HER-2 negative + ER positive

Short-course preoperative ET induces rapid and reproducible morphological and immunophenotypic changes in ER-positive, HER2-negative breast cancer. Ki67-defined response is associated with genomic risk and PR expression, whereas microenvironmental features appear to have limited predictive value.

Obesity was associated with lower ORR with letrozole alone, whereas this association was not observed in patients treated with taselisib.

The need for chemotherapy in postmenopausal HR + , HER2- breast cancer patients might be further informed by integrating the results of the Oncotype DX test with the response to NET.

P1, N=32, Active, not recruiting, Patrick Dillon, MD | Recruiting --> Active, not recruiting

P1, N=23, Recruiting, Deborah Doroshow | Trial completion date: Dec 2027 --> Jul 2028

P2, N=240, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2026 --> Jun 2027

Overall concordance between Ki-67-based proliferation categories and RS-based genomic risk was 56.2%, with discordant cases in both directions. Ki-67 shows a modest association with Oncotype DX RS, but substantial discordance indicates Ki-67 should not substitute genomic testing in HR-positive/HER2-negative early breast cancer.

P=N/A, N=0, Available, Genentech, Inc.

P2, N=119, Recruiting, Università Vita-Salute San Raffaele | Not yet recruiting --> Recruiting | Phase classification: PN/A --> P2 | N=221 --> 119 | Trial completion date: Nov 2028 --> Dec 2029 | Trial primary completion date: May 2027 --> Jun 2029

ER-low (1-10 %) expression was rare in the study group. Low ER expression was linked with more aggressive features at diagnosis and seems to have worse DFS which was more pronounced after adjustment for different clinic-pathological factors.

Unlike the canonical activation of PAR1 by thrombin, which enhances cell proliferation via mechanistic target of rapamycin (mTOR) signaling, HAP-induced noncanonical activation downregulates mTOR activation and triggers autophagy in both estrogen receptor positive/ progesterone receptor positive/ HER2 negative (ER+/PR+/HER2-) and triple negative (ER-/PR-/HER2-) breast cancer cells...Importantly, the lack of PAR1 expression in normal, healthy breast epithelial cells facilitates the peptide to selectively target breast cancer cells with relatively high PAR1 expression, highlighting its potential as a therapeutic agent against low-grade malignant breast tumor. These findings provide valuable insights into autophagy activation by a synthetic peptide that targets breast cancer cells with high PAR1 expression and for the first time shows peptide mediated targeted therapy of low-grade malignant breast tumor.

P=N/A, N=68, Active, not recruiting, Mayo Clinic | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2028