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Care of Older Adults With HRpos HER2neg MBC
Navigating Optimal Care for Older Adults With HR+/HER2- Metastatic Breast Cancer: Practical Strategies for Overcoming Clinical Barriers

Released: September 02, 2025

Erika Hamilton
Erika Hamilton, MD
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Key Takeaways
  • Older adults with HR-positive, HER2-negative metastatic breast cancer have unique complexities that should be considered when recommending treatment approaches.
  • Employ geriatric assessments routinely in patients 70 years of age or older to guide treatment personalization and optimize patient outcomes.
  • Incorporate regular drug interaction screening and proactively involve interdisciplinary teams to manage potential polypharmacy risks.
  • Frequent patient check-ins and early dose modifications can improve treatment adherence, reduce discontinuation, and enhance quality of life for older patients receiving CDK4/6 inhibitors.

Older adults with hormone receptor–positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) have unique complexities inherent in this patient population that should be considered when discussing and recommending specific treatment options. Age-related factors such as frailty, comorbidities, polypharmacy, and competing priorities around quality of life (QoL) can significantly influence treatment decisions. Despite advancements in therapy—particularly with the use of endocrine-based therapies (ET) in combination with a CDK4/6 inhibitor—the underrepresentation of older patients in clinical trials means that our clinical approach must be highly individualized, balancing therapeutic efficacy with tolerability and patient values.

Balancing Treatment Efficacy and QoL
Older patients may prioritize QoL and daily function over aggressive treatment strategies. In HR+ HER2- MBC, the favorable profile of ET in combination with CDK4/6 inhibitors, particularly in the first-line setting, aligns well with these patient priorities. These treatments typically delay the need for chemotherapy, which can help preserve QoL for a prolonged period.

The MONALEESA, MONARCH, and PALOMA series of clinical trials established the role of 3 CDK4/6 inhibitors—ribociclib, abemaciclib, and palbociclib—and have continued to reinforce their use as a first-line treatment  for patients with HR+/HER2- MBC. These trials have consistently shown a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with the addition of a CDK4/6 inhibitor to ET with strikingly similar hazard ratios of approximately 0.50-0.60. However, differences in overall survival (OS) varied in the trials. There was significant improvement in median OS with the addition of ribociclib to ET in MONALEESA-2 and MONALEESA-7. There was a trend toward median OS improvement with the addition of abemaciclib in MONARCH 3, but statistical significance was not reached. In PALOMA-2, there was no statistically significant difference in median OS with the addition of palbociclib to ET. All 3 CDK4/6 inhibitors have also shown significant PFS benefits when added to fulvestrant in the second-line setting after first-line single-agent ET based on results from PALOMA-3, MONARCH 2, and MONALEESA-3. Abemaciclib and ribociclib have been shown to also improve OS in this setting whereas palbociclib showed a clinically meaningful, but not statistically significant improvement in OS.

It is important to acknowledge that no direct, randomized head-to-head trials comparing the CDK4/6 inhibitors currently exist, and clinical decisions should therefore be based primarily on individual patient factors and available indirect evidence. Although the ribociclib data are compelling in terms of OS, each CDK4/6 inhibitor has its own unique safety profile and administration considerations. Patients are more likely to experience hepatotoxicity and QTc prolongation with ribociclib, abemaciclib is associated with increased gastrointestinal toxicity, and all 3 CDK4/6 inhibitors may result in some cytopenias. Particularly for our older patients with HR+ /HER2- MBC, it is reasonable to consider palbociclib for patients with comorbidities that may make the other CDK4/6 inhibitors less ideal.

Polypharmacy and Drug–Drug Interactions
Polypharmacy remains a pervasive issue for older patients, complicating cancer management due to heightened risk of drug–drug interactions. As healthcare professionals, we frequently encounter patients taking multiple medications for chronic conditions such as hypertension, cardiovascular disease, diabetes, and gastrointestinal disorders. These medications increase the complexity of prescribing effective yet safe cancer therapies.

To mitigate these risks, I recommend routine assessment of potential drug interactions, especially when introducing a new anticancer therapy or encountering unfamiliar medications. Pharmacists represent invaluable resources in identifying and managing potential interactions and toxicities.

Ribociclib, in particular, requires careful consideration due to potential for QT prolongation, necessitating baseline and follow-up ECG monitoring during the first cycle of treatment. This caution is especially important when patients are concurrently taking other medications that prolong the QT interval, such as cardiac antiarrhythmics. In addition, ribociclib has also been associated with rare but serious  interstitial lung disease (ILD), severe cutaneous adverse reactions, hepatotoxicity, and neutropenia. Similarly, patients treated with abemaciclib must be monitored for signs and symptoms of venous thromboembolism, ILD, hepatotoxicity, and neutropenia and may also experience severe diarrhea necessitating antidiarrheal medications and increases in oral fluids. Patients treated with palbociclib should be monitored for ILD, hepatotoxicity, and neutropenia. Additional polypharmacy considerations for CDK 4/6 inhibitors include their interactions with medications metabolized by CYP3A4, necessitating careful review for potential drug–drug interactions that may increase toxicity or reduce therapeutic efficacy. Ribociclib, abemaciclib, and palbociclib are similarly metabolized via CYP3A4 and require vigilance regarding potential interactions, particularly with strong CYP3A inhibitors or inducers, to avoid changes in drug exposure and associated risks.

Integrating Geriatric Assessments Into Clinical Practice
Comprehensive geriatric assessment can be invaluable for patients 70 years of age or older in order to improve individualized treatment planning and overall patient outcomes. Extended conversations with patients about how they spend an average day, how often they are seeing family or their social network, and their activities of daily living can be used as an assessment to provide a holistic view of a patient’s health. Evaluating domains such as functional status, cognitive function, emotional health, and social support networks allows us to look beyond chronological age and tailor treatment strategies that optimize tolerability and preserve QoL. Integrating geriatric assessments does require a shift in clinical workflow, but the long-term benefits include improved adherence, better risk stratification, and enhanced shared decision-making. Recent discussions indicate a growing recognition of the importance of these assessments, signaling progress toward more inclusive and nuanced patient care.

Addressing Patient and Caregiver Challenges
Another set of critical barriers involves challenges such as treatment adherence, comprehension of disease and treatment goals, emotional coping, caregiver burden, and practical issues like transportation or financial difficulties. These factors significantly affect the efficacy of therapy and patient outcomes.

To support adherence and patient understanding, frequent patient check-ins can be helpful—especially in the early phases of therapy. Regular follow-ups within the initial weeks of starting a CDK4/6 inhibitor can reassure patients and caregivers, address side effects promptly, and build trust. Clear communication regarding side effects and how dose adjustments can alleviate them often empowers patients and caregivers, reinforcing adherence.

It is important to explicitly discuss the rationale behind dose adjustments, emphasizing that efficacy can typically be preserved at reduced doses—a message strongly supported by recent clinical experience. For instance, the monarchE and NATALEE trials demonstrated that dose reductions with abemaciclib and ribociclib maintained treatment efficacy, providing reassurance that dose modification for tolerability does not compromise clinical outcomes in CDK 4/6 inhibitors.

Caregiver burden and emotional distress are common yet underrecognized barriers. Social support is often limited, and caregiving stress can negatively influence treatment adherence and decision-making. Proactively addressing emotional and practical challenges involves involving multidisciplinary teams—nurses, pharmacists, social workers, patient navigators, and mental health professionals—but establishing a strong interdisciplinary approach can significantly enhance patient and caregiver resilience. Referral to social work and psychosocial support services is particularly impactful for addressing emotional and logistical concerns.

Summary
Optimal management of older adults with HR+/HER2- MBC requires nuanced and proactive strategies addressing polypharmacy, comprehensive geriatric assessment, and balancing efficacy with QoL. Although barriers such as adherence, caregiver stress, and logistical challenges are prevalent, collaborative efforts and personalized strategies can markedly improve outcomes for these vulnerable patients.

Your Thoughts
How do you integrate geriatric assessments into your practice, and what methods do you use to support QoL for older patients with  HR+/HER2-MBC? Join the conversation and let us know what additional tools or resources you would find helpful to better support your older patients in the discussion box below.

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Which clinical factor most strongly guides your treatment approach in the management of older patients with HR-positive/HER2-negative MBC?

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