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.

Referral Criteria

Refer to secondary care if ANY of the points in the right-sided column:

Single 1st degree relative criteria	One 1st-degree male relative with breast cancer, at ANY age One 1st-degree female relative with breast cancer, at <40 y/o One 1st-degree relative with bilateral breast cancer, at <50 y/o
Multiple relative criteria	Two relatives (two 1st-degree, or one 1st-degree and one 2nd-degree) with breast cancer, at any age Three 1st-degree or 2nd-degree relatives with breast cancer, at any age
Breast and ovarian cancer	One relative (1st / 2nd-degree) with breast cancer at any age + one relative (1st / 2nd-degree) with ovarian cancer at any age One should be a 1st-degree relative

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

Aetiology

The risk factors for breast cancer can be categorised into 3 categories: ^[Ref1][Ref2]

Patient risk factors	Advancing age Female High breast density Prior chest irradiation Smoking and alcohol consumption Certain past medical histories History of benign / high-risk breast lesions (e.g. atypical ductal hyperplasia) Previous contralateral breast cancer Previous endometrial / ovarian cancer
Hormonal risk factors	Essentially ↑ oestrogen exposure (exogenous or endogenous) & ↑ exogenous progesterone Early menarche, late menopause Nulliparity No breastfeeding Exogenous oestrogen / progesterone All hormonal contraception Hormone replacement therapy (combined oestrogen-progesterone > oestrogen-only HRT) Obesity in post-menopausal women (adipose tissue secretes oestrogen)
Genetic risk factors (~10-15% breast cancers are hereditary)	Mutations in BRCA1, BRCA2 (→ hereditary breast and ovarian cancer syndrome) (autosomal dominant pattern) – most common Apart from breast cancer, also increases the risk of ovarian, pancreatic and prostate cancer Mutation in TP53 (→ Li-Fraumeni syndrome) (autosomal dominant pattern) Presents as multiple cancers at a young age Main cancers associated with Li-Fraumeni syndrome are breast cancer, sarcomas, leukaemias, lymphomas, brain tumours and adrenocortical carcinoma Peutz-Jegher syndrome (STK11 mutation) Cowden syndrome (PTEN mutation) Familial diffuse gastric cancer (E-cadherin mutation)

Breast Cancer Diagnosis

Suspected Breast Cancer Referral Pathway

Refer via the suspected breast cancer pathway if:	≥30 y/o + unexplained breast lump, or ≥50 y/o + unilateral nipple discharge / retraction / other changes of concern
CONSIDER refer via suspected breast cancer pathway if:	Skin changes suggest breast cancer, or ≥30 y/o + unexplained lump in the axilla
Consider non-urgent referral if:	<30 y/o + unexplained breast lump

Investigation and Diagnosis

Triple assessment is the gold standard diagnostic approach for any breast lump / suspected breast cancer.

Step 1 – Clinical Assessment

Clinical features of breast cancer can be categorised as following: ^[Ref]

Local breast changes	Palpable breast mass Hard mass, with irregular borders, that is fixed to the underlying tissue (a mobile breast mass is more indicative of fibroadenoma) Most common location: upper lateral quadrant Skin changes Retraction / dimpling (due to fixation to pectoral muscle / deep fascia / Cooper ligament) Peau d’orange Nipple changes Nipple inversion Blood-tinged nipple discharge Asymmetrical breast
Regional metastasis	Axillary lymphadenopathy is most common Non-tender, enlarged lymph nodes that are fixed (i.e. non-mobile)   Other less commonly involved lymph nodes: Supraclavicular Infraclavicular Parasternal lymph node
Distant metastasis	Sites of distant metastasis (in descending order): [Ref] Bone – most common (~50%) Liver (~20%) Lung / pleura (~15%) Brain (~5%)

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

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

Choice of imaging modality depends on the patient’s age:

• <40 y/o → ultrasound (due to denser breast tissue)
• ≥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

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 The extent of disease is not clear from the mammogram and ultrasound, or Accurate mammographic assessment is difficult because of breast density, or Breast-conserving surgery is being considered for invasive lobular cancer to assess tumour size
Receptor status (ER, PR, HER2)	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

Definitive Management

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 SLNB)
• 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 / 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

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

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 & Men → tamoxifen (selective oestrogen receptor modulator)
• Post-menopausal women → aromatase inhibitors (e.g. anastrazole, letrozole)

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

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-L1

 

• Olapaib / talazoparib
  • Used in BRCA1/2 mutated breast cancers
  • MoA: PARP 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	1st line: compression therapy 2nd line: kinesiology tape   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: Pain → reflective guarding Fibrosis Scar contracture Adhesions	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