A Nurse’s Overview of First-Line Treatment for HR+ Metastatic Breast Cancer

Kelsey Martin, APRN, AG-ACNP-BC, AOCNP

With hormone receptor (HR)–positive, HER2-negative breast cancer comprising about 70% of breast cancer diagnoses,¹ an understanding of frontline treatments for this patient population is key to managing their breast cancer. In her presentation during the 9^th Annual School of Nursing Oncology, hosted by Physicians’ Education Resource®, LLC, on the treatment landscape for this cancer type, Kelsey Martin, APRN, AG-ACNP-BC, AOCNP, gave an overview of the preferred treatments at this line of therapy as well as adverse effects (AEs) that can be expected.²

Martin, a nurse practitioner at Sarah Cannon Research Institute Oncology Partners in Nashville, Tennessee, explained, in the first line of therapy, the NCCN recommends treating patients with a combination of endocrine therapy—either an aromatase inhibitor or fulvestrant (Faslodex)—and a CDK4/6 inhibitor.

How Do CDK4/6 Inhibitors Work?

CDK4/6 inhibitors work by targeting cyclin-dependent kinase proteins 4 and 6, which control the rate at which cells multiply. Overactivity of these proteins in breast cancer results in uncontrollable cell growth, which CDK4/6 inhibitors interrupt.³

In her presentation, Martin added that because CDK4/6 proteins determine the rate of multiplication, inhibiting these proteins can stop or slow the spread of cancer.

How to Select the Right CDK4/6 Inhibitor

The approved CDK4/6 inhibitors recommended by NCCN guidelines for patients with HR-positive, HER2-negative metastatic breast cancer include ribociclib (Kisqali), abemaciclib (Verzenio), and palbociclib (Ibrance).

While commonalities, such as risk for gastrointestinal issues and neutropenia, exist between the three, they have unique safety profiles that makes it possible to tailor treatment to the individual based on preexisting comorbidities, lifestyle, and other underlying conditions or concerns, Martin explained.

Regarding the common concerns among the drug class, Martin shared in an interview with Oncology Nursing News that patients are monitored closely for neutropenia, but other toxicities that could be dangerous or affect quality of life, such as severe diarrhea, are also watched for early on.

After a Case-Based Roundtable discussion with peer oncology advanced practice providers (APPs) about CDk4/6 inhibitor use, moderator Kimberly Podsada, BSN, RN, MSN, NP-C, CNS, a nurse practitioner at the University of California San Diego, shared that to make these treatment decisions, nurses and APPs should evaluate the patient in their entirety, focusing not just on their disease.

“We have the luxury now of having a variety of CDK4/6 inhibitors to choose from, and we can tailor our choice based on the patient’s comorbidities, lifestyle obstacles, and preferences,” Podsada said. “We can look at the whole picture of the patient. How are their kidneys functioning? How is their liver functioning? What sort of support services do they have? Are they going to be able to get to clinic?”

Tailoring treatment requires an understanding of each CDK4/6 inhibitor’s safety profile. Below are the AEs most associated with each CDK4/6 inhibitor.

• Ribociclib
  • Most common AE: elevated LFT, QTc prolongation
  • Other possible AEs: nausea and vomiting, fatigue, diarrhea, neutropenia, headache, back pain, pneumonitis
• Abemaciclib
  • Most common AE: diarrhea
  • Other possible AEs: neutropenia, nausea and vomiting, abdominal pain, anemia, headache, hair loss, thrombocytopenia, elevated LFT, pneumonitis
• Palbociclib
  • Most common AE: neutropenia
  • Other possible AEs: anemia, fatigue, pneumonitis, nausea and vomiting, diarrhea, hair thinning, mouth sores

These unique safety profiles can be harnessed to treat patients with the therapy that fits best with the individual and can even allow for switching between therapies to find what works for a patient, Martin explained.

“It is nice to be able to switch between [CDK4/6 inhibitors] and try different things for patients,” shared Martin. “But it has to take a personalized approach to all of these choices, because not everything is right for every person.

Courtney Moore, APRN, FNP-C, OCN, a nurse practitioner at the University of California San Diego and another moderator for a Case-Based Roundtable on the topic, explained that existing health issues must be considered when deciding on a CDK4/6 inhibitor.

“Between the CDK4/6 inhibitors, there are a couple that lean more toward neutropenia as a major AE, and we want to be aware of whether the patient is on any immunosuppressive therapies or has any other rheumatologic disorders or autoimmune disorders so that we can keep a close eye on them,” said Moore.

“Ribociclib has the potential to cause some cardiology AEs. If we have patients that already has arrhythmias such as atrial fibrillation, we want to avoid ribociclib because it can prolong the QTc interval.”

Handling Aromatase Inhibitors in HR+ Breast Cancer

Regarding the other components of endocrine therapy, aromatase inhibitors are often paired with CDK4/6 inhibitors to target hormone overactivity. This class of drugs converts androgen into estrogen, thereby blocking estrogen throughout the body.

As Martin noted in her presentation the drug class is often used, and recommended by the NCCN, in postmenopausal women, or in combination with a drug that suppresses the ovaries. Aromatase inhibitors do not stop estrogen production in the ovaries.

Aromatase inhibitors currently available include anastrozole, letrozole, and exemestane. Across the drug class, arthralgias, bone density loss, hot flashes, and vaginal dryness can occur.

To manage hot flashes, Martin highlighted several key methods:

1. Avoiding triggers like hot showers and tubs, hot weather, spicy or hot food, alcohol, and caffeine
2. Decreasing fat in diet
3. Practicing meditation or yoga, massage
4. Medications including antidepressants, fexolinetant, and hot flash/night swear relief along with targeted hot flash relief

Martin noted that patients may benefit from natural solutions or medications, depending on the needs of the individual.

“There’s some bee extract that can be really helpful for those patients. Other patients benefit from something as easy as antidepressant,” said Martin. “It certainly can be helpful if they have a little bit of anxiety as well.”

References

1. Cancer stat facts: female breast cancer subtypes. National Cancer Institute; Surveillance, Epidemiology, and End Results Program. 2019. Updated 2025. https://seer.cancer.gov/statfacts/html/breast-subtypes.html
2. Martin K. Navigating treatment in HR+ metastatic breast cancer. Presented at: 9th Annual School of Nursing Oncology; August 9, 2025; Nashville, TN.
3. Conner K. What are CDK4/6 inhibitors?. BreastCancer.org. Updated January 13, 2025.