Breast Cancer in 2026: What APPs Need to Know About a Rapidly Changing Treatment Landscape

Key Takeaways

• Molecular profiling and increasingly nuanced biomarker classification are expanding personalized treatment options across metastatic breast cancer, requiring APPs to understand how results influence treatment selection and sequencing.
• As targeted therapies and antibody-drug conjugates expand, oncology APPs play a critical role in recognizing and managing treatment-specific toxicities, coordinating monitoring, and educating patients about increasingly complex treatment plans.
• Despite the growing number of treatment options, APPs should maintain a patient-centered approach that balances disease control with toxicity, quality of life, practical considerations, and individual patient needs.

Sally Fang, MSN, RN, FNP-BC, an advanced practice provider specializing in breast medical oncology at the University of California, San Francisco, discusses the increasingly complex treatment landscape for breast cancer and the evolving responsibilities of oncology APPs. She highlights the growing importance of molecular profiling and biomarkers in metastatic disease, including ESR1 and PIK3CA mutations and expanded HER2 classifications, as well as the increasing use of targeted therapies, antibody-drug conjugates, and immunotherapy. Fang also emphasizes the APP’s role in coordinating biomarker testing, educating patients, managing treatment-specific toxicities, and ensuring appropriate laboratory, imaging, and other safety monitoring. As treatment options and sequencing decisions become more complex, she encourages APPs to remain focused on the whole patient, balancing disease control with treatment tolerability, quality of life, and individual circumstances.

Transcript

Sally Fang, MSN, RN, FNP-BC: Hi, my name is Sally. I’m an advanced practice provider at the University of California, San Francisco, specializing in breast medical oncology. As an advanced practice provider, we are no longer just monitoring shared toxicities from traditional chemotherapy. Given the recent advancements in breast cancer treatments, we now have to navigate the complexities of targeted agents, novel antibody-drug conjugates, also known as ADCs, and dynamic biomarker testing.

The core of breast cancer treatment still uses the receptor status, such as ER, PR, and HER2, as a backbone to guide us on treatment options. We also use other factors, such as surgical pathology, burden of disease, ECOG performance status, and prior lines of therapy, to help decide and sequence the various available options. In the early-stage setting, we continue to rely on the receptor status, disease subtype, and PD-L1 status for treatment recommendations. But where it gets more complex is in the metastatic setting, where molecular profiling tests help drive treatment choices. Molecular profiling tests such as Caris, Guardant, and FoundationOne identify somatic mutations that we can target with currently approved FDA drugs and even help identify eligible clinical trials.

This is a good kind of complexity, because this means there are more options available for our patients. Today we’ll focus on the discussion of metastatic disease.

We as APPs need to know how to navigate this intricate paradigm to help with symptom management, patient education, and, in collaboration with our oncologists, decide our next line of therapy. Now let’s break down the major therapeutic shifts across the breast cancer spectrum.

In the hormone receptor-positive, HER2-negative space, we no longer stop at standard endocrine therapy such as tamoxifen and aromatase inhibitors. When a patient experiences progression, we aggressively look for actionable mutations through molecular profiling tests. For instance, finding an ESR1 mutation allows us to use oral SERDs, while PIK3CA or AKT pathway mutations unlock targeted pathway inhibitors. For instance, identifying a PIK3CA mutation changed how we treat newly diagnosed ER-positive, HER2-negative metastatic patients. We now add inavolisib, palbociclib, and fulvestrant based on the INAVO120 study.

Furthermore, recent data from trials like PATINA demonstrate that adding CDK4/6 inhibitors to HER2-targeted approaches is even redefining overlapping hormone receptor-positive, HER2-positive metastatic treatments.

In the HER2 disease space, we not only look at HER2 3+ on IHC anymore; we now recognize HER2-low and HER2-ultralow. HER2-low includes IHC 1+ or IHC 2+ with a negative FISH test, while HER2-ultralow includes IHC 0 with faint membrane staining. Therapies like Enhertu utilize the HER2 receptor merely as a docking site. Because of a high drug-to-antibody ratio and a bystander effect, these ADCs destroy neighboring cancer cells even when HER2 expression is very low. Additionally, our sequencing choices now prioritize agents with strong central nervous system penetration to aggressively combat brain metastases.

Enhertu has added another line of therapy for traditionally defined HER2-negative disease, as seen in the DESTINY-Breast04 study. Historically, triple-negative disease had limited options since the mainstay of treatment was cytotoxic chemotherapy, such as paclitaxel or gemcitabine/carboplatin. The advancements of antibody-drug conjugates and immunotherapy have dramatically improved the options we have to treat these patients. For example, we now use sacituzumab govitecan and pembrolizumab as first-line treatment in metastatic breast cancer with PD-L1–positive disease on molecular profiling. And for patients with PD-L1–negative disease, BRCA-positive patients, we are now using PARP inhibitors as first line.

As we have more and more options, we now run into the issue of sequencing. This is a good problem to have. When deciding on next treatment options, there are a lot of factors to consider, such as burden of disease, functional status, potential side effects, and even social aspects, such as how far a person lives, because that can really change doing every-3-week treatment versus doing day 1, day 8, every 21 days.

It is no longer a well-organized, one-way path, but it’s more of an art in sequencing and the finesse in navigating this complex map. With all these advancements comes an evolution in our daily APP role and responsibilities. We are coordinating biomarker and molecular testing, educating patients on molecular profiling tests and what the results mean and how they can impact their treatment. We must ensure that the tissue and liquid biopsies are ordered at the correct clinical inflection points, such as time of progression or once we suspect signs of progression.

We are the first line of defense against highly specific toxicities, such as ILD, or interstitial lung disease, associated with T-DXd, or Enhertu, and even CDK4/6 inhibitors; eye toxicities with datopotamab deruxtecan; and elevated glucose levels with PI3K inhibitors.

There’s just so much more treatment-specific toxicity now that we have to monitor and help treat. Aside from these more specific drug side effects, we still have to keep in mind the more common adverse events that we commonly see, such as nausea, vomiting and diarrhea, neutropenia, elevated liver function tests, fatigue, and so on.

Depending on the toxicity, we also help manage toxicity with dose reductions. With all the new novel agents, there are many safety procedures patients have to follow, and we APPs have to monitor closely, such as specific lab schedules to follow neutrophil counts and glucose levels, ECGs, and CT chest to monitor for ILD. This is especially critical in the first 8 to 12 weeks of starting new therapy for most of these novel agents.

Most of our molecular profiling tests are done at third-party companies, so now we have to keep track of those results in the usual way of other results in our in-basket. And don’t forget, we have to coordinate care with our attendings, nursing team and infusion centers, specialty pharmacies, and referrals to specialties such as dermatology and cardio-oncology, all while we ensure labs, scans, and prescriptions are all placed in a timely manner and test results are well communicated with the patients. The role and responsibilities of APPs continue to expand as our treatment landscape continues to evolve.

To wrap this up, to me, the most important key points and takeaways are that the treatment of breast cancer in the early and metastatic settings is ever-changing and growing. This allows our patients to live longer lives and potentially be cured. The diagnosis of breast cancer, especially in the metastatic setting, can now be treated as a chronic disease for some patients. The treatment toxicity is much more tolerable as we are more sophisticated with dosing and symptom management.

Antibody-drug conjugates and utilization of molecular profiling tests have been a game changer, and this is basically going into personalized medicine. I think this is just the beginning, and there’s going to be so much more to come. Lastly, with a fast-changing treatment landscape, APPs have to be vigilant about the different drug toxicities and management, cadence of labs, and other tests for monitoring of adverse events.

With breast cancer care changing so quickly, what is the one thing every oncology APP should be doing differently in their practice? I think it’s important not to get lost in all the treatment choices, all the sequencing, but I think it’s important to take into consideration the patient as a whole. We treat the patient as a whole. It’s a balancing of treatment, of treating the disease and preserving the patient’s quality of life. We’re there to also advocate for the patient. I think that’s very important when we are navigating through these evolving treatment choices in breast cancer.