The clinical utility of the 70-gene signature (MammaPrint®) to guide chemotherapy use in T1-3N0-1M0 breast cancer was demonstrated in the Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy (MINDACT) study. One thousand four ninety seven of 3356 (46.2%) enrolled patients with high clinical risk (in accordance with the modified Adjuvant! Online clinical-pathological assessment) had a low-risk 70-gene signature. Using patient-level data from the MINDACT trial, the cost-effectiveness of using the 70-gene signature to guide adjuvant chemotherapy selection for clinical high risk, estrogen receptor positive (ER+), human epidermal growth factor 2 negative (HER2-) patients was analysed. A hybrid decision tree-Markov model simulated treatment strategies in accordance with the 70-gene signature with clinical assessment versus clinical assessment alone, over a 10-year time horizon. Primary outcomes were quality-adjusted life years (QALYs), country-specific costs and incremental cost-effectiveness ratios (ICERs) for six countries: Belgium, France, Germany, Netherlands, UK and the US. Treatment strategies guided by the 70-gene signature result in more QALYs compared with clinical assessment alone. Costs of the 70-gene signature strategy were lower in five of six countries. This led to dominance of the 70-gene signature in Belgium, France, Germany, Netherlands and the US and to a cost-effective situation in the UK (ICER £22,910/QALY). Annual national cost savings were €4.2M (Belgium), €24.7M (France), €45.1M (Germany), €12.7M (Netherlands) and $244M (US). UK budget increase was £8.4M. Using the 70-gene signature to safely guide chemotherapy de-escalation in clinical high risk patients with ER+/HER2- tumours is cost-effective compared with using clinical assessment alone. Long-term follow-up and outcomes from the MINDACT trial are necessary to address uncertainties in model inputs.

Purpose: Results from active surveillance trials for ductal carcinoma in situ (DCIS) will not be available for > 10 years. A model based on real-world data (RWD) can demonstrate the comparative impact of non-intervention for women with low-risk features. Methods: Multi-state models were developed using Surveillance, Epidemiology, and End Results Program (SEER) data for three treatment strategies (no local treatment, breast conserving surgery [BCS], BCS + radiotherapy [RT]), and for women with DCIS low-risk features. Eligible cases included women aged ≥ 40 years, diagnosed with primary DCIS between 1992 and 2016. Five mutually exclusive health states were modelled: DCIS, ipsilateral invasive breast cancer (iIBC) ≤ 5 years and > 5 years post-DCIS diagnosis, contralateral IBC, death preceded by and death not preceded by IBC. Propensity score-weighted Cox models assessed effects of treatment, age, diagnosis year, grade, ER status, and race. Results: Data on n = 85,982 women were used. Increased risk of iIBC ≤ 5 years post-DCIS was demonstrated for ages 40–49 (Hazard ratio (HR) 1.86, 95% Confidence Interval (CI) 1.34–2.57 compared to age 50–69), grade 3 lesions (HR 1.42, 95%CI 1.05-1.91) compared to grade 2, lesion size ≥ 2 cm (HR 1.66, 95%CI 1.23–2.25), and Black race (HR 2.52, 95%CI 1.83–3.48 compared to White). According to the multi-state model, propensity score-matched women with low-risk features who had not died or experienced any subsequent breast event by 10 years, had a predicted probability of iIBC as first event of 3.02% for no local treatment, 1.66% for BCS, and 0.42% for BCS+RT. Conclusion: RWD from the SEER registry showed that women with primary DCIS and low-risk features demonstrate minimal differences by treatment strategy in experiencing subsequent breast events. There may be opportunity to de-escalate treatment for certain women with low-risk features: Hispanic and non-Hispanic white women aged 50–69 at diagnosis, with ER+, grade 1 + 2, < 2 cm DCIS lesions.

As ongoing trials study the safety of an active surveillance strategy for low-risk ductal carcinoma in situ (DCIS), there is a need to explain why particular choices regarding treatment strategies are made by eligible women as well as their oncologists, what factors enter the decision process, and how much each factor affects their choice. To measure preferences for treatment and surveillance strategies, women with newly-diagnosed, primary low-risk DCIS enrolled in the Dutch CONTROL DCIS Registration and LORD trial, and oncologists participating in the Dutch Health Professionals Study were invited to complete a discrete choice experiment (DCE). The relative importance of treatment strategy-related attributes (locoregional intervention, 10-year risk of ipsilateral invasive breast cancer (iIBC), and follow-up interval) were discerned using conditional logit models. A total of n = 172 patients and n = 30 oncologists completed the DCE. Patient respondents had very strong preferences for an active surveillance strategy with no surgery, irrespective of the 10-year risk of iIBC. Extensiveness of the locoregional treatment was consistently shown to be an important factor for patients and oncologists in deciding upon treatment strategies. Risk of iIBC was least important to patients and most important to oncologists. There was a stronger inclination toward a twice-yearly follow-up for both groups compared to annual follow-up.

The authors found 52% of eligible women with primary ductal carcinoma in situ consistently adhered to imaging surveillance guidelines across the first 5 years after treatment. Background Guidelines recommend annual surveillance imaging after diagnosis of ductal carcinoma in situ (DCIS). Guideline adherence has not been characterized in a contemporary cohort. Purpose To i...

Up to 60% of metastatic breast cancer (mBC) cases historically classified as human epidermal growth factor receptor 2 (HER2)-negative may be HER2-low, expanding options towards new HER2 targeted treatments. Greater understanding of the current therapeutic journey of this population can help with assessing the potential impact of these novel therapies. We conducted a real-world retrospective database study using a United States-based cohort to describe the characteristics, treatment patterns, and outcomes among HER2-low, hormone receptor-positive mBC patients who initiated chemotherapy (index line of therapy [ILOT]) in the metastatic setting either within 6 months of 1 line (L) endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitor ("rapid ILOT initiators") or after ≥2L of ET ("index 3L+ group"). Of the 963 patients included, 131 (13.6%) were rapid ILOT initiators and 832 (86.4%) were in the index 3L+ group. Most (80.0%) received single-agent chemotherapy as ILOT, and either a chemotherapy-based regimen (57.0%) or ET ± targeted therapy (26.2%) as a subsequent line (N = 702). Median real-world overall survival (rwOS) from start of ILOT was 18.7 months (95% CI: 17.3, 20.2). Median real-world time to treatment discontinuation or death (rwTTD/D) and real-world time to next treatment or death (rwTTNT/D) were 4.9 (95% CI: 4.6, 5.2) and 5.6 months (95% CI: 5.3, 6.0), respectively. Outcomes were particularly poor among rapid ILOT initiators (median rwOS, rwTTD/D and rwTTNT/D of 15.2, 4.3 and 4.9 months, respectively). Patients receiving chemotherapy following ET had limited benefit from available treatments, highlighting unmet treatment needs in this population.

Purpose Real-world outcomes are poorly understood for patients with human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry 1+ or 2+ with negative in situ hybridization) metastatic breast cancer (mBC). Methods Using for the first time a nationwide electronic health record-derived de-identified database, we assessed demographics, treatment patterns, and outcomes of patients with HER2-low mBC who previously received one line of chemotherapy in the metastatic setting. The post-chemotherapy line was termed the index line of therapy (LOT). Results 3765 patients [hormone receptor (HR)-positive: 78.8%, HR-negative: 21.0%] met the inclusion criteria (1 January 2011–30 April 2023). 61.7% of HR-positive patients received endocrine therapy prior to the index LOT. The largest patient percentage received single-agent chemotherapy at the index and subsequent two LOTs. For the overall cohort, the median real-world time to treatment discontinuation/death was 4.1 months (95% CI: 3.9–4.2) and the median real-world time to next treatment/death was 5.1 months (95% CI: 4.8–5.3) from the index LOT. Median real-world overall survival (all patients) was 15.8 months (95% confidence interval: 15.2–16.5, median follow-up = 54.5 months) from the index LOT. Conclusion These data highlight the unmet clinical needs of patients with HER2-low mBC by characterizing the treatment patterns and poor outcomes in this population on the current standard of care.