQR] age, 45 [40-48] years), 2647 individuals satisfied SOFT and TEXT eligibility criteria. There were 2260 patients who initiated TAM, 232 patients who initiated T-OFS, and 155 patients who initiated AI-OFS; 192 patients received H-OFS for 2 or more years, and 195 patients received H-OFS for less than 2 years. The 5-year recurrence risks were not significantly lower in AI-OFS vs TAM (HR, 0.76; 95% CI, 0.38-1.33) or T-OFS vs TAM (HR, 0.87; 95% CI, 0.50-1.45) groups. Patients receiving H-OFS for 2 or more years had significantly better 5-year recurrence-free survival compared with those receiving H-OFS for less than 2 years (HR, 0.69; 95% CI, 0.54-0.90). Conclusions and Relevance: This study found no significant reductions in recurrence risk for AI-OFS and T-OFS compared with TAM alone. H-OFS duration for at least 2 years was associated with significantly improved recurrence-free survival.

Breast Cancer After Reduction Mammoplasty: A Population-Based Analysis of Incidence, Treatment and Screening Patterns.

Background: The risk of breast cancer may be decreased in women who undergo reduction mammoplasty. The purpose of this study was to describe the incidence and treatment of breast cancer after reduction mammoplasty and to better understand the use of breast cancer screening modalities in these patients. Methods: This population-based retrospective analysis utilized the Discharge Abstract Database held by the Canadian Institute for Health Information and the National Ambulatory Care Reporting System to identify all women aged 20 years or older who underwent reduction mammoplasty in Alberta, Canada. The incidence and treatment of breast cancer were compared among patients who underwent reduction mammoplasty and age-sex-matched controls. Imaging utilization, including the use of mammography, ultrasound, and breast biopsy, was also compared. Results: Between 2003 and 2007, 8021 patients over 20 years old underwent reduction mammoplasty in Alberta. Patients were followed for an average of 12.6 years. Eighty-nine (1.1%) patients who underwent reduction mammoplasty developed breast cancer after surgery, compared to 453 (1.9%) controls (P < 0.0001). Among patients diagnosed with breast cancer, there was no difference in patient and tumor characteristics. Women who underwent reduction mammoplasty were more likely to undergo mastectomy for cancer (41.6% vs 1.5%; P < 0.0001) and were more likely to undergo mammography (66.7% vs 58.7%; P < 0.0001), ultrasound (29.2% vs 26.2%; P < 0.0001) and biopsy for benign disease (7.2% vs 6%, P < 0.0001) compared to controls. Conclusions: Despite an increased frequency of breast cancer screening, the incidence of breast cancer is lower after reduction mammoplasty compared with women who did not undergo breast reduction. After a diagnosis of breast cancer, surgical treatment patterns differ between groups, whereby mastectomy is more common after reduction mammoplasty.

Investigating Factors Associated with Postmastectomy Emergency Department Visits: A Population-Based Analysis.

BACKGROUND: In 2016, a multi-pronged pathway was implemented across 13 hospitals to improve the mastectomy perioperative care experience with one objective being to safely allow same day surgery mastectomy. While the pathway successfully increased same day mastectomy rates from 1.7 to 73.0%, the rate of postoperative emergency department (ED) visits remained high at > 20%, despite focused interventions to enhance perioperative support. AIM: To investigate potential factors associated with high postoperative ED visits following mastectomies in Alberta, Canada. METHODS: Data was collected using the Discharge Abstract Database and the National Ambulatory Care Reporting System database. Eligible patients included all women over 18 years old who underwent a mastectomy province-wide between 2004 and 2020. Patient demographics were collected. Primary outcome of interest was ED visit within 30 days of mastectomy. Univariate and multivariable analyses were performed to identify independent predictors for post-operative ED visits. RESULTS: A total of 19,974 patients had mastectomy during the study period, of which 4590 (23%) had an ED visit within 30 days of surgery. Independent factors associated with ED visits were increasing age, overnight stay mastectomy, reconstruction, certain comorbidities, and living rurally. CONCLUSIONS: Post-operative ED visits remain high despite initiating a province-wide surgical pathway in 2016 which emphasizes patient education and improved perioperative care and supports. Currently, the majority of ED visits are manageable in non-emergent settings. Patient populations at higher risk for ED visits groups may benefit from additional targeted support and resources to reduce unplanned ED visits.

Improvement in patient-reported pain among patients with metastatic cancer and its association with opioid prescribing.

PURPOSE: Opioids are a mainstay of cancer pain management; however, patients with metastatic cancer are often excluded from studies, leading to a lack of evidence on whether increased prescribing (dosage and/or duration) results in improved outcomes for this population. This study aimed to investigate whether increased opioid prescribing is associated with an improvement in patient-reported pain among patients with metastatic cancer. PATIENTS AND METHODS: A retrospective cohort of all adult patients diagnosed with stage IV cancers, who completed at least two patient-reported outcomes (PROs) within 30 days of each other, was identified from administrative data. Opioid prescriptions were categorized by dosage level and number of prescription days. Multivariable logistic regression was used to investigate the association between opioid prescribing and clinically important improvement in pain score (≥ 1 point change on the Edmonton Symptom Assessment System). RESULTS: A total of 2169 patients were included, 770 (35.5%) of whom had active opioid prescription between PROs, with an average daily dosage of 86.1 mg of oral morphine equivalent. Active prescription was associated with improvement in pain (OR = 2.17, P < 0.001). However, among patients with active prescription, neither dosage nor number of prescription days was significantly associated with pain improvement. CONCLUSION: Opioid prescription is important for treating cancer-related pain; however, increased dosage or duration may not be leading to greater improvements in pain. Patients with metastatic cancer who are receiving increased opioid prescribing may have difficult-to-treat pain and may benefit from multidisciplinary pain management strategies to supplement opioid prescription and improve outcomes.

Incorporating Lymphovenous Anastomosis in Clinically Node-Positive Women Receiving Neoadjuvant Chemotherapy: A Shared Decision-Making Model and Nuanced Approached to the Axilla.

INTRODUCTION: Lymphedema remains a risk for 13-34% of breast cancer patients who require an axillary dissection (ALND) and radiation. Immediate lymphovenous anastomosis (LVA) may mitigate lymphedema by up to 30% by restoring the physiologic lymphatic drainage immediately after ALND. Currently, completion of ALND (cALND) versus radiation after neoadjuvant therapy (NAC) is being addressed by the Alliance A11202 trial, leaving a paucity of data to guide practice. Our study describes the implementation process of LVA into clinical practice after NAC for node-positive breast cancer in the current clinical context. METHODS: We reviewed a prospective database of LVA in node-positive patients (cT1-4,Nany) who received NAC followed by axillary surgery ± immediate LVA from October 2021 to 2022. The evolution of the surgical approach is described. Specifically, patients who downstaged to clinically negative nodes post-NAC were offered targeted SLNB with dual-tracer and intraoperative frozen section (FS). Patients were reminded that the standard of care for any node positive is cALND. Immediate cALND with LVA was performed for grossly positive nodes or all positive SLNs; cALND was omitted for those with negative SLNs. For a microscopic disease on a frozen section, a shared decision was made pre-operatively, given each patient's differing valuations of the benefit and risks of cALND ± LVA versus no cALND with planned regional radiation postoperatively. LVA was offered as an option as part of our institutional evaluation of the procedure. RESULTS: A total of 15 patients were included; the mean age was 49.9 (range 32-75) with stage IIA to IIIB breast cancer. Of these, 6 (40%) were triple negative, 5 (33.3%) HER-2 positive, and 4 (26.7%) ER/PR+ HER-2 negative. There were 13 women (86.7%) who had persistent axillary adenopathy based on clinical and/or ultrasound assessment, with 8 patients proceeding directly to ALND with LVA. Among these patients, 3 (37.5%) had pathologic nodal disease, and 5 (62.5%) were node negative, confirming the limitations of pre-operative imaging. As a result, the subsequent 7 (46.7%) underwent targeted SLNB with FS, with 3 patients (42.9%) avoiding an ALND as a result of a negative FS. A total of 4 patients (57.1%) had 1 or more positive lymph nodes on FS: 3 proceeded with a cALND and LVA, and 1 patient (14.2%) opted for no cALND based on a pre-operative discussion and received adjuvant radiation and chemotherapy. Of the 11 patients who underwent ALND and LVA, 1 patient (9.1%) developed lymphedema at 6.9 months following their surgery. The accuracy, sensitivity, and specificity of pre-operative US were 46.7%, 85.7%, and 12.5% and intraoperative FS were 88.0%, 72.7%, and 100%, respectively. CONCLUSIONS: As adjuvant nodal radiation and systemic therapy continue to improve, the benefit of a cALND in patients with the limited residual disease remains unclear as we await the outcomes from clinical trials. In the era of clinical uncertainty, we propose a nuanced approach to the axilla by utilizing a shared decision model with patients, incorporating targeted SLNB with FS and completion node dissection when required and desired by the patient, coupled with LVA in a simple stepwise treatment pathway.

The Association between Early-Onset Diagnosis and Clinical Outcomes in Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis.

Early-onset diagnosis, defined by age <40 years, has historically been associated with inferior outcomes in breast cancer. Recent evidence suggests that this association is modified by molecular subtype. We performed a systematic review and meta-analysis of the literature to synthesize evidence on the association between early-onset diagnosis and clinical outcomes in triple-negative breast cancer (TNBC). Studies comparing the risk of clinical outcomes in non-metastatic TNBC between early-onset patients and later-onset patients (≥40 years) were queried in Medline and EMBASE from inception to February 2023. Separate meta-analyses were performed for breast cancer specific survival (BCSS), overall survival (OS), and disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and pathological complete response (pCR). In total, 7581 unique records were identified, and 36 studies satisfied inclusion criteria. The pooled risk of any recurrence was significantly greater in early-onset patients compared to later-onset patients. Better BCSS and OS were observed in early-onset patients relative to later-onset patients aged >60 years. The pooled odds of achieving pCR were significantly higher in early-onset patients. Future studies should evaluate the role of locoregional management of TNBC and the implementation of novel therapies such as PARP inhibitors in real-world settings, and whether they improve outcomes.

Patient and disease characteristics, treatment practices and oncologic outcomes among patients with colorectal cancer: a population-based analysis.

BACKGROUND: The incidence of colorectal cancer (CRC) is increasing among young adults. We sought to report on patient and disease characteristics, treatment practice patterns and outcomes in this population. METHODS: We conducted a retrospective cohort study using administrative health data from the Alberta Cancer Registry (2004-2015), including demographic and tumour characteristics, and treatment received. Outcome measures included overall and cancer-specific deaths. We used Cox regression and Kaplan-Meier curves to assess for factors associated with survival. RESULTS: We included 18 070 patients with CRC (n = 1583 [8.8%] < 50 yr, n = 16 487 [91.2 %] ≥ 50 yr). Younger patients were more likely to present with locally advanced disease (21.0% v. 18.0%, p < 0.0001), stage III (16.4 % v. 14.6%, p < 0.0001) or metastatic (16.7% v. 13.8%, p < 0.0001) involvement. Younger patients were more likely to receive surgery (87.2% v. 80.9%, p < 0.0001), chemotherapy (59.6% v. 34.1%, p < 0.0001) or radiation therapy (49.5% v. 37.2%, p < 0.001). At 5 years, overall and cancer-specific survival was better among younger patients than older patients (30.6% v. 51.5% overall deaths, 27.5% v. 38.4% cancer-specific deaths, p < 0.0001). CONCLUSION: Despite higher stage and higher grade disease, young patients with CRC had more favourable oncologic outcomes than stage-matched older patients, which may be related to younger patients receiving more aggressive treatment. Further investigation should focus on optimal treatment patterns for young patients with CRC.

Outcomes and Healthcare Utilization Among New Persistent Opioid Users and Nonopioid Users After Curative-intent Surgery for Cancer.

OBJECTIVE: The aim of the study was to compare the health outcomes and resource use of cancer patients who were new persistent opioid users with those who were not, after undergoing curative intent surgery for cancer. BACKGROUND: Little is known about long-term health outcomes (overdose, mortality) and resource utilization of new persistent opioid users among cancer patients undergoing curative-intent surgery. METHODS: This retrospective cohort study included all adults with a diagnosis of solid cancers who underwent curative-intent surgery during the study period (2011-2015) in Alberta, Canada and were opioid-naïve before surgery, with a follow-up period until December 31, 2019. The key exposure, "new persistent opioid user," was defined as a patient who was opioid-naive before surgery and subsequently filled at least 1 opioid prescription between 60 and 180 days after surgery. The primary outcome was opioid overdose that occurred within 3 years of surgery. All-cause death, noncancer caused death, and department visit (yes vs. no), and hospitalization (yes vs. no) in the follow-up periods were also included as outcomes. RESULTS: In total, 19,219 patients underwent curative intent surgery with a median follow-up of 47 months, of whom 1530 (8.0%) were identified as postoperative new persistent opioid users. In total, 101 (0.5%) patients experienced opioid overdose within 3 years of surgery. Compared with nonopioid users, new persistent opioid users experienced a higher rate of opioid overdose (OR = 2.37, 95% CI: 1.44-3.9) within 3 years of surgery. New persistent opioid use was also associated with a greater likelihood of being hospitalized (OR = 2.03, 95% CI: 1.76-2.33) and visiting an emergency room (OR = 1.83, 95% CI: 1.62-2.06) in the first year after surgery, and a higher overall (HR = 1.28, 95% CI: 1.1-1.49) and noncancer caused mortality (HR = 1.33, 95% CI: 1.12-1.58), when compared with nonopioid users. CONCLUSION: Postoperative new persistent opioid use among cancer patients undergoing curative-intent surgery is associated with subsequent opioid overdose, worse survival, and more health resource utilization.

A New Method of Identifying Pathologic Complete Response After Neoadjuvant Chemotherapy for Breast Cancer Patients Using a Population-Based Electronic Medical Record System.

BACKGROUND: Accurate identification of pathologic complete response (pCR) from population-based electronic narrative data in a timely and cost-efficient manner is critical. This study aimed to derive and validate a set of natural language processing (NLP)-based machine-learning algorithms to capture pCR from surgical pathology reports of breast cancer patients who underwent neoadjuvant chemotherapy (NAC). METHODS: This retrospective cohort study included all invasive breast cancer patients who underwent NAC and subsequent curative-intent surgery during their admission at all four tertiary acute care hospitals in Calgary, Alberta, Canada, between 1 January 2010 and 31 December 2017. Surgical pathology reports were extracted and processed with NLP. Decision tree classifiers were constructed and validated against chart review results. Machine-learning algorithms were evaluated with a performance matrix including sensitivity, specificity, positive predictive value (PPV), negative predictive value [NPV], accuracy, area under the receiver operating characteristic curve [AUC], and F1 score. RESULTS: The study included 351 female patients. Of these patients, 102 (29%) achieved pCR after NAC. The high-sensitivity model achieved a sensitivity of 90.5% (95% confidence interval [CI], 69.6-98.9%), a PPV of 76% (95% CI, 59.6-87.2), an accuracy of 88.6% (95% CI, 78.7-94.9%), an AUC of 0.891 (95% CI, 0.795-0.987), and an F1 score of 82.61. The high-PPV algorithm reached a sensitivity of 85.7% (95% CI, 63.7-97%), a PPV of 81.8% (95% CI, 63.4-92.1%), an accuracy of 90% (95% CI, 80.5-95.9%), an AUC of 0.888 (95% CI, 0.790-0.985), and an F1 score of 83.72. The high-F1 score algorithm obtained a performance equivalent to that of the high-PPV algorithm. CONCLUSION: The developed algorithms demonstrated excellent accuracy in identifying pCR from surgical pathology reports of breast cancer patients who received NAC treatment.

Locoregional Management of Breast Cancer: A Chronological Review.

Locoregional management of breast cancer is founded on evidence generated over a vast time period, much longer than the career span of many practicing physicians. Oncologists rely on specific patient and tumour characteristics to recommend modern-day treatments. However, some of this information may not have been available during prior periods in which the evidence was generated. For example, the comprehensive Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analyses published in the 2000s typically included older trials accruing patients between the 1960s and 1980s. This raises some uncertainty about whether conclusions from studies conducted in prior eras are as relevant or applicable to modern-day patients and treatments. Reviewing the chronological order and details of the evidence can be beneficial to understanding these nuances. This review discusses the evolution of locoregional management through some key clinical trials. We aim to highlight the time period in which the evidence was generated and emphasize the 10-year outcomes for the comparability of results. Evidence supporting surgical management of the breast and axilla, as well as details of radiotherapy are discussed briefly for all stages of breast cancer.

Predictors of Sentinel Lymph Node Metastasis in Patients with Thin Melanoma: An International Multi-institutional Collaboration.

BACKGROUND: Consideration of sentinel lymph node biopsy (SLNB) is recommended for patients with T1b melanomas and T1a melanomas with high-risk features; however, the proportion of patients with actionable results is low. We aimed to identify factors predicting SLNB positivity in T1 melanomas by examining a multi-institutional international population. METHODS: Data were extracted on patients with T1 cutaneous melanoma who underwent SLNB between 2005 and 2018 at five tertiary centers in Europe and Canada. Univariable and multivariable logistic regression analyses were performed to identify predictors of SLNB positivity. RESULTS: Overall, 676 patients were analyzed. Most patients had one or more high-risk features: Breslow thickness 0.8-1 mm in 78.1% of patients, ulceration in 8.3%, mitotic rate > 1/mm2 in 42.5%, Clark's level ≥ 4 in 34.3%, lymphovascular invasion in 1.4%, nodular histology in 2.9%, and absence of tumor-infiltrating lymphocytes in 14.4%. Fifty-three patients (7.8%) had a positive SLNB. Breslow thickness and mitotic rate independently predicted SLNB positivity. The odds of positive SLNB increased by 50% for each 0.1 mm increase in thickness past 0.7 mm (95% confidence interval [CI] 1.05-2.13) and by 22% for each mitosis per mm2 (95% CI 1.06-1.41). Patients who had one excised node (vs. two or more) were three times less likely to have a positive SLNB (3.6% vs. 9.6%; odds ratio 2.9 [1.3-7.7]). CONCLUSIONS: Our international multi-institutional data confirm that Breslow thickness and mitotic rate independently predict SLNB positivity in patients with T1 melanoma. Even within this highly selected population, the number needed to diagnose is 13:1 (7.8%), indicating that more work is required to identify additional predictors of sentinel node positivity.

Validated algorithms for identifying timing of second event of oropharyngeal squamous cell carcinoma using real-world data.

BACKGROUND: Understanding occurrence and timing of second events (recurrence and second primary cancer) is essential for cancer specific survival analysis. However, this information is not readily available in administrative data. METHODS: Alberta Cancer Registry, physician claims, and other administrative data were used. Timing of second event was estimated based on our developed algorithm. For validation, the difference, in days between the algorithm estimated and the chart-reviewed timing of second event. Further, the result of Cox-regression modeling cancer-free survival was compared to chart review data. RESULTS: Majority (74.3%) of the patients had a difference between the chart-reviewed and algorithm-estimated timing of second event falling within the 0-60 days window. Kaplan-Meier curves generated from the estimated data and chart review data were comparable with a 5-year second-event-free survival rate of 75.4% versus 72.5%. CONCLUSION: The algorithm provided an estimated timing of second event similar to that of the chart review.

New method for determining breast cancer recurrence-free survival using routinely collected real-world health data.

BACKGROUND: In cancer survival analyses using population-based data, researchers face the challenge of ascertaining the timing of recurrence. We previously developed algorithms to identify recurrence of breast cancer. This is a follow-up study to detect the timing of recurrence. METHODS: Health events that signified recurrence and timing were obtained from routinely collected administrative data. The timing of recurrence was estimated by finding the timing of key indicator events using three different algorithms, respectively. For validation, we compared algorithm-estimated timing of recurrence with that obtained from chart-reviewed data. We further compared the results of cox regressions models (modeling recurrence-free survival) based on the algorithms versus chart review. RESULTS: In total, 598 breast cancer patients were included. 121 (20.2%) had recurrence after a median follow-up of 4 years. Based on the high accuracy algorithm for identifying the presence of recurrence (with 94.2% sensitivity and 79.2% positive predictive value), the majority (64.5%) of the algorithm-estimated recurrence dates fell within 3 months of the corresponding chart review determined recurrence dates. The algorithm estimated and chart-reviewed data generated Kaplan-Meier (K-M) curves and Cox regression results for recurrence-free survival (hazard ratios and P-values) were very similar. CONCLUSION: The proposed algorithms for identifying the timing of breast cancer recurrence achieved similar results to the chart review data and were potentially useful in survival analysis.

Developing a Prediction Model for Pathologic Complete Response Following Neoadjuvant Chemotherapy in Breast Cancer: A Comparison of Model Building Approaches.

PURPOSE: The optimal characteristics among patients with breast cancer to recommend neoadjuvant chemotherapy is an active area of clinical research. We developed and compared several approaches to developing prediction models for pathologic complete response (pCR) among patients with breast cancer in Alberta. METHODS: The study included all patients with breast cancer who received neoadjuvant chemotherapy in Alberta between 2012 and 2014 identified from the Alberta Cancer Registry. Patient, tumor, and treatment data were obtained through primary chart review. pCR was defined as no residual invasive tumor at surgical excision in breast or axilla. Two types of prediction models for pCR were built: (1) expert model: variables selected on the basis of oncologists' opinions and (2) data-driven model: variables selected by trained machine. These model types were fit using logistic regression (LR), random forests (RF), and gradient-boosted trees (GBT). We compared the models using area under the receiver operating characteristic curve and integrated calibration index, and internally validated using bootstrap resampling. RESULTS: A total of 363 cases were included in the analyses, of which 86 experienced pCR. The RF and GBT fits yielded higher optimism-corrected area under the receiver operating characteristic curves compared with LR for the expert (RF: 0.70; GBT: 0.69; LR: 0.65) and data-driven models (RF: 0.71; GBT: 0.68; LR: 0.64). The LR fit yielded the lowest integrated calibration indices for the expert (LR: 0.037; GBT: 0.05; RF: 0.10) and data-driven models (LR: 0.026; GBT: 0.06; RF: 0.099). CONCLUSION: Our models demonstrated predictive ability for pCR using routinely collected clinical and demographic variables. We show that machine learning fit methods can be used to optimize models for pCR prediction. We also show that additional variables beyond clinical expertise do not considerably improve predictive ability and may not be of value on the basis of the burden of data collection.

Surgeon and Patient Reports of Fertility Preservation Referral and Uptake in a Prospective, Pan-Canadian Study of Young Women with Breast Cancer.

BACKGROUND: Prompt referral by their surgeon enables fertility preservation (FP) by young women with breast cancer (YWBC) without treatment delay. Following a FP knowledge intervention, we evaluated surgeon and patient reports of fertility discussion, FP referral offer and uptake, and FP choices and reasons for declining FP among patients enrolled in the Reducing Breast Cancer in Young Women, prospective pan-Canadian study. METHODS: Between September 2015 and December 2020, 1271 patients were enrolled at 31 sites. For each patient, surgeons were sent a questionnaire inquiring whether: (1) fertility discussion was initiated by the surgical team; (2) FP referral was offered; (3) referral was accepted; a reason was requested for any "no" response. Patients were surveyed about prediagnosis fertility plans and postdiagnosis oncofertility management. RESULTS: Surgeon questionnaires were completed for 1068 (84%) cases. Fertility was discussed with 828 (84%) and FP consultation offered to 461 (47%) of the 990 YWBC with invasive disease. Among the 906 responding YWBC, referral was offered to 220 (82%) of the 283 (33%) with invasive disease who stated that they had definitely/probably not completed childbearing prediagnosis. Of these, 133 (47%) underwent FP. The two most common reasons for not choosing FP were cost and unwillingness to delay treatment. CONCLUSIONS: Although the rates of surgeon fertility discussion and FP referral was higher than most reports, likely due to our previous intervention, further improvement is desirable. FP should be offered to all YWBC at diagnosis, regardless of perceived childbearing intent. Cost remains an important barrier to FP uptake.