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
Disclaimer
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 Background Information
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.
Aetiology
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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Breast Cancer Diagnosis
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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Investigation and Diagnosis
Triple assessment is the gold standard diagnostic approach for any breast lump / suspected breast cancer.
For exam purposes, it is important to be aware of the tumour marker CA 15-3 which is typically raised in metastatic / advanced breast cancer. However, note that it is NOT used to diagnose / screen breast cancer. Its role is limited to monitoring treatment effect and disease recurrence.
Step 1 – Clinical Assessment
Clinical features of breast cancer can be categorised as following: [Ref]
| Local breast changes |
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| Regional metastasis | Axillary lymphadenopathy is most common
Other less commonly involved lymph nodes:
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| Distant metastasis | Sites of distant metastasis (in descending order): [Ref]
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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
For both males and females, choice of imaging modality depends primarily on the patient’s age:
- <40 y/o → ultrasound (due to denser breast tissue)
- Also preferred modality in pregnant or lactating women
- ≥40 y/o → mammogram (with mediolateral oblique and craniocaudal views)
2 major suspicious findings on mammogram:
- Microcalcifications (clusters of fine, irregular linear / branching pattern) are classic for ductal carcinoma in situ
- High-density mass with irregular margins and lack of a well-defined capsule is classic for invasive breast cancers
Step 3 – Biopsy and Histology
A biopsy allows definitive diagnosis or exclusion of malignancy
Gold standard method: core needle biopsy
NB that 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.
Breast Cancer Management
Pre-Treatment Assessment
Note that the following investigations are performed AFTER a breast cancer diagnosis has been established by triple assessment. They do NOT form part of the triple assessment itself.
| Investigation | Notes |
|---|---|
| Ultrasound of the axilla | Perform on all patients
If ultrasound axilla identifies abnormal lymph nodes → perform ultrasound-guided needle sampling |
| MRI breast | Only perform in those with invasive breast cancer, and if
|
| Receptor status (EROestrogen receptor, PRProgesterone receptor, HER2Human epidermal growth factor receptor 2) | Perform on all invasive breast cancers
This should be performed at the time of histopathological diagnosis |
| Genetic testing (BRCA1 and BRCA2 mutation) | Do not routinely perform
Only perform if the patient has triple-negative breast cancer |
Some important information regarding breast cancer prognosis depending on receptor status:
- Triple negative breast cancer (-ve for ER, PR, HER2) is associated with the worst prognosis
- ER / PR +ve breast cancer is associated with the best prognosis (esp. if both are +ve)
- HER2+ve alone is associated with a poor prognosis
Definitive Management
Disclaimer: the full NICE guideline contains extensive and detailed recommendations on the management of breast cancer, which is specialist- not undergraduate-level.
This section presents a concise student-friendly summary of selected key investigations and concepts based on the guidelines. It is not a complete reproduction of the full guidance.
A simplified treatment approach as outlined by NICE:
- Localised, early disease → surgical resection +/- adjuvant systemic therapy
- Localised, advanced disease → neoadjuvant systemic therapy → surgical resection → adjuvant systemic therapy
- Unresectable / metastatic disease → systemic therapy
Whenever appropriate, endocrine / targeted biological therapy should be offered (i.e. ER +ve or HER2 +ve)
Surgery
NICE acknowledges both mastectomy and breast-conserving surgery (also called lumpectomy or partial mastectomy) as valid options for the management of early and locally advanced breast cancer.
- NICE does not give a clean-cut recommendation on when a specific surgical approach is preferred, it emphasises a shared decision-making process with the patient, while taking individual factors into account
- If tumour cells are present on the margin (“tumour on ink”) after breast-conserving surgery → further surgery (re-excision / mastectomy) is necessary to achieve clear margins
- Breast reconstruction surgery should be offered to those who have had mastectomy
To provide some context, a mastectomy is generally necessary (instead of breast-conserving surgery) if:
- –ve tumour margins cannot be achieved by breast-conserving surgery
- Multifocal / diffuse disease
- Historically, larger tumour size (≥4 cm) was considered a relative contraindication to breast-conserving surgery due to concerns about achieving negative margins and acceptable cosmetic outcomes
Axilla Lymph Node Intervention
Do not routinely offer axillary lymph node intervention to all patients
Approach:
- If pre-treatment axillary ultrasound-guided biopsy confirms nodal metastasis → offer axillary node intervention (surgical clearance/radiotherapy) (without performing SLNBSentinel lymph node biopsy)
- If pre-treatment axillary ultrasound-guided biopsy is -ve → perform SLNBSentinel lymph node biopsy to decide if further treatment is necessary
- ONLY offer axillary node intervention (surgical clearance / radiotherapy) if SLNBSentinel lymph node biopsy shows ≥1 macrometastasis
- Do NOT offer axillary node intervention if there are micrometastases or isolated tumour cells in the sentinel lymph nodes
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
Axillary radiotherapy and surgical axillary clearance yield equivalent oncologic outcomes in early-stage breast cancer with limited nodal involvement. [Ref]
Axillary radiotherapy has a substantially lower risk of lymphedema compared to surgical axillary clearance.
SLNBSentinel lymph node biopsy 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
- SLNBSentinel lymph node biopsy 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.
Do not offer people with invasive breast cancer adjuvant radiotherapy to the axilla after axillary clearance.
Do not offer adjuvant radiotherapy to regional lymph nodes to people with invasive breast cancer who have histologically lymph node-negative breast cancer.
Radiotherapy
Whole breast radiotherapy is generally indicated after breast-conserving surgery for invasive breast cancer
- To reduce the risk of local recurrence and achieve outcomes equivalent to mastectomy
Whole breast radiotherapy after mastectomy is NOT routinely indicated, unless there is:
- Presence of lymph node macrometastasis (offer)
- -ve Lymph nodes but T3 / T4 invasive breast cancer (consider)
Cancer with low-risk of local recurrence (e.g. lymph node -ve breast cancer) following mastectomy does NOT require radiotherapy
Systemic Therapy
Chemotherapy
Chemotherapy for breast cancer typically contains a taxane and an anthracycline
- Standard regimen: doxorubicin (an anthracycline) + cyclophosphamide followed by docetaxel / paclitaxel (a taxane)
- For triple-negative invasive breast cancer, a platinum (e.g. cisplatin) is often added as well due to its poor prognosis
Endocrine Therapy
Endocrine therapy is indicated for those with ER +ve status.
The choice of drugs depends on menopausal status:
- Pre-menopausal women
Including trans men and non-binary people, who currently have ovaries
& MenIncluding trans women and non-binary people, who currently have testes
→ tamoxifen (selective oestrogen receptor modulatorActs as a competitive oestrogen receptor antagonist in breast tissue, blocking oestrogen-driven tumour growth.
Acts as a partial agonist in other tissues (e.g. bone and endometrium)) - Post-menopausal women (includes those with hysterectomy)
Including trans men and non-binary people, who currently have ovaries
→ aromatase inhibitors (e.g. anastrazole, letrozole)
Tamoxifen’s complications come from its oestrogen partial agonist effect in non-breast tissue:
- Risk of endometrial hyperplasia & cancer
- Risk of DVT and PE
- But it is bone protective
Aromatase inhibitors‘ complications come from their oestrogen-depleting effect:
- Risk of osteoporosis
- Baseline DEXA scan required for ALL patients starting aromatase inhibitors (who are NOT receiving adjuvant bisphosphonates)
- Post-menopausal-like symptoms (e.g. hot flushes, night sweats, vaginal dryness, sleep disturbances)
- Management: consider SSRIs (particularly effective for hot flushes); HRTHormone replacement therapy is contraindicated in current/past/suspected breast cancer
Biologics
Biologics are available for HER2+ve breast cancer:
- Trastuzumab is the mainstay of HER2-targeted therapy and the foundation of all treatment regimens for HER2+ve breast cancer
- Other anti-HER2 drugs like pertuzumab, tucatinib, and neratinib are used as adjuncts or 2nd line options
Trastuzumab is cardiotoxic and should be used with caution if there history of cardiac disease, including:
- LVEF ≤55%
- Congestive heart failure
- Ischaemic heart disease (previous MI, stable angina)
- Cardiomyopathy
- Arrhythmias requiring medical treatment
- Clinically significant valvular heart disease
- Poorly controlled hypertension
A few selected biologics for triple-negative breast cancer (less commonly examined):
- Pembrolizumab
- Licensed for neoadjuvant and adjuvant therapy in triple-negative breast cancer
- MoA: anti-PD-L1anti–programmed death-ligand 1
- Olaparib / talazoparib
- Used in BRCA1/2 mutated breast cancers
- MoA: PARPpoly(ADP-ribose) polymerase inhibitor (enzyme involved in single DNA strand repair)
Bisphosphonates
NICE recommends offering bisphosphonates (zoledronic acid or sodium clodronate) as adjuvant therapy to postmenopausal women with node-positive invasive breast cancer
- Rationale: to prevent bone metastasis, protect bone health, and evidence shows reduced recurrence and improved survival in post-menopausal women
Complications of Surgery
Most complications arise from axillary intervention (node clearance / 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 |
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:
|
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
References
NHS Breast Screening Programme
NICE guideline Early and locally advanced breast cancer: diagnosis and management
NICE guideline Advanced breast cancer: diagnosis and treatment