Breast Cancer
This article should be read in conjunction with the benign breast conditions article.
NHS Breast Cancer Screening Programme
| Target population | 50-71 y/o (women ≥71 y/o may self-refer every 3 years) |
| Frequency | Every 3 years |
| Screening modality | mammogram |
Familial Breast Cancer Guidelines
This section applies to those WITHOUT a personal history of breast cancer, but with a family history of breast cancer.
Note that the NICE guidelines on familial breast cancer are highly detailed, which is unlikely to be examined in the UKMLA. Therefore, this article focuses primarily on the referral criteria for primary care, which outline key red flags of familial breast cancer to be aware of.
Referral Criteria
Refer to secondary care if ANY of the points in the right-sided column:
| Single 1st degree relative criteria |
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| Multiple relative criteria |
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| Breast and ovarian cancer |
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In secondary care, certain high-risk individuals may be further referred to a specialist genetic clinic
If the patient’s family history has only one relative (1st / 2nd degree) with breast cancer at >40 y/o, there is NO need for secondary care referral, if there is none of the following:
- Bilateral breast cancer
- Male breast cancer
- Ovarian cancer
- Jewish ancestry
- Sarcoma in a relative younger than age 45 years
- Glioma or childhood adrenal cortical carcinomas
- Complicated patterns of multiple cancers at a young age
- Paternal history of breast cancer (2 or more relatives on the father’s side of the family)
Breast Cancer
Types and Classification
Invasive cancers (defined by the breach of cancer cells through the basement membrane) are more common (~85% of all breast cancer) than non-invasive breast cancer (~15% of all breast cancer)
Histological subtypes of invasive breast cancer: [Ref]
- Invasive ductal carcinoma – most common type (~75% cases)
- Invasive lobular carcinoma – 2nd most common (~10% cases)
- Rarer subtypes (collectively account for ~10-15% cases): mucinous, tubular, medullary, mixed, papillary, cribriform, metaplastic, micropapillary carcinomas
Histological subtypes of non-invasive breast cancer:
- Ductal carcinoma in situ – most common type
- Lobular carcinoma in situ – rare
In conclusion, the overall most common type of breast cancer is invasive ductal carcinoma.
For educational purposes, it is important to be aware of the new breast cancer classification system that distinguishes between no special type (NST) and special types. The majority of invasive breast cancers are categorised as NST, which essentially represents invasive ductal carcinoma without distinctive features of special histological subtypes.
Special types, in contrast, include less common but histologically distinct cancers such as lobular, mucinous, tubular, medullary, papillary, and metaplastic carcinomas. These subtypes have unique pathological and clinical characteristics that can influence prognosis and management.
The main takeaway is to know that NST represents the most common breast cancer type and mainly represents invasive ductal carcinoma.
Causes and Risk Factors
The risk factors for breast cancer can be categorised into 3 categories: [Ref1][Ref2]
| Patient risk factors |
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| Hormonal risk factors | Essentially ↑ oestrogen exposure (exogenous or endogenous) & ↑ exogenous progesterone
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| Genetic risk factors (~10-15% breast cancers are hereditary) |
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Suspected Breast Cancer Referral Pathway
| Refer via the suspected breast cancer pathway if: |
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| CONSIDER refer via suspected breast cancer pathway if: |
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| Consider non-urgent referral if: |
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Assessment and Diagnosis
Initial Work-Up – Triple Assessment
Patients referred through the suspected breast cancer pathway are assessed in a specialist breast clinic, usually using triple assessment to establish or exclude a diagnosis of breast cancer
Step 1 – Clinical Assessment
Typical breast cancer findings: [Ref]
| Local breast changes |
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| Regional metastasis | Axillary lymphadenopathy is most common
Other less commonly involved lymph nodes:
An important feature of metastatic lymphadenopathy is the presence of enlarged, non-tender lymph nodes that are fixed (non-mobile) |
| Distant metastasis | Sites of distant metastasis (in descending order): [Ref]
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Clinical features of distinct subtypes of breast cancer:
Paget’s Disease of the Nipple
This is a rare form of breast cancer, characterised by malignant glandular epithelial cells (Paget cells) invading into the epidermis of the nipple-areolar complex [Ref]
- Seen in ~1-2% of breast cancer
- 90% associated with an invasive carcinoma or ductal carcinoma in situ
Clinical features: [Ref]
- Unilateral eczematous changes of the nipple and areola (erythema / scaling / crusting)
- Nipple retraction, bloody discharge (from ulceration) can be seen in advanced cases
Differentiating Paget’s disease of the nipple and benign dermatological conditions affecting the nipple-areolar complex (e.g. eczema, psoriasis):
- Paget’s disease of the nipple is typically unilateral and primarily affects the nipple
- Dermatological conditions are typically bilateral and typically spare the nipple
The presence of bloody discharge (in addition to eczematous changes on the nipple-areola complex) would strongly suggest Paget’s disease of the nipple.
Inflammatory Breast Cancer
This is a rare, but aggressive form of breast cancer, characterised by the tumour obstructing dermal lymphatic drainage. [Ref]
Presents with a rapid onset (<6 months) of: [Ref]
- Peau d’orange appearance (French for ‘skin of an orange’) – dimpled or pitted skin texture (due to lymphatic obstruction causing localised oedema and skin thickening)
- Signs of inflammation – breast oedema, warmth, and erythema (the erythema must occupy at least 1/3 of the breast)
- It is possible to NOT have a palpable mass
Step 2 – Imaging
There are 2 imaging pathways if breast cancer is suspected, depending on the patient’s age:
| Age | Imaging pathway |
|---|---|
| <40 y/o | Initial imaging of choice: breast ultrasound
If the ultrasound shows suspicious findings → mammogram |
| ≥40 y/o | Initial imaging of choice: mammogram
If the mammogram shows suspicious findings → further mammographic views and targeted ultrasound |
If an invasive breast cancer is suspected (based on ultrasound or mammogram) → axilla ultrasound
Step 3 – Biopsy and Histology
Standard procedure: image-guided core needle biopsy
- A core biopsy provides tissue for histological examination
- Definitive test to confirm or exclude malignancy
Fine needle aspiration (FNA) is NOT the same as core needle biopsy; FNA provides a cytology sample (cells only) rather than a histology sample (intact tissue section).
Fine needle aspiration can be used as an adjunct to biopsy for rapid analysis or in resource-limited settings.
In summary, core needle biopsy is the gold standard test for breast cancer.
Post-Diagnosis Further Investigations
| Investigation | Indications / description |
|---|---|
| Ultrasound of the axilla | Perform on all patients with suspected invasive breast cancer
If ultrasound of the axilla identifies any abnormal lymph nodes → perform ultrasound-guided needle sampling |
| Receptor status (ER, PR, HER2) | Perform on all patients with suspected invasive breast cancer
This should be performed at the time of histopathological diagnosis Some important information regarding breast cancer prognosis depending on receptor status:
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| Staging with CECT-TAP or PET-CT | Indicated in suspected advanced breast cancer to assess the presence and extent of distant metastasis |
| MRI breast | Do not routinely perform
Only perform in those with invasive breast cancer, and if
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| Genetic testing (BRCA1 and BRCA2 mutation) | Do not routinely perform
Only perform in <50 y/o with triple-negative breast cancer |
For exam purposes, be aware of the tumour marker CA 15-3, which is typically raised in metastatic / advanced breast cancer.
However, it is NOT used to diagnose / screen breast cancer. Its role is limited to monitoring treatment effect and disease recurrence.
Management
NICE has made 2 separate guidelines covering the management of:
| Cancer category | Definition |
|---|---|
| Early and locally advanced breast cancer | Breast cancer with no distant metastasis (M0)
Specifically invasive adenocarcinoma of any size (T1-T4) with or without spread to lymph nodes (N0 to N3) but with no distant metastasis (M0) This category also covers ductal carcinoma in situ and Paget’s disease of the breast |
| Advanced breast cancer |
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Disclaimer: The full NICE guideline contains extensive, detailed recommendations on breast cancer management, much of which is aimed at a specialist level.
This section aims to provide a concise, non-specialist-friendly summary of selected management principles. It does not reproduce the guideline in full.
Early and Locally Advanced Breast Cancer
Shared overview approach (in order):
- Neoadjuvant systemic anti-cancer therapy
- For locally advanced breast cancer, this is the standard 1st step management
- For early breast cancer, it is NOT mandatory but is considered where indicated
- Surgery
- Consider axillary lymph node intervention and/or radiotherapy
- Adjuvant systemic anti-cancer therapy
Surgery
General approach as per cancer stage / type:
| Breast cancer stage / type | Management |
|---|---|
| Early breast cancer | Standard option: breast-conserving surgery (lumpectomy)
If the tumour is relatively large, neoadjuvant therapy is often used to shrink the tumour enough to allow breast-conserving surgery, instead of requiring a mastectomy |
| Locally advanced breast cancer | Standard option: mastectomy |
| Inflammatory breast cancer | |
| Localised Paget’s disease of the nipple | Standard option: breast-conserving surgery OR mastectomy |
Some key other points:
- If a -ve tumour margin cannot be achieved by breast-conserving surgery (e.g. due to multifocal disease or large tumour size) → mastectomy is necessary
- After breast-conserving surgery, if tumour cells are present on the margin (“tumour on ink”) → further surgery (re-excision / mastectomy) is necessary to achieve -ve tumour margins
- Breast reconstruction surgery should be offered to those who have had mastectomy
Axillary Lymph Node Intervention
Do not routinely offer axillary lymph node intervention to all patients
Decision approach in invasive adenocarcinoma:
- If pre-treatment axillary ultrasound-guided biopsy confirms nodal metastasis → offer axillary node intervention (surgical clearance)
- If pre-treatment axillary ultrasound-guided biopsy is -ve → perform SLNB to decide if further treatment is necessary
- ONLY offer axillary node intervention (surgical clearance or axilla radiotherapy) if SLNB shows ≥1 macrometastasis
- Do NOT offer axillary node intervention if there are micrometastases or isolated tumour cells in the sentinel lymph nodes
SLNB is the gold-standard method for axillary staging in invasive breast cancer
- Sentinel lymph node: 1st lymph node(s) that receives lymphatic drainage from the primary tumour site
- SLNB involves injecting a dye / radioactive substance near the tumour to identify the sentinel node(s). The sentinel lymph node(s) are then removed and examined for cancer cells.
NICE recommends NOT to routinely perform SLNB in those with ductal carcinoma in situ and who are having breast-conserving surgery (due to low risk of node spread), unless there is a palpable mass or extensive tumour microcalcifications
Radiotherapy
The decision to offer radiotherapy post-surgery largely depends on what type of surgery was performed:
| Performed surgery | Indications / description |
|---|---|
| Breast-conserving surgery | Post-operative whole-breast radiotherapy is routinely recommended to reduce risk of recurrence and increase overall survival |
| Mastectomy | Post-operative radiotherapy (chest-wall radiotherapy) is NOT routinely indicated
Indications to offer:
Cancer with low risk of local recurrence (e.g. lymph node -ve breast cancer) following mastectomy does NOT require radiotherapy |
Systemic Anti-Cancer Therapy
A simplified, non-specialist summary of systemic therapies:
| Receptor status | Choice of systemic anti-cancer therapy |
|---|---|
| Oestrogen receptor (ER)-positive | Key options:
Disclaimer: traditional teaching often states the following in ER-positive breast cancer:
However, the choice between tamoxifen and aromatase inhibitors is no longer a simple binary choice based on menopausal status. NICE now heavily factors in the patient’s overall risk of the cancer recurring, as well as the use of medications that suppress reproductive organ function. Click to view what NICE recommends, included for completeness. This is a complex, and specialist-led decision. Tamoxifen’s complications come from its partial agonistic oestrogen effect in non-breast tissue:
Aromatase inhibitors‘ complications come from their oestrogen-depleting effect:
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| HER2-positive | Trastuzumab (anti-HER2) |
| Triple-negative (ER, PR, HER2 negative) | Corestone: chemotherapy
Other therapy that can be given along chemotherapy:
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| Any receptor status who needs chemotherapy | In a patient of ANY receptor status who needs standard adjuvant chemotherapy, the regimen should contain 2 specific classes:
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Bisphosphonates (zoledronic acid or sodium clodronate) can be used in post-menopausal women with invasive breast cancer as an adjuvant therapy to improve disease-free and overall survival:
- Offer if they have node-positive breast cancer
- Consider if they have node-negative breast cancer but at high risk of recurrence
Advanced Breast Cancer
Mainstay of treatment: systemic anti-cancer therapy
A simplified, non-specialist summary of systemic therapies in advanced breast cancer:
| Receptor status | Choice of systemic anti-cancer therapy |
|---|---|
| Oestrogen receptor (ER)-positive | Corestone: aromatase inhibitor (e.g. anastrozole, letrozole) PLUS CDK4/6 inhibitor (e.g. abemaciclib, ribociclib, or palbociclib) |
| HER2-positive | 1st line: trastuzumab
Often given alongside pertuzumab and chemotherapy (e.g. docetaxel or paclitaxel) |
| Triple-negative (ER, PR, HER2 negative) | Corestone: sequential chemotherapy (e.g. using taxanes, anthracyclines, or carboplatin)
Other therapy that can be given along chemotherapy:
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If breast cancer is complicated by bone metastases → bisphosphonates are recommended to prevent skeletal-related events (e.g. fractures) and reduce bone pain
Denosumab is also recommended to prevent skeletal-related events (e.g. fracture) in breast cancer with bone metastases
Complications of Surgery
Most complications arise from axillary node intervention (surgical node clearance / axilla radiotherapy)
| Complication | Mechanism | Management |
|---|---|---|
| Upper limb lymphoedema | Normal lymphatic drainage pathway from the arm is disrupted → upper limb lymphoedema
Typical onset: 12-24 months post-operatively |
Refer to a specialist lymphoedema service
Advise that physical activity will NOT worsen the lymphoedema and may improve the overall quality of life |
| Restricted shoulder movement / arm stiffness | Multiple mechanisms, including:
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Upper limb exercises +/- physiotherapy referral |
Nerves at risk of injury during surgical axillary node clearance
- Intercostobrachial nerve (T2 intercostal nerve) – provides sensory supply to the axilla and upper medial arm
- Long thoracic nerve – innervates the serratus anterior (→ winged scapula)
Follow-Up
Offer yearly mammograms for 5 years until they enter the NHS Breast Screening Programme