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Among 1,545 women included with a median follow-up of 9.4 years in postmenopausal women, breast cancer events occurred in 40 of 335 receiving low-dose tamoxifen versus 93 of 401 controls HR, 0.51, with a 10-year absolute reduction of 11.2%. Among premenopausal women, no significant reduction was observed dose was 5mg daily of 10mg every other day in ductal carcinoma in situ (DCIS) and high-risk pts. Less is as good.

644 patients who are triple-negative breast cancer (TNBC) not candidates for immunotherapy were randomly assigned to receive Dato-DXd (n = 323) or chemotherapy (n = 321). Median progression-free survival (PFS) was 10.8 months with Dato-DXd and 5.6 months with chemotherapy. Median overall survival (OS) was 23.7 months and 18.7 months with Dato-DXd and chemotherapy, respectively HR 0.79; P = 0.029]. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in 105 (33%) and 89 (29%) patients who received Dato-DXd and chemotherapy, respectively, they were more treatment discontinuation in the chemotherapy arm secondary to treatment related adverse events in 14 (4%) and 23 (7%) patients. There were no treatment-related deaths in either arm. New standard of care? Recall this is on patients not eligible for immunotherapy.

Less radiation (40Gy vs 50 Gy) was non inferior in preventing locoregional recurrence and distant mets, also lymphedema rates were not worse. Would love feedback from our rad onc, but it seems less is as good.

Progression-free survival (PFS) was statistically significantly improved with addition of tucatinib versus placebo 24.9 v 16.3 months regardless of the presence/absence of BM or hormone receptor status.

1467 pts with RS > 25 and 551 with clinically (neoadjuvant cohort in ADAPT-HR+/HER2-) or pathologically N2, (longer) docetaxel-based CTx showed better distant, invasive disease-free survival in N2-3 pts patients with RS ≤25, OS was also shown in pts with RS>25 anthracycline regimens did not show a significant survival difference in high-risk HR+/HER2 whether used in neoadjuvant or adjuvant setting. So may be no anthracycline for HR+ve pts who are high risk disease.

Primary objective not met, ctDNA clearance post- neoadjuvant therapy (NAT) cannot reliably predict pathologic complete response (pCR) and shouldn't be used to defer surgery. But the prognostic data are striking: post-NAT ctDNA positivity independently predicted recurrence in triple-negative breast cancer (TNBC) (HR 8.9), and the postsurgical landmark analysis is essentially binary, 100% of ctDNA-positive patients recurred while 94% of ctDNA-negative patients were disease-free at 5 years (HR 128). Not practice-changing yet pending prospective utility trials, but this strongly validates ultrasensitive ctDNA as a prognostic tool and a smart enrollment biomarker for future escalation/de-escalation trials.

Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway. PFS was 9.3 m in the gedatolisib-triplet group vs 2.0 m in the fulvestrant group (hazard ratio) HR 0.24, and 7.4 m in the gedatolisib-doublet group HR 0.33 v fulvestrant.

This is impressive. However, there is no reported placebo trastuzumab deruxtecan arm, so this is not truly a “no chemotherapy” regimen. It is important to remember that deruxtecan is itself a chemotherapy agent. So, this is really comparing deruxtecan vs taxol or more accurately, a comparison of chemotherapy delivery systems.

The QUIWI study used quizartinib, a FLT3 drug added to standard chemo induction/consolidation in FLT-negative acute myeloid leukemia (AML) patients. There was a meaningful overall survival (OS) improvement across all age and risk groups including the NPM1+ population. They purposefully used a higher dose to achieve what is felt to be off-target TKI activity in familiar pathways of KIT, PDGRF…etc.

This really feels like a first-line practice changer in PD-L1+ MTNBC—the sacituzumab govitecan/pembrolizumab combination delivering a 3.4-month progression-free survival (PFS) improvement and pushing median PFS past 11 months is quite meaningful. Mature overall survival (OS) data will be interesting to see. Remember to watch closely and consider screening for drug-induced interstitial lung disease(ILD).