Validation of large language models for detecting pathologic complete response in breast cancer using population-based pathology reports.

AIMS: The primary goal of this study is to evaluate the capabilities of Large Language Models (LLMs) in understanding and processing complex medical documentation. We chose to focus on the identification of pathologic complete response (pCR) in narrative pathology reports. This approach aims to contribute to the advancement of comprehensive reporting, health research, and public health surveillance, thereby enhancing patient care and breast cancer management strategies. METHODS: The study utilized two analytical pipelines, developed with open-source LLMs within the healthcare system's computing environment. First, we extracted embeddings from pathology reports using 15 different transformer-based models and then employed logistic regression on these embeddings to classify the presence or absence of pCR. Secondly, we fine-tuned the Generative Pre-trained Transformer-2 (GPT-2) model by attaching a simple feed-forward neural network (FFNN) layer to improve the detection performance of pCR from pathology reports. RESULTS: In a cohort of 351 female breast cancer patients who underwent neoadjuvant chemotherapy (NAC) and subsequent surgery between 2010 and 2017 in Calgary, the optimized method displayed a sensitivity of 95.3% (95%CI: 84.0-100.0%), a positive predictive value of 90.9% (95%CI: 76.5-100.0%), and an F1 score of 93.0% (95%CI: 83.7-100.0%). The results, achieved through diverse LLM integration, surpassed traditional machine learning models, underscoring the potential of LLMs in clinical pathology information extraction. CONCLUSIONS: The study successfully demonstrates the efficacy of LLMs in interpreting and processing digital pathology data, particularly for determining pCR in breast cancer patients post-NAC. The superior performance of LLM-based pipelines over traditional models highlights their significant potential in extracting and analyzing key clinical data from narrative reports. While promising, these findings highlight the need for future external validation to confirm the reliability and broader applicability of these methods.

Use and impact of virtual resources for peer support by young adults living with cancer: A systematic review.

Background: Young adults (YA) with cancer often have unmet psychosocial needs. The impact of peer support delivered in an online format to fulfil these needs in the populations of YA with cancer has not been thoroughly examined. Methods: We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, and Medline databases. We included articles about online peer support interventions for YA cancer survivors between the ages of 18 to 40 years old. Results: Our literature search yielded n = 2,773 articles and we obtained consensus on 12 articles for inclusion. We qualitatively synthesized these articles using data abstraction based on the Template for Intervention and Replication (TIDierR) checklist. Overall, six studies demonstrated correlation between online peer support and improved wellbeing of participants. Thus, online peer support may be useful for young cancer patients. Conclusion: This systematic review summarizes the current state of knowledge regarding the availability and evaluation of online YA peer support programs and reveals the need for further research in this field.

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.

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.

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.

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.

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.

Associations Between Physician Prescribing Behavior and Persistent Postoperative Opioid Use Among Cancer Patients Undergoing Curative-intent Surgery: A Population-based Cohort Study.

OBJECTIVE: This study aimed to evaluate the association between prescribers' opioid prescribing history and persistent postoperative opioid use in cancer patients undergoing curative-intent surgery. BACKGROUND: Study has shown that patients may be over-prescribed analgesics after surgery. However, whether and how the prescriber's opioid prescribing behavior impacts persistent opioid use is unclear. METHODS: All adults with a diagnosis of solid cancers who underwent surgery during the study period (2009-2015) in Alberta, Canada and were opioid-naïve were included. The key exposure was the historical opioid-prescribing pattern of a patient's most responsible prescriber. The primary outcome was "new persistent postoperative opioid user," was defined as a patient who was opioid-naïve before surgery and subsequently filled at least 1 opioid prescription between 60 and 180 days after surgery. RESULTS: We identified 24,500 patients. Of these, 2106 (8.6%) patients became a new persistent opioid user after surgery. Multivariate analysis demonstrated that patients with most responsible prescribers that historically prescribed higher daily doses of opioids (≥50 vs <50 mg oral morphine equivalent) had an increased risk of new persistent opioid use after surgery (odds ratio = 2.41, P < 0.0001). In addition to the provider's prescribing pattern, other factors including younger age, comorbidities, presurgical opioid use, chemotherapy, type of tumor/surgical procedure were also found to be independently associated with new persistent postoperative opioid use. CONCLUSIONS: Our results suggest that prescriber with a history of prescribing a higher opioid dose is an important predictor of persistent postoperative opioid use among cancer patients undergoing curative-intent surgery.

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.

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.

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.

Geospatial access predicts cancer stage at presentation and outcomes for patients with breast cancer in southwest Nigeria: A population-based study.

BACKGROUND: The majority of women in Nigeria present with advanced-stage breast cancer. To address the role of geospatial access, we constructed a geographic information-system-based model to evaluate the relationship between modeled travel time, stage at presentation, and overall survival among patients with breast cancer in Nigeria. METHODS: Consecutive patients were identified from a single-institution, prospective breast cancer database (May 2009-January 2019). Patients were geographically located, and travel time to the hospital was generated using a cost-distance model that utilized open-source data. The relationships between travel time, stage at presentation, and overall survival were evaluated with logistic regression and survival analyses. Models were adjusted for age, level of education, and socioeconomic status. RESULTS: From 635 patients, 609 were successfully geographically located. The median age of the cohort was 49 years (interquartile range [IQR], 40-58 years); 84% presented with ≥stage III disease. Overall, 46.5% underwent surgery; 70.8% received systemic chemotherapy. The median estimated travel time for the cohort was 45 minutes (IQR, 7.9-79.3 minutes). Patients in the highest travel-time quintile had a 2.8-fold increase in the odds of presenting with stage III or IV disease relative to patients in the lowest travel-time quintile (P = .006). Travel time ≥30 minutes was associated with an increased risk of death (HR, 1.65; P = .004). CONCLUSIONS: Geospatial access to a tertiary care facility is independently associated with stage at presentation and overall survival among patients with breast cancer in Nigeria. Addressing disparities in access will be essential to ensure the development of an equitable health policy.

Examining the etiology of early-onset breast cancer in the Canadian Partnership for Tomorrow's Health (CanPath).

PURPOSE: Breast cancer incidence among younger women (under age 50) has increased over the past 25 years, yet little is known about the etiology among this age group. The objective of this study was to investigate relationships between modifiable and non-modifiable risk factors and early-onset breast cancer among three prospective Canadian cohorts. METHODS: A matched case-control study was conducted using data from Alberta's Tomorrow Project, BC Generations Project, and the Ontario Health Study. Participants diagnosed with breast cancer before age 50 were identified through provincial registries and matched to three control participants of similar age and follow-up. Conditional logistic regression was used to examine the association between factors and risk of early-onset breast cancer. RESULTS: In total, 609 cases and 1,827 controls were included. A body mass index ≥ 30 kg/m2 was associated with a lower risk of early-onset breast cancer (OR 0.65; 95% CI 0.47-0.90), while a waist circumference ≥ 88 cm was associated with an increased risk (OR 1.58; 95% CI 1.18-2.11). A reduced risk was found for women with ≥ 2 pregnancies (OR 0.76; 95% CI 0.59-0.99) and a first-degree family history of breast cancer was associated with an increased risk (OR 1.95; 95% CI 1.47-2.57). CONCLUSIONS: In this study, measures of adiposity, pregnancy history, and familial history of breast cancer are important risk factors for early-onset breast cancer. Evidence was insufficient to conclude if smoking, alcohol intake, fruit and vegetable consumption, and physical activity are meaningful risk factors. The results of this study could inform targeted primary and secondary prevention for early-onset breast cancer.

Breast Biopsy During Post-treatment Surveillance of Screen-Detected Breast Cancer Patients Yields High Rates of Benign Findings.

BACKGROUND: The incidence of breast biopsy following treatment for breast cancer is not well-characterized. We sought to determine the frequency and outcomes of breast biopsy and the need for subsequent surgery in patients treated with breast-conserving surgery (BCS). METHODS: Using a prospective database, we identified patients in Alberta, Canada, treated with BCS for screen-detected breast cancer or ductal carcinoma in situ (DCIS) from 2010 to 2014. Post-treatment breast procedures were identified from physician claims data. Multivariable analysis was performed to identify factors associated with biopsy. RESULTS: We included 2065 patients with a median of 6.4 years of follow-up; most had DCIS (n = 426, 20.6%) or stage I disease (n = 1385, 67.1%). Post-treatment core biopsy was performed in 389 (18.8%, 95% confidence interval [CI] 17.2-20.6%) patients, and excisional biopsy was performed in 19 (0.9%, 95% CI 0.6-1.4%) patients. The per-patient benign-to-malignant biopsy ratio was 3.2 to 1, and the overall malignancy rate was 6.1% (95% CI 5.1-7.2%). Younger age, proximity to a cancer center, positive margins, and the use of magnetic resonance imaging were associated with biopsy (p < 0.05). Additional surgery was performed in 150 (7.3%, 95% CI 6.2-8.5%) patients; 93 (4.5%, 95% CI 3.6-5.4%) patients underwent mastectomy. Surgery was performed for local recurrence/ipsilateral cancer in 62 (3.0%) patients, contralateral breast cancer in 60 (2.9%) patients, bilateral breast cancer in 3 (0.1%) patients, and benign indications/prophylaxis in 25 (1.2%) patients. CONCLUSIONS: One in five patients required breast biopsy during post-treatment surveillance following BCS and most revealed benign findings. Rates of additional surgery, especially subsequent mastectomy due to ipsilateral or contralateral malignancy, were low. Patients can be reassured of these findings during pre-treatment counseling and post-treatment surveillance.

Effect of a Knowledge-Translation Intervention on Breast Surgeons' Oncofertility Attitudes and Practices.

BACKGROUND: The breast surgeon, generally the first oncology specialist consulted, is ideally suited to offer fertility preservation (FP) referral to young women with breast cancer (YWBC). In the authors' 2015 survey of 84 surgeons participating in the pan-Canadian RUBY study of YWBC, oncofertility knowledge and rates of FP referral were suboptimal. The authors designed an oncofertility knowledge-translation intervention for surgeons. METHODS: A customized oncofertility toolbox was created including a seminar/webinar, an option grid, a three-question FP survey sent upon registration of each RUBY patient, and a management checklist. In 2018, the 28 site lead surgeons were re-invited to participate in a follow-up telephone interview, and 85 non-site lead surgeons were invited to complete a follow-up online questionnaire. RESULTS: A total of 27 site lead surgeons consented to be re-interviewed. After the intervention, 85% indicated that they "routinely" initiated a fertility discussion compared with 54% at baseline (p < 0.005), with 56% stating that the toolbox had been helpful for making positive changes in their practice regarding oncofertility, and 44% stating that they found it easier to initiate a fertility discussion. Among the 55 non-site lead surgeons who completed the questionnaire, a significant improvement in oncofertility knowledge was found. The percentage reporting "rarely" or "never" discussing FP options decreased from 41 to 14% (p < 0.005), and 84% stated that they referred patients who had not completed their families and were at risk for infertility to FP consultation compared with 32% before the intervention (p < 0.001). CONCLUSIONS: A multi-pronged but simple knowledge-translation intervention improved the attitudes, knowledge, and FP practice of Canadian breast surgeons.

Mutational landscape differences between young-onset and older-onset breast cancer patients.

BACKGROUND: The incidence of breast cancer among young women (aged ≤40 years) has increased in North America and Europe. Fewer than 10% of cases among young women are attributable to inherited BRCA1 or BRCA2 mutations, suggesting an important role for somatic mutations. This study investigated genomic differences between young- and older-onset breast tumours. METHODS: In this study we characterized the mutational landscape of 89 young-onset breast tumours (≤40 years) and examined differences with 949 older-onset tumours (> 40 years) using data from The Cancer Genome Atlas. We examined mutated genes, mutational load, and types of mutations. We used complementary R packages "deconstructSigs" and "SomaticSignatures" to extract mutational signatures. A recursively partitioned mixture model was used to identify whether combinations of mutational signatures were related to age of onset. RESULTS: Older patients had a higher proportion of mutations in PIK3CA, CDH1, and MAP3K1 genes, while young-onset patients had a higher proportion of mutations in GATA3 and CTNNB1. Mutational load was lower for young-onset tumours, and a higher proportion of these mutations were C > A mutations, but a lower proportion were C > T mutations compared to older-onset tumours. The most common mutational signatures identified in both age groups were signatures 1 and 3 from the COSMIC database. Signatures resembling COSMIC signatures 2 and 13 were observed among both age groups. We identified a class of tumours with a unique combination of signatures that may be associated with young age of onset. CONCLUSIONS: The results of this exploratory study provide some evidence that the mutational landscape and mutational signatures among young-onset breast cancer are different from those of older-onset patients. The characterization of young-onset tumours could provide clues to their etiology which may inform future prevention. Further studies are required to confirm our findings.

Identifying opportunities to support patient-centred care for ductal carcinoma in situ: qualitative interviews with clinicians.

BACKGROUND: Women with ductal carcinoma in situ (DCIS) report poor patient-clinician communication, and long-lasting confusion and anxiety about their treatment and prognosis. Research shows that patient-centred care (PCC) improves patient experience and outcomes. Little is known about the clinician experience of delivering PCC for DCIS. This study characterized communication challenges faced by clinicians, and interventions they need to improve PCC for DCIS. METHODS: Purposive and snowball sampling were used to recruit Canadian clinicians by specialty, gender, years of experience, setting, and geographic location. Qualitative interviews were conducted by telephone. Data were analyzed using constant comparison. Findings were mapped to a cancer-specific, comprehensive PCC framework to identify opportunities for improvement. RESULTS: Clinicians described approaches they used to address the PCC domains of fostering a healing relationship, exchanging information, and addressing emotions, but do not appear to be addressing the domains of managing uncertainty, involving women in making decisions, or enabling self-management. However, many clinicians described challenges or variable practices for all PCC domains but fostering a healing relationship. Clinicians vary in describing DCIS as cancer based on personal beliefs. When exchanging information, most find it difficult to justify treatment while assuring women of a good prognosis, and feel frustrated when women remain confused despite their efforts to explain it. While they recognize confusion and anxiety among women, clinicians said that patient navigators, social workers, support groups and high-quality information specific to DCIS are lacking. Despite these challenges, clinicians said they did not need or want communication interventions. CONCLUSIONS: Findings represent currently unmet opportunities by which to help clinicians enhance PCC for DCIS, and underscore the need for supplemental information and supportive care specific to DCIS. Future research is needed to develop and test communication interventions that improve PCC for DCIS. If effective and widely implemented, this may contribute to improved care experiences and outcomes for women diagnosed with and treated for DCIS.

Recommendations to improve patient-centred care for ductal carcinoma in situ: Qualitative focus groups with women.

BACKGROUND: Patient-centred care (PCC) improves health-care experiences and outcomes. Women with ductal carcinoma in situ (DCIS) and clinicians have reported communication difficulties. Little prior research has studied how to improve communication and PCC for DCIS. OBJECTIVE: This study explored how to achieve PCC for DCIS. DESIGN: Canadian women treated for DCIS from five provinces participated in semi-structured focus groups based on a 6-domain cancer-specific PCC framework to discuss communication about DCIS. Data were analysed using constant comparative technique. SETTING AND PARTICIPANTS: Thirty-five women aged 30 to 86 participated in five focus groups at five hospitals. RESULTS: Women said their clinicians used multiple approaches for fostering a healing relationship; however, most described an absence of desired information or behaviour to exchange information, respond to emotions, manage uncertainty, make decisions and enable self-management. Most women were confused by terminology, offered little information about the risks of progression/recurrence, uninformed about treatment benefits and risks, frustrated with lack of engagement in decision making, given little information about follow-up plans or self-care advice, and received no acknowledgement or offer of emotional support. DISCUSSION AND CONCLUSIONS: By comparing the accounts of women with DCIS to a PCC framework, we identified limitations and inconsistencies in women's lived experience of communication about DCIS, and approaches by which clinicians can more consistently achieve PCC for DCIS. Future research should develop and evaluate informational tools to support PCC for DCIS.

National consensus recommendations on patient-centered care for ductal carcinoma in situ.

PURPOSE: The purpose of this research was to generate recommendations on strategies to achieve patient-centered care (PCC) for ductal carcinoma in situ (DCIS). METHODS: Thirty clinicians (surgeons, medical/radiation oncologists, radiologists, nurses, navigators) who manage DCIS and 32 DCIS survivors aged 18 or older were nominated. Forty-six recommendations to support PCC for DCIS were derived from primary research, and rated in a two-round Delphi process from March to June 2018. RESULTS: A total of 29 clinicians and 27 women completed Round One, and 28 clinicians and 22 women completed Round Two. The 29 recommendations retained by both women and clinicians reflected the PCC domains of fostering patient-physician relationship (5), exchanging information (5), responding to emotions (1), managing uncertainty (4), making decisions (9), and enabling patient self-management (5). An additional 13 recommendations were retained by women only: fostering patient-physician relationship (1), exchanging information (3), responding to emotions (2), making decisions (3), and enabling patient self-management (4). Some recommendations refer to processes (i.e., ask questions about lifestyle or views about risks/outcomes to understand patient preferences); others to tools (i.e., communication aid). Panelists recommended a separate consensus process to refine the language that clinicians use when describing DCIS. CONCLUSIONS: This is the first study to generate guidance on how to achieve PCC for DCIS. Organizations that deliver or oversee health care can use these recommendations on PCC for DCIS to plan, evaluate, or improve services. Ongoing research is needed to develop communication tools, and establish labels and language for DCIS that optimize communication.

Improving Wait Times and Patient Experience Through Implementation of a Provincial Expedited Diagnostic Pathway for BI-RADS 5 Breast Lesions.

BACKGROUND: Long diagnostic intervals following abnormal breast imaging (DI) cause patient anxiety and possibly poorer prognosis. This study evaluates the effect of a provincial diagnostic pathway for BI-RADS 5 lesions on wait times and the patient-reported experience (PRE). METHODS: With multidisciplinary input, we developed a pathway for BI-RADS 5 lesions featuring expedited biopsy, early surgical referral, and nurse (RN) navigator support. Key diagnostic intervals were captured prospectively and compared with a prepathway control cohort. PRE data were obtained from a voluntary survey. RESULTS: 1205 patients were managed on the BI-RADS 5 pathway with 797 primary care physicians, 57 imaging centers, and 2 regional breast programs participating. Median duration from DI to biopsy was 6 days, from biopsy to pathology report was 5 days, DI to surgical referral was 6 days, and DI to surgical consult was 21 days. Compared with 128 prepathway controls, median intervals from DI to surgical referral and consult were significantly improved (15 vs. 6 days, 26 vs. 21 days, p < 0.001). Amongst 294 women who completed the survey, 92% experienced ≥ 1 anxiety complaint during assessment; prompt surgical consultation and multiple features of RN support reduced anxiety, and wait time satisfaction was high (70%). Patient preferences varied for receiving biopsy results from a surgeon (57%) vs. another provider (43%). CONCLUSIONS: A diagnostic pathway for BI-RADS 5 lesions reduced wait times and improved the patient experience through prompt surgical referral and RN navigator support. Differing preferences for receiving biopsy results emerged, and future iterations should incorporate individualized patient wishes.