New study results on breast cancer

1. Early breast cancer:

If breast cancer is detected early (at a stage where the tumor is locally confined and has not yet spread), there are very good chances of recovery today. Many women survive the disease in the long term and have good options for therapy that is not only effective but often also well tolerated. However, there are differences in the treatment of various forms and risk groups. Depending on age, tumor biology, and risk of recurrence, therapy and follow-up care can vary significantly. Medical progress is constantly bringing new studies and findings, which is why we have compiled a clear video collection from the ESMO Congress 2025 to make it easier to understand current recommendations and options.

Recommended videos here:

• HR+ new study results
• HER2+ new study results
• HR+/HER2+ new study results
• Sports in treatment: current study results

2. Advanced breast cancer:

If breast cancer has already formed metastases, i.e. has spread to other organs such as bones, lungs, liver or, rarely, the brain, it is referred to as advanced or metastatic breast cancer. In this situation, the focus is less on cure and more on controlling the disease in the long term, alleviating symptoms and maintaining the best possible quality of life. Thanks to modern therapies, e.g. hormone treatment, chemotherapy, targeted drugs and increasingly also new combinations, many patients today have the opportunity to live with the disease for months or even years. Here, too, we have compiled a video collection of results from the ESMO Congress 2025, which provides information on current study results.

Recommended videos here:

• HER2+ new study results
• TNBC new study results

The 26th NOGGO update on gynecologic oncology took place at the end of June, where important studies on breast cancer from ASCO 2025 were presented. We were there and would like to share the most important findings:

1. new molecular therapy approaches for advanced breast cancer

Here is an overview of current studies investigating innovative molecular therapies for hormone-dependent breast cancer:

1️⃣ PF-07248144: New KAT6 inhibitor as an option for endocrine resistance

In a phase 1 trial, PF-07248144, a novel KAT6 inhibitor, was tested in combination with fulvestrant in patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer. Daily 5 mg PF-07248144 plus fulvestrant showed a response rate of approximately 37% and an average survival without disease progression of 10.7 months . The overall tolerability was acceptable. As KAT6 is in many cases associated with endocrine resistance (= situation in which breast cancer cells no longer respond to hormone therapy), this active substance could become a therapeutic option in future as soon as phase III data follows.

A KAT6 inhibitor is an active substance that specifically blocks the KAT6 protein. This protein influences certain genes (e.g. those of the oestrogen receptors) and thus changes their activity. In this way, tumor cell activity can be suppressed and hormone therapy supplemented.

2️⃣ Vepdegestrant: PROTAC-based estrogen receptor degradation

The Phase III VERITAC-2 trial compared vepdegestrant, a novel PROTAC-ER degrader, with fulvestrant in estrogen receptor-positive, HER2-negative breast cancer with ESR1 mutation. In this subgroup, progression-free survival was significantly prolonged (median 5.0 vs. 2.1 months) . However, the overall population did not show a clear advantage, so further data remains to be seen.

A PROTAC-ER degrader is a new type of drug that specifically destroys the estrogen receptor (ER) in tumor cells – by using the cell’s natural protein disposal pathway.

ESR1 is a gene that contains information on the construction of the oestrogen receptor α (ERα). This receptor reacts to the hormone oestrogen and its signal leads to cell growth.

3️⃣ Ipatasertib + fulvestrant: AKT inhibition shows effect

The FINER study investigated the combination of ipatasertib with fulvestrant in oestrogen receptor-positive, HER2-negative patients after treatment failure with CDK4/6 inhibitor plus aromatase inhibitor. The median survival without disease progression was 5.3 months compared to 1.9 months in the control arm . In particular, patients with changes in the AKT signaling pathway (= central cellular control cascade that regulates the growth, survival and metabolism of cells) benefited more (5.5 vs 1.9 months). Tolerability was moderate, but no discontinuation rates have been reported to date.

4️⃣ SERENA-6: Paradigm shift with liquid biopsy and camizestrant

The SERENA-6 study shows a new approach: patients with an ESR1 mutation, detected by regular testing of circulating tumor DNA (ctDNA tests), switched to Camizestrant early, which reduced tumor progression by around 56% (median PFS around 16 instead of 9 months). A more favorable quality of life was also observed . The highlight: the change in therapy takes place before a relapse is radiologically or symptomatically visible – a real step towards individualized, biomarker-controlled treatment. However, the question still remains as to when and how often optimal testing should take place.

Conclusion for the clinic and patients

These studies show promising progress in molecularly controlled therapy for hormone-dependent breast cancer. In particular, the approaches with KAT6 inhibitors, PROTAC degraders and biomarker-based control via ctDNA mark the beginning of a new therapeutic era.

However, the following still applies: there are no changes to the guidelines for most areas – only phase III or long-term data can establish new standards.

2. current findings on hormone therapy in early breast cancer

The combination of ovarian function suppression (OFS) and hormone therapy has been investigated in detail in several large studies with premenopausal patients.

• In the SOFT and TEXT studies, the benefit of exemestane plus OFS versus tamoxifen plus OFS was monitored for more than ten years. Disease-free survival improved by around 4.6 % after twelve years. Overall survival was almost the same in the group with a low risk of relapse – but in women with a higher risk of relapse, a survival benefit of up to 5.5 % was achieved with Exemestane plus OFS .

• The Korean ASTRRA study compared tamoxifen alone with tamoxifen combined with OFS in women younger than 45 years who still had cycles. The results showed a clear absence of recurrence over five years in the women with additional OFS – particularly relevant in the case of previous chemotherapy .

• In young women with BRCA mutations, it has been shown that the combination of OFS with aromatase inhibitors offers the best chances of survival at high risk of relapse – while tamoxifen alone may be sufficient at low risk.

• The active ingredient elinzanetant was also tested as part of the OASIS-4 phase III trial: It can alleviate hot fl ushes (“hot flashes”) and sleep disorders caused by hormone therapy. After just a few weeks, a reduction in these symptoms of more than 50% was achieved – with good tolerability – and thus a clear improvement in quality of life .

Conclusion: What does this mean for patients?

At low risk: Patients can be treated well with tamoxifen alone – often sufficiently and with fewer side effects.
Medium risk: A decision between tamoxifen alone or tamoxifen/aromatase inhibitors plus OFS is possible. The side effect problems should be taken into account.
For patients at high risk: Exemestane plus OFS currently appears to be the most effective option for patients at high risk of relapse.

In addition, the development of new drugs such as elinzanetant shows that side effect management is becoming increasingly important to ensure that patients can withstand hormone therapies in the long term.

3. current therapeutic approaches in metastatic breast cancer

1️⃣ HR+ HER2 breast cancer: Inavolisib plus palbociclib & fulvestrant

The INAVO120 study showed the greatest therapeutic success in patients with hormone receptor-positive (HR+), HER2-negative, metastatic breast cancer with a PIK3CA mutation – and rapid progression during or within one year of adjuvant hormone therapy. The combination of inavolisib, palbociclib and fulvestrant doubled survival without disease progression and prolonged overall survival by around seven months (34 vs. 27 months) compared to standard therapy .

Important: A PIK3CA test prior to first-line therapy is therefore now crucial. In addition, proactive side effect management is necessary, as oral mucosal inflammation (stomatitis) and diarrhea can occur .

PIK3CA is a gene that provides the blueprint for an enzyme that plays an important role in the PI3K/AKT signaling pathway. This pathway controls cell growth, survival and division.

2️⃣ Triple-negative breast cancer (TNBC): sacituzumab govitecan + pembrolizumab

In the international ASCENT-04/KEYNOTE-D19 study, the combination of the antibody-drug conjugate sacituzumab govitecan and pembrolizumab significantly improved survival without disease progression (median 11.2 vs. 7.8 months) in PD-L1-positive, metastatic TNBC. The overall survival data are not yet complete, but initial trends indicate a benefit. The safety profile and tolerability corresponded to the known properties, with no new risks . An extension of approval for first-line use is still pending.

3️⃣ HER2-positive metastatic breast cancer: T-DxD (trastuzumab deruxtecan) + pertuzumab

The phase III DESTINY-Breast09 trial showed that the combination of T-DxD and pertuzumab significantly extended survival without disease progression compared to the previous standard therapy(paclitaxel + trastuzumab + pertuzumab) in HER2-positive breast cancer (median 40.7 vs. 26.9 months). T-DxD therefore has the potential to become the new first-line therapy in future. The extension of approval and data on the efficacy of T-DxD as a monotherapy are still pending.

Conclusion for patients & clinics

These new therapy combinations show enormous progress in the targeted treatment of metastatic breast cancer:

• Inavolisib + palbociclib + fulvestrant offers a significant survival benefit to patients with PIK3CA-mutated HR+, HER2- breast cancer – PIK3CA testing prior to initiation is essential.

• Sacituzumab govitecan + pembrolizumab could be a promising new option for PD-L1-positive TNBC patients – if approval is granted.

• T-DxD + pertuzumab showed outstanding efficacy in HER2+ breast cancer and could soon replace the previous standard.

However, there are currently no official changes to the guidelines here either. However, these data mark an important step towards even more effective and targeted therapies for metastatic breast cancer.

New Approaches against Metastatic Breast Cancer: Mini-Tumors from Circulating Tumor Cells

On January 3, 2025, the German Cancer Research Center (DKFZ) published an exciting press release on the results of a DKFZ research team that was able to develop a new approach to specifically eliminate tumor cells using blood samples from breast cancer patients.

Here is the press release:

Circulating tumor cells in the blood are the “germ cells” of breast cancer metastases. They are very rare and could not be propagated in cell culture dishes until now, which made the research of therapy resistances difficult. A team from the German Cancer Research Center (DKFZ), the Heidelberg Stem Cell Institute HI-STEM*, and the NCT Heidelberg** has now succeeded for the first time in cultivating stable tumor organoids directly from blood samples of breast cancer patients. Using these mini-tumors, the researchers were able to decipher a molecular signaling pathway that ensures the survival and therapy resistance of cancer cells. With this knowledge, the researchers succeeded in developing an approach to specifically eliminate the tumor cells in laboratory experiments.

Metastases are dangerous offshoots of tumors that spread to vital organs such as the liver, lungs, or brain and are usually difficult to treat. Even though the prognosis for breast cancer patients has significantly improved in recent decades, metastatic breast cancer still poses a major challenge, as metastases often respond only temporarily to therapies.
Cancer cells that detach from the primary tumor and migrate into other organs via the bloodstream are considered triggers of breast cancer metastases. These circulating cancer cells (CTCs) are extremely rare and hide among the billions of blood cells circulating in the blood vessels.

Andreas Trumpp, head of department at DKFZ and HI-STEM director, had already shown several years ago that only a few of the circulating tumor cells are capable of forming a new secondary tumor in another organ. These mostly therapy-resistant “germ cells” of metastases are very rare, difficult to isolate, and could not be propagated in the laboratory until now. “This makes it difficult to specifically develop new therapies that directly attack the metastasis-causing cells. However, if we understand how these cells survive the initial therapy and what drives their growth, we could combat the formation of breast cancer metastases at the root and perhaps even prevent them entirely one day,” explains the first author of the work, Roberto Würth from Trumpp’s research department.
The team around Andreas Trumpp has succeeded for the first time worldwide in propagating CTCs from blood samples of breast cancer patients and cultivating them as stable tumor organoids in cell culture. Until now, an detour was always necessary, namely the complex and lengthy propagation of CTCs in immunodeficient mice. To understand how tumor cells become resistant to therapies, researchers need tumor material from different time points in the course of the disease. Unlike surgical removal of tissue samples (biopsy), blood draws are simple and can be performed repeatedly.

The three-dimensional and patient-specific mini-tumors can be cultivated multiple times during the disease from blood samples and are excellently suited to investigate the molecular mechanisms that enable the survival of tumors despite therapy. Preclinical tests for the effectiveness of already available cancer drugs can also be carried out quickly and on a large scale on organoids in cell culture.
The clinical registry study CATCH (ClinicalTrials.gov ID: NCT05652569) at NCT Heidelberg analyzes the genetic diversity of tumor cells from breast cancer patients. Thanks to the successful cultivation of the organoids, the interdisciplinary research team around Trumpp, in close cooperation with the CATCH study, was able to identify a key signaling pathway that ensures the growth and survival of breast cancer CTCs in the blood. The protein NRG1 (Neuregulin 1) acts like a vital ‘fuel’. It binds to the HER3 receptor on the cancer cells and, together with the HER2 receptor, activates signaling pathways that ensure cell growth and survival. What’s also exciting: Even if this fuel runs out or the receptors are blocked by medication, the cells find new tricks. An alternative signaling pathway, controlled by the Fibroblast Growth Factor Receptor 1 (FGFR1), steps in and ensures growth and survival.

“Tumors react to external influences, for example, targeted therapies against HER2, by using such ‘bypass roads’. This is a crucial mechanism in the development of therapy resistance,” explains Roberto Würth. But there are ways out: The researchers showed on the organoids that a combined blockade of both signaling pathways (NRG1-HER2/3 and FGFR) can effectively stop the proliferation of tumor cells and induce cell death.

Andreas Trumpp summarizes: “The ability to cultivate CTCs from the blood of breast cancer patients at different time points as tumor organoids in the laboratory is a decisive breakthrough. This allows us to investigate much better how tumor cells become resistant to therapies. On this basis, we can develop new treatments that may also specifically kill resistant tumor cells. Another conceivable approach is to adapt existing therapies in such a way that the development of resistances and metastases is reduced or even prevented from the outset. Since the organoids are specific for each patient, the method is suitable for identifying or developing individually tailored therapies that are optimally adapted to the individual disease.” Before the method can be used in the care of breast cancer patients, it must first be tested in clinical studies.

*The Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH was founded in 2008 as a public-private partnership by DKFZ and Dietmar Hopp Foundation

** The National Center for Tumor Diseases (NCT) Heidelberg is a long-term cooperation between the German Cancer Research Center (DKFZ), the University Hospital Heidelberg (UKHD), the Medical Faculty of Heidelberg University, and the Thoraxklinik Heidelberg.

Source: DKFZ

Breast Cancer Study Showed Improved Progression-Free Survival in Advanced HR+, HER2- Breast Cancer

A new Phase III breast cancer study, led by Dr. Kümmel, shows promising results for the treatment of advanced HR+, HER2- breast cancer. The so-called postMONARCH study is the first of its kind to investigate the benefit of “treatment beyond progression” with CDK4/6 inhibitors. Patients whose disease had progressed despite prior therapy with CDK4/6 inhibitors and endocrine therapy benefited from continued treatment with abemaciclib. The study recorded a 27% risk reduction for disease progression and demonstrated a significant improvement in progression-free survival (PFS)

Study Design and Results

Study Lead: Dr. Kümmel

Design: Randomized, placebo-controlled Phase III study

Treatment: Abemaciclib

Results:

1. Abemaciclib showed a significant improvement in progression-free survival (PFS).
2. There was a 27% risk reduction for disease progression.
3. The control arm performed better than expected, but the results confirmed the benefit of continued CDK4/6 inhibitor therapy.

This study shows for the first time that continued treatment with CDK4/6 inhibitors after disease progression can be beneficial.

Change from July 1 – Mammography Screening also for Women Aged 70-75

From July 1, 2024, the mammography screening program for early detection of breast cancer will be extended to women aged 70 to 75. Previously, the program was limited to women between 50 and 69 years of age. From this date, women can register for an appointment with the responsible central offices if their last examination was at least 22 months ago. A personal invitation is not yet being sent.

Further information can be found on the G-BA website.

What is a mammography screening?

Merck’s Phase 3 Study Shows Success in Breast Cancer Treatment

Merck announced that the Phase 3 KEYNOTE-522 study of Keytruda (anti-PD-1 therapy) met its overall survival endpoint in high-risk early-stage triple-negative breast cancer (TNBC). In combination with chemotherapy as a pre-operative treatment and subsequent monotherapy after surgery, Keytruda showed significant improvement compared to chemotherapy alone. No new safety concerns were identified. This is the first time an immunotherapy-based treatment has shown a survival benefit in TNBC patients.

More information…