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Breast cancer susceptibility gene (BRCA) mutation carriers have an increased risk of breast cancer. Mitigation of this risk can be achieved via surveillance or prophylactic mastectomy with or without breast reconstruction. Those that choose surgery expect to reduce their chance of developing cancer. The purpose of this study was to determine the incidence of patients developing breast cancer prior to surgery and to identify modifiable contributing factors within the patient journey. This is a historical cohort study of all BRCA mutation carriers identified through the British Columbia Cancer Hereditary Cancer Program between 2000 and 2012. Patients were divided into two groups: surveillance (S) and prophylactic mastectomy with immediate breast reconstruction (PM/IBR). The incidence of cancer, time to PM/IBR and patient journeys were analyzed. A total of 333 women were identified. The time to surgery from mutation disclosure was a median of 31 (5.3, 75.7) months. During this period, 6% of patients developed breast cancer compared with a 14% incidence of breast cancer in patients choosing surveillance. The majority of time to surgery was attributed to the period between mutation disclosure and the decision to proceed with surgery. Strategies to facilitate decision-making as well as wait list prioritization and dedicated operative time should be targeted to this population to decrease the number of women developing an interval cancer prior to surgery. [ABSTRACT FROM AUTHOR]

Background: Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.Methods: We constructed a Markov model of annual MRI and mammography screening for BRCA1/2 carriers, using local data and published values. We calculated cost-effectiveness as cost per quality-adjusted life-year gained (QALY), and conducted one-way and probabilistic sensitivity analysis.Results: The incremental cost-effectiveness ratio (ICER) of annual mammography plus MRI screening, compared to annual mammography alone, was $50,900/QALY. After incorporating parameter uncertainty, MRI screening is expected to be a cost-effective option 86% of the time at a willingness-to-pay of $100,000/QALY, and 53% of the time at a willingness-to-pay of $50,000/QALY. The model is highly sensitive to the cost of MRI; as the cost is increased from $200 to $700 per scan, the ICER ranges from $37,100/QALY to $133,000/QALY.Conclusions: The cost-effectiveness of using MRI and mammography in combination to screen for breast cancer in BRCA1/2 mutation carriers is finely balanced. The sensitivity of the results to the cost of the MRI screen itself warrants consideration: in jurisdictions with higher MRI costs, screening may not be a cost-effective use of resources, but improving the efficiency of MRI screening will also improve cost-effectiveness. [ABSTRACT FROM AUTHOR]

Importance: The association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear., Objective: To study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy., Design, Setting, and Participants: Retrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy., Exposure: TIL abundance in breast tissue from resected primary tumors., Main Outcomes and Measures: The primary outcome was invasive disease-free survival [iDFS]. Secondary outcomes were recurrence-free survival [RFS], survival free of distant recurrence [distant RFS, DRFS], and overall survival. Associations were assessed using a multivariable Cox model stratified by participating center., Results: This study included 1966 patients with TNBC (median age, 56 years [IQR, 39-71]; 55% had stage I TNBC). The median TIL level was 15% (IQR, 5%-40%). Four-hundred seventeen (21%) had a TIL level of 50% or more (median age, 41 years [IQR, 36-63]), and 1300 (66%) had a TIL level of less than 30% (median age, 59 years [IQR, 41-72]). Five-year DRFS for stage I TNBC was 94% (95% CI, 91%-96%) for patients with a TIL level of 50% or more, compared with 78% (95% CI, 75%-80%) for those with a TIL level of less than 30%; 5-year overall survival was 95% (95% CI, 92%-97%) for patients with a TIL level of 50% or more, compared with 82% (95% CI, 79%-84%) for those with a TIL level of less than 30%. At a median follow-up of 18 years, and after adjusting for age, tumor size, nodal status, histological grade, and receipt of radiotherapy, each 10% higher TIL increment was associated independently with improved iDFS (hazard ratio [HR], 0.92 [0.89-0.94]), RFS (HR, 0.90 [0.87-0.92]), DRFS (HR, 0.87 [0.84-0.90]), and overall survival (0.88 [0.85-0.91]) (likelihood ratio test, P < 10e-6)., Conclusions and Relevance: In patients with early-stage TNBC who did not undergo adjuvant or neoadjuvant chemotherapy, breast cancer tissue with a higher abundance of TIL levels was associated with significantly better survival. These results suggest that breast tissue TIL abundance is a prognostic factor for patients with early-stage TNBC.

Objective: To help facilitate economic evaluations of oncology treatments, we mapped responses on cancer-specific instrument to generic preference-based measures., Methods: Cancer patients (n = 367) completed one cancer-specific instrument, the FACT-G, and two preference-based measures, the EQ-5D and SF-6D. Responses were randomly divided to form development (n = 184) and cross-validation (n = 183) samples. Relationships between the instruments were estimated using ordinary least squares (OLS), generalized linear models (GLM), and censored least absolute deviations (CLAD) regression approaches. The performance of each model was assessed in terms of how well the responses to the cancer-specific instrument predicted EQ-5D and SF-6D utilities using mean absolute error (MAE) and root mean squared error (RMSE)., Results: Physical, functional, and emotional well-being domain scores of the FACT-G best explained the EQ-5D and SF-6D. In terms of accuracy of prediction as measured in RMSE, the CLAD model performed best for the EQ-5D (RMSE = 0.095) whereas the GLM model performed best for the SF-6D (RMSE = 0.061). The GLM predicted SF-6D scores matched the observed values more closely than the CLAD and OLS., Conclusion: Our results demonstrate that the estimation of both EQ-5D and SF-6D utility indices using the FACT-G responses can be achieved. The CLAD model for the EQ-5D and the GLM model for the SF-6D are recommended. Thus, it is possible to estimate quality-adjusted life years for economic evaluation from studies where only cancer-specific instrument have been administered.

Objective: Residents of rural communities have decreased access to cancer screening and treatments compared to urban residents, though use of resources and patient outcomes have not been assessed with a comprehensive population-based analysis. The objectives of this study were to investigate whether breast cancer screening and treatments were utilized less frequently in rural BC and whether this translated into differences in outcomes., Methods: All patients diagnosed with breast cancer in British Columbia (BC) during 2002 were identified from the Cancer Registry and linked to the Screening Mammography database. Patient demographics, pathology, stage, treatments, mammography use and death data were abstracted. Patients were categorized as residing in large, small and rural local health authorities (LHAs) using Canadian census information. Use of resources and outcomes were compared across these LHA size categories. We hypothesized that mastectomy rates (instead of breast-conserving surgery) would be higher in rural areas, since breast conservation is standardly accompanied by adjuvant radiotherapy, which has limited availability in rural BC. In contrast we hypothesized that cancer screening and systemic therapy use would be similar, as they are more widely dispersed across BC. Exploratory analyses were performed to assess whether disparities in screening and treatment utilization translated into differences in survival., Results: 2,869 breast cancer patients were included in our study. Patients from rural communities presented with more advanced disease (p=0.01). On multivariable analysis, patients from rural, compared to urban, LHAs were less likely to be screening mammography attendees (OR=0.62; p<0.001). Women from rural communities were less likely to undergo breast-conserving surgery (multivariable OR=0.47; p<0.001). There was no significant difference in use of chemotherapy (p=0.54) or hormonal therapy (p=0.36). The 5-year breast cancer-specific survival for large, small and rural LHAs was 90%, 88% and 86%, respectively (p=0.08), while overall survival was 84%, 81% and 77%, respectively (p=0.01). On multivariable analysis with 7.4 years of median follow-up, neither breast cancer-specific survival (HR=1.16; 0.76-1.76; p=0.49) nor overall survival (HR=1.25; 0.92-1.70; p=0.16) was significantly worse for patients from rural compared to large LHAs., Conclusion: There was a significant difference in screening mammography use, stage distribution and loco-regional treatments use by population size of LHA. After controlling for differences in patient and tumour factors by LHA, survival was not significantly different.

Purpose: Human epidermal growth factor receptor 2 gene (HER2) is associated with a poorer outcome in node-positive breast cancer, but the results are conflicting in node-negative disease. This study assessed the prognostic impact of HER2 overexpression/amplification in a large series of node-negative breast cancers., Patients and Methods: A tissue microarray (TMA) series was constructed consisting of 4,444 invasive breast cancers diagnosed in British Columbia from 1986 to 1992. Within this series, 2,026 patients were node negative, of whom 70% did not receive adjuvant systemic therapy. The TMA series was assessed for estrogen receptor (ER) and HER2. Logistic regression modeling was used to estimate odds ratios at the 10-year follow-up., Results: HER2 was positive in 10.2% of the node-negative cohort. In this cohort, an inferior outcome was seen in patients with HER2-positive tumors compared with HER2-negative tumors for 10-year relapse-free survival (RFS; 65.9% v 75.5%, respectively; P = .01), distant RFS (71.2% v 81.8%, respectively; P = .004), and breast cancer-specific survival (BCSS; 75.5% v 86.3%, respectively; P = .001). A trend for a worse overall survival was also seen (P = .06). HER2 was an independent poor prognostic factor for RFS and BCSS at 10 years, with odds ratios of 1.71 (P = .01) and 2.03 (P = .003), respectively. The number of HER2-positive tumors that were

Background: Over the past decade, a number of new therapeutic agents have become available in the treatment of metastatic breast cancer (MBC). This study characterized the use and assessed the impact on survival of population-based access to new agents for the treatment of MBC., Methods: The dates of release in British Columbia of 7 new systemic agents for MBC during the 1990s were used to construct 4 time cohorts. All patients with a first diagnosis of distant metastases in each of the time cohorts were identified and characterized, and their survival was compared. Cox proportional regression modeling was used to assess for predictors of survival., Results: In total, 2150 patients with a first distant metastases diagnosed during 1 of the 4 cohort intervals were identified. Baseline characteristics between cohorts were similar, except a greater proportion of the later cohorts received adjuvant chemotherapy (P < .001), had positive estrogen receptor status (P = .01), and had a longer median time from initial diagnosis to MBC (P < .001). Survival in Cohort 1 (1991-1992) and Cohort 2 (1994-1995; median, 438 days and 450 days, respectively) was similar. Survival was longer in Cohort 3 (1997-1998; median, 564 days; P = .002) and improved further in Cohort 4 (1999-2001; median, 667 days; P = .05). In multivariate analysis, the later cohorts were associated independently with improved survival (P = .01 and P < .001, respectively)., Conclusions: Population-based access to new therapeutic agents for MBC appeared to be associated with improved survival. To the authors' knowledge, this is the first study to date that demonstrates, from a population-based perspective, improving survival over the past decade for women with MBC.