Purpose: Elacestrant has shown significantly prolonged progression-free survival compared with standard-of-care endocrine therapy in estrogen receptor–positive (ER-positive), HER2-negative metastatic breast cancer, whereas potential benefit in early-stage disease requires further exploration. The SOLTI-ELIPSE window-of-opportunity trial investigated the biological changes induced by a short course of preoperative elacestrant in postmenopausal women with early breast cancer. Patients and Methods: Eligible patients with untreated T1c (≥1.5 cm)-T3, N0, ER-positive/HER2-negative breast cancer with locally assessed Ki67 ≥10% received elacestrant at a daily dose of 345 mg for 4 weeks. The primary efficacy endpoint was complete cell cycle arrest, defined as Ki67 ≤2.7%, on day 28. Results: Overall, 22 patients were evaluable for the primary endpoint. Elacestrant was associated with a complete cell cycle arrest rate of 27.3% and a statistically significant Ki67 geometric mean change of −52.9% (P = 0.007; 95% confidence interval, −67.4 to −32.1). Notably, the treatment with elacestrant led to a shift toward a more endocrine-sensitive and less proliferative tumor phenotype based on PAM50-based gene signatures. Elacestrant increased the expression of immune-response genes (GZMB, CD4, and CD8A) and suppressed proliferation and estrogen-signaling genes (MKI67, ESR1, and AR). These biological changes were independent of the levels of Ki67 suppression on day 28. The most common adverse events were grade 1 anemia (21.7%), hot flushes (8.7%), constipation (8.7%), and abdominal pain (8.7%). One patient experienced a grade 3 cutaneous rash, leading to treatment discontinuation. No other serious adverse events were reported. Conclusions: Preoperative treatment with elacestrant in early breast cancer demonstrated relevant biological and molecular responses and exhibited a manageable safety profile. These findings support further investigation of elacestrant in the early setting.

HER2DX is a clinically available genomic assay that provides prognostic (relapse risk score), predictive [pathological complete response (pCR) likelihood score], and ERBB2 expression data in stage I-III human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). This real-world study evaluated its clinical impact. This prospective study enrolled newly diagnosed patients with stage I-III HER2-positive BC across 12 hospitals in Spain (November 2021-September 2024). Thirty-four oncologists ordered HER2DX and completed questionnaires before and after receiving results to assess treatment changes (primary objective). Secondary objectives included evaluating the HER2DX pCR likelihood score association with pCR, test turnaround time, changes in physician confidence regarding treatment decisions, and cost-effectiveness. Among 297 recruited patients, 48.1% (95% confidence interval 42.5% to 53.7%) experienced treatment adjustments after HER2DX. Within these cases, 73.5% involved reduced treatment intensity, 24.5% involved increased treatment intensity, and the remaining cases (2.0%) involved mixed adjustments. Of the cases with reduced treatment intensity, 56.2% had a reduction in chemotherapy intensity, 26.7% had a reduction in anti-HER2 therapy, and 17.1% in both. Among the 182 patients with available pathological data at surgery, the pCR likelihood score was a significant predictor of pCR (P < 0.001). In 69 patients with pCR-high disease, less intensive treatment achieved similar pCR rates compared with multi-agent chemotherapy (81.5% versus 69.0%; odds ratio = 1.97, P = 0.256). Physician confidence improved (P < 0.001) and the estimated total cost savings, including direct drug costs, vein access devices, and HER2DX costs, amounted to €98 031. HER2DX impacts clinical management in stage I-III HER2-positive BC by supporting treatment adjustments, enhancing physician confidence, maintaining pCR rates, and reducing health care costs.

Improved selection of cancer patients who are most likely to respond to immune checkpoint inhibitors remains an unmet clinical need. Recently, a positive correlation between levels of PD1 mRNA and ... Tweetable abstract Considering previous data, we hypothesized that anti-PD1 monotherapy is effective across multiple cancer types in patients with PD1-high mRNA expressing tumors. Given these obser...

Early decrease in Ki67 after a short preoperative course of endocrine therapy (ET) has shown prognostic and predictive value in clinical research, but its applicability and reproducibility in routine clinical practice remain largely unknown. We therefore assessed on-treatment Ki67 changes following a short preoperative ET and its association with biological variables, such as intrinsic subtype and risk of recurrence (ROR), plus long-term outcomes, in a real-world cohort of patients with early estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-negative) breast cancer. We conducted a retrospective, registry-based analysis of 230 consecutive patients with early ER+/HER2- breast cancer treated as per standard clinical care at the Breast Unit of the Clinic Barcelona Comprehensive Cancer Center between 2014 and 2023. All patients received preoperative ET, tamoxifen, or an aromatase inhibitor (AI), for 2-12 weeks before surgery. Clinical and pathological variables were collected and stratified by Ki67 response: "responders" (post-treatment Ki67 0% to 10%) and "complete cell cycle arrest (CCCA) responders" (Ki67 ≤2.7%). PAM50/Prosigna was used to determine intrinsic subtypes and ROR-score. Event-free survival was estimated using Kaplan-Meier curves, and associations were tested using Cox proportional hazards regression. The median duration of preoperative ET was 5 weeks (min-max range, 2-12 weeks). Overall, 196 patients (85.2%) met the Ki67 response criterion and 111 (48.3%) achieved CCCA. Response rates were significantly higher in postmenopausal compared with premenopausal women (P = 0.004). Notably, 95.6% of postmenopausal patients received an AI, whereas all premenopausal women were treated with tamoxifen. Additionally, response varied by intrinsic subtype, favoring Luminal A tumors (P = 0.047). In multivariable models, postmenopausal status and higher baseline ER expression were independently associated with both Ki67 response and CCCA, whereas a lower baseline ROR-score predicted CCCA. After a median follow-up of 47 months, CCCA was associated with significantly improved event-free survival [hazard ratio (HR) = 0.19; 95% CI (confidence interval) 0.05-0.72; P value = 0.012]. In routine practice, a short course of preoperative ET yields substantial reductions in tumor proliferation. Early assessment of Ki67 suppression offers a readily accessible indicator of endocrine sensitivity, and achieving CCCA identifies patients who have a more favorable prognosis and thus are potentially eligible to de-escalate in treatment strategies.

Background: Adjuvant radiotherapy and hormonotherapy after breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) have been shown to reduce the risk of local recurrence. To predict the risk of ipsilateral breast tumor relapse (IBTR) after BCS, the Memorial Sloan Kettering Cancer Center (MSKCC) developed a nomogram to analyze local recurrence (LR) risk in our cohort and to assess its external validation. Methods: A historical cohort study using data from 296 patients treated for DCIS at the Hospital Clínic of Barcelona was carried out. Patients who had had a mastectomy were excluded from the analysis. Results: The mean age was 58 years (42–75), and the median follow-up time was 10.64 years. The overall local relapse rate was 13.04% (27 patients) during the study period. Actuarial 5- and 10-year IBTR rates were 5.8 and 12.9%, respectively. The external validation of the MSKCC nomogram was performed using a multivariate logistic regression analysis on a total of 207 patients, which did not reach statistical significance in the studied population for predicting LR (p = 0.10). The expression of estrogen receptors was significantly associated with a decreased risk of LR (OR: 0.25; p = 0.004). Conclusions: In our series, the LR rate was 13.4%, which was in accordance with the published series. The MSKCC nomogram did not accurately predict the IBTR in this Spanish cohort of patients treated for DCIS (p = 0.10).