Breast Cancer

In 2022, there were 2.3 million women diagnosed with breast cancer and 670,000 deaths globally. Breast cancer was the most common cancer in women in 157 countries out of 185.

Definition

"Primary invasive breast cancer is a malignancy originating in the ducts or lobules which has penetrated past the basement membrane and has spread to the surrounding tissue" [1][2]

Epidemiology

• Annual incidence: 55,500 women and 370 men diagnosed in the UK each year [1]

• Most common cancer in the UK [1]

• 1 in 7 women in the UK develop breast cancer during their lifetime

• Mainly affects women but men can get it

Risk Factors / Causes

Risk factors [1], [2]

• Age

• Female sex

• Family history

• Genetic mutations: BRCA1, BRCA2, CHEK2, PALB2, ATM, PTEN, STK11, TP53

• Endogenous oestrogen exposure

  • Early menarche and late menopause

  • Nulliparity

  • No breastfeeding

• High BMI

• Alcohol consumption

• Contraceptive pill - increased risk goes back to normal 10 years after stopping the COCP

• HRT - higher if using combined HRT than oestrogen-only HRT

• Ionising radiation
  

Anatomy / Pathophysiology

Breast is made up of fat, glandular tissue (divided into lobes), ducts and connective tissue [1]

Younger women have more dense breasts due to a higher amount of glandular tissue, while post-menopausal women have more fat in the breasts, which are less dense.

Breast cancer is classified according to the site:

• Invasive ductal carcinoma when it starts in cells lining ducts of the breast

• Invasive lobular cancer when it starts in lobules

• Ductal or lobular carcinoma in situ if cancer cells are confined within ducts or lobules
  

Signs and Symptoms

Signs:

• New firm lump or thickening in breast or armpit

• Change in size, shape or feel of the breast

• Skin changes - puckering, dimpling, rash or redness

• Fluid leaking from the nipple in non-breastfeeding women

• Change in position of the nipple

Investigations

• Mammography (>30 years) or ultrasound (<30 years)

• Image-guided core biopsy is required for the definite diagnosis

• Hormone receptor testing: oestrogen receptor, progesterone receptor, and HER2 testing

Staging / Grading

The TNM staging system is a universal standard for classifying the extent of cancer. There are 3 components of this system:

• Tumour (T): size and extent of the primary tumour

• Node (N): regional lymph node involvement

• Metastasis (M): presence of metastatic spread

As the TNM staging system is updated regularly, we recommend you stick to the version that your hospital uses. You can find the information about the TNM staging system version 8.0 here: https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-grades/tnm-staging

Breast cancer can also be classified according to its hormone receptor status [3]:

1. Oestrogen receptor (ER) - 70-75% of breast cancers

2. Progesterone receptor (PR) - about 35% of breast cancers

3. Human Epidermal Growth Factor Receptor (HER2) - about 10-15% of breast cancers

4. Triple Negative Breast Cancer (TNBC) - about 20% of all breast cancers, associated with poor prognosis

Management

Multidisciplinary approach - breast surgeons, medical and clinical oncologists

Early stage (stages I to IIB)

• Neoadjuvant chemotherapy/immunotherapy

• Lumpectomy or total mastectomy

• Sentinel lymph node biopsy or axillary lymph node dissection
  

• Adjuvant hormone therapy

Locally advanced breast cancer (stages IIB to III)

• Neoadjuvant chemotherapy

• Lumpectomy or total mastectomy

• Sentinel lymph node biopsy or axillary lymph node dissection

• Adjuvant hormone therapy or chemotherapy

Referral Criteria

2-week-wait referral

• New lump in breast or axillary in women aged 30 or above

• Nipple changes of concern including discharge and retraction, age 50 or above

Routine referral

• New lump in women aged less than 30

References: [4]

Screening

3 yearly routine screening with mammography [5]

• Women aged 50-70 years

• Women older than 70 can continue to receive breast screening by self-referral

• Women at increased risk may be eligible for screening before age 50

Benefits:

• Early detection and reduction in breast cancer mortality

Harms:

• Over-diagnosis which leads to unnecessary treatment

• False positives leading to unnecessary further investigations

• False negatives leading to missed cancer

• Pain, discomfort and psychological distress

Resources

[1] What is breast cancer? (2023) Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/breast-cancer/about (Accessed: 29 March 2024). 

[2] Primary invasive breast cancer - guidelines | BMJ best practice (2024) BMJ Best Practice. Available at: https://bestpractice.bmj.com/topics/en-gb/716/guidelines (Accessed: 29 March 2024). 

[3] Orrantia-Borunda E, Anchondo-Nuñez P, Acuña-Aguilar LE, Gómez-Valles FO, Ramírez-Valdespino CA. Subtypes of breast cancer. Breast Cancer [Internet]. 2022 Aug 6.

[4] Suspected cancer referral guidelines (2023) Cancer Research UK. Available at: https://www.cancerresearchuk.org/health-professional/diagnosis/suspected-cancer-referral-best-practice/nice-cancer-referral-guidelines (Accessed: 29 March 2024). 

[5] Breast screening (2022) NICE. Available at: https://cks.nice.org.uk/topics/breast-screening/ (Accessed: 29 March 2024).