Breast Cancer

Table of contents
Key points ⚡
Succinct notes to superpower your revision
Breast cancer\: most common cancer in women; second most common worldwide; around 50,000 new UK cases annually;
early detection crucial for prognosis.
Genetic mutations\: BRCA1/BRCA2 (tumour suppressors, increase risk when mutated); HER2 (oncogene, promotes cell
proliferation).
Non-invasive breast cancer\:
DCIS\: ductal carcinoma in situ, four subtypes (papillary, cribriform, solid, comedo).
LCIS\: lobular carcinoma in situ, more common in pre-menopausal women, often bilateral.
Invasive breast cancer\:
Invasive ductal carcinoma\: most common, no speci
Invasive lobular carcinoma.
Rare breast cancers\:
In
Paget’s disease\: erythematous, ulcerated nipple skin, often mistaken for eczema.
Risk factors\:
Oestrogen exposure\: nulliparity, late menopause, HRT, obesity.
Genetic\: BRCA1/BRCA2 mutations, family history.
Age, female gender, radiation therapy, lifestyle (alcohol, high-fat diet).
Clinical features\:
Painless lump in breast/axilla, nipple discharge (unilateral/bloody suspicious), late symptoms include weight loss, bone
pain, jaundice.
Examination\: lump characteristics (hard, irregular,
d’orange).
Investigations\:
Triple assessment\: clinical exam, radiological imaging (ultrasound for \<40 years, mammogram for ≥40 years), core
biopsy/FNA.
Staging\: TNM system, receptor status (ER, PR, HER2).
Management\:
Medical\: endocrine therapy (tamoxifen, aromatase inhibitors), biologics (trastuzumab for HER2+), chemotherapy,
radiotherapy.
Surgical\: wide local excision, mastectomy, sentinel node sampling, axillary node clearance if metastasis, reconstruction.
Complications\:
Metastasis\: direct spread (skin, muscle), lymphatic (axillary nodes), haematogenous (lungs, bones, liver, brain).
Surgical\: brachial plexus damage, lymphoedema.
Article 🔍
A comprehensive topic overviewIntroduction
Breast cancer is the most common cancer in women. 1 2
It is the second most common cancer worldwide.
Every year in the UK around 50,000 new cases of breast cancer are diagnosed.
3
Patients can present with a range of symptoms, but most often they will present with a painless breast lump. However,
many breast cancers are initially detected by routine screening in asymptomatic patients. It can a
females but is much less common in men.
Each year a full-time GP will likely diagnose 1-2 cases of breast cancer. It is an important diagnosis to make as early
detection and intervention dramatically improves prognosis.
3

Aetiology

Breast cancer occurs due to damaged DNA and genetic mutations. Exposure to oestrogen also has an e
mutations and hence it is more common in women.
There are some important genetic mutations to be aware of. BRCA1 and BRCA2 are anti-oncogenes that both code for
tumour suppressor proteins which reduce the risk of breast cancer when functioning normally. Mutations in either of these
genes, therefore, increases the risk of breast cancer as well as an increased risk of ovarian cancer. 4,5
These mutations are
often inherited in an autosomal dominant fashion and families may require genetic counselling as a result.
5
Human epidermal growth factor receptor 2 (HER2 receptor) is a transmembrane glycoprotein that plays a key role in cell
survival, proliferation and di
6
The aetiology of breast cancer is multifactorial with many modi
some basic breast anatomy to help us understand where these cancers arise from.

Breast anatomy

The female breast is found anterior to the pectoralis muscles and is composed of a network of lobules and ducts (see
Figure 1). Lobules are the secretory units of the breast that are made up of many epithelial acini cells. These secrete milk
into a series of ducts which eventually form the lactiferous ducts that empty onto the surface of the nipple. Adipose tissue
and
The lymphatics of the breast run in the sub-mammary space. There are di
through and there are between 20 to 40 lymph nodes. These can be grouped anatomically and can also be divided into
surgical levels. 7
For more information on how the axillary lymph nodes are grouped, please refer to the Geeky Medics
guide to breast examination. Most importantly, surgeons must be able to locate the lymph nodes so that it can be
determined if the cancer has metastasised to the local lymphatic system.
Figure 1. Anatomy
of the female
breast.
8

Classi

Breast cancer is typically divided into two classi
cancer to be aware of.
Non-invasive breast cancer
These tumour cells have not invaded the basement membrane and can be referred to as premalignant or pre-cancerous.
They may progress to an invasive form of breast cancer.
9
They can arise from\:The epithelial cells lining the ducts\: this is called ductal carcinoma in situ (DCIS). There are four subtypes of DCIS\:
papillary, cribriform, solid, and comedo. Knowing the subtype of cancer can help predict the rate of transformation to
invasive cancer.
10
The epithelial cells inside the lobules\: this is called lobular carcinoma in-situ (LCIS) and is con
LCIS predominantly occurs in pre-menopausal women and is more often found in both breasts compared to DCIS which
is usually unilateral.
Invasive breast cancer
These tumour cells have invaded the basement membrane\:
Invasive ductal carcinoma (also called ‘no special type’)\: the most common type of breast cancer. It is called ‘no special
type’ because when it is examined under the microscope the cancer cells have no particular features.
Invasive lobular carcinoma
Rare breast cancers
There are two rare types of breast cancer that are important to know about, as they can easily be mistaken for other benign
conditions\:
In
(mastitis) or breast abscess. Note\: patients will not have a fever, chills or elevated white cell count.
11,12
Paget’s disease of the nipple\: presents with rough, dry, erythematous and ulcerated skin surrounding the nipple. It can
look similar to eczema, however, it must be distinguished from this as Paget’s disease is often associated with an
underlying in-situ or invasive cancer.
Other rare types of breast cancer - described as ‘special type’ as they have features under the microscope which allow us
to classify them more speci
metaplastic; basal-like and primary breast lymphoma.

Risk factors

There are many risk factors associated with developing breast cancer, most of which increase the risk of most types of
cancer. 4,13,14
Increased exposure to oestrogen is one of the more important and speci
Increased exposure to oestrogen
Increased exposure to oestrogen may be due to a range of factors including\:
Nulliparity and increasing age of
Early menarche (menstruation starting in girls under 12 years old)\: causing early exposure to oestrogen
Late menopause (>55-years-old)\: increasing the length of exposure to oestrogen
Hormone replacement therapy (HRT) with oestrogen and progestogen
Obesity\: increases oestrogen levels because more adipose tissue leads to increased expression of an enzyme called
aromatase which increases the synthesis of oestrogen
Other risk factors
Other risk factors for breast cancer include\:
Age\: risk increases with age
Female gender
Family history\:
Previous breast cancer
Genetics\: BRCA1 and BRCA2 mutations
Radiation therapy to the chest
Not having breastfed
Lifestyle\: excessive alcohol and fat intake
There has been debate over whether the combined hormonal contraceptive pill increases the risk of breast cancer. Recent
data suggests a dose-response relationship (i.e. earlier use of oral contraception increases the risk of breast cancer).
15
Recent guidelines also suggest that there is a small increased risk of breast cancer when taking the pill, but this reduces
over time after stopping it.
16Protective factors
Breastfeeding is a protective factor against breast cancer.

Clinical features

History
Most patients present with a painless lump in the breast or axilla. The patient may have noticed nipple discharge.
Bilateral clear or milky nipple discharge is usually benign and is not associated with breast cancer, although further
investigation is required to rule out other causes.
If the nipple discharge is unilateral or bloody this is abnormal and needs investigating for breast cancer.
17
If patients present late, they may have more systemic symptoms suggesting the disease has metastasised. These include
weight loss, anorexia, bone pain, jaundice, fatigue and breathlessness.
Many women present with breast pain, but it is very rarely a symptom of breast cancer.
Clinical examination
It is always important to perform a thorough examination of both breasts and axillary lymph nodes when the patient
presents with a breast lump or features suspicious of breast cancer. See the Geeky Medics guide to breast examination for
more details. The main features that may be found on examination are a lump, nipple changes and/or skin changes.
Breast lumps
Breast lump features more commonly associated with breast cancer include\:
Hard with a gritty texture
Ill-de
Tethered (attached to the surrounding breast tissue or skin) or
Most breast cancers arise in the upper outer quadrant of the breast 18
(see Figure 2).
A suspicious lump felt in the axilla may indicate metastasis to the lymph nodes.
Nipple changes
Nipple changes associated with breast cancer include\:
Bleeding, discharge, inversion or deviation of the nipple.
Paget’s disease, as explained earlier, can mislead clinicians as the rough, dry, erythematous, and ulcerated skin
surrounding the nipple can be misdiagnosed as eczema (this requires a punch biopsy to distinguish between Paget’s
and eczema).
Skin changes
Skin changes associated with breast cancer include\:
Rough, dry, erythematous, and ulcerated skin surrounding the nipple can be caused by Paget's disease
A cancerous breast lump beneath the skin can cause dimpling or puckering of the skin.
Peau d’orange\: the skin looks like the surface of an orange. This occurs when the lymphatic system that drains the skin is
blocked by cancer cells causing the skin to become oedematous. 20This can be easily misdiagnosed as an infection.Figure 2. Regions of the breast on examination.
19

Di

There is a wide range of potential di
below.
Table 1. Di
Di
Fibroadenoma
Breast cyst
Intraductal papilloma
Breast abscess
Fat necrosis
Benign overgrowth of collagenous
mesenchyme of one breast lobule
Firm, non-tender, highly mobile
palpable lumps
Palpable, benign,
lumps that are not
tissue
Benign, warty lesion usually located
just behind the areola
Present as a small lump and a sticky,
possibly blood-stained discharge may
be noticed
Most common in breastfeeding
mothers
Presents with malaise and fever
accompanied by a throbbing pain
The breast will be hot and red and may
have tender ipsilateral
lymphadenopathy in the axilla
Fibrosis and calci
tissue usually due to trauma and can
present as an irregular craggy mass,
skin tethering, nipple retraction, thus
mimicking a cancerInvestigations
Most patients will present to their GP with a breast lump, nipple or skin changes and will be referred urgently under the
two-week wait (2WW) scheme for suspected cancer.
Once referred, the patient will be seen in a secondary care breast clinic for a triple assessment. This is a ‘one-stop’ clinic
where all three parts of the assessment occur on the same day. This is so all the information can be gathered to be
discussed at a multidisciplinary team meeting if needed.
The triple assessment consists of\:
1. Clinical history and examination by a breast surgeon
2. Radiological imaging (see below)
3. Core biopsy or
Imaging
Ultrasound
Ultrasound imaging is typically used for younger women, usually under the age of 40 to investigate a breast lump. This is
because younger women tend to have denser breast tissue, this makes mammography less sensitive for detecting breast
cancers, so ultrasound is used instead.
21
Mammogram
Mammograms are usually taken in two views (mediolateral oblique and craniocaudal) to image as much of the breast
tissue as possible. This also allows the radiologist to see structures that would be superimposed in one view from another
angle so they are less likely to miss smaller sinister masses.
Denser tissue appears whiter (e.g.
appears grey. See Figure 3 showing a bilateral mammogram in the mediolateral oblique view.
Figure 3. Bilateral mammography, mediolateral oblique view.
22
Histology and cytology
Fine needle aspiration
Fine needle aspiration (FNA) uses a single
technique is often used for smaller more cystic lumps and is usually performed under ultrasound guidance.
Core biopsy
Core biopsy uses a wider needle often performed under ultrasound guidance. It takes a core of tissue, which provides
much more information about the cancer and its involvement with surrounding tissues leading to a higher diagnostic yield
compared to FNA.
ScreeningThere is a breast cancer screening program in the UK for women aged 50 to 70 in which a two-view mammogram is
performed every 3 years.Diagnosis
Staging
The TNM (tumour, node, metastasis) staging system is used to work out the stage of a breast cancer when all the
information is collected. You can read more about the TNM staging system here.
Receptor status
Laboratory investigations also reveal the hormone receptor status of breast cancer. They look at whether the cancer is
positive for progesterone receptors (PR+) and oestrogen receptors (ER+). These receptors have proliferative e
cells and are driven by their respective hormones. Thus, by knowing the receptor status of the cancer we can use targeted
treatments that act on these receptors (see below in the medical management section of the article). Some patients are
diagnosed with triple-negative breast cancer, which means they are negative for oestrogen, progesterone and HER2
receptors. This, unfortunately, limits treatment options and often has a poor prognosis.
23

Management

There are both medical and surgical approaches to treating breast cancer, the exact combination of these depends on the
stage of the cancer, its size, the age of the patient and the molecular signature of the cancer.
Medical management
Sometimes medical treatment alone is preferred for older patients in whom surgery is not appropriate, but it is often used
in conjunction with surgical approaches.
Endocrine therapy
Endocrine medications essentially aim to reduce oestrogen activity to reduce tumour growth\:
Tamoxifen\: used in premenopausal women with ER+ cancer, works by blocking oestrogen receptors
Aromatase inhibitors (Letrozole, Anastrozole, Exemestane)\: only used in postmenopausal women with ER+ cancer. They
work by blocking the enzyme aromatase which converts androgens into oestrogen.
Biologics
that targets HER2.
For cancers that express HER2, a drug called trastuzumab (also called Herceptin) is used, which is a monoclonal antibody
Chemotherapy
Chemotherapy can be divided into neoadjuvant and adjuvant. Neoadjuvant chemotherapy is used prior to surgery to help
shrink the cancer to allow for breast-conserving surgery. Adjuvant chemotherapy is used after surgery to try and prevent
the recurrence of the cancer and increase survival.
Oncotype DX breast recurrence score assay\: the patient's breast cancer cells are sent for genetic testing, where a 21 gene
panel is used to analyse the cells and produces a score between 0 and 100. The higher the score the more likely the
cancer will recur. So, it is used to decide if adjuvant chemotherapy is warranted, helping to avoid patients from being
subject to chemotherapy that they may not bene
24
Gonadotropin-releasing hormone agonists like goserelin can be used in premenopausal women to help protect their
ovaries from premature ovarian failure which is a potential side e
25
Radiotherapy
Radiotherapy is recommended to most patients with invasive cancer after wide local excision. It is also used to treat bone
lesions from metastatic breast cancer.
Surgical management
Wide local excision
Wide local excision removes the breast cancer with a margin of healthy tissue around the cancer. This approach is used if
the cancer is small. This surgical option is favoured as it conserves the breast.
Mastectomy
Mastectomy involves removing the entire breast and skin overlying it. This approach is used for larger breast cancers or
multifocal cancers where a wide local excision would not be successful.The approach used also depends on the size of the breasts. A small cancer but small breasts may require a mastectomy to
safely remove the cancer, so it is patient dependant.
Sentinel node sampling
Axillary node sampling is performed intraoperatively with the aim of ruling out lymphatic involvement. The lymph nodes
are located by injecting radioactive technetium into the nipple on the a
up the lymphatic vessels to the
is anaesthetised, blue dye is injected around the nipple. This again travels along the lymphatic vessels to the sentinel
lymph node. The sentinel lymph node is thus detected in two ways, the radioactive technetium using a Geiger counter, and
visually with blue dye. The sentinel node is removed and sent to the lab for analysis. If it shows evidence of metastasis then
surgical clearance of the axillary nodes is performed. Some hospitals have the ability to send the sentinel node to the lab
during the operation so the patient can have axillary node clearance at the same time, thus avoiding a second operation.
Reconstruction
Breast reconstruction is an important part of the treatment and is discussed with the patient. It can be performed later or
at the same time as the cancer removal.
Ovarian ablation
Ovarian ablation via surgery or radiotherapy is used to stop oestrogen synthesis. An oophorectomy is rarely performed
because preventing oestrogen synthesis can be achieved through drugs or radiotherapy. It is most often used in women
with a BRCA1 or BRCA2 mutation as this also predisposes them to ovarian cancer.

Complications

The most important complication of breast cancer is metastases, which can occur via three mechanisms\:
Direct spread\: into skin and muscle, causing skin ulceration
Lymphatic spread\: the axillary nodes are the commonest initial site of metastasis
Haematogenous spread\: blood-borne metastasis often occurs to the lungs, bones, liver and brain
There are also important complications that can arise from the surgery. Notably, if the patient requires axillary node
clearance due to lymphatic spread of the cancer there is a risk of damage to the brachial plexus and due to removal of
the lymphatics, there is a risk of developing lymphoedema in the arm of the operated side.

References

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Reviewer

Miss Chrissie Laban BSc, MRCS, MD, FRCS
Consultant Oncoplastic Breast Surgeon

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