Breast cancer advances took centre stage at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, with several high-impact clinical trials pointing to a shift in treatment paradigms. From rethinking progression in hormone receptor–positive disease to advancing therapies earlier in the treatment course, new data from SERENA-6, DESTINY-Breast09, and ASCENT-04 could reshape standards of care across subtypes. Below, Dr Sara Tolaney (Dana-Farber Cancer Institute, Boston, MA, USA) and Dr Erika Hamilton (Sarah Cannon Research Institute, Nashville, TN, USA) share their key take-aways.
Dr Sara Tolaney
Chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
“SERENA-6 challenges the way we’ve traditionally managed progression…a game-changer in how we approach hormone receptor–positive metastatic breast cancer”
“ASCO this year was really exciting for breast cancer – we saw a number of potentially practice-changing trials. One of these was the SERENA-6 trial (LBA4), which was presented in a plenary session. I think it could represent a paradigm shift in how we think about treating metastatic hormone receptor–positive breast cancer.
Traditionally, we treat patients until they develop anatomic progression, usually identified through staging scans. But this trial introduces a new concept – can we use molecular progression, such as the emergence of resistance mutations, to guide treatment changes even before anything shows up on imaging? The idea is that if a resistance mutation develops but the patient doesn’t yet show radiographic progression, we might consider switching therapy earlier to overcome that resistance – rather than waiting for it to show up on scans. I think it’s a very clever and innovative strategy.
SERENA-6 studied patients who were on first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor. After at least six months on treatment, they were monitored with liquid biopsies – so, ctDNA blood draws every 2–3 months. If one of those tests showed the emergence of an ESR1 mutation, patients could then be randomised to either switch to camizestrant plus the same CDK4/6 inhibitor, or to continue with their current aromatase inhibitor and CDK4/6 inhibitor. The idea was to test whether using an oral SERD at the time the ESR1 mutation emerges – rather than waiting for radiographic progression – might lead to better outcomes.
What the study showed was that progression-free survival for the patients who received camizestrant plus CDK4/6 inhibition was about 16 months, compared to roughly 9 months in the group that stayed on the aromatase inhibitor with CDK4/6 inhibition. So, around a 7-month improvement in progression-free survival.
One natural question is whether early switching truly improves long-term outcomes. Could it be just as effective to wait and switch therapies after anatomical progression? To explore that, we usually look at what’s called PFS2 – the time from randomisation to progression on the subsequent line of therapy. Right now, PFS2 is trending in favour of the camizestrant arm, but those data are not yet mature – so we’ll have to wait and see.
Interestingly, the study also showed better quality of life for the patients who received camizestrant plus CDK4/6 inhibition, compared to those who stayed on their aromatase inhibitor regimen. That raises the possibility that earlier switching might help patients avoid symptoms associated with disease progression and maintain a better quality of life for longer.
This was a very innovative trial – we haven’t seen a registration trial like this before. It could be a game changer in how we manage patients receiving aromatase inhibitors and CDK4/6 inhibitors, potentially supporting earlier introduction of SERD therapy.
Big congratulations to the authors – it was really exciting to see this work presented.”
Dr Erika Hamilton
Director, Breast Cancer Research, Sarah Cannon Research Institute, Nashville, TN, USA
“The theme this year was clear – taking therapies we know work and moving them earlier in treatment”
“ASCO 2025 was a big year for breast cancer, and we love to see that. Multiple New England Journal of Medicine publications, multiple major abstracts. I think one of the standouts was DESTINY-Breast09 (LBA1008). This was the trial looking at trastuzumab deruxtecan in the first-line HER2-positive setting, building on previous data from DESTINY-Breast03 in the second-line setting. Progression-free survival was lengthened by more than 13 months, so this really does have the potential to be practice-changing – bringing trastuzumab deruxtecan into the first-line setting for HER2-positive disease. I think the remaining question is what we’re going to do about maintenance when we use trastuzumab deruxtecan.
Another example – along a similar theme of moving an existing therapy earlier – was sacituzumab govitecan in ASCENT-04 (LBA109). Sacituzumab govitecan is currently approved for triple-negative breast cancer, but not in the first-line setting. This trial specifically looked at patients with first-line disease who were PD-L1 positive, comparing chemotherapy plus pembrolizumab versus sacituzumab govitecan plus pembrolizumab. And again, we saw improved progression-free survival.
We’ve also seen a press release – though no data yet – that the companion trial, ASCENT-03 (NCT02574455), which looked at PD-L1-negative tumours, was also positive, so we anticipate seeing that data in the next couple of months. It’s a potential opportunity for sacituzumab govitecan to have a role in the first-line triple-negative setting.
I think the most controversial abstract in breast cancer was probably SERENA-6 trial, which was presented in the plenary session. It had some really interesting data – it looked at the emergence of ESR1 mutations in the first-line setting. These were patients on an aromatase inhibitor and a CDK4/6 inhibitor who did not initially have an ESR1 mutation but subsequently developed one. We know that’s a resistance mechanism. The trial then randomized patients to either stay on their current therapy or switch to camizestrant with the CDK4/6 inhibitor.
This showed a statistically significant improvement in progression-free survival. The trick is how to interpret that data. We know that if resistance develops, switching to another therapy can be beneficial – we showed that here with camizestrant. They also looked at progression-free survival 2, or PFS2, the next line of therapy and overall how patients do across lines of treatment. However, because of the design – switching to camizestrant with CDK4/6 inhibition in the absence of clinical progression – it ended up being almost like comparing three lines of therapy to two. So we’re definitely looking to get more mature PFS2 data, as well as overall survival, to determine whether we really should be checking for ESR1 mutations if it’s ultimately going to improve quality of life, length of life and how well our patients do over time.”
View full #ASCO25 coverage here!
Cite: #ASCO25: SERENA-6, DESTINY-Breast09, ASCENT-04 – top breast cancer breakthroughs you need to know! touchONCOLOGY. June 18th, 2025
Disclosures: Dr Sara Tolaney is a consultant for Novartis, Pfizer/SeaGen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, Summit Therapeutics. She has received grant/research support from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, AstraZeneca, NanoString Technologies, Gilead, SeaGen, OncoPep, Daiichi Sankyo, Menarini/Stemline, Jazz Pharma. She is a member of the Advisory Board for Novartis, Pfizer/SeaGen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, Summit Therapeutics. She has received honoraria/honorarium from Novartis, Pfizer/SeaGen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, Summit Therapeutics. Dr Erika Hamilton is a consultant/advisor for Accutar Biotechnology, Arvinas, AstraZeneca, Daiichi Sankyo, Gilead Sciences, Lilly, Mersana Therapeutics, Olema Pharmaceuticals, Pfizer, Roche/Genentech and Stemline Therapeutics (all payments to institution).
SIGN UP to touchONCOLOGY!
Join our global community today for access to thousands of peer-reviewed articles, expert insights, and learn-on-the-go education across 150+ specialties, plus concise email updates and newsletters so you never miss out.
