The objective of this trial, DBCG R25, will be to evaluate the effect of trastuzumab-deruxtecan versus standard of care on progression-free survival (PFS) in first-line for patients with non-Luminal A, ER-positive/HER2-negative metastatic breast cancer

Start Date01 May 2025

Sponsor / Collaborator

Danish Breast Cancer Cooperative Group

NCT06263543

/ RecruitingPhase 2IIT

SERIES: SEquencing Sacituzumab Govitecan AfteR T-DXd In ER+/HER2 LOW MetaStatic Breast Cancer

The purpose of this research study is to see if the medication sacituzumab govitecan (SG) is effective at the currently approved dose and schedule in people who have previously received trastuzumab deruxtecan (T-DXd) for the treatment of metastatic, hormone receptor positive (HR+)/human epidermal growth factor 2 low (HER2 low) breast cancer. Although SG is approved to treat metastatic HR+/HER2 negative breast cancer, the aim of this study is to determine if SG is still effective specifically in people who have already received T-DXd.

Start Date17 Jun 2024

Sponsor / Collaborator

Baptist Health South Florida, Inc.

[+1]

NCT03321981

/ CompletedPhase 2

Phase 2 Study of MCLA-128-based Combinations in Metastatic Breast Cancer (MBC): MCLA-128/Trastuzumab/Chemotherapy in HER2-positive MBC and MCLA-128/Endocrine Therapy in Estrogen Receptor Positive and Low HER2 Expression MBC

A Phase 2, open-label, multicenter international study will be performed to evaluate the efficacy of MCLA-128-based combinations. Three combination treatments will be evaluated, two in Cohort 1 and one in Cohort 2.
MCLA-128 (zenocutuzumab) is given in combinations in two metastatic breast cancer (MBC) populations, Human Epidermal Growth Factor Receptor (HER) 2-positive/amplified (Cohort 1) and Estrogen Receptor-positive/low HER2 expression (Cohort2).
Two combinations treatments will be evaluated in Cohort 1, the doublet and triplet. Initially zenocutuzumab is given in combination with trastuzumab in the doublet. After the safety of the doublet has been assessed in 4-6 patients, MCLA-128 is given in combination with trastuzumab and vinorelbine in the triplet, in parallel to the efficacy expansion of the doublet.
The doublet and triplet combinations are both evaluated in two steps with an initial safety run-in followed by a cohort efficacy expansion. In total up to 40 patients evaluable for efficacy are included in both the doublet and triplet.
In Cohort 2 zenocutuzumab is administered in combination with the same previous endocrine therapy on which progressive disease is radiologically documented. A total of up to 40 patients evaluable for efficacy are included in the Cohort 2.

Start Date15 Jan 2018

Sponsor / Collaborator

Merus NV

100 Clinical Results associated with ER Positive/HER2 Low Breast Cancer

100 Translational Medicine associated with ER Positive/HER2 Low Breast Cancer

0 Patents (Medical) associated with ER Positive/HER2 Low Breast Cancer

Literatures (Medical) associated with ER Positive/HER2 Low Breast Cancer

01 Jun 2025·Breast Cancer Research and Treatment

Oncotype DX recurrence score in node-positive patients in the post-RxPONDER era: a single-institution experience

Article

Author: Han, Rachel ; Wen, Hannah Y ; Morrow, Monica ; El-Tamer, Mahmoud ; Brogi, Edi ; Thompson, Donna

PURPOSERxPONDER showed that in postmenopausal women with early-stage hormone receptor + /HER2- breast cancer (BC) with 1-3 positive axillary lymph nodes (LN) and a recurrence score ≤ 25, the addition of chemotherapy to endocrine therapy did not improve distant recurrence-free survival. We sought to evaluate Oncotype DX recurrence score (ODX RS) distribution in LN negative and LN positive patients aged ≥ 50 years (y) and to determine clinicopathologic factors associated with RS.METHODSODX RS, demographic, and pathologic information was collected for patients with ER + /HER2- BC with 0 (patients < 50y) or 0-3 positive (patients ≥ 50y) LN treated at our institution between January 2021 and December 2022. Statistical analyses were conducted using Pearson chi-square and two-tailed t tests.RESULTSThe study cohort included 2378 BC from 2285 women. Among women ≥ 50y, there was no significant difference in RS distribution between pN0, pN1mi, and pN1a patients; with 85.4%, 86.5%, and 81% having a RS ≤ 25, respectively. Among LN + women ≥ 50y, RS > 25 was significantly associated with higher grade (P = .001), lower ER (P = .007), and lower PR (P < .001). Among LN- women ≥ 50y, RS > 25 was significantly associated with higher grade (P < .001), lower ER (P < .001), and lower PR (P < .001).CONCLUSIONODX RS distribution among LN + and LN- women aged ≥ 50y was similar. In this population, RS is significantly associated with tumor grade, ER, and PR, regardless of LN status. In our post-RxPONDER era cohort, over 80% of women aged ≥ 50y with early-stage ER + /HER2- BC with ≤ 3 positive axillary LN would be spared chemotherapy based on RS, regardless of nodal status.

01 Sep 2024·Oncology and Therapy

Exploring a Novel Approach to Spare Classic Chemotherapy in HER2-Low, ER-Positive Breast Cancer Based on Trastuzumab Deruxtecan Combined with Endocrine Therapy

Author: Sabbatino, Francesco ; Cascella, Marco ; Di Lauro, Vincenzo ; Marra, Antonio ; Di Lorenzo, Giuseppe ; Tortora, Vincenzo ; Buonerba, Carlo ; Liguori, Luigi ; Curigliano, Giuseppe ; Tarantino, Paolo ; Trapani, Dario ; Giuliano, Mario ; Arpino, Grazia ; Diana, Anna ; Scafuri, Luca ; Sciarra, Antonella

BACKGROUNDBreast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy.OBJECTIVEThis editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer.METHODSWe propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects.CONCLUSIONSThis study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach.

01 Jul 2024·ESMO Open

Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer

Article

Author: Mension, E ; Vidal Losada, M J ; Pascual, T ; Seguí, E ; Prat, A ; Cebrecos, I ; González-Farre, B ; Bergamino, M ; Martínez-Sáez, O ; Adamo, B ; Galván, P ; Rivera, P ; Jares, P ; Mollà, M ; Muñoz, M ; Nucera, S ; García Fructuoso, I ; Vidal-Sicart, S ; Brasó-Maristany, F ; Gómez Bravo, R ; Ganau, S ; Oses, G ; Conte, B ; De Santo, I ; Sanfeliu, E ; Schettini, F ; Rodríguez, A B

BACKGROUNDThe characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low versus HR+/HER2-0 breast cancer (BC) has not been conducted so far. Most evidence on the association of HER2 status with pathologic responses and prognosis in HR+/HER2-negative BC is controversial and restricted to NACT-treated disease. Similarly, a temporal heterogeneity in HER2 status has been described only with NACT.METHODSWe retrospectively recruited a consecutive cohort of 186 patients with stage I-IIIB HR+/HER2-negative BC treated with neoadjuvant therapy (NAT). Available diagnostic biopsies and surgical samples were characterized for main pathological features, PAM50 IS and ROR-P score, and gene expression. Associations with pathologic complete response, residual cancer burden-0/I, event-free survival (EFS) and overall survival (OS) based on HER2 status were assessed. Pre/post pathologic/molecular changes were analyzed in matched samples.RESULTSThe HER2-low (62.9%) and HER2-0 (37.1%) cohorts did not differ significantly in main baseline features, treatments administered, breast-conserving surgery, pathologic complete response and residual cancer burden-0/I rates, EFS, and OS. NAT induced, regardless of HER2 status, a significant reduction of estrogen receptor/progesterone receptor and Ki67 levels, a down-regulation of PAM50 proliferation- and luminal-related genes/signatures, an up-regulation of selected immune genes, and a shift towards less aggressive IS and lower ROR-P. Moreover, 25% of HER2-0 changed to HER2-low and 34% HER2-low became HER2-0. HER2 shifts were significant after NACT (P < 0.001), not neoadjuvant endocrine therapy (P = 0.063), with consistent ERBB2 mRNA level dynamics. HER2 changes were not associated with EFS/OS.CONCLUSIONSHER2-low and HER2-0 status change after NAT in ∼30% of cases, mostly after NACT. Targeted adjuvant strategies should be investigated accordingly. Molecular downstaging with current chemo/endocrine agents and immunotherapy should not rely on HER2 immunohistochemical levels in HR+/HER2-negative BC. Instead, HER2-low-targeted approaches should be explored to pursue more effective and/or less toxic dimensional downstaging.

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