Background: Breast cancer (BC) treatment is rapidly evolving with new and costly therapeutics. Existing costing models have a limited ability to capture current treatment costs. We used an Activity-Based Costing (ABC) method to determine a per-case cost for BC treatment by stage and molecular subtype. Methods: ABC was used to proportionally integrate multidisciplinary evidence-based patient and provider treatment options for BC, yielding a per-case cost for the total duration of treatment by stage and molecular subtype. Diagnostic imaging, pathology, surgery, radiation therapy, systemic therapy, inpatient, emergency, home care and palliative care costs were included. Results: BC treatment costs were higher than noted in previous studies and varied widely by molecular subtype. Cost increased exponentially with the stage of disease. The per-case cost for treatment (2023C$) for DCIS was C$ 14,505, and the mean costs for all subtypes were C$ 39,263, C$ 76,446, C$ 97,668 and C$ 370,398 for stage I, II, III and IV BC, respectively. Stage IV costs were as high as C$ 516,415 per case. When weighted by the proportion of molecular subtype in the population, case costs were C$ 31,749, C$ 66,758, C$ 111,368 and C$ 289,598 for stage I, II, III and IV BC, respectively. The magnitude of cost differential was up to 10.9 times for stage IV compared to stage I, 4.4 times for stage III compared to stage I and 35.6 times for stage IV compared to DCIS. Conclusion: The cost of BC treatment is rapidly escalating with novel therapies and increasing survival, resulting in an exponential increase in treatment costs for later-stage disease. We provide real-time, case-based costing for BC treatment which will allow for the assessment of health system economic impacts and an accurate understanding of the cost-effectiveness of screening.

Background: Adjuvant trastuzumab for early-stage (I-III) HER2-positive breast cancer (BC) has led to statistically significant improvement in cancer outcomes but carries a risk of cardiotoxicity. Trastuzumab is discontinued early in many patients for asymptomatic changes in left ventricular ejection fraction. We evaluated the impact of early discontinuation of trastuzumab on cancer outcomes.Methods: We conducted a retrospective population-based cohort study of early BC patients treated with adjuvant trastuzumab in Ontario, Canada, 2007-2016. Four groups were analyzed: group A was full treatment, 17-18 cycles trastuzumab; group B was cardiac event (CE) within treatment period; group C was ≤16 cycles, no CEs, stopped within 30 days from last cardiac imaging; and group D was ≤16 cycles, no CEs, stopped more than 30 days from cardiac imaging. Primary outcome was disease-free survival (DFS); secondary outcomes were: overall survival, cancer-specific mortality, and cardiovascular mortality. Sensitivity analyses were performed 14 months after cycle 1 trastuzumab to control for early relapse.Results: A total of 5547 patients met the inclusion criteria: group A = 3921, group B = 309, group C = 362, and group D = 955. The 5-year DFS was 94.1% in group A, 80.1% in group B, 81.4% in group C, and 82.4% in group D. Using a Cox model, the hazard ratio for 5-year DFS was 3.15 (95% confidence interval [CI] = 2.13 to 4.65) for group B, 1.94 (95% CI = 1.30 to 2.89) for group C, and 1.92 (95% CI = 1.46 to 2.53) for group D. Overall, 26 patients (0.5%) died of cardiac causes.Conclusions: BC patients in Ontario who did not complete adjuvant trastuzumab had a statistically significantly higher risk of BC relapse and death and low incidence of cardiac death. These findings support 1 year of adjuvant trastuzumab in early-stage BC.

We conducted a population-based, retrospective, matched-cohort study to examine the impact of breast cancer diagnosis and treatment on fertility outcomes. Relative risks of infertility, childbirth, premature ovarian insufficiency (POI; age < 40) and early menopause (age < 45) were calculated using modified Poisson regression. Our primary cohort included young women (15–39) with early stage BC diagnosed 1995–2014. Five cancer-free patients were matched to each BC patient by birth year and census subdivision. The BC cohort was further divided by treatment with chemotherapy vs. no chemotherapy treatment. 3903 BC patients and 19,515 cancer-free women. BC patients treated with chemotherapy were at increased risk of infertility (RR 1.81; 95% CI 1.60–2.04), and POI (RR 6.25; 95% CI 5.15–7.58) and decreased childbirth (RR 0.85; 95% CI 0.75–0.96), compared to women without cancer. BC patients who did not receive chemotherapy were also at increased risk of infertility (RR 1.80 95% CI 1.48–2.18) and POI (RR 2.12 95% CI 1.37–3.28). All young BC survivors face an increased risk of diagnosed infertility and POI relative to women without cancer, independent of chemotherapy. These results emphasize the importance of pre-treatment fertility counselling for young women diagnosed with BC.

Young adults aged 40 years and younger with breast cancer represent less than 5% of all breast cancer cases, yet it is the leading cause of death among young women with cancer worldwide. Breast cancer that develops at a young age is more aggressive and has biological features that carry an increased risk of relapse and death. Young adults are more likely to have a genetic predisposition and key biomarkers, including endocrine receptors, the HER2 receptor, and proliferation biomarkers, that appear different compared to older adults. Despite being more aggressive, management strategies are largely the same irrespective of age. Given the higher rates of genetic predisposition, fast access to genetic counselling and testing is a necessity. In this review, the biological differences in young adult breast cancer and the current role precision medicine holds in the treatment of young adults with breast cancer are explored. Given the relatively high risk of relapse, developing novel genomic tools to refine the treatment options beyond the current standard is critical. Existing predictive genomic tests require careful interpretation with consideration of the patient’s clinical and pathological features in the young patient cohort. Careful evaluation is also required when considering extended endocrine therapy options. Improved characterization of mutations occurring in tumors using next-generation sequencing could identify important driver mutations that arise in young women. Applying the advances of precision medicine equitably to patients in resource-rich and low- and middle-income countries will be critical to impacting the survival of young adults with breast cancer worldwide.