Can Anastrazole (Aromatase Inhibitor) cause neutropenia?

Anastrozole and Neutropenia

Yes, anastrozole can cause neutropenia, particularly when used in combination with CDK 4/6 inhibitors, though it is less common when used as monotherapy. 1

Neutropenia Risk with Anastrozole

As Monotherapy

• Anastrozole as a single agent is generally well tolerated with most common adverse events being gastrointestinal disturbances (29-33%), headache (≤18%), and musculoskeletal symptoms 2
• When used alone, anastrozole is not commonly associated with severe neutropenia, unlike when combined with other agents 1
• In clinical practice, neutropenia is not listed among the most frequent adverse events for anastrozole monotherapy 3

In Combination Therapy

• When anastrozole is combined with CDK 4/6 inhibitors such as abemaciclib, the risk of neutropenia increases significantly 1
• In the MONARCH trial, the combination of abemaciclib with an aromatase inhibitor (including anastrozole) resulted in grade 3 or higher neutropenia in 21.1% of patients compared to only 1.2% with aromatase inhibitor monotherapy 1
• Similar findings were observed with other CDK 4/6 inhibitors:
  • Palbociclib with letrozole: grade 3-4 neutropenia in 66.5% vs 1.4% with letrozole alone 1
  • Ribociclib with letrozole: grade 3-4 neutropenia in 62% vs 1.2% with letrozole alone 1

Clinical Implications and Management

Monitoring Recommendations

• Complete blood count monitoring is recommended when anastrozole is used in combination with CDK 4/6 inhibitors due to the increased risk of neutropenia 1
• For patients on anastrozole monotherapy, routine monitoring for neutropenia is not specifically required but should be considered in patients with other risk factors for bone marrow suppression 1

Risk Factors for Increased Toxicity

• Prior chemotherapy may increase the risk of hematologic adverse events 3
• Advanced age and multiple prior therapies may contribute to increased susceptibility to bone marrow suppression 3
• Patients with renal impairment do not require dose adjustment as anastrozole is not significantly eliminated through renal pathways 4

Comparative Safety Profile

• Anastrozole has a different side effect profile compared to tamoxifen:
  • Anastrozole is associated with more fractures, musculoskeletal events, and hypercholesterolemia 1
  • Tamoxifen is associated with more thromboembolic events, gynecologic symptoms, and vasomotor symptoms 1
• Among aromatase inhibitors, there appear to be differences in toxicity profiles:
  • Exemestane and letrozole have shown early signs of cardiac side effects compared to tamoxifen, while anastrozole has not demonstrated significant increases in cardiovascular events in longer-term studies 1
  • All aromatase inhibitors are associated with increased bone fracture risk compared to tamoxifen 1

Other Rare Adverse Events

• Anastrozole has been associated with other rare adverse events not related to neutropenia:
  • Dermatologic reactions occurring 2 months after initiation (including vasculitis, erythema nodosum, and subacute cutaneous lupus erythematosus) 5
  • Rare cases of sclerosing glomerulonephritis have been reported 4

In conclusion, while neutropenia is not a prominent concern with anastrozole monotherapy, clinicians should be vigilant about this potential adverse effect, especially when anastrozole is combined with CDK 4/6 inhibitors or used in heavily pretreated patients 1, 3.