What is the next best step in managing a 62-year-old with a history of hormone receptor positive, HER2 negative breast cancer, now presenting with fatigue, progressive back pain, and imaging findings suggestive of metastatic disease?

From the Guidelines

The next best step in managing this 62-year-old patient with suspected metastatic hormone receptor positive, HER2 negative breast cancer is to obtain a tissue biopsy of the suspected metastatic lesion to confirm the diagnosis and reassess receptor status. This approach is based on the most recent and highest quality evidence available, which emphasizes the importance of confirming the diagnosis and assessing receptor status to guide treatment decisions 1.

Rationale for Biopsy

The rationale for obtaining a tissue biopsy is to confirm the presence of metastatic disease and to reassess the hormone receptor status, as this information is crucial for guiding treatment decisions. According to the European Society for Medical Oncology (ESMO) guidelines, efforts should be made to obtain histopathological confirmation whenever technically feasible, particularly in the situation of an isolated metastatic lesion 1.

Comprehensive Staging

Following the biopsy, comprehensive staging with imaging studies such as CT chest/abdomen/pelvis, bone scan, and possibly brain MRI should be performed to determine the full extent of metastatic disease. Laboratory tests including complete blood count, comprehensive metabolic panel, and tumor markers (CA 15-3, CA 27.29) should also be ordered.

Treatment Approach

Once metastatic disease is confirmed, first-line treatment typically involves endocrine therapy such as an aromatase inhibitor (anastrozole 1mg daily, letrozole 2.5mg daily, or exemestane 25mg daily) combined with a CDK4/6 inhibitor (palbociclib 125mg daily for 21 days followed by 7 days off, ribociclib 600mg daily for 21 days followed by 7 days off, or abemaciclib 150mg twice daily). For significant bone metastases, bone-modifying agents like zoledronic acid 4mg IV every 3-4 weeks or denosumab 120mg subcutaneously every 4 weeks should be added to prevent skeletal-related events. Pain management with appropriate analgesics is essential for symptom control.

Key Considerations

The choice of therapy should be made after consideration of factors such as previous therapies and response to them, disease-free interval, endocrine responsiveness, HER2 status, tumour burden, menopausal status, biological age, and co-morbidities 1. Patients' preferences should always be taken into account, not only about treatment options but also methods of treatment administration.

In this case, given the patient's history of hormone receptor positive, HER2 negative breast cancer, and the presence of suspected metastatic lesions, obtaining a tissue biopsy to confirm the diagnosis and reassess receptor status is the most appropriate next step, as it will guide further treatment decisions and ensure that the patient receives the most effective therapy for their disease.

From the Research

Next Steps in Management

Given the patient's history of hormone receptor positive, HER2 negative breast cancer and current presentation with fatigue, progressive back pain, and imaging findings suggestive of metastatic disease, the following options are considered:

• Biopsy of one of the lesions: This is recommended as it can histologically confirm the diagnosis of metastasis, evaluate discrepancies between ER, PR, and HER2 status, and exclude secondary malignancy, which might change the therapeutic strategy for breast cancer patients 2, 3.
• PET scan: This can be useful in assessing the extent of disease and evaluating response to therapy, especially with the development of novel radioactively labeled ligands for PET/CT imaging in metastatic breast cancer 4.
• MRI of the brain with or without contrast: This may not be immediately necessary unless there are specific symptoms suggesting brain involvement, but it can be considered as part of a comprehensive staging workup.

Rationale

The rationale behind these recommendations includes:

• The importance of confirming the diagnosis of metastasis and assessing the receptor status of the metastatic lesions, as there can be discordance between the primary tumor and metastatic sites 2, 3.
• The role of advanced imaging techniques, such as PET/CT, in evaluating the extent of disease and monitoring response to therapy 5, 4.
• The potential of liquid biopsy, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), in predicting clinical outcome and guiding therapy choices in metastatic breast cancer 6.

Considerations

When deciding on the next steps, considerations should include:

• The patient's overall clinical condition and symptoms.
• The potential benefits and limitations of each diagnostic and therapeutic approach.
• The importance of multidisciplinary discussion and consideration of the patient's preferences and values in decision-making.