Breast cancer is the most common form of cancer in the UK. It mostly affects women and is rare in men (about 1% of UK cases). Around 1 in 8 women will develop breast cancer in their lifetime.
Risk Factors
- Female (99% of breast cancers)
- Increased oestrogen exposure (earlier onset of periods and later menopause)
- More dense breast tissue (more glandular tissue)
- Obesity
- Smoking
- Family history (first-degree relatives)
The combined contraceptive pill gives a small increase in the risk of breast cancer, but the risk returns to normal ten years after stopping the pill.
Hormone replacement therapy (HRT) increases the risk of breast cancer, particularly combined HRT (containing both oestrogen and progesterone).
Genetics
BRCA refers to the BReast CAncer gene. The BRCA genes are tumour suppressor genes. Mutations in these genes lead to an increased risk of breast cancer (as well as ovarian and other cancers).
The BRCA1 gene is on chromosome 17. In patients with a faulty gene:
- Around 70% will develop breast cancer by aged 80
- Around 50% will develop ovarian cancer
- Also increased risk of bowel and prostate cancer
The BRCA2 gene is on chromosome 13. In patients with a faulty gene:
- Around 60% will develop breast cancer by aged 80
- Around 20% will develop ovarian cancer
There are other rarer genetic abnormalities associated with breast cancer (e.g., TP53 and PTEN genes).
Types
Ductal Carcinoma In Situ (DCIS)
- Pre-cancerous or cancerous epithelial cells of the breast ducts
- Localised to a single area
- Often picked up by mammogram screening
- Potential to spread locally over years
- Potential to become an invasive breast cancer (around 30%)
- Good prognosis if full excised and adjuvant treatment is used
Lobular Carcinoma In Situ (LCIS)
- A pre-cancerous condition occurring typically in pre-menopausal women
- Usually asymptomatic and undetectable on a mammogram
- Usually diagnosed incidentally on a breast biopsy
- Represents an increased risk of invasive breast cancer in the future (around 30%)
- Often managed with close monitoring (e.g., 6 monthly examination and yearly mammograms)
Invasive Ductal Carcinoma – NST
- NST means no special/specific type, where it is not more specifically classified (e.g., medullary or mucinous)
- Also known as invasive breast carcinoma of no special/specific type (NST)
- Originate in cells from the breast ducts
- 80% of invasive breast cancers fall into this category
- Can be seen on mammograms
Invasive Lobular Carcinomas (ILC)
- Around 10% of invasive breast cancers
- Originate in cells from the breast lobules
- Not always visible on mammograms
Inflammatory Breast Cancer
- 1-3% of breast cancers
- Presents similarly to a breast abscess or mastitis
- Swollen, warm, tender breast with pitting skin (peau d’orange)
- Does not respond to antibiotics
- Worse prognosis than other breast cancers
Paget’s Disease of the Nipple
- Looks like eczema of the nipple/areolar
- Erythematous, scaly rash
- Indicates breast cancer involving the nipple
- May represent DCIS or invasive breast cancer
- Requires biopsy, staging and treatment, as with any other invasive breast cancer
Rarer Types of Breast Cancer
- Medullary breast cancer
- Mucinous breast cancer
- Tubular breast cancer
- Multiple others
Breast Cancer Screening
The NHS breast cancer screening program offers a mammogram every 3 years to women aged 50 – 70 years.
Screening aims to detect breast cancer early, which improves outcomes. Roughly 1 in 100 women are diagnosed with breast cancer after going for a mammogram.
There are some potential downsides to screening:
- Anxiety and stress
- Exposure to radiation, with a very small risk of causing breast cancer
- Missing cancer, leading to false reassurance
- Unnecessary further tests or treatment where findings would not have otherwise caused harm
Generally, the benefits far outweigh the downsides and breast cancer screening is recommended.
High-Risk Patients
There are different recommendations for screening patients with a higher risk due to a family history of breast cancer. These are in the NICE guidelines (2013, updated 2019).
There are specific criteria for a referral from primary care for patients that may be at higher risk due to their family history. For example:
- A first-degree relative with breast cancer under 40 years
- A first-degree male relative with breast cancer
- A first-degree relative with bilateral breast cancer, first diagnosed under 50 years
- Two first-degree relatives with breast cancer
Depending on their risk factors, they may be seen in a secondary care breast clinic or a specialist genetic clinic.
Patients require genetic counselling and pre-test counselling before performing genetic tests. This is to discuss the benefits and drawbacks of genetic testing, such as the implications for family members and offspring.
Annual mammogram screening is offered to women with increased risk, between specific age ranges, depending on their level of risk (potentially starting from aged 30, if high risk).
Chemoprevention may be offered for women at high risk, with:
- Tamoxifen if premenopausal
- Anastrozole if postmenopausal (except with severe osteoporosis)
Risk-reducing bilateral mastectomy or bilateral oophorectomy (removing the ovaries) is an option for women at high risk. This is suitable for only a small number of women and requires significant counselling and weighing up risks and benefits.
Presentation
Clinical features that may suggest breast cancer are:
- Lumps that are hard, irregular, painless or fixed in place
- Lumps may be tethered to the skin or the chest wall
- Nipple retraction
- Skin dimpling or oedema (peau d’orange)
- Lymphadenopathy, particularly in the axilla
Referral Criteria
The NICE guidelines (updated January 2021) recommend a two week wait referral for suspected breast cancer for:
- An unexplained breast lump in patients aged 30 or above
- Unilateral nipple changes in patients aged 50 or above (discharge, retraction or other changes)
The NICE guidelines recommend also considering a two week wait referral for:
- An unexplained lump in the axilla in patients aged 30 or above
- Skin changes suggestive of breast cancer
The NICE guidelines suggest considering non-urgent referral for unexplained breast lumps in patients under 30 years.
Triple Diagnostic Assessment
Once a patient has been referred for specialist services under a two week wait referral for suspected cancer, they should initially receive a triple diagnostic assessment comprising of:
- Clinical assessment (history and examination)
- Imaging (ultrasound or mammography)
- Biopsy (fine needle aspiration or core biopsy)
Imaging
Younger women generally have more dense breasts with more glandular tissue.
Ultrasound scans are typically used to assess lumps in younger women (e.g., under 30 years). They are helpful in distinguishing solid lumps (e.g., fibroadenoma or cancer) from cystic (fluid-filled) lumps.
Mammograms are generally more effective in older women. They can pick up calcifications missed by ultrasound.
MRI scans may be used:
- For screening in women at higher risk of developing breast cancer (e.g., strong family history)
- To further assess the size and features of a tumour
Lymph Node Assessment
Women diagnosed with breast cancer require an assessment to see if cancer has spread to the lymph nodes. All women are offered an ultrasound of the axilla (armpit) and ultrasound-guided biopsy of any abnormal nodes.
A sentinel lymph node biopsy may be used during breast cancer surgery where the initial ultrasound does not show any abnormal nodes.
Sentinel Lymph Node Biopsy
Sentinel node biopsy is performed during breast surgery for cancer. An isotope contrast and a blue dye are injected into the tumour area. The contrast and dye travel through the lymphatics to the first lymph node (the sentinel node). The first node in the drainage of the tumour area shows up blue and on the isotope scanner. A biopsy can be performed on this node, and if cancer cells are found, the lymph nodes can be removed.
Breast Cancer Receptors
Breast cancer cells may have receptors that can be targeted with breast cancer treatments. These receptors are tested for on samples of the tumour and help guide treatment. There are three types of receptors:
- Oestrogen receptors (ER)
- Progesterone receptors (PR)
- Human epidermal growth factor (HER2)
Triple-negative breast cancer is where the breast cancer cells do not express any of these three receptors. This carries a worse prognosis, as it limits the treatment options for targeting the cancer.
Gene Expression Profiling
Gene expression profiling involves assessing which genes are present within the breast cancer on a histology sample. This helps predict the probability that the breast cancer will reoccur as a distal metastasis (away from the original cancer site) within 10 years.
The NICE guidelines (2018) [DG34] recommend this for women with early breast cancers that are ER positive but HER2 and lymph node negative. It helps guide whether to give additional chemotherapy.
Metastasis (2 Ls 2 Bs)
You can remember the notable locations that breast cancer metastasis occur using 2 Ls and 2 Bs:
- L – Lungs
- L – Liver
- B – Bones
- B – Brain
TOM TIP: Breast cancer can spread to any region of the body. In patients with a metastatic tumour, regardless of where it is, the primary could be breast cancer. This is worth remembering, as you may be asked “where might this metastasis have originated” in an exam or OSCE scenario. If the patient is female, answering “breast cancer” will be a good answer. The other cancer that can spread practically anywhere, and may be less obvious, is melanoma (a type of skin cancer).
Staging
The first step in staging is with triple assessment (clinical assessment, imaging and biopsy). Additional investigations may be required to stage the breast cancer:
- Lymph node assessment and biopsy
- MRI of the breast and axilla
- Liver ultrasound for liver metastasis
- CT of the thorax, abdomen and pelvis for lung, abdominal or pelvic metastasis
- Isotope bone scan for bony metastasis
The TNM system is used to stage breast cancer. This grades the tumour (T), nodes (N) and metastasis (M).
Multidisciplinary Team
All patients are discussed with the multidisciplinary team (MDT) for treatment planning:
- After the initial diagnosis
- After abnormal staging tests
- After further pathology and results
- After recurrence of the disease
- At any point where a treatment decision will be made
Surgery
Tumour Removal
The objective is to remove the cancer tissue along with a clear margin of normal breast tissue. The options are:
- Breast-conserving surgery (e.g., wide local excision), usually coupled with radiotherapy
- Mastectomy (removal of the whole breast), potentially with immediate or delayed breast reconstruction
Axillary Clearance
Removal of the axillary lymph nodes is offered to patients where cancer cells are found in the nodes. Usually, the majority or all lymph nodes are removed from the axilla. This increases the risk of chronic lymphoedema in that arm.
Chronic Lymphoedema
Lymphoedema is a chronic condition caused by impaired lymphatic drainage of an area. Lymphoedema can occur in an entire arm after breast cancer surgery on that side, with removal of the axillary lymph nodes in the armpit.
The lymphatic system is responsible for draining excess fluid from the tissues. The tissues in areas affected by an impaired lymphatic system become swollen with excess, protein-rich fluid (lymphoedema).
The lymphatic system also plays an important role in the immune system. Areas of lymphoedema are prone to infection.
There are specialist lymphoedema services that can help manage patients. Non-surgical treatment options include:
- Massage techniques to manually drain the lymphatic system (manual lymphatic drainage)
- Compression bandages
- Specific lymphoedema exercises to improve lymph drainage
- Weight loss if overweight
- Good skin care
TOM TIP: It is important to remember that you should avoid taking blood or putting a cannula in the arm on the side of previous breast cancer removal surgery. This is because there is a higher risk of complications and infection due to the impaired lymphatic drainage on that side.
Radiotherapy
Radiotherapy is usually used in patients with breast-conserving surgery to reduce the risk of recurrence. High-dose radiation is delivered from multiple angles to concentrate radiation on a targeted area. Patients will have a course of radiotherapy after surgery, for example, with a session of radiotherapy every day for 3 weeks.
Common radiotherapy side effects include:
- General fatigue from the radiation
- Local skin and tissue irritation and swelling
- Fibrosis of breast tissue
- Shrinking of breast tissue
- Long term skin colour changes (usually darker)
Chemotherapy
Oncologists will guide chemotherapy. Chemotherapy is used in one of three scenarios:
- Neoadjuvant therapy – intended to shrink the tumour before surgery
- Adjuvant chemotherapy – given after surgery to reduce recurrence
- Treatment of metastatic or recurrent breast cancer
Hormone Treatment
Patients with oestrogen-receptor positive breast cancer are given treatment that disrupts the oestrogen stimulating the breast cancer.
There are two main first-line options for this:
- Tamoxifen for premenopausal women
- Aromatase inhibitors for postmenopausal women (e.g., letrozole, anastrozole or exemestane)
Tamoxifen is a selective oestrogen receptor modulator (SERM). It either blocks or stimulates oestrogen receptors, depending on the site of action. It blocks oestrogen receptors in breast tissue, and stimulates oestrogen receptors in the uterus and bones. This means it helps prevent osteoporosis, but it does increase the risk of endometrial cancer.
Aromatase is an enzyme found in fat (adipose) tissue that converts androgens to oestrogen. After menopause, the action of aromatase in fat tissue is the primary source of oestrogen. Aromatase inhibitors work by blocking the creation of oestrogen in fat tissue.
Tamoxifen or an aromatase inhibitor are given for 5 – 10 years to women with oestrogen-receptor positive breast cancer.
TOM TIP: It is worth committing tamoxifen and aromatase inhibitors (e.g., letrozole) to memory, their relationship to menopausal status and their basic mechanism of action. These are good facts for examiners to test you on.
Other options for women with oestrogen-receptor positive breast cancer, used in different circumstances, are:
- Fulvestrant (selective oestrogen receptor downregulator)
- GnRH agonists (e.g., goserelin or leuprorelin)
- Ovarian surgery
Targeted Treatments
Trastuzumab (Herceptin) is a monoclonal antibody that targets the HER2 receptor. It may be used in patients with HER2 positive breast cancer. Notably, it can affect heart function; therefore, initial and close monitoring of heart function is required.
Pertuzumab (Perjeta) is another monoclonal antibody that targets the HER2 receptor. It may be used in patients with HER2 positive breast cancer. This is used in combination with trastuzumab (Herceptin).
Neratinib (Nerlynx) is a tyrosine kinase inhibitor, reducing the growth of breast cancers. It may be used in patients with HER2 positive breast cancer.
Follow-up
The NICE guidelines (2018) recommend all patients treated for breast cancer have surveillance mammograms yearly for 5 years (longer if they are not yet old enough for the regular breast screening programme).
Patients treated for breast cancer are given an individual written care plan, including details on:
- Designated contacts and details
- Adjuvant treatment review dates
- Surveillance dates
- Advice on identifying recurrence
- Support service details
Reconstructive Surgery
Reconstructive surgery is offered to all patients having a mastectomy. There are two options:
- Immediate reconstruction, done at the time of the mastectomy
- Delayed reconstruction, which can be delayed for months or years after the initial mastectomy
There are several different methods for reconstructing the breasts. The most suitable will depend on individual factors and preferences.
After breast-conserving surgery, reconstruction may not be required. The standard options, if needed, are:
- Partial reconstruction (using a flap or fat tissue to fill the gap)
- Reduction and reshaping (removing tissue and reshaping both breasts to match)
After mastectomy, the options for reconstructing the breast(s) include:
- Breast implants (inserting a synthetic implant)
- Flap reconstruction (using tissue from another part of the body to reconstruct the breast)
Implants
Inserting an implant is a relatively simple procedure (compared with a flap) with minimal scarring. It gives an acceptable appearance but can feel less natural (e.g., cold, less mobile and static size and shape). There can also be long-term problems, such as hardening, leakage and shape change.
Latissimus Dorsi Flap
The breast can be reconstructed using a portion of the latissimus dorsi and the associated skin and fat tissue. The tissue is tunnelled under the skin to the breast area.
“Pedicled” refers to keeping the original blood supply and moving the tissue under the skin to a new location.
“Free flap” refers to cutting the tissue away completely and transplanting it to a new location.
Transverse Rectus Abdominis Flap (TRAM Flap)
The breast can be reconstructed using a portion of the rectus abdominis, blood supply and skin. This can be either as a pedicled flap (tunnelled under the skin) or a free flap (transplanted). It poses a risk of developing an abdominal hernia due to the weakened abdominal wall.
Deep Inferior Epigastric Perforator Flap (DIEP Flap)
The breast can be reconstructed using skin and subcutaneous fat from the abdomen (no muscle) as a free flap. The deep inferior epigastric artery, with the associated fat, skin and veins, is transplanted from the abdomen to the breast. The vessels are attached to branches of the internal mammary artery and vein. This is a complex procedure involving microsurgery. There is less risk of an abdominal wall hernia than with a TRAM flap, as the abdominal wall muscles are left intact.
Last updated June 2021
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