Breast Cancer — Clinical Case

DCE Long Case

Patient profile

Mrs M is a 62-year-old woman who presents to the emergency department with a 6-week history of progressive lower thoracic back pain, worse on movement and at night, not relieved by paracetamol or ibuprofen. She has a history of ER-positive, HER2-negative breast cancer treated 7 years ago with breast-conserving surgery, adjuvant radiotherapy, and 5 years of anastrozole. She had been well and attending annual mammographic surveillance. She is referred by her general practitioner after an X-ray showed a possible pathological compression fracture at T12. [1]

Presenting concern: Mrs M describes 6 weeks of worsening mid-to-lower back pain that radiates around her rib cage. The pain is worse at night, wakes her from sleep, and is not relieved by over-the-counter analgesics. She has noticed increasing fatigue and has had two episodes of urinary hesitancy in the past week. She has no leg weakness, but she is frightened that her cancer has returned — her oncologist had told her the 5-year mark was an important milestone, and she had been told she was doing well at her last mammogram 8 months ago. [1]

Past medical history:

• ER-positive, HER2-negative invasive ductal carcinoma of the left breast (T1c N0 M0, stage IA), diagnosed at age 55.
• Treated with wide local excision and sentinel lymph node biopsy (negative), adjuvant whole-breast radiotherapy, and 5 years of adjuvant anastrozole (completed 2 years ago).
• Hypertension (on perindopril 5 mg daily).
• Osteopenia (diagnosed on DEXA 3 years ago, on calcium and vitamin D supplementation).
• Cholecystectomy at age 40. [1]

Medications: Perindopril 5 mg daily, calcium 1000 mg daily, vitamin D 1000 IU daily. She completed anastrozole 2 years ago. [1]

Family history: Her mother had breast cancer at 68 (ER-positive). No ovarian cancer in the family. No known hereditary cancer syndrome. Her father died of ischaemic heart disease at 72. [1]

Social: Married, two adult children. Retired schoolteacher. Non-smoker, drinks alcohol occasionally. She and her husband had been planning travel in retirement, and she is distressed that this may now be impossible. [1]

Examination:

• Well-appearing but anxious. ECOG performance status 1 (restricted in strenuous activity but ambulatory and able to do light work).
• Mild pallor. No jaundice, no lymphadenopathy.
• Left breast: well-healed surgical scar in the upper outer quadrant, no palpable masses, no skin changes. Right breast: unremarkable. No axillary or supraclavicular lymphadenopathy.
• Back examination: tenderness over the lower thoracic spine (T11 to T12). No step deformity.
• Neurological examination: lower limb power 5/5 bilaterally, normal sensation, normal reflexes, plantar responses downgoing. No sensory level. Bowel and bladder function reported as normal (with mild hesitancy).
• Respiratory and abdominal examination: unremarkable. No hepatomegaly. [1]

Investigations:

• Haemoglobin 106 g/L (normocytic), calcium 2.45 mmol/L (normal), alkaline phosphatase 165 U/L (mildly elevated), liver function otherwise normal. Renal function normal.
• Tumour markers: CA 15-3 elevated at 78 U/mL (normal under 30).
• Thoracolumbar spine X-ray: compression deformity at T12.
• CT chest-abdomen-pelvis: multiple sclerotic lesions in the thoracic and lumbar spine, pelvis, and right femur, consistent with bone metastases. No visceral metastases (liver, lung clear). Left breast: post-surgical changes, no local recurrence.
• MRI thoracolumbar spine: multiple vertebral metastases with a compression fracture at T12. No epidural extension or spinal cord compression. The canal is not narrowed. [1]

Candidate's opening statement (SASPOP)

"This is Mrs M, a 62-year-old woman presenting with metastatic (stage IV) ER-positive, HER2-negative breast cancer, recurring as bone-only disease 7 years after her initial diagnosis and 2 years after completing adjuvant anastrozole. The metastatic disease involves multiple vertebral bodies and the pelvis, with a pathological compression fracture at T12, but there is no spinal cord compression on MRI and no visceral metastases. The key features that shape her management are that the disease is bone-only (favourable prognosis compared with visceral metastases), ER-positive (endocrine therapy is the preferred first-line approach), and she has a T12 compression fracture (needs orthopaedic and radiation oncology assessment for stability and pain control). Her main problems are: the metastatic breast cancer and the systemic therapy decision (CDK4/6 inhibitor plus endocrine therapy); the pathological compression fracture at T12 (palliative radiotherapy, possible vertebroplasty); bone-targeted therapy (zoledronic acid or denosumab); the mild urinary hesitancy (needs monitoring for early cord compression, though the MRI is reassuring); the osteopenia from prior anastrozole; and the psychosocial impact of cancer recurrence after 7 years, including her fears about the future and her retirement plans. My priorities are to arrange urgent palliative radiotherapy to the T12 lesion for pain control and fracture prevention, to commence systemic therapy with a CDK4/6 inhibitor plus fulvestrant, to start bone-targeted therapy with zoledronic acid, to monitor for cord compression, and to provide psychosocial support and early palliative care involvement." [1]

Structured problem list (numbered, prioritised)

1. Metastatic (stage IV) ER-positive, HER2-negative breast cancer, bone-only — the central problem; favourable biology (bone-only, ER-positive) means endocrine-based therapy is preferred.
2. Pathological compression fracture at T12 with multiple vertebral metastases — needs palliative radiotherapy, orthopaedic assessment for stability, and pain management.
3. Risk of spinal cord compression — no cord compression on current MRI, but the urinary hesitancy is a warning sign requiring vigilance and a low threshold for repeat imaging.
4. Bone-targeted therapy — zoledronic acid or denosumab to reduce skeletal-related events.
5. Osteopenia from prior anastrozole — ongoing bone health management.
6. Psychosocial impact of recurrence — fear, uncertainty, disruption of retirement plans; needs psychological support and early palliative care. [1]

Integrated management plan

Step 1 — The systemic therapy decision: [1]

The defining decision is that Mrs M has ER-positive, HER2-negative, bone-only metastatic breast cancer that has progressed after adjuvant anastrozole. For this clinical scenario — bone-only or low-burden visceral disease, ER-positive, asymptomatic or minimally symptomatic — endocrine-based therapy is preferred over chemotherapy, as it is better tolerated, maintains quality of life, and provides equivalent or superior disease control. [1]

The standard first-line approach after progression on a non-steroidal aromatase inhibitor (anastrozole) is a CDK4/6 inhibitor combined with fulvestrant. CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) block cyclin-dependent kinases 4 and 6, preventing cell cycle progression from G1 to S phase in ER-positive breast cancer cells. Combined with fulvestrant (a selective oestrogen receptor degrader), this combination significantly improves progression-free survival compared with fulvestrant alone (typically 20 to 25 months versus 10 to 15 months). [1]

An alternative is exemestane plus everolimus (an mTOR inhibitor), which is also effective after non-steroidal AI failure. The choice between a CDK4/6 inhibitor and everolimus depends on toxicity profile, subsidised access, and patient factors (CDK4/6 inhibitors are generally preferred as first-line due to better tolerability and efficacy). [1]

Chemotherapy is not the first choice for this patient — it is reserved for symptomatic visceral crisis, rapid progression, or endocrine resistance. Her bone-only disease with ECOG 1 is the ideal scenario for endocrine-based therapy. [1]

Step 2 — Palliative radiotherapy to T12: [1]

Mrs M has a pathological compression fracture at T12 with significant pain. Palliative radiotherapy is the most effective treatment for painful bone metastases — a single 8 Gy fraction provides pain relief in 60 to 80 percent of patients within 1 to 4 weeks. Radiotherapy also reduces the risk of further progression at the treated site. [1]

The MRI shows no epidural extension or cord compression, which is reassuring. However, the urinary hesitancy is a concerning symptom that warrants close monitoring. I would educate Mrs M and her husband about the red flags of spinal cord compression (progressive leg weakness, sensory changes, bowel or bladder dysfunction) and arrange an urgent repeat MRI if any new neurological symptoms develop. A spinal surgery consultation would be considered if there is instability on imaging (e.g. a kyphotic deformity or a large lytic component) to assess whether vertebroplasty or kyphoplasty (cement augmentation) would stabilise the fracture and provide pain relief. [1]

Step 3 — Bone-targeted therapy: [1]

I would commence zoledronic acid (4 mg IV every 4 weeks, with dose adjustment for renal function) or denosumab (120 mg subcutaneously every 4 weeks) to reduce skeletal-related events — pathological fractures, spinal cord compression, hypercalcaemia, and the need for radiotherapy or surgery to bone. Both are effective; denosumab is superior in head-to-head trials for delaying skeletal-related events but is more expensive and has a higher risk of hypocalcaemia. Bisphosphonates require renal function monitoring and carry a small risk of osteonecrosis of the jaw (dental review before starting). Both agents should be supplemented with calcium and vitamin D. [1]

Step 4 — Pain management: [1]

Pain control is a priority. I would use a stepwise approach:

• Regular paracetamol and a non-steroidal anti-inflammatory (if no contraindication).
• A short-acting opioid (e.g. oxycodone immediate-release) for breakthrough pain, titrated to effect.
• Once the pain pattern is established, convert to a sustained-release opioid (e.g. oxycodone SR or morphine SR) with breakthrough doses.
• Consider a laxative prophylactically with opioids.
• The palliative radiotherapy should reduce pain within 1 to 4 weeks, potentially allowing opioid de-escalation. [1]

Step 5 — Monitoring for spinal cord compression: [1]

Although the current MRI shows no cord compression, the T12 fracture and multiple vertebral metastases place Mrs M at high risk. The urinary hesitancy is a borderline symptom. I would:

• Perform daily neurological observations while an inpatient.
• Educate the patient and family about the red flags.
• Have a low threshold for repeat MRI if any new symptoms develop.
• Ensure the patient knows to present immediately if she develops leg weakness, numbness, or urinary retention. [1]

Step 6 — Osteopenia and bone health: [1]

Mrs M has osteopenia from 5 years of anastrozole therapy. The zoledronic acid (or denosumab) she will receive for bone metastases will also have a bone-protective effect. I would continue calcium and vitamin D supplementation, ensure she has had a recent DEXA (though the metastatic disease makes interpretation more complex), and ensure adequate vitamin D levels (check and supplement if deficient). [1]

Step 7 — Genetic testing and hereditary risk assessment: [1]

Mrs M's mother had breast cancer at 68 (ER-positive), which is relatively common and does not by itself strongly suggest a hereditary syndrome. Mrs M's own tumour was ER-positive and HER2-negative, diagnosed at 55. She does not meet the most urgent criteria for BRCA testing (early-onset, triple-negative, bilateral, male breast cancer, or ovarian cancer in the family). However, I would take a careful three-generation family history and consider referral to a familial cancer service if the pedigree reveals additional affected relatives. The result, if positive, would have implications for ovarian cancer risk management and cascade family testing, though it would not change the metastatic treatment plan (olaparib is for early-stage adjuvant therapy, not metastatic ER-positive disease in the first line). [1]

Step 8 — Communication and psychosocial support: [1]

This is a devastating moment for Mrs M — she had passed the 5-year milestone and believed she was cured, only to have the cancer return 7 years later. I would be honest and compassionate: the cancer has returned in the bones, it is not curable, but it is treatable, and endocrine-based therapy can control it for years while maintaining her quality of life. I would explain the treatment plan — a tablet (CDK4/6 inhibitor) plus an injection (fulvestrant), bone-strengthening treatment, and radiotherapy for the painful area — and emphasise that this is not chemotherapy, so the side effects are different (fatigue, low blood counts, mild nausea, but no hair loss). I would involve a cancer nurse coordinator, offer psychological support, and introduce palliative care early — not for end-of-life care, but for symptom management and goals-of-care discussions alongside active treatment. I would address her fears about travel and reassure her that with disease control, travel may still be possible. I would document advance care planning and ensure her husband is involved in the discussions. [1]

Probing questions the examiner would ask

Q: Why is endocrine therapy preferred over chemotherapy for this patient? [1]

A: "Mrs M has ER-positive, HER2-negative, bone-only metastatic breast cancer with minimal symptoms (ECOG 1) and no visceral crisis. For this clinical scenario, endocrine-based therapy — specifically a CDK4/6 inhibitor plus fulvestrant — is preferred over chemotherapy for several reasons: it is better tolerated and maintains quality of life; it provides equivalent or superior progression-free survival; and it avoids the toxicity of chemotherapy (alopecia, neuropathy, myelosuppression, nausea). Chemotherapy is reserved for endocrine-resistant disease, symptomatic visceral crisis (e.g. liver dysfunction, symptomatic brain metastases), or rapidly progressive disease. The paradigm has shifted: ER-positive metastatic breast cancer is now managed as a chronic disease with sequential lines of endocrine-based therapy, reserving chemotherapy for later. The CDK4/6 inhibitors have been the major advance — combining palbociclib, ribociclib, or abemaciclib with fulvestrant after AI progression nearly doubles progression-free survival compared with fulvestrant alone." [1]

Q: How do you decide between zoledronic acid and denosumab for bone-targeted therapy? [1]

A: "Both zoledronic acid (a bisphosphonate) and denosumab (a RANKL inhibitor) reduce skeletal-related events in bone metastases. Denosumab is superior in head-to-head trials for delaying the first skeletal-related event and is not renally cleared, making it preferable in renal impairment. However, it is more expensive, requires more frequent dosing (monthly subcutaneous), and carries a higher risk of hypocalcaemia (which can be severe) and osteonecrosis of the jaw. Zoledronic acid is given as a 15-minute IV infusion every 4 weeks, requires renal function monitoring (dose adjustment for eGFR), and also carries a risk of osteonecrosis of the jaw and, rarely, atypical femoral fracture. For Mrs M, whose renal function is normal, either agent is appropriate. I would involve a dentist for a baseline assessment before starting either agent (to minimise osteonecrosis risk), ensure adequate calcium and vitamin D supplementation, and monitor calcium levels. The choice may also be influenced by subsidised access and patient preference for route of administration." [1]

Q: What would you do if she developed acute leg weakness while an inpatient? [1]

A: "Acute leg weakness in a patient with vertebral metastases is spinal cord compression until proven otherwise — this is an oncological emergency. I would: (1) perform an immediate neurological examination to document the level and severity of the deficit; (2) arrange an urgent whole-spine MRI (not just the area of known disease, as metastases can occur at multiple levels and the level of compression may differ from the level of known disease); (3) administer IV dexamethasone 10 mg stat then 4 mg every 6 hours to reduce cord oedema and preserve neurological function; (4) urgently contact the radiation oncology and spinal surgery teams for emergency radiotherapy or surgical decompression. The prognosis for neurological recovery depends on the duration and severity of the deficit — ambulatory patients at presentation have a much better prognosis than those who are non-ambulatory or have lost bowel or bladder function. Time is of the essence: the goal is to start treatment within 24 hours of the onset of neurological symptoms." [1]

Q: What is the prognosis for ER-positive bone-only metastatic breast cancer? [1]

A: "ER-positive, bone-only metastatic breast cancer has the most favourable prognosis of any metastatic breast cancer subtype. The median overall survival for patients with bone-only ER-positive disease treated with modern endocrine-based therapy (including CDK4/6 inhibitors) is now in the range of 4 to 6 years, and some patients live much longer. The reasons for the favourable prognosis are: bone-only disease is generally less aggressive than visceral disease; ER-positive tumours are indolent and respond to multiple lines of endocrine therapy; and the bone microenvironment, while a site of metastasis, is more amenable to local control (radiotherapy, bone-targeted therapy) than visceral sites. However, the disease is not curable, and over time it will become endocrine-resistant and may evolve to involve viscera. The goal of treatment is to maintain quality of life and control disease for as long as possible with the least toxic therapy." [1]

Q: How would you counsel a woman about starting an aromatase inhibitor in the adjuvant setting, and how does that relate to this patient's osteopenia? [1]

A: "I would counsel that aromatase inhibitors (anastrozole, letrozole, exemestane) are the standard adjuvant endocrine therapy for postmenopausal ER-positive breast cancer, based on the ATAC trial showing superiority over tamoxifen [3]. The key side effects to discuss are: hot flushes and vasomotor symptoms; arthralgia and myalgia (common, may limit adherence, often improves with time); vaginal dryness and dyspareunia; and osteoporosis — AIs reduce bone mineral density by 2 to 4 percent per year. For bone health, I would arrange a baseline DEXA scan before starting, supplement with calcium and vitamin D, and recommend weight-bearing exercise. If the DEXA shows osteopenia or osteoporosis, I would add a bisphosphonate (zoledronic acid) or denosumab for bone protection — interestingly, bisphosphonates in the adjuvant setting also have a modest anti-tumour effect and may reduce bone recurrence. For Mrs M, her 5 years of anastrozole contributed to her osteopenia, and now that she has bone metastases, the zoledronic acid she receives for skeletal-related event prevention will also address her bone density."

Communication and shared decision-making

*"Mrs M, I want to be honest and clear with you. The tests show that your breast cancer has come back, this time in your bones — in the spine, pelvis, and right thigh bone. I know this is devastating news, especially after you had passed the 5-year mark and thought you were through the worst of it. I want to tell you what this means and what we can do. [1]

The good news is that this is a type of cancer that we can often control for years with tablet treatment, not chemotherapy. Your original cancer was driven by oestrogen, and this metastatic disease likely is too. We have newer medications — a tablet called a CDK4/6 inhibitor, combined with an injection called fulvestrant — that work together to block the cancer's ability to grow. This is different from chemotherapy — it does not cause hair loss, and while it can cause fatigue and lower blood counts, most women tolerate it well and continue their normal activities. [1]

For your back, the pain is coming from a fracture in one of the vertebrae where the cancer has weakened the bone. We will arrange radiotherapy — a single treatment, usually — to that area to relieve the pain and strengthen the bone. We will also start a bone-strengthening medication called zoledronic acid, given as a drip every month, to protect your bones from further problems. [1]

I want you to know that this cancer is not curable, but it is treatable, and many women with this type of disease live for years with good quality of life. The treatment is designed to keep the cancer under control while allowing you to live as normally as possible. I will connect you with a cancer nurse coordinator who will be your point of contact, and I would like to introduce the palliative care team — not because you are dying, but because they are experts in managing symptoms and helping us plan your care alongside the active treatment. Your husband and family will be part of these conversations. [1]

I know you had travel plans, and I do not want to take that away from you yet. Once we have the pain under control and the treatment started, we can talk about what is safe and feasible. Let us take this one step at a time."* [1]

Outcome and follow-up

Mrs M is admitted for pain stabilisation and palliative radiotherapy. She receives a single 8 Gy fraction of radiotherapy to the T12 vertebra with good pain relief within 10 days. A dental review clears her for bone-targeted therapy, and she commences zoledronic acid 4 mg IV monthly with calcium and vitamin D supplementation. [1]

She is commenced on palbociclib (125 mg daily, 3 weeks on and 1 week off) plus fulvestrant (500 mg intramuscular injection on days 1, 15, and 29, then monthly). Her blood counts are monitored every 2 weeks initially — she develops grade 2 neutropenia (managed with dose reduction of palbociclib to 100 mg) but tolerates the regimen well. Her arthralgia improves (paradoxically, the CDK4/6 inhibitor seems to have helped the AI-related joint pain she had previously). Her CA 15-3 falls from 78 to 35 over 3 months. [1]

A repeat CT at 3 months shows stable sclerotic bone metastases with no new lesions and no visceral disease. The T12 compression fracture is stable on imaging. Her pain is well controlled on a reduced opioid dose (oxycodone SR 10 mg twice daily with breakthrough immediate-release oxycodone). Her neurological examination remains normal, and the urinary hesitancy has resolved. [1]

She is discharged home with community palliative care nursing support and regular medical oncology review. She and her husband engage with psychology and palliative care. She documents advance care planning. At 6 months, she is pain-free, has returned to gentle exercise, and has taken a modified domestic trip with her husband. She understands that the disease will eventually progress but is grateful for the quality of life she has regained. The medical oncology team has a plan for second-line endocrine therapy (exemestane plus everolimus) and, if needed, later-line chemotherapy, with the goal of maintaining her quality of life for as long as possible. [1]