ASCO 2025 Updates in Early Stage Breast Cancer

Promise study, WinPRO trial, NATALEE updates, and the TRADE study

There is so much incredible breast cancer research being presented at the ASCO (American Society of Clinical Oncology) 2025 Annual Meeting (largest oncology meeting in the world!). In this post, I am going to review four studies: the Promise Study (Duavee, which is a form of HRT, in DCIS); WinPro trial (endocrine therapy with and without prometrium in early stage HR+ BC); updates from NATALEE (ribociclib (Kisqali) in early stage breast cancer); and the TRADE Study (abemaciclib (Verzenio) dose escalation in early stage HR+/HER2- BC). Let’s get into it!

Photo by Pedro Lastra on Unsplash

The Promise study: A presurgical randomized clinical trial of CE/BZA vs placebo in postmenopausal women with ductal carcinoma in situ. (Abstract 512, Kulkarni S et al).

The Promise study looked at Duavee (conjugated estrogen with bazedoxifene CE/BZA), which is a form of menopausal hormone therapy. Duavee is an oral medication that contains estrogen and bazedoxidene (BZA). BZA is a selective estrogen receptor modulator (SERM), meaning that it works as a pro-estrogen in some areas and anti-estrogen in others. BZA works as an anti estrogen in the breast and uterus so there’s a lot of excitement in using it because it does not stimulate the breast tissue. It also does not require a progesterone because of the anti estrogen activity in the uterus. Preclinical studies have shown that CE/BZA reduces proliferation of cells in the milk ducts of the breast and increased expression of markers in surrounding breast tissue that may be protective against cancer.

The Promise trial looked at whether short-term treatment with CE/BZA before surgery could lower Ki67 (a marker of cell growth/proliferation) in women with estrogen receptor–positive (ER+) DCIS, while also monitoring for side effects and quality of life changes. They looked at 117 women (average age 60) with HR+ DCIS: 58 received placebo and 59 received CE/BZA for 28 days and then they had surgery.

The results were promising: CE/BZA significantly reduced Ki67 in breast tissue compared to placebo, suggesting a potential protective effect. Importantly, women taking CE/BZA did not experience any worsening in quality of life—and their hot flashes actually improved. There were no serious treatment-related side effects. Although we cannot say based on this study that CE/BZA can safely be used in hormone receptor positive DCIS (this is a small study and patients only received the medication for 4 weeks before surgery), the Ki67 reduction is exciting and I think it is a good step forward in research for menopause hormone therapy in breast cancer. I would love to see longer studies of Duavee in DCIS!

The WinPro trial: A window of opportunity study of endocrine therapy with and without prometrium in postmenopausal women with early stage hormone receptor-positive breast cancer. (Abstract 513, Haggstrom L et al).

Next up, we have the WinPro trial which looked at using progesterone in postmenopausal women with early stage ER+/PR+/HER2- breast cancer. There are conflicting preclinical studies of progesterone in breast cancer. Some studies say it can be beneficial and other studies show that it may increase cancer growth. Remember that preclinical studies are in cell lines, mouse models etc and we can’t extrapolate what happens in cells to humans. In this study, patients with postmenopausal patients with ER+/PR+/HER2- breast cancer received progesterone + letrozole or letrozole alone or tamoxifen+ progesterone preoperatively for 2 weeks. Patients with metastatic or inoperable disease were not part of the study. Patients received Prometrium which is an oral microionized progesterone.

After 2 weeks, participants had surgery and they looked at pre-treatment and post-treatment Ki67 levels. Remember from above that Ki67 is a marker of proliferation and cell growth. The majority of patients had tumors <5cm, about a third were lymph node positive, ~15% had lobular breast cancer. 189 patients were enrolled. The average Ki67 was about 8-10% (which is low).

What were the results? Ki67 suppression was similar in both progesterone + letrozole and letrozole arms (less effective in tamoxifen+ progesterone…but that may be more tamoxifen related rather than anything to do with the progesterone). The addition of progesterone to letrozole was well tolerated and led to a reduction in hot flashes.

This is a very early study and we really cannot make further conclusions about the use of progesterone in HR+ breast breast cancer aside from what this study tells us but it is certainly a step in the right direction of trials looking at HRT in HR+ breast cancer.

Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in NATALEE: Analysis across menopausal status and age. (Abstract 516, Kalinsky K et al).

The NATALEE study looks at adding ribociclib (CDK 4/6 inhibitor) (Kisqali) to an aromatase inhibitor for early stage HR+/HER2- breast cancer. For more on the study, I have a lot of videos on Instagram (here’s the one from when the study was originally presented.) This specific analysis presented at ASCO 2025 looked to see if there was a difference in the benefit by age and menopausal status, which is a really important question. They found that there were similar benefits across menopausal status and age subgroups and the benefit persisted after stopping ribociclib (which is given for 3 years). At a median follow-up of 44.2 months, invasive disease free survival was 90.6% in premenopausal patients who received ribociclib (compared to 85.3% in those who did not, =5.3% absolute benefit). Similar results were seen in postmenopausal patients: 86.8% versus 82.2% (4.6% absolute benefit for ribociclib). Remember that these are averages. There were fewer discontinuations of ribociclib for side effects in younger premenopausal patients.

The TRADE study: A phase 2 trial to assess the tolerability of abemaciclib dose escalation in early-stage HR+/HER2- breast cancer. (Abstract 517, Mayer E et al).

Abemaciclib (Verzenio) is a CDK 4/6 inhibitor used in combination with endocrine therapy in early stage HR+/HER2- breast cancer at higher risk of recurring. Patients who are eligible to receive abemaciclib had breast cancer with 4 or more positive lymph nodes or had 1-3 positive lymph nodes and either a tumor >=5cm or grade 3. This was based on the MonarchE study. Some of the common side effects of abemaciclib are diarrhea, neutropenia, fatigue and some patients cannot tolerate the full dose of 150 mg twice daily and have to dose reduce. The TRADE study attempted to see whether we can do a dose escalation to start abemaciclib starting at a low dose and working upwards. Patients received 50 mg twice daily for 2 weeks then 100 mg twice daily for 2 weeks and then increased to 150 mg twice daily. 63/89 patients (~70%) were able to reach the target dose. 12 patients could not maintain the target dose, 8 could not reach the target dose and 6 discontinued it early. This was a higher amount of patients that were able to reach and maintain the full dose at 12 weeks compared to what was originally reported in the MonarchE study (60%). An early dose escalation strategy could be an option when starting abemaciclib.

There are still lots more updates to come but all 4 studies are important (especially the last one as I think it can be immediately impactful to how we take care of patients!). Let me know your questions and thoughts.