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Patient Communication on Targeted Therapy in HR Positive HER2 Negative Breast Cancer
Targeted Therapy in HR+/HER2- Breast Cancer: A Focus on Patient Communication to Promote Adherence to Therapy

Released: May 28, 2026

Kayla Freeman
Kayla Freeman, DNP, APRN, FNP-C
Kimberly Podsada
Kimberly Podsada, MSN, NP-C, CNS
Cierra K. Ryan
Cierra K. Ryan, PA-C
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Key Takeaways
  • Several factors need to be considered for the use of adjuvant abemaciclib or ribociclib in patients with high-risk HR-positive/HER2-negative early breast cancer, as each agent has a different indication, duration of therapy, and toxicity profile.
  • Targeted therapies are available for patients with advanced breast cancer and certain mutations, including ESR1, PI3K, and AKT.
  • Education tailored to the individual patient is an important component of shared decision-making in both early and advanced breast cancer when describing the disease and the variety of treatment options available to each patient.

In this ClinicalThought commentary, oncology advanced practice provider faculty discuss practical communication strategies for helping patients understand the rationale for targeted therapy, anticipate adverse events, and remain engaged in treatment decisions across early-stage and metastatic hormone receptor (HR)–positive/HER2-negative breast cancer.

Case 1: High-Risk HR-Positive/HER2-Negative EBC
A 48-year-old premenopausal woman with high-risk HR-positive/HER2-negative early breast cancer (EBC) presents after a lumpectomy and a sentinel lymph node biopsy. Pathology shows estrogen receptor (ER) 95%, progesterone receptor (PR) 80%, HER2-negative disease, a 2.8-cm grade 3 tumor, Ki-67 35%, and 3 of 12 axillary lymph nodes positive. She completed dose-dense AC followed by weekly paclitaxel and adjuvant radiation, and started goserelin plus letrozole 8 weeks ago. Her hypertension is well controlled, baseline QTc is 420 ms, and she is concerned that treatment-related adverse events may interfere with work and daily functioning.

How would you describe the rationale for adjuvant CDK4/6 inhibitor therapy to this patient?
Kimberly Podsada, MSN, NP-C, CNS: It is key to explain to our patients that we have identified them as having a high risk of recurrence and what that means. Then I explain that our goal with additional medication, a CDK4/6 inhibitor, is to reduce that risk of recurrence. It is important that they understand the rationale for a medication that may result in more side effects, but whose goal is to help keep them cancer-free.

Kayla Freeman, DNP, APRN, FNP-C: It is important to discuss the data supporting an approximately 25% to 30% reduction in risk of invasive disease–free recurrence and distant recurrence–free survival with the addition of a CDK4/6 inhibitor to endocrine therapy (ET). This is helpful if your patient is numbers driven. Another option is an analogy. I like to think about ET as the lock on the door that keeps the cancer out, and then the CDK4/6 inhibitor as an alarm system we add.

What key differences between adjuvant CDK4/6 inhibitors would you discuss during shared decision-making with your patient?
Kimberly Podsada, MSN, NP-C, CNS: I want my patients to understand the clinical trial designs in very simplified language. In simplified terms, monarchE enrolled patients with node-positive, high-risk EBC, whereas NATALEE enrolled a broader stage II/III high-risk population, including some patients with node-negative disease. Dosing also differs: abemaciclib is given for 2 years vs ribociclib for 3 years. Administration differs as well: twice daily for abemaciclib vs once daily for 3 weeks on treatment followed by 1 week off for ribociclib. It is also important to learn about your patient. Do they already have baseline diarrhea? Are they already neutropenic from chemotherapy? Examining the adverse event profiles of each agent is important.

Kayla Freeman, DNP, APRN, FNP-C: This is not an uncommon scenario where you may talk to patients about both agents. Adjuvant CDK4/6 inhibitors are not interchangeable; each agent has distinct characteristics and an FDA-approved population. In terms of follow-up and evidence on overall survival (OS), monarchE has longer follow-up than NATALEE. In the primary OS analysis, abemaciclib plus ET demonstrated a statistically significant OS benefit in the monarchE node-positive, high-risk population.

One practical difference is the ET backbone: adjuvant ribociclib is used with an aromatase inhibitor (AI), whereas adjuvant abemaciclib may be paired with tamoxifen or an AI. Ribociclib also requires more attention to QTc, electrolytes, and CYP3A/QT-prolonging concomitant medications. If a patient uses supplements or is taking many medications, I would review the full medication list carefully before choosing therapy. Taking all these things into consideration and collaborating with the patient will help guide decision-making. Although data drive our decisions, these are opportunities to get input from our patients so that we are making decisions together.

How do you frame treatment duration, monitoring, and patient preferences when choosing between agents?
Cierra K. Ryan, PA-C: I always tell people, the patient is what sits in the room, the human is what is outside. I tell them what I think is going to happen based on my experience and what the data indicate, but I do not know what is going to happen with an individual patient. It is important to let them know that there are options when adverse events occur, including dose reductions and supportive medication. I explain early in the decision-making process that consistency is better than taking the highest dose possible. If a lower dose results in fewer dose interruptions and the CDK4/6 inhibitor can be taken more consistently, that is more important than remaining on a higher dose. I think it is helpful for them to understand that we plan to treat them as humans and ensure that they can live their daily lives. It is important to remember that we see this scenario daily, but it is likely the first time for the patient. I also discuss when they need to call us and which supportive medications to keep at home.

Kayla Freeman, DNP, APRN, FNP-C: Talking about these things upfront, providing more information, is better. It allows your patient to walk away knowing they can make informed decisions, but also with an understanding that adverse events can be managed along the way. We want to support our patients every step of the way. It is important to state upfront that there is flexibility in how we manage our patients with an adjuvant CDK4/6 inhibitor.

Case 2: Management of Adverse Events With Abemaciclib to Promote Adherence to Therapy
A 49-year-old woman with high-risk HR-positive/HER2-negative breast cancer is receiving adjuvant abemaciclib plus ET. At Week 3, she reports diarrhea that is affecting work despite loperamide and says treatment may not be “worth it” if symptoms continue.

How would you manage supportive care, and when would you consider holding the treatment vs reducing the dose?
Kayla Freeman, DNP, APRN, FNP-C: First, I try to optimize antidiarrheal medications. How often are they used? Are they working? I consider adding additional antidiarrheal medication depending on the day-to-day of what the patient is doing. If antidiarrheal medications are optimized, but symptoms are not being well controlled, then I would suggest we consider a dose reduction. The data support that abemaciclib is effective at a lower dose, and lowering the dose can improve quality of life. I would also assess how the patient feels about moving to a lower dose and explain that dose reduction can improve quality of life while helping them stay on therapy.

Cierra K. Ryan, PA-C: Quality of life is important. They are patients when they are in our office, but they are also humans with lives to live. I tell them that if the studies did not find efficacy at different doses, those doses would not be an option.

Kimberly Podsada, MSN, NP-C, CNS: I start by explaining how to take loperamide. But if the patient does not feel like doing it that way, that is not a failure. Each patient must find what works for them. Some patients will wake up every morning and take loperamide proactively. I let them know that there is no right or wrong answer. We must work together to find the right solution for them. Sometimes that may mean a dose reduction so we can continue them on therapy.

Case 3: Newly Diagnosed HR-Positive/HER2-Negative Metastatic Breast Cancer
A 52-year-old postmenopausal woman with HR-positive/HER2-negative breast cancer who was originally diagnosed with stage II, pT2N1, grade 3 invasive ductal carcinoma and was treated with lumpectomy/sentinel lymph node biopsy, adjuvant TC x 4 cycles, radiation, and 5 years of adjuvant AI plus ovarian suppression reported new onset of back pain and cough. Current imaging shows 3 lytic bone metastases and 3 small lung nodules, with no liver lesions. Biopsy confirms metastatic breast primary with ER 90%, PR 20%, and HER2-negative disease. Her ECOG performance status is 0, and comorbidities include controlled hypertension and mild osteopenia.

How does the metastatic diagnosis affect the patient?
Kimberly Podsada, MSN, NP-C, CNS: In addition to thinking about the treatment, we need to really think about the patient and other support services that we can offer them emotionally and psychologically, to start adjusting their life to living with a metastatic diagnosis.

Cierra K. Ryan, PA-C: This is an unfortunate situation, but I would note that we now have more options than ever for metastatic disease.

How would you explain the rationale for first-line ET plus a CDK4/6 inhibitor?
Kayla Freeman, DNP, APRN, FNP-C: I would review the data and note that a CDK4/6 inhibitor paired with ET is a guideline-recommended standard first-line approach for most fit patients with HR-positive/HER2-negative metastatic breast cancer without a need for immediate chemotherapy. We know from the MONALEESA-2 and MONALEESA-7 trials that ribociclib has demonstrated a significant OS benefit. Then I would direct the conversation to adverse events, monitoring, and how therapy is tolerated.

Kimberly Podsada, MSN, NP-C, CNS: I agree that the data for CDK4/6 inhibitors are robust, and ET plus a CDK4/6 inhibitor is the standard first-line approach for most patients with HR-positive/HER2-negative metastatic breast cancer. Endocrine therapy alone is generally reserved for selected patients when a CDK4/6 inhibitor is not appropriate or feasible because of comorbidity, access, frailty, or patient preference.

What baseline assessments and biomarker tests do you order before or around treatment initiation, and which results would or would not delay starting therapy?
Cierra K. Ryan, PA-C: Before starting a CDK4/6 inhibitor, I would obtain a baseline complete blood count and a comprehensive metabolic panel, including liver function tests. If choosing ribociclib, I would also confirm baseline ECG/QTc and electrolytes and review QT-prolonging and CYP3A-interacting medications. I would send next-generation sequencing (NGS) and germline testing when indicated, but I would not delay treatment while waiting for genomic results if the required safety assessments are complete. A DEXA scan would be lower priority in this case because the patient has lytic bone metastases, and I would recommend a bone-strengthening agent. Regardless of osteopenia or osteoporosis status, she is going to receive bone-directed treatment.

Kayla Freeman, DNP, APRN, FNP-C: I would not delay treatment for any of these tests. I think the timing of NGS testing can either be upfront or at the time of progression.

Kimberly Podsada, MSN, NP-C, CNS: I would definitely want to order NGS to determine eligibility for a PARP inhibitor, if not previously done. I think most healthcare professionals start with a CDK4/6 inhibitor plus ET, reserving a PARP inhibitor for later. We do not always perform NGS testing at the initial diagnosis of metastatic disease because the evidence is so robust with CDK4/6 inhibitors. Mutations can be acquired during therapy, and we would want to capture that information if they experience disease progression.

Case 4: Progression After AI Plus CDK4/6 inhibitor
A 52-year-old postmenopausal woman with HR-positive/HER2-negative metastatic breast cancer has been receiving an AI plus ribociclib for 24 months. She now reports new and worsening abdominal pain, and staging scans show disease progression with new liver lesions. Liver biopsy confirms metastatic breast primary with ER 70%, PR 20%, and HER2 ultralow (immunohistochemistry 0). Tissue NGS identifies a PIK3CA E545K mutation, and liquid NGS identifies ESR1 D538G and PIK3CA E545K.

How would you explain the significance of the ESR1 and PIK3CA results to the patient in plain language?
Kayla Freeman, DNP, APRN, FNP-C: I would highlight that she received great benefit from CDK4/6 inhibitor plus AI therapy for 24 months. Over time, acquired resistance can develop, and the current ET may not work as well. An ESR1 mutation can change the ER in a way that makes AI therapy less effective; options for ESR1-mutated advanced/metastatic disease after prior ET include oral SERDs such as elacestrant and imlunestrant, as well as vepdegestrant, a PROTAC ER degrader recently approved for ER-positive/HER2-negative, ESR1-mutated advanced or metastatic breast cancer after progression on at least 1 line of ET. A PIK3CA mutation activates the PI3K/AKT pathway. A pathway-directed option is capivasertib plus fulvestrant for PIK3CA/AKT1/PTEN-altered disease after progression on an endocrine-based regimen.

Kimberly Podsada, MSN, NP-C, CNS: Often, my challenge is translating complex medical concepts in oncology into basic language. I use visual aids and draw pictures. I will try to present the information using a variety of different teaching and learning tools. I want to reinforce the information so that patients feel informed and partner with them in making shared decisions.

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