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: <\/p>\n
Here is an overview of current studies investigating innovative molecular therapies for hormone-dependent breast cancer:<\/span><\/p>\n In a phase 1 trial, PF-07248144,<\/strong> a novel KAT6 inhibitor<\/em>, was tested in combination with fulvestrant<\/em> in patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer. Daily 5 mg PF-07248144 plus fulvestrant<\/em> showed a response rate of approximately 37% and an average survival without disease progression of 10.7 months<\/strong> <\/span>. 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. <\/span><\/p>\n 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. <\/p>\n The Phase III VERITAC-2 trial compared vepdegestrant<\/em>, a novel PROTAC-ER degrader, with fulvestrant<\/em> 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<\/strong>) <\/span>. However, the overall population did not show a clear advantage, so further data remains to be seen.<\/span><\/p>\n 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.<\/p>\n ESR1 is a gene that contains information on the construction of the oestrogen receptor \u03b1 (ER\u03b1). This receptor reacts to the hormone oestrogen and its signal leads to cell growth. <\/p>\n The FINER study investigated the combination of ipatasertib <\/em>with fulvestrant<\/em> 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<\/strong> compared to 1.9 months in the control arm <\/span>. 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. <\/span><\/p>\n The SERENA-6 study<\/strong> shows a new approach: patients with an ESR1 mutation, detected by regular testing of circulating tumor DNA (ctDNA tests), switched to Camizestrant<\/em> early, which reduced tumor progression by around 56%<\/strong> (median PFS around 16 instead of 9 months). A more favorable quality of life was also observed <\/span>. 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. <\/span><\/p>\n These studies show promising progress in molecularly controlled therapy for hormone-dependent breast cancer. In particular, the approaches with KAT6 inhibitors<\/strong>, PROTAC degraders<\/strong> and biomarker-based control via ctDNA<\/strong> mark the beginning of a new therapeutic era. <\/p>\n However, the following still applies: there are no changes to the guidelines<\/strong> for most areas – only phase III or long-term data can establish new standards.<\/p>\n The combination of ovarian function suppression (OFS)<\/strong> and hormone therapy<\/strong> has been investigated in detail in several large studies with premenopausal patients.<\/span><\/p>\n The Korean ASTRRA study<\/strong> compared tamoxifen<\/em> alone with tamoxifen<\/em> 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 <\/span>.<\/p>\n<\/li>\n In young women with BRCA mutations<\/strong>, 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<\/em> alone may be sufficient at low risk.<\/span><\/p>\n<\/li>\n The active ingredient elinzanetant <\/em>was also tested as part of the OASIS-4<\/strong> phase III trial: It can alleviate hot fl<\/strong> ushes (“hot flashes”) and sleep disorders <\/strong>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 <\/span>.<\/p>\n<\/li>\n<\/ul>\n At low risk<\/strong>: Patients can be treated well with tamoxifen alone<\/strong> – often sufficiently and with fewer side effects. In addition, the development of new drugs such as elinzanetant shows that side effect management is becoming increasingly important<\/strong> to ensure that patients can withstand hormone therapies in the long term.<\/p>\n The INAVO120 study<\/strong> 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<\/em>, palbociclib <\/em>and fulvestrant<\/em> doubled survival without disease progression and prolonged overall survival by around seven months (34 vs. 27 months) compared to standard therapy <\/span>.<\/p>\n Important: A PIK3CA test prior to first-line therapy<\/strong> is therefore now crucial. In addition, proactive side effect management is necessary, as oral mucosal inflammation (stomatitis) and diarrhea can occur <\/span>.<\/p>\n PIK3CA<\/strong> 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. <\/p>\n In the international ASCENT-04\/KEYNOTE-D19 study<\/strong>, the combination of the antibody-drug conjugate sacituzumab govitecan<\/em> and pembrolizumab<\/em> significantly improved survival without disease progression (median 11.2 vs. 7.8 months) in PD-L1-positive, metastatic TNBC.<\/span> 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 <\/span>. An extension of approval for first-line use is still pending.<\/span><\/p>\n The phase III DESTINY-Breast09<\/strong> trial showed that the combination of T-DxD<\/em> and pertuzumab <\/em>significantly extended survival without disease progression compared to the previous standard therapy(paclitaxel + trastuzumab + pertuzumab<\/em>) in HER2-positive breast cancer (median 40.7 vs. 26.9 months)<\/span>. T-DxD<\/em> 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<\/em> as a monotherapy are still pending. <\/span><\/p>\n These new therapy combinations show enormous progress in the targeted treatment of metastatic breast cancer:<\/p>\n Inavolisib + palbociclib + fulvestrant<\/strong> offers a significant survival benefit to patients with PIK3CA-mutated HR+, HER2- breast cancer – PIK3CA testing prior to initiation is essential<\/strong>.<\/p>\n<\/li>\n Sacituzumab govitecan + pembrolizumab<\/strong> could be a promising new option for PD-L1-positive TNBC patients – if approval is granted.<\/p>\n<\/li>\n T-DxD + pertuzumab<\/strong> showed outstanding efficacy in HER2+ breast cancer and could soon replace the previous standard.<\/p>\n<\/li>\n<\/ul>\n 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. <\/p>\n","protected":false},"excerpt":{"rendered":" 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 […]<\/p>\n","protected":false},"author":7,"featured_media":5065,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[52],"tags":[],"class_list":["post-4990","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news-en"],"acf":[],"_links":{"self":[{"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/posts\/4990","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/comments?post=4990"}],"version-history":[{"count":2,"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/posts\/4990\/revisions"}],"predecessor-version":[{"id":5106,"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/posts\/4990\/revisions\/5106"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/media\/5065"}],"wp:attachment":[{"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/media?parent=4990"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/categories?post=4990"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/studienportal-brustkrebs.de\/en\/wp-json\/wp\/v2\/tags?post=4990"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}1\ufe0f\u20e3 PF-07248144: New KAT6 inhibitor as an option for endocrine resistance<\/h4>\n
2\ufe0f\u20e3 Vepdegestrant: PROTAC-based estrogen receptor degradation<\/h4>\n
3\ufe0f\u20e3 Ipatasertib + fulvestrant: AKT inhibition shows effect<\/h4>\n
4\ufe0f\u20e3 SERENA-6: Paradigm shift with liquid biopsy and camizestrant<\/h4>\n
Conclusion for the clinic and patients<\/h4>\n
2. current findings on hormone therapy in early breast cancer<\/h3>\n
\n
Conclusion: What does this mean for patients?<\/h4>\n
\nMedium risk<\/strong>: A decision between tamoxifen alone<\/strong> or tamoxifen\/aromatase inhibitors plus OFS<\/strong> is possible. The side effect problems should be taken into account.
\nFor patients at high risk<\/strong>: Exemestane plus OFS<\/strong> currently appears to be the most effective option for patients at high risk of relapse.<\/p>\n3. current therapeutic approaches in metastatic breast cancer<\/h3>\n
1\ufe0f\u20e3 HR+ HER2 breast cancer: Inavolisib plus palbociclib & fulvestrant<\/em><\/h4>\n
2\ufe0f\u20e3 Triple-negative breast cancer (TNBC): sacituzumab govitecan + pembrolizumab<\/em><\/h4>\n
3\ufe0f\u20e3 HER2-positive metastatic breast cancer: T-DxD (trastuzumab deruxtecan) + pertuzumab<\/em><\/h4>\n
Conclusion for patients & clinics<\/h4>\n
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