The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan–Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0–10, 17.8%; RS 11–25, 62.5%; RS 26–100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0–10, 11–25, and 26–100: 2.6% (95% confidence interval [CI], 1.1–6.2%), 6.1% (95% CI, 4.4–8.6%), and 13.1% (95% CI, 9.4–18.3%), respectively (P < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1–5.1%), 2.2% (95% CI, 1.3–3.7%), and 9.5% (95% CI, 6.0–14.9%) (P < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0–10/11–25), 10-year distant recurrence and BCSM rates for RS 0–10 patients were 2.7% (95% CI, 1.1–6.5%) and 0.8% (95% CI, 0.1–5.3%), respectively, and for RS 11–25 patients, 5.7% (95% CI, 3.9–8.3%) and 2.0% (95% CI, 1.1–3.7%), respectively. For RS 11–25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0–25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26–100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches.

Purpose: ⁶⁸Ga–fibroblast activation protein inhibitor (FAPI), a new PET/CT radiotracer targeting cancer-associated fibroblasts in tumor microenvironment, can detect many types of cancer. We aimed to assess whether it can also be used for response assessment and follow-up. Methods: We followed up patients with FAPI-avid invasive lobular breast cancer (ILC) before and after treatment changes and correlated qualitative maximal intensity projection images and quantitative tumor volume with CT results and blood tumor biomarkers. Results: Six consenting ILC breast cancer patients (53 ± 8 years old) underwent a total of 24 scans (baseline for each patient and 2–4 follow-up scans). We found a strong correlation between ⁶⁸Ga-FAPI tumor volume and blood biomarkers (r = 0.7, P < 0.01), but weak correlation between CT and ⁶⁸Ga-FAPI maximal intensity projection–based qualitative response assessment. Conclusions: We found a strong correlation between ILC progression and regression (as assessed by blood biomarkers) and ⁶⁸Ga-FAPI tumor volume. ⁶⁸Ga-FAPI PET/CT could possibly be used for disease response assessment and follow-up.

Background: Neoadjuvant systemic therapy is the preferred treatment approach for stage II–III HER2-positive breast cancer (BC). Real-life data comparing regimens with or without anthracyclines combined with two HER2 drugs is lacking. We compared the efficacy and toxicity of two commonly used regimens. Methods: Retrospective data were collected on patients newly diagnosed with clinical stage II–III HER2-positive BC and treated at Sheba Medical Center, Israel, between September 2017 and June 2022 with either neoadjuvant DCbHP (docetaxel, carboplatin, trastuzumab, pertuzumab) or ACTHP (doxorubicin, cyclophosphamide, paclitaxel trastuzumab pertuzumab). PCR (pathological complete response) (ypT0/isN0) was evaluated in both cohorts and according to HER2 immunohistochemistry (IHC) staining (3+ or 2+ and fluorescence in situ hybridization [FISH] positive), estrogen receptor (ER), tumor size and nodal status. The toxicity indices evaluated were reductions in left ventricle ejection fraction (LVEF), dose reductions, hospitalizations and febrile neutropenia. Results: Here, 106 received ACTHP and 73 received DCbHP. Median age at diagnosis, ER status, HER2 IHC (2+/FISH pos or 3+) and nodal status were balanced. PCR occurred in 63.1% of patients, 67.0% and 57.5% in the ACTHP and DCbHP groups, respectively (p = 0.129). In patients with HER2 3+ IHC, pCR rates were significantly better with the ACTHP regimen than with DCbHP (83% vs. 62.9%, p < 0.039). No difference was observed among patients with HER2 +2 IHC FISH pos. Symptomatic LVEF decrease was observed in seven patients (6.6%) receiving ACTHP vs. none (0%) receiving DCbHP (p < 0.001). Conclusions: PCR rates were similar overall between ACTHP and DCbHP; however, in the HER2 3+ subgroup, ACTHP demonstrated increased efficacy. DCbHP was significantly less cardiotoxic.