Breast Cancer Management Clinical Overview
Breast Cancer Management: A Practical Guide for the House Officer
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: Breast cancer is the most common cancer among Malaysian women. You will encounter it in surgical, oncology, and even medical wards with complications. A solid understanding is non-negotiable.
High-Yield Definition: A malignant proliferation of epithelial cells lining the ducts or lobules of the breast. The key is its potential for local invasion and distant metastasis.
Clinical One-Liner: Basically, it's a lump in the breast that can spread. Our job is to find out what type it is and how far it has gone, so we can decide whether to cut it out, radiate it, or give systemic drugs.
II. Core Principles: Staging & Subtyping
Before we talk about treatment, you must be able to classify the disease. Everything hinges on these two factors.
Staging (AJCC 8th Edition): This tells us the anatomical spread. We use a combination of clinical and pathological staging.
T (Tumour Size): How big is the primary tumour?
N (Nodal Status): Has it spread to the axillary or other regional lymph nodes?
M (Metastasis): Has it spread to distant organs like bone, liver, lung, or brain?
Prognostic Stage Group: The 8th Edition is clever. It combines the anatomical TNM stage with tumour grade, ER, PR, and HER2 status to give a more accurate prognostic stage (e.g., Stage IA, IIB, etc.). A small, aggressive triple-negative tumour can have a worse prognosis than a larger, slow-growing luminal A tumour.
Molecular Subtypes: This is the tumour's biology. It dictates which systemic therapies will work. We determine this from the biopsy report via immunohistochemistry (IHC).
Luminal A (HR+/HER2-): Oestrogen Receptor (ER) positive, Progesterone Receptor (PR) positive, HER2 negative, and low Ki-67 (a proliferation marker). These are slow-growing and respond well to hormone therapy.
Luminal B (HR+/HER2- or HR+/HER2+): ER positive, but has a higher Ki-67 or is HER2 positive. More aggressive than Luminal A. Needs hormone therapy and often chemotherapy.
HER2-Enriched (HR-/HER2+): ER/PR negative, but HER2 positive. Aggressive, but we have excellent targeted therapies against HER2.
Triple-Negative (TNBC) (HR-/HER2-): ER, PR, and HER2 negative. Often associated with BRCA mutations. Very aggressive, and our main weapon is chemotherapy, though immunotherapy and PARP inhibitors are changing the game.
III. Management by Stage and Subtype
This is the core of it. Don't get lost in the details. Focus on the principles for each stage.
Stage 0 (Ductal Carcinoma In Situ - DCIS)
What it is: Pre-invasive cancer. The cells are malignant but are confined to the milk duct.
Goal: Prevent progression to invasive cancer.
Management:
Surgery: The standard is Breast-Conserving Surgery (BCS), also known as a lumpectomy, to get clear margins. Mastectomy is reserved for large or multifocal DCIS.
Adjuvant Radiation: For patients undergoing BCS, whole breast radiotherapy is standard to reduce the risk of local recurrence.
Adjuvant Endocrine Therapy: If the DCIS is ER-positive, consider Tamoxifen (for pre- and postmenopausal women) or an Aromatase Inhibitor (for postmenopausal women) for 5 years to reduce the risk of future breast cancer events.
Stage I-II (Early-Stage Invasive Cancer)
What it is: The tumour is invasive but generally confined to the breast and possibly a few axillary lymph nodes.
Goal: Cure. This involves treating the local disease (breast and axilla) and reducing the risk of systemic recurrence.
Management Workflow:
Local Therapy (Surgery & Radiation):
Surgery: BCS followed by radiation OR Mastectomy. Patient preference and tumour characteristics guide this choice.
Axillary Staging: Sentinel Lymph Node Biopsy (SLNB) is the standard of care for clinically node-negative patients. Based on the ACOSOG Z0011 trial, if 1-2 sentinel nodes are positive in a patient undergoing BCS and whole breast radiation, we can often omit a full Axillary Lymph Node Dissection (ALND). This reduces the risk of lymphoedema. ALND is reserved for those with bulky nodes or more extensive nodal disease.
Radiation: Always after BCS. Considered after mastectomy if the tumour is large (>5cm) or nodes are positive.
Systemic Therapy (Adjuvant): This is decided by the molecular subtype.
Luminal A/B (HR+/HER2-):
Endocrine Therapy: The backbone of treatment. Tamoxifen or Aromatase Inhibitors for 5-10 years. For high-risk premenopausal women, we add Ovarian Function Suppression (OFS) with GnRH agonists like Goserelin.
Chemotherapy: The big question is who needs it. We use prognostic tools like the Oncotype DX score (if available and affordable) or assess clinicopathological features (Grade, tumour size, nodal status, Ki-67). Generally reserved for higher-risk patients (e.g., node-positive, high grade, high Ki-67). Common regimens are Anthracycline/Taxane-based (e.g., AC-T).
HER2-Enriched (HR-/HER2+ or HR+/HER2+):
Chemotherapy + Anti-HER2 Therapy: This is mandatory. Standard regimen is a taxane-based chemotherapy (e.g., Paclitaxel) plus Trastuzumab (Herceptin). For higher-risk patients (node-positive or large tumours), we add Pertuzumab. This dual blockade is very effective.
Endocrine Therapy: Given sequentially after chemo if the tumour is also HR-positive.
Triple-Negative (TNBC):
Chemotherapy: This is the mainstay. Dose-dense AC followed by Paclitaxel is a standard regimen.
Immunotherapy: For high-risk Stage II TNBC, adding Pembrolizumab to chemotherapy is now a standard of care to reduce recurrence.
PARP Inhibitors: For patients with a germline BRCA mutation, adjuvant Olaparib for one year after chemotherapy significantly improves outcomes.
Stage III (Locally Advanced Cancer)
What it is: Large tumours or extensive nodal involvement (e.g., matted nodes, internal mammary nodes). No distant metastasis yet.
Goal: Cure, but requires a multi-modality approach.
Management Workflow (Neoadjuvant Approach): The sequence is flipped. We give systemic therapy before surgery.
Neoadjuvant Systemic Therapy:
Rationale: To shrink the tumour to allow for BCS, to treat micrometastatic disease early, and to gauge the tumour's response to treatment, which is a powerful prognostic indicator.
Regimens: The choice is based on subtype, similar to adjuvant therapy for Stage I-II, but it's given upfront.
HR+/HER2-: Often chemotherapy, but neoadjuvant endocrine therapy is an option for select postmenopausal women.
HER2+: Chemotherapy + dual anti-HER2 therapy (Trastuzumab + Pertuzumab).
TNBC: Chemotherapy + Pembrolizumab.
Local Therapy (Surgery & Radiation):
Surgery: Performed after neoadjuvant therapy. The extent depends on the response. If the response is good, BCS may become possible. ALND is often still required if nodes were initially positive.
Radiation: Almost always indicated after surgery for Stage III disease, targeting the breast/chest wall and regional lymph nodes.
Adjuvant Therapy:
If there is residual disease after neoadjuvant treatment, we may consider additional therapy. For example, in HER2+ patients, we might switch to T-DM1 (Kadcyla). In TNBC patients, we might add Capecitabine.
Stage IV (Metastatic Cancer)
What it is: The cancer has spread to distant sites.
Goal: Palliative. We aim to control the disease, manage symptoms, and prolong good quality of life. Cure is generally not possible.
Management Principles:
Biopsy the Metastasis: Re-check the ER/PR/HER2 status. It can change from the primary tumour.
Systemic Therapy is Mainstay: Surgery and radiation are used for symptom control (e.g., fixing a pathological fracture, relieving spinal cord compression).
Treatment is Sequential: We use one line of therapy until it stops working (progression) or causes unacceptable toxicity, then move to the next.
Management by Subtype:
HR+/HER2-:
First-line: Endocrine therapy + a CDK4/6 inhibitor (e.g., Palbociclib, Ribociclib). This has significantly improved progression-free survival compared to endocrine therapy alone. Chemotherapy is reserved for visceral crisis (rapid organ failure).
Subsequent lines: Other endocrine agents, PI3K inhibitors (if PIK3CA mutation present), or single-agent chemotherapy.
HER2+:
First-line: Chemotherapy (Taxane) + dual anti-HER2 therapy (Trastuzumab + Pertuzumab).
Second-line: An antibody-drug conjugate like Trastuzumab Deruxtecan (Enhertu) has shown outstanding results and is now a preferred option.
TNBC:
First-line: If the tumour expresses PD-L1, chemotherapy + Pembrolizumab. If the patient has a germline BRCA mutation, a PARP inhibitor (Olaparib) is a good option.
Subsequent lines: Single-agent chemotherapy or other antibody-drug conjugates like Sacituzumab Govitecan.
IV. How to Present to Your Senior
Be concise and structured.
"Dr, for review please. This is Puan [Name] in Bed X, a [Age]-year-old lady, who presented with a right breast lump. Biopsy confirmed an invasive ductal carcinoma, Grade 3. IHC shows ER/PR negative, HER2 positive. Staging scans are clear for distant metastasis. Clinically, it's a T2N1M0, Stage IIB tumour. My plan is to discuss for neoadjuvant chemotherapy with a taxane plus dual HER2 blockade, as per standard guidelines for this high-risk, HER2-positive cancer. I've sent off the pre-chemo bloods and booked a cardiology review for an ECHO."
V. Summary & Further Reading
Top 3 Takeaways:
Management is dictated by Stage (anatomical spread) and Subtype (ER/PR/HER2).
Early-stage disease (I-II) is treated with a "surgery first" approach followed by adjuvant therapy. Locally advanced disease (III) is treated with a "systemic therapy first" (neoadjuvant) approach.
Metastatic disease (IV) is incurable; treatment is palliative, with systemic therapy chosen based on subtype to control the disease.
Key Resources:
Malaysian CPG: Management of Breast Cancer (3rd Edition), 2019
UpToDate: Search "Overview of the treatment of early-stage breast cancer" and "Systemic treatment of metastatic breast cancer".
NCCN Guidelines: NCCN Guidelines for Breast Cancer (Requires free registration, but is the gold standard).
Now, go and apply this. See the patients, read their histology reports, and think through the plan. That's how you'll learn.
