CDK4/6 inhibitors in Breast Cancer: Benefits, Side Effects and When They’re Used

CDK4/6 inhibitors are an important group of tablets used to treat the most common type of breast cancer, hormone receptor positive (ER positive), HER2 negative breast cancer. This guide explains, in plain language, what they are, how they work alongside hormone therapy, and the two main situations in which they are used: in high-risk early breast cancer after surgery, to lower the chance of the cancer coming back, and in secondary (metastatic) breast cancer, to control the cancer for as long as possible. We follow UK guidance from NICE and the NHS, and note where things differ in the United States and Europe. 

Key takeaways

  • CDK4/6 inhibitors are tablets that block two proteins (CDK4 and CDK6) that cancer cells need in order to divide. They are given together with hormone (endocrine) therapy.
  • Three are available: palbociclib (Ibrance®), ribociclib (Kisqali®) and abemaciclib (Verzenios®).
  • In secondary (metastatic) ER positive, HER2 negative breast cancer, a CDK4/6 inhibitor with hormone therapy is a standard treatment that can control the cancer for longer and delay the need for chemotherapy.
  • In high-risk early breast cancer, abemaciclib and ribociclib can be added to hormone therapy after surgery to lower the risk of the cancer returning. Palbociclib is not used in this setting, because its early breast cancer trials did not show a benefit. 
  • The three drugs have different schedules and side effects, for example lower blood counts with palbociclib and ribociclib, and diarrhoea with abemaciclib, so the choice and monitoring are tailored to you.
  • Tracking how you feel in the OWise app, and sharing it with your team, can help keep side effects manageable and treatment on track. 

In this article

  • What are CDK4/6 inhibitors and how do they work? 
  • How CDK4/6 inhibitors are used 
  • Secondary (metastatic) breast cancer 
  • High-risk early breast cancer (after surgery) 
  • The three CDK4/6 inhibitors compared 
  • Side effects and monitoring 
  • Who they are for, and testing 
  • Questions to ask your care team 

What are CDK4/6 inhibitors and how do they work?  

Healthy cells only divide when they receive the right signals. Two proteins called CDK4 and CDK6 act like a switch that lets a cell move forward and divide. In hormone receptor positive breast cancer, the oestrogen signal helps keep this switch turned on, so the cancer cells keep dividing. 

CDK4/6 inhibitors block that switch. By pausing cell division, they slow or stop the cancer from growing. They are taken as tablets and are always combined with hormone therapy, so the treatment works in two ways at once: hormone therapy turns down the oestrogen signal, and the CDK4/6 inhibitor blocks the dividing switch. 


CDK4/6 proteins are needed for cell division. CDK4/6 inhibitors stop these proteins from working properly, which can slow or stop cancer cells from dividing.There are three CDK4/6 inhibitors: palbociclib (brand name Ibrance®), ribociclib (Kisqali®) and abemaciclib (Verzenios® in the UK / EU and Verzenio® elsewhere). They work in a similar way but differ in how they are taken and in their side effects

How CDK4/6 inhibitors are used 

CDK4/6 inhibitors are used in two quite different situations. The aim of treatment, and the way it is given, is different in each. 

Secondary (metastatic) breast cancer 

In secondary (also called metastatic or advanced) breast cancer, the aim is to control the cancer and keep you well for as long as possible. A CDK4/6 inhibitor combined with hormone therapy is a standard first treatment on the NHS. It is usually given with an aromatase inhibitor as the first option, or with fulvestrant if hormone therapy has been used before1,2. Before the menopause, it is combined with treatment to switch off the ovaries. You can read more in our Secondary (metastatic) hormone positive breast cancer blog.

Large trials have shown that adding a CDK4/6 inhibitor to hormone therapy lengthens the time before the cancer grows, and for some it helps people live longer, while delaying the need for chemotherapy3,4,5,6. All three are recommended on the NHS by NICE in this setting, and they are also standard in the United States and Europe. 

On the left, early (high-risk) breast cancer, with a CDK4/6 inhibitor added to hormone therapy after surgery to lower the risk of return; on the right, secondary (metastatic) breast cancer, with a CDK4/6 inhibitor plus hormone therapy used to control the cancer.

High-risk early breast cancer (after surgery)

In early breast cancer, the aim of treatment after surgery (called adjuvant treatment) is to lower the chance of the cancer ever coming back. Most people with hormone receptor positive early breast cancer take hormone therapy for several years. For people whose cancer has features that make a return more likely, adding a CDK4/6 inhibitor for a fixed period can lower that risk further. 

Two of the three CDK4/6 inhibitors are used here. Abemaciclib is taken with hormone therapy for two years, and on the NHS NICE recommends it for lymph node-positive early breast cancer at high risk of recurrence (for example, cancer in several nodes, or in one to three nodes together with a larger or higher-grade tumour)7,8,9. Ribociclib is taken with an aromatase inhibitor for three years, and is recommended for a slightly broader group at high risk, which can include some people whose cancer has not spread to the lymph nodes10,11. The right choice and dose depends on your cancer and how well you tolerate each drug. 

Palbociclib is not used as an adjuvant treatment, because its early breast cancer trials did not show a benefit12,13. In the United States and EU, both abemaciclib and ribociclib are approved in the adjuvant high-risk setting, in line with UK practice. 

Table 1. The three CDK4/6 inhibitors used in breast cancer treatment: palbociclib (Ibrance), ribociclib (Kisqali) and abemaciclib (Verzenios) and information about how they are taken, when they may be used and the side effects to be aware of during treatment.

Side effects and monitoring

CDK4/6 inhibitors are generally manageable, but they do need monitoring, and the main side effects differ between them. Palbociclib and ribociclib commonly lower the number of white blood cells, which help fight infection, so you will have regular blood tests, and your dose may be adjusted. Ribociclib can also affect heart rhythm and the liver, so you will usually have heart tracings (ECGs) and liver blood tests, especially at the start. Abemaciclib is more likely to cause diarrhoea, which is usually manageable and often settles, particularly if treated early, and it can cause tiredness and a small increase in the risk of blood clots. Rarely, these drugs can cause inflammation of the lungs. Tell your team promptly about new breathlessness, a persistent cough, fever, or diarrhoea that does not settle. 

Many side effects can be eased by adjusting the dose, and a lower dose does not necessarily mean the treatment works less well. The key is to report symptoms early so they can be managed before they become a problem. 

 

OWise Joint PainStarting a CDK4/6 inhibitor? Keeping a simple record of how you feel makes side effects easier to manage. With the OWise app you can track symptoms such as tiredness, diarrhoea and temperature, see the pattern over time, and share it with your care team, so any change can be acted on quickly. 

Who they are for and testing

CDK4/6 inhibitors are for hormone receptor positive, HER2 negative breast cancer. Whether they are an option depends on your hormone receptor and HER2 status, which come from the tests done on your cancer, rather than on any extra genetic test. You can read about these results in The pathology report explained. If hormone therapy with a CDK4/6 inhibitor stops working in secondary breast cancer, there are further options, which we cover in our Hormone therapy resistance blog. 

Questions to ask your care team

Use the OWise app to create your own question lists and add the questions below to make sure you cover everything you need:

  • Why are you recommending a CDK4/6 inhibitor for me, and which one? 
  • Is this to lower the risk of my cancer coming back, or to control cancer that has spread? 
  • How is it taken, for how long, and what hormone therapy goes with it? 
  • What side effects should I look out for, and which ones should I report straight away? 
  • What monitoring (such as blood tests, ECGs or liver tests) will I need, and how often? 
  • What happens if I get side effects, and can the dose be adjusted? 

Related OWise blogs

You may also find these helpful: 

A CDK4/6 inhibitor is often a long course of treatment:

Staying on it, at the right dose, gives it the best chance to work. Use the OWise app to keep your symptoms, treatments and questions in one place, and bring the full picture to each appointment, so you and your team can manage side effects and decisions together.  

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Editorial Information 

Written by: OWise editorial team  |  Clinically reviewed by: A. Bruinvels, MSc PhD  |  Last reviewed: July 2026 

References 

  1. Johnston SRD, Harbeck N, Hegg R, et al. (2020) Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk early breast cancer (monarchE). Journal of Clinical Oncology 38:3987-3998. 
  2. Rastogi P, O’Shaughnessy J, Martin M, et al. (2024) Adjuvant abemaciclib plus endocrine therapy in high-risk early breast cancer: monarchE overall survival interim analysis and 5-year outcomes. Journal of Clinical Oncology.
  3. National Institute for Health and Care Excellence (2022) Abemaciclib with endocrine therapy for adjuvant treatment of hormone receptor-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence. NICE technology appraisal guidance TA810. 
  4. Slamon DJ, Stroyakovskiy D, Yardley DA, et al. (2024) Adjuvant ribociclib plus a nonsteroidal aromatase inhibitor in HR+/HER2- early breast cancer (NATALEE). New England Journal of Medicine. 
  5. National Institute for Health and Care Excellence (2025) Ribociclib with an aromatase inhibitor for adjuvant treatment of hormone receptor-positive HER2-negative early breast cancer at high risk of recurrence. NICE technology appraisal guidance TA1086. 
  6. Hortobagyi GN, Stemmer SM, Burris HA, et al. (2022) Overall survival with ribociclib plus letrozole in advanced breast cancer (MONALEESA-2). New England Journal of Medicine 386:942-950. 
  7. Finn RS, Martin M, Rugo HS, et al. (2016) Palbociclib and letrozole in advanced breast cancer (PALOMA-2). New England Journal of Medicine 375:1925-1936. 
  8. Goetz MP, Toi M, Campone M, et al. (2017) MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. Journal of Clinical Oncology 35:3638-3646. 
  9. Cristofanilli M, Turner NC, Bondarenko I, et al. (2016) Fulvestrant plus palbociclib versus fulvestrant plus placebo (PALOMA-3). Lancet Oncology 17(4):425-439. 
  10. National Institute for Health and Care Excellence (2022) Palbociclib with fulvestrant for hormone receptor-positive HER2-negative advanced breast cancer after endocrine therapy. NICE technology appraisal guidance TA836. Ribociclib with fulvestrant (TA593) and abemaciclib with fulvestrant (TA725) are also recommended. 
  11. National Institute for Health and Care Excellence (2019) Abemaciclib with an aromatase inhibitor for untreated hormone receptor-positive, HER2-negative advanced breast cancer. NICE technology appraisal guidance TA563. 
  12. Mayer EL, et al. (2021) Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS)
  13. Loibl S, et al. (2021) Palbociclib for residual high-risk early breast cancer (PENELOPE-B). Neither trial (12,13) showed a benefit from adjuvant palbociclib.