A 56-Year-Old Teacher With Worsening Hip Pain

Avan Armaghani, MD

Disclosures

April 06, 2020

This case is an example of a patient with breast cancer who first presented after metastasis. De novo metastatic breast cancer accounts for as many as 5% of all new breast cancer diagnoses.[1] In addition, as many as 30% of patients with early-stage cancer at presentation develop metastatic disease. The clinical presentation of metastatic breast cancer varies and depends on the organs that are involved. For example, metastatic disease to the lungs can present as cough or shortness of breath. Abdominal pain, nausea, or jaundice can suggest liver involvement. Persistent back or hip pain can suggest bone involvement.[2]

In this case, the patient presented with oligometastatic disease, with one site of metastatic disease in the left femoral neck. As many as 10% of newly diagnosed metastatic breast cancer cases present with oligometastatic disease.[2] An aggressive approach to treatment is oftentimes considered in an attempt to achieve cure.[3] This requires a multidisciplinary approach that includes surgery, radiation oncology, and medical oncology.

Although hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer cannot be cured, recent scientific advancements in therapies have provided significant improvements in prolonging patient lives and maintaining a good quality of life. Various strategies are used in treatment of metastatic breast cancer in postmenopausal women. The first involves eliminating the production of estrogen with aromatase inhibitors (AIs), which include anastrozole, letrozole, and exemestane. Tamoxifen improved breast cancer recurrence and mortality by 30%-40% compared with placebo in a meta-analysis that included trials with both premenopausal and postmenopausal women.[4]

Although AI monotherapy is not the preferred first-line therapy in postmenopausal women with HR+/HER2- metastatic breast cancer, it can be used in selected patients who may not be able to tolerate other combination treatment regimens. A meta-analysis showed that AI monotherapy had a statistically significant survival benefit in postmenopausal women compared with tamoxifen and other endocrine therapies.[4]

The development of targeted therapies, including cyclin-dependent kinase (CDK) 4/6 inhibitors and mammalian target of rapamycin (mTOR) inhibitors, have transformed the treatment of HR+/HER2- metastatic breast cancer. Palbociclib, ribociclib, and abemaciclib are the three CDK 4/6 inhibitors currently approved by the US Food and Drug Administration. Palbociclib in combination with an AI as first-line therapy in the treatment of estrogen receptor-positive (ER+)/HER2- metastatic breast cancer has shown to have a significant improvement in progression-free survival (PFS).[5] Similar findings have also been found with ribociclib and abemaciclib.[6,7]

Given the significant improvement in PFS with CDK 4/6 inhibitors in combination with AI, this is the preferred first-line treatment in metastatic ER+/HER2- metastatic breast cancer. Fulvestrant is an alternative to first-line treatment for HR+/HER2- metastatic breast cancer.[8] This is a selective estrogen degrader and has shown to be effective as monotherapy and in combination therapy in the treatment of metastatic breast cancer.[9] Fulvestrant in combination with ribociclib has shown improved PFS in patients with HR+/HER2- metastatic breast cancer who have not received any prior treatment or as much as one line of prior endocrine therapy.[10] The mTOR inhibitor everolimus, in combination with exemestane, has shown to improve PFS in patients with HR+/HER2- metastatic breast cancer who were previously treated with nonsteroidal AI.[10]

Subsequent lines of therapy in HR+/HER2- metastatic breast cancer include abemaciclib, which has been shown to be effective monotherapy in patients whose disease progressed on or after prior endocrine therapy and who had one or two chemotherapy regimens.[11] Abemaciclib has also shown to have overall survival benefit in combination with fulvestrant for women with disease progression after endocrine therapy.[12]

Chemotherapy remains an acceptable treatment option; however, with the advent of effective nonchemotherapy treatment modalities that are associated with fewer side effects, chemotherapy is generally used in much later lines of treatment.

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