🧙🏻♀️Metastatic Breast Ca Flashcards
📩 If you have any questions or notice any errors, please feel free to email ericgansy18@gmail.com (17 cards)
Overview of Metastatic Breast Cancer Management
What is the long term survival rate for mBC?
<5%
What is the treatment aim for mBC?
Evaluation:
-Confirm diagnosis: CNB (HPE, ER/PR, HER2)
- Staging : CT scan, bone scintigraphy, MRI and positron emission tomography / computerized tomography (PET/CT)
- Operability : ECOG status, ASA, (ECHO, LFT if indicated)
- Resectability
Aim:
- Prolong survival
- Maintain QOL
- Palliation of symptoms
What is the endocrine therapy for mBC?
For HR+/ERBB2- initial endocrine therapy with CDK 4/6 inhibitors is 1st line followed by chemotherapy
* If symptoms allow, wait 3-4 months until best response
* If unable to wait for response, chemotherapy can be considered in initial part of treatment
AI is preferred 1st line in post-menopausal women, but recent studies show survival advantage of fulvestrant (Direct estrogen receptor inhibitor) 500mg vs anastrozole 1mg (FIRST, FALCON trial)
Pre-menopausal patient should be considered for medical or surgical menopause to maximized effect of endocrine therapy.
What is the role of targeted therapy for mBC?
- Progression-free survival prolonged but not OS with addition targeted therapy to endocrine agents
- CDK 4/6 inhibitor (palbociclib) + letrozole - longer PFS in post-menopausal women (PALOMA-1, PALOMA-2)
- In progression disease or relapsed on previous endocrine therapy, combination of palbociclib and fulvestrant proven to prolong PFS (PALOMA-3)
- Newer CDK 4/6 inhibitor in the trials are ribociclib and abemaciclib.
- RCT showed better PFS with ribociclib + letrozole (MONALEESA-2) and abemaciclib + anastrazole/letrozole (MONARCH-3)
-
mTOR inhibitor (everolimus) + exemestane substantially prolonged PFS but not OS in post-menopausal women
Everolimus + exemestane (steroidal AI) can be considered as 2nd line therapy in HR+ mBC
What is the role of HER2 treatment in mBC?
- ERBB2 targeted therapy should be started as early as possible in ERBB2+ mBC
- Trastuzumab + Taxane-based chemotherapy showed improved PFS at 1 year (HERA)
- Addition of pertuzumab to trastuzumab + taxane regimen (docetaxel) further improved PFS and OS (CLEOPATRA)
- After treatment with 1st line or rapid progression on trastuzumab, T-DM1 (combination of trastuzumab and emtansine (anti-tubulin cytotoxic) is superior to lapatinib + capecitabine (EMILIA)
What is the role of chemotherapy in mBC?
-
Indicated in:
1. metastatic TNBC
2. Luminal BC after exhaustion of endocrine therapy
3. Highly symptomatic patient requiring rapid response (Visceral crisis) - Monotherapy is proven as effective with lesser toxicity.
- Combination therapy reserve for rapid progression disease
- No standard sequence of monotherapy exists but should be tailor base on patient’s preference and tolerance, previous side effect and toxicity
Role of surgery in mBC
Primary role is for palliation of symptoms and use to control symptomatic primary tumor (bleeding, infection or ulcerating, fungating tumor)
- No clear benefit for treatment of asymptomatic primary tumor in mBC
landmark Trials for mBC ( surgery)
- Indian trial subject patient to surgery following anthracycline-based chemo; no difference in OS but worsen distant DFS; study affected by non-standard chemo and no anti-ERBB2 therapy in 92% of the patients
- Turkey trial randomized patients into surgery or not followed by systemic chemotherapy; no difference at 3- year survival but slightly improved 5-year survival; affected by bias as most patients in surgery group has lower TNBC and visceral mets, more patients with solitary bone metastasis.
- US/Canada (E2108 Trial) randomized patient who did not progress after 4-8 months on optimal systemic therapy into surgery or not; no difference in term of OS and PFS. Systemic therapy alone associated with higher LR progression, but surgery does not improved QOL. (Journal Clin Oncol 2020)
-
Japan (JCOG 2017) : Primary Tumour Resection (PTR) improved survival in patients with ER-positive tumors, pre-menopausal status or single-organ metastasis.
PTR is not recommended for all de novo- stage 4 BC patients but can control local disease and is acceptable in a select population of patients because of the clear improvement in local control.
What is the treatment for brain mets in mBC?
- Brain mets; excision, stereotactic radiosurgery (SRS) or whole brain radiotherapy.
- SRS associated with lower toxicity and morbidity
- If not operable, Symptom control - WBRT + steroids.
- Median survival 3 – 6 months. Without intervention, median survival is 1 – 2 months.
What is the treatment for bone mets in mBC?
Bone (SRE) : Bone pain, pathological fracture, spinal cord compression, hypercalcemia
* Bone mets; short course palliative radiotherapy or surgical fixation.
* Indication for local therapy include fracture or impending fracture, bone pain and spinal cord compression.
* Bone metastasis only is associated with slower progression.
* Bone stabilizing drugs may be used to prevent skeletal related events (SRE) such as fracture and hypercalcemia
- Cord compression
- Acute : Dexamethasone, Cord decompression & fixation, postoperative RT
- Chronic : Dexamethasone, analgesia, RT
Local therapy:
- RT - gives adequate pain control in 75 - 85 % of patients even without analgesics
- Fracture site fixation
Systemic therapy:
1)Denosumab (first line)
- Monoclonal antibody to RANKL (key in osteoclast formation & activation)
- S/c 120mg 4 weekly for 9 doses then 12 weekly indefinitely.
- Superior to biphosphonates in ↓ SRE but same DFS, OS.
- Can be used in renal impairment.
2) Osteoclast inhibitor - Biphosphonates
- IV (Zoledronate - 4 mg infusion over 15 mins 4 weekly for 9 doses then 12 weekly indefinitely) or
- Oral (Ibandronate, Clodronate)
- Cannot be used in renal impairment.
What is the treatment for lung mets in mBC?
- Lung mets; Rarely required aggressive local control as majority of pulmonary parenchymal metastasis are asymptomatic.
- Metastatectomy associated with significant morbidity and mortality and no randomized data to support such practice.
- Expert opinions suggest reserving the surgery for good PS patient, single lung metastasis, disease free interval (DFI) >36 months and HR+ disease (Level III evidence).
- Other option includes RFA and SBRT (stereotactic body RT)
Symptom control - Effusion - Pigtail drainage, chemical pleurodesis - bleomycin, talc powder
What is the treatment for Liver mets in mBC?
- Liver mets; >50% of mBC and usually disseminated disease with poor prognosis.
- Indication for local control are intractable pain, bleeding and biliary obstruction.
- Strict patient selection like in lung metastasis but evidence still lacking to support aggressive local control over systemic therapy.
* Commonest modalities are hepatic resection, SBRT and RFA.
Local Therapy:
Symptom control - palliative stenting (metallic stent preferred) for biliary obstruction
Ascites - paracentesis with IVI human albumin 20% 8g/L, LeVeen shunt.
Systemic Therapy:
- Chemotherapy
- Bottomline in visceral mets: systemic therapy is mainstay.
- Aggressive local control therapy is not driven by high level evidence and NOT CONSIDERED AS STANDARD OF CARE.
What is primary endocrine resistance?
- Relapse while on first 2 years of adjuvant ET or
- Progression of disease within first 6 months of first-line ET for advanced Breast CA on ET.
What is secondary endocrine resistance ?
- Relapse while on ET but after first 2 years or
- Relapse within 1 year of completing adjuvant ET or
- Progression of disease > 6 months after initiating ET for advanced breast cancer while on ET.
How to treat malignancy hypercalcaemic in mBC?
- Bone metastasis → ↑ osteoclastic activity → ↑ bone resorption
- Symptoms: Bone, moan & groans
- Hypercalcemia : 2.6 – 3 mmol/L (mild), 3 – 3.5 (moderate), > 3.5 (severe)
Treatment:
🍎Rehydration & forced diuresis: First line, 3 – 4L/day NS over 2 – 3 days (hyper hydration achieved if > 1ml/kg urine output). - **Frusemide**: 20 – 40mg t.d.s to prevent overloading & ↑ Calciuria (check BP prior). 🍎Biphosphonates: IV Zoledronate 4mg (infusion over 15 minutes) single dose. 🍎Mithramycin (plicamycin): Toxic to osteoblasts & inhibit bone resorption. C/I in liver & renal ds. 🍎Calcitonin: 4IU/kg s.c t.d.s 3 days. Acute lowering of Ca. Can be used in CKD. 🍎Oral phosphate: 1 – 3g/day. ↓ GI Ca absorption as long as PO4 level < 1.3 mmol/L 🍎Dialysis: Quick & effective in severe hyper Ca > 4.5 mmol/L & neurologic signs 🍎Denosumab( monoclonal antibodies to RANKL)
Visceral crisis in Metastatic breast carcinoma
🫀 Common Types of Visceral Crisis:
- 🩸 Hepatic Crisis
Rapidly rising bilirubin, AST/ALT
Liver metastases causing hepatic failure
Symptoms: jaundice, ascites, coagulopathy - 🫁 Pulmonary Crisis
Lymphangitic carcinomatosis
Massive pleural effusion or lung mets causing:
Hypoxia
Severe dyspnea
Respiratory failure - 🧠 CNS Crisis
Increased intracranial pressure from brain metastases
Neurologic deterioration
May not always fall under “visceral crisis,” but is still urgent - 🩸 Bone Marrow Crisis
Extensive bone marrow involvement
Causes pancytopenia or severe anemia/thrombocytopenia
Risk of bleeding/infection
