Applying the Latest Developments in Metastatic Breast Cancer: My Takeaways From a Recent Educational Program for Healthcare Providers

Key Takeaways

• Precision medicine has generated a wealth of novel therapeutic options for metastatic breast cancer and genetic testing is essential to guide treatment recommendations.
• Equity in metastatic breast cancer care remains an area of unmet need; patient checklists and other resources can help ensure that healthcare professionals have a productive and equitable conversation with each patient about their goals of care and available treatments.

The treatment landscape for metastatic breast cancer (MBC) is becoming increasingly complex. In 2023, Clinical Care Options (CCO) and Breastcancer.org partnered to develop education and resources for healthcare professionals (HCPs) and patients with updates on the growing list of treatment options and molecular biomarkers used by experts to help inform therapy selection for patients with MBC. Moreover, a patient–provider communication checklist and 2 versions of an interactive decision support tool (IDST) for MBC—one for HCPs (link ) and a patient-friendly version (link )—were created to improve common understanding and promote productive guided conversations between HCPs and patients.

In this commentary, I share my thoughts and takeaways from this collaborative program, including strategies for empowering patients to take charge and become more involved in the care they receive for MBC.

Overview of Recent Changes in MBC: How HCPs Can Stay Up-to-Date

Women diagnosed with MBC, which is breast cancer that has spread beyond the breast area and the local lymph nodes, are frequently terrified and immediately think this is a fatal disease and that they could die sooner rather than later. They also think about all the possible symptoms and side effects associated with the disease and treatments, respectively. In addition, it is often challenging to distinguish the etiology of symptoms due to lingering side effects from past treatments (eg, CIPN), ongoing treatment adverse effects, complications from the disease itself, or aging/comorbid conditions. The ability to make these distinctions is important because the over-attribution of symptomatology to current treatments leads to the discontinuation of essential therapies.

Unfortunately, a patient diagnosed with MBC may require continuous treatment to make the cancer respond, potentially go into remission, and hopefully even disappear. To gain a better understanding of the cancer, the oncologist spends some time evaluating the patient’s tumor, including size, spread, hormone receptor status, potential HER2 expression status, and other novel genetic markers (via next generation sequencing), which can be useful to guide best treatment decisions. Patients with HR-positive MBC who experience disease relapse during or after initial therapy may receive subsequent treatments based on mutations identified in cancerous tissue or blood samples.?

Text-Based Lecture and Strategies for Contemporary Management of MBC

My colleagues in the program developed short lectures covering the standard of care treatments for MBC and included interesting new treatment options recently approved or in development. The good news is that there are many more effective medicines today than there were ever before and HCPs have access to targeted therapies for different types of MBC —namely hormone receptor (HR)-positive, human epidermal grow factor receptor 2 (HER2)-positive, or triple-negative MBC. The new treatment modalities and strategies are more likely to eliminate the cancer while minimizing toxicity towards normal tissue. In all, that translates into greater anti-cancer benefits with generally fewer side effects. In the short lectures from Dr. O’Shaughnessy, she covered the novel treatment options for HR-positive/HER2-negative MBC such as the CDK4/6 inhibitors (eg, abemaciclib, palbociclib, and ribociclib) plus an aromatase inhibitor or fulvestrant. Patients can live with metastatic HR-positive disease for a long time and go from one treatment to the next. However, it is good that we have more innovative therapies that go beyond tamoxifen, the aromatase inhibitors (eg, anastrozole, exemestane, letrozole), oral selective estrogen receptor degraders (eg, elacestrant and fulvestrant), and the CDK4/6 inhibitors (abemaciclib, palbociclib, or ribociclib). In the data presented by Dr. O’Shaughnessy we saw that the patients with HER2-positive MBC can benefit from anti-HER2–targeted therapies such as trastuzumab plus pertuzumab with docetaxel, trastuzumab deruxtecan (an antibody–drug conjugate [ADC]), and tucatinib (a HER2 tyrosine kinase inhibitor) combined with chemotherapy. Patients with triple-negative MBC may receive either chemotherapy, PARP inhibitors, or some of the newer treatment modalities with immunotherapy (eg, pembrolizumab) in combination with chemotherapy, or ADCs such as sacituzumab govitecan or trastuzumab deruxtecan.

Dr. O’Shaughnessy also covered data that show patients with HR-positive HER2-low disease can benefit from the newer medicines. Some of the newer therapies are still able to target cancer cells with HER2-low status , or low signal on the surface of cancer cells, including the novel ADC trastuzumab deruxtecan in patients who have received a previous chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. For patients with HER2-negative disease, experts recommend sacituzumab govitecan—which is an ADC targeting the TROP2-receptor—in patients with resectable locally advanced or metastatic HR-positive/HER2-negative MBC after endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting. These are 2 good examples of how targeted therapies can hit a target within MBC cancer cells while minimizing off-target toxicity.

Capivasertib plus fulvestrant was FDA approved in November 2023 for adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with 1 or more PIK3CA, AKT1, or PTEN-alteration, as detected by an FDA-approved test after progression on at least 1 endocrine-based regimen in the metastatic setting or disease recurrence on or within 12 months of completing adjuvant therapy for early-stage breast cancer.

While it is true that new innovative targeted therapies promise to cause fewer side effects, patients often start these treatments after weathering the effects of many prior treatments, from which they may have lingering side effects which can mean that they are more run down before starting these newer treatments. Their ability to tolerate the accumulative effects of heavy-duty sequential therapies must be addressed.

Many years ago, we only looked at inherited genetic testing to help a family understand if they were at an elevated risk of developing breast cancer and other related cancers. In addition to using genetic testing as a prognostic tool, we may now use it to select the role of treatment. Genetic testing results can help pus predict the likelihood of response to PARP inhibitors (eg, olaparib and talazoparib) in those with a germline BRCA1/2 or PALB2 mutation. PARP inhibitors target cancer cells that have an inherited germline genetic abnormality. Occasionally, we find a somatic mutation in the BRCA1/2 gene that is only present in the tumor cells. As we employ these various strategies and get smarter at identifying the nature of the challenge, including updating our assumptions and testing for new biomarkers along the way when the disease loses previous molecular markers or they become less relevant for treatment, we may be able to address rapid changes in MBC tumor biology.

The last thing I would say about novel therapies is that we need to work on improving access to newer medicines because they can be very expensive and challenging to access. If a given patient does not exactly meet the guideline recommendations, getting a medication approved by the insurance companies can be difficult and payers can refuse to cover it. Improving access may involve a concerted effort from the physician and other members of the care team to effectively advocate for the patient to get the approvals for therapy.

Disparities, Providing Patient Education, and Reinforcing Clinical Trial Participation

Despite all the recent progress in MBC, young women with children remain among the most vulnerable patients with MBC. This is particularly so for non-Hispanic Black patients when compared with non-Hispanic White patients with MBC . Many women fear they may be abandoning their young children at home to receive treatment. They may also experience great financial toxicity, anxiety, and/or depression—as well as accumulative lingering side effects from all past therapies. All patients with MBC also should be considered for clinical trials to gain access to new medicines that may have not been previously available. The good news is that novel treatments can be more selective in targeting cancer cells while sparing the normal tissue nearby.

I believe that the best care for MBC now and in the future is to have shared decision-making between HCPs and patients using available resources to level the playing field. When the doctor and the patient meet, many patients feel like the doctor has the upper hand. Visiting with their doctor can be challenging for patients: medical terminology is like learning a new language, wearing a hospital gown while the doctor is dressed in a formal white coat can feel diminishing. The physician has the expertise on the disease and is in full control of how much time the patient gets to spend with him or her. Thus, it can be an uneven dynamic. Shared decision-making is essential and providing guides for the conversation can help make patients more comfortable in knowing what questions to ask and how to ask. Patients need to get the answers to identify the best treatments for them, including what tests are required to inform those treatments. Individualized conversations aided by patient forums , patient-friendly education, and communication checklists create an environment in which we can individualize the care of each patient.

I find that it is good to have a structure in place that can ensure a productive conversation with each patient. The idea of having a checklist that a patient can bring when meeting with their doctor helps to facilitate this dialogue. We need to help the patient understand the extent and nature of the challenge, which becomes the basis for the selection of appropriate treatment in their situation. We also should ask about any barriers that may impede patients' access to care (eg, transportation, childcare, health insurance, job flexibility, or out of pocket costs). After we have identified the key challenges, we can then work on improving access and adherence to their prescribed medication.

Patient IDST

A great deal of information on MBC, including subtypes and treatments, can be easily accessed day or night in digital form. It is important that patients take advantage of online resources, but it is similarly important that they are accessing information that is in a language that they can fully understand and that has been peer reviewed by both clinical experts and patients. To help with patients’ need for education on MBC and available therapy, breastcancer.org and CCO codeveloped a patient-friendly IDST to provide ?patients with MBC access to plain-language education, including examples of available therapies based on tumor subtype and resources and other considerations that they can discuss with the care team to guide these really important conversations where so much is at stake.

I think it is important to have guides and resources like this patient IDST, which had not been available before. I think it will increase patients’ confidence and help them take an active role in their care. I believe that having a framework to use when entering these meetings with their care team will really help them be better prepared.

Remaining Barriers After the Program and Final Takeaways

In regard to remaining challenges and barriers to overcome, I believe that in general, women tend to take care of everyone else before themselves. We need to continue to empower patients with MBC to take an active role in their care and find their voice and speak up, because they are their own best advocate. Patients, particularly Black patients and other underserved populations, need to be more vocal to ensure their care team is providing the best care possible. That said, gaps will remain. I believe that by being proactive about going to their care team prepared for a conversation, patients can potentially help their doctors do a better job of providing care. Patients should not feel like they are a nuisance, they should be confident that becoming an advocate for themselves will help them receive the best care, respect, and trust from their care team. Patients should be encouraged to call their care team if they are in pain and tell their provider where they are experiencing pain, what their symptoms are, if the pain moves, what makes it better or worse, how long it lasts, and if they have ever had it before. By answering those questions, the care team can then take better care of the patient.

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Your Thoughts?

We want to hear from you! Which topics related to applying new treatment options for optimizing outcomes for MBC would you like to learn more about? I invite you to review additional resources from this CCO program , and to join the conversation by leaving a comment.