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HER2+ Metastatic Breast Cancer: Personalized Maintenance & Endocrine Therapy

Medical oncology

Metastatic Breast Cancer

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Description

This program is supported by an independent education grant from Pfizer Global Medical Grants. This online education program has been designed for healthcare professionals globally.

Prefer to read instead? Read the Key Clinical Summary for Learning Objective 1 here and for Learning Objective 2 here.

In this on-demand video, leading expert Rupert Bartsch, MD explores the evolution and rationale for maintenance de-escalation in first-line HER2-positive metastatic breast cancer (LO1) and the role of endocrine therapy ± CDK4/6 inhibitors in HER2+/HR+ disease (LO2). Dr. Bartsch will summarize the shift from the CLEOPATRA model to contemporary de-escalation trials, describe survival and quality-of-life gains, and define optimal timing to begin maintenance therapy. He will also review evidence for endocrine–HER2 cross-talk, highlight key data from trials such as PERTAIN, PATINA, and monarcHER, and provide practical guidance for selecting, sequencing, and managing ET/CDK4/6 inhibitors in clinical practice.

Accreditation: 0.5 AMA PRA Category 1 Credits™

This is a rapidly evolving field: Don't forget to read out latest update summary from San Antonio Breast Cancer Symposium 2025 >

Session Highlights

Historical to Contemporary Approaches: Compare the CLEOPATRA trial model with modern de-escalation strategies in HER2+ MBC.
Survival and QoL Impact: Review evidence demonstrating gains in patient outcomes with timely maintenance transition.
Optimal Timing for Maintenance: Define when to transition from induction chemotherapy to maintenance therapy.
Endocrine Integration: Review HER2–ER cross-talk, endocrine layering strategies, and evidence from PERTAIN, PATINA, and monarcHER.
Practical Decision-Making: Identify clinical markers that guide safe chemotherapy shortening, re-escalation, or integration of ET/CDK4/6 inhibitors.

Who Should Watch

Medical Oncologists
Nurse Practitioners
Physician Assistants
Oncology Nurses
Oncology Fellows
Pharmacists
Internal Medicine Physicians with an oncology focus
other HCPs involved in the care of metastatic breast cancer.

Presented by

Rupert Bartsch, MD – Professor and Chair, Division of Breast Oncology, Comprehensive Cancer Center Vienna; Principal Investigator, European HER2+ MBC Consortium. Dr. Bartsch’s research has shaped de-escalation and endocrine-integration paradigms in HER2-positive metastatic disease.

Disclosures

Dr Rupert Bartsch has disclosed financial relationships with the following ineligible companies within the past 24 months: Amgen, AstraZeneca, Bristol Myers Squibb (BMS), Daiichi Sankyo, Eisai, Eli Lilly, Grünenthal, MSD, Novartis, Roche Pharmaceuticals, and Gilead Sciences. These relationships include advisory roles, lecture honoraria, research support, and travel support.

These disclosures are made in accordance with ACCME standards to ensure transparency and objectivity in continuing education. Dr Bartsch intends to discuss non-FDA uses of drug products and/or devices and their unlabelled indications and will disclose to the audience when this discussion takes place.

AffinityCE staff, MedAll staff, and all planners and reviewers have no relevant financial relationships with ineligible companies to disclose.

Activity Accreditation for Health Professions

This activity will be planned and implemented in accordance with the accreditation requirements and policies of both the Accreditation Council for Continuing Medical Education (ACCME) and the European Board for Accreditation of Continuing Education for Health Professionals (EBAC). Through joint providership with AffinityCE (ACCME-accredited) and MedAll (EBAC-accredited), continuing education credit will be provided for both live and enduring activities.

EBAC Compliance and Credit Conversion

This activity has been planned and implemented in accordance with the accreditation requirements and policies of EBAC.

In compliance with EBAC guidelines, all speakers and chairpersons participating in this programme have disclosed or indicated potential conflicts of interest which might cause a bias in the presentations. The Organizing Committee/Course Director is responsible for ensuring that all potential conflicts of interest relevant to the event are declared to the audience prior to the CE activities.

Through an agreement between EBAC and the American Medical Association, physicians may convert EBAC External CME credits to AMA PRA Category 1 Credits™. Information on the process to convert EBAC credit to AMA credit can be found on the AMA website at https://edhub.ama-assn.org/pages/applications. Other healthcare professionals may obtain from the AMA a certificate of having participated in an activity eligible for conversion of credit to AMA PRA Category 1 Credit™.

The Accreditation Council for Continuing Medical Education (ACCME) and the Royal College of Physicians and Surgeons of Canada hold an agreement on substantial equivalency of accreditation systems with EBAC.

How to Earn Your CME Credit

In order to obtain your CME credit and receive your certificate, please join the webinar and complete the assessment at the end. You will receive a link to your certificate automatically after completing the assessment.

Participation Costs

There is no cost to participate in this program.

ACCME Continuing Education Information

Commercial support: This activity received monetary support through an independent education grant from Pfizer

This continuing education activity will be provided by AffinityCE and MedAll. This activity will provide continuing education credit for physicians. A statement of participation is available to other attendees.

AffinityCE staff, MedAll staff, as well as planners and reviewers, have no relevant financial relationships with ineligible companies to disclose. Faculty disclosures will be declared prior to the event.

Mitigation of Relevant Financial Relationships

AffinityCE adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible companies. Relevant financial relationships were mitigated by the peer review of content by non-conflicted reviewers prior to the commencement of the program.

Activity Accreditation for Health Professions

Physicians

This activity will be planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and Medall. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring activity a maximum of 0.5 AMA PRA Category 1 Credits™.

Physician Assistants

This activity will be planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and MedAll AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring activity a maximum of 0.5 AMA PRA Category 1 Credits™. Physician assistants should claim only the credit commensurate with the extent of their participation in the activity.

Nurse Practitioners

This activity will be planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and MedAll. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring activity a maximum of 0.5 AMA PRA Category 1 Credits™. Nurse practitioners should claim only the credit commensurate with the extent of their participation in the activity.

Nurses & Other Professionals

All other health care professionals completing this continuing education activity will be issued a statement of participation indicating the number of hours of continuing education credit. This may be used for professional education CE credit. Please consult your accrediting organization or licensing board for their acceptance of this CE activity.

Pharmacists

Pharmacists AffinityCE is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education (CPE).

CE Title: HER2+ Metastatic Breast Cancer Grand Rounds: Latest Advances - Individualizing First-Line Therapy in Metastatic HER2-positive Breast Cancer

Format: Enduring Portion

UAN: 0829-9999-25-155-H01-P

Activity Type: Knowledge-based

CEUs: 0.5

No cost to participate.

Participant CE records will be electronically communicated to CPE Monitor.

Pharmacist Learning Objectives

At the conclusion of this web conference, participants should be able to:

Explain evolution and rationale for maintenance de-escalation in 1L HER2⁺ MBC:
Understand the role of endocrine therapy ± CDK4/6 inhibitors in HE2R+/HR+ MBC 1L setting:

System Requirements

Mobile device (e.g., large-format smart phone; laptop or tablet computer) or desktop computer with a video display of at least 1024 × 768 pixels at 24-bit color depth, capable of connecting to the Internet at broadband or faster speeds, with a current version Internet browser and popular document viewing software (e.g., Microsoft Office, PDF viewer, image viewer) installed. Support for streaming or downloadable audio-visual materials (e.g., streaming MP4, MP3 audio) in hardware and software may be required to view, review, or participate in portions of the program

Participation Costs

There is no cost to participate in this program.

Unapproved and/or off-label use disclosure

AffinityCE/MedAll requires CE faculty to disclose to the participants:

1. When products or procedures being discussed are off-label, unlabeled, experimental, and/or investigational (not US Food and Drug Administration [FDA] approved); and

2. Any limitations on the information presented, such as data that are preliminary or that represent ongoing research, interim analyses, and/or unsupported opinion.

Learning objectives

Explain evolution and rationale for maintenance de-escalation in 1L HER2⁺ MBC:

Summarise the shift from CLEOPATRA’s model to current de-escalation trials, describing survival and QoL gains.
Define optimal timing to begin maintenance therapy
Identify clinical markers for safely shortening or re-escalating cytotoxic therapy in practice.

Understand the role of endocrine therapy ± CDK4/6 inhibitors in HE2R+/HR+ MBC 1L setting:

Review ER–HER2 cross-talk and key data (including PERTAIN, PATINA, monarcHER) supporting endocrine layering.
Select and sequence ET agents and CDK4/6 inhibitors based on patient factors, exposure, and toxicity.
Manage resistance and adherence through dual-targeting strategies and patient engagement.

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Computer generated transcript

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The following transcript was generated automatically from the content and has not been checked or corrected manually.

Ladies and gentlemen, dear colleagues, welcome to this educational program. My name is Rupert Barel. I'm a breast medical oncologist based at the Medical University of Vienna in Vienna, Austria and with ABCSG. This is about individualizing first-line therapy in metastatic HER2 positive breast cancer, and I will mainly focus on the combination of endocrine therapy or endocrine therapy plus CDK46 inhibitors, plus HEER2 direct treatment. These are my disclosures. Now, this is what we are talking about, HER2 positive breast cancer, so 3+ positive as defined by immunohistochemistry or in case of 2+ positive with an amplification of the ERP2 gene on chromosome 17 by in cyto hybridization analysis. We know that in this type of breast cancer, the introduction of HER2 directed treatment has massively improved our patient's outcome. If we go back to the late 1990s, patients with HER2 positive metastatic breast cancer actually had a very dismal prognosis. Similar or even poorer than patients with metastatic triple negative breast cancer today, with the median overall survival in the range below 2 years. With the introduction of tristuzumab, the first HER2 directed treatment, the monoclonal antibody, this of course has massively changed, and suddenly the overall survival of these patients was improved to more than 2 years. These were the pivotal trials, Dennis Lehman's study with resusumab, either combination with Paclitaxel or AC and what we've also learned from this trial was the increased cardiotoxicity when you combine tracyclins and HERR2 directed treatment. It's highly relevant to realize how important the predictive biomarker HER2 is for justice. In this trial, the vast majority of patients were HER2 3+ by immunohistochemistry, but there were also about a quarter of patients included with 2+ and no-ish analysis was performed, so probably a part of these patients were indeed what we would today deem HER2 negative or HER2 low by the newest definition. Now, if indeed. This trial would have been conducted in an unselected population. The hypothetical hazard ratio would have been 0.9, and there would have been no significant improvement in aggression-free and overall survival. And this really takes us back to the development of EGFR inhibitors in lung cancer, where initially only based upon the expression of EGFR. Gifetinib was investigated in the INTAC one trial and there was no improvement seen by the addition of gefetinib to chemotherapy. But when Indeed, later on, these trials were conducted in a population with activating mutations in the EGFR gene. There was a high benefit seen in those patients. So it really highlights once again how important it is to have the biological rationale, the biomarker for targeted treatment. Now, of course, in the first-line setting today, our standard is not resusumab plus chemotherapy anymore, but based upon the Cleopatra trial, it's the combination of those Taxol, resumab, and the second HER2 directed antibody, HERtuusumab. If you look at the population of the trial, these were patients without any previous chemotherapy. About 10% of the patients, and that's due to the time when the trial was conducted, had received prior adjuvant stuzumab, and half of the population was hormone receptor positive. And we go into more detail about this a little bit later, but just remember here that No endocrine treatment was allowed in this trial. Patients received 6 or more cycles of those Taxol followed by trastuzumab, pertuzumab, or only trestuzumab maintenance here in the controller. You know the results, of course, and that have led to the approval of the combination. Improvement in progression-free survival, clinically relevant improvement in overall survival, and this is the end of study analysis with a very impressive 16-month benefit in terms of overall survival, so nearly an improvement by 1.5 years. And still, you have questions, what's the optimal duration of those taxes and, and that's also an important question in the light of the Destiny Breast 9 trial where upfront TDXD. Was being investigated and we'll go into this later. What about potential role of endocrine therapy during the maintenance phase? Do all patients require toxin-based chemotherapy? Is there indeed in those patients with luminal B HER2 positive disease, so hormone receptor and HER2 positive disease, a role for chemotherapy, free treatment, and what about the incidence of brain metastasis, which of course are a major issue. In the field of HER2 positive metastatic disease, but let's first of all look at the duration of those taxes, and while we can say that probably both in terms of progression-free survival and overall survival, more than 6 cycles are not necessarily better than 6 cycles, less than 6 cycles definitely are, so 6 cycles, that is what we should aim at when. Deciding to go for induction chemotherapy, but about the brain metastasis incident, and this clearly tells us that the incidence is the same irrespective of the control group or the protriumab group. So with superior systemic treatment with antibodies, we have no preventive properties. Large molecules don't have preventive properties, and therefore we can only delay the onset of brain metastasis. Indeed, in patients with brain metastasis, overall survival was improved. But again, with large molecules, we cannot prevent the onset of brain that asks questions, of course. For maintenance strategies including terrain kinase inhibitors which might prevent the onset of pre tests. Do all patients need taxane-based chemotherapy? Are there any alternatives? Well, in the days before pertuzumab, vinorelbine was widely used in combination with trastuzumab. And uh we have seen quite convincing disease control data here. There's a phase two trial looking into mineral bind plus tristuzumab pertum of the velvet study, and as you can see, in the somewhat more heavily pred to population median progression free survival was 14 months, but this was not looked into in any phase 3 design. So in the end, the taxin plus trisusuma perteusuma was the standard of care. There's one very interesting study looking into further de-escalation with oral cyclophospham. Hans Wilders' group looked into elderly and frail patients. It's a prospective randomized phase 2 trial comparing resusma pertuzumab alone or the antibody combination with oral cyclophosphamide, and as you can see, no major increase in grade 34 toxicity that's relevant, of course, in the frail population. And the progression-free survival was 12.7 months in the oral cyclophosphamide plus DP group, which is quite convincing here and which shows that this is a potential option perhaps in high-risk patients with hormone receptor negative or positive disease. But as mentioned before, I would really like to focus a bit more on the hormone receptor story because somehow the hormone receptor was underestimated in HER2 positive disease for the longest period. Now, what we know is that growth factor signaling can induce resistance to anti-hormonal treatment and. Of course, the best known growth factor, the one we are talking about here, that is downstream signaling via MTOR, results in a phosphorylation of the estrogen receptor, dimerization, translocation into the nucleus binding to estrogen responding element, and in the end transcription of estrogen-dependent genes, even if there is no estrogen present, for example, in the presence of an aromatase inhibitor treatment. But interestingly, this is a bi-directional. So in the other direction, Inhibition of HER2 results in an up-regulation of the estrogen receptor pathway. So, the best result that is achieved if we block both HER2 and the estrogen receptor pathway. And, and in the next couple of slides, this is what I would like to look into. So the first trial I would like to discuss with you, that's the Pertains study. 13. Looking into aromatase inhibitor treatment either with tristuzumab alone or tristuzumab plus pertuzumab, and about half of the population received induction doseax. It's not surprising that the combination of both antibodies was superior to tristuzumab plus endocrine therapy in terms of progression-free survival with the benefits seen in all the predefined subgroups. What's perhaps more relevant is this group of pop, this group of patients, excuse me, and that's the population of patients without induction dose Taxol. So these patients have received endocrine treatment plus tristuzumab or tristuzumab pertuzumab, and of course, it's a selected population because these, the investigators decided that these patients might not need induction chemotherapy. So probably