HER2 Negative Breast Cancer

P=N/A, N=50, Recruiting, University of Pittsburgh

Early clinical data demonstrated activity of BLU-222, a potent and selective CDK2 inhibitor, both as monotherapy (CCNE1 amplified) and in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer. These findings provide evidence that CDK2i combined with CDK4/6i can address multiple known mechanisms of resistance to CDK4/6i, enhancing antitumor responses in preclinical breast cancer models.

In the two cases we reported, first-line palbociclib therapy shows adequate and timely responses for premenopausal HR+/HER2- metastatic breast cancer patients. Although not widely utilized, frontline therapy with palbociclib combined with endocrine treatments may be a choice for HR+/HER2- metastatic breast cancer patients experiencing severe visceral metastasis.

Despite unchanged guideline recommendations, fewer patients started ET over time. This trend, and regional variation, suggests that a more reticent approach by physicians to initiating ET for HR+/HER2- breast cancer may be contributing to it.

Sapacitabine with olaparib produces high rates of hematologic toxicity. However, the ORR of 50%, mPFS of 9.7 months, and durability of response in some patients suggest possible combinatorial benefit. Further exploration of olaparib with different sapacitabine schedules or substitution of a PARP1-selective inhibitor to potentially decrease hematological toxicity is warranted.

Patients with PR values <20% tended to have shorter PFS, unlike the Ki-67 value, which did not demonstrate an impact on PFS. This suggests a prognostic value of PR expression levels in this scenario.

Collectively, our study demonstrates that ITPC exhibits a robust accuracy for detecting SLN metastases in cN + breast cancer patients treated with NAC. The findings support the implementation of molecular subtype-specific SLN management: ITPC alone may be adequate for HER2-positive and TNBC tumors; for hormone receptor-positive (Luminal) subtypes, ITPC may need to be combined with molecular/immunohistochemical analysis.

P3, N=1000, Recruiting, Olema Pharmaceuticals, Inc. | Not yet recruiting --> Recruiting

P2, N=35, Not yet recruiting, Sun Yat-sen University

In a neoadjuvant immunotherapy real-world cohort (n = 111), HER2-low primary tumors had lower midcourse (28% vs. 44%) and pathological complete response (64% vs. 72%) compared to HER2-0. These findings show that HER2 expression defines immune-cold HER2-negative EBC, hindering immunotherapy and supporting HER2-targeted combination in HER2-low EBC patients.

Our study supports a dual regulatory hypothesis, in which CCR5 expression may influence immune dynamics and therapeutic response, while its structural stability may serve as a potential modulatory factor. This hypothesis-generating observation suggests that CCR5 could represent a potential prognostic and predictive biomarker, particularly in NAC-refractory or immune-inflamed breast cancers.

ERpHER2n-Basal breast cancer represents a clinically high-risk subgroup whose molecular resemblance to TNBC highlights potential therapeutic opportunities, particularly for immunotherapy and DNA repair-targeting treatments.