Introduction 

Breast cancer develops in the breast connective tissue, lobules or the tubes and is the most frequent cancer in women.¹ Breast cancer is considered the foremost contributor to deaths caused by cancer.² Metastatic breast cancer, also known as stage four breast cancer, is the advanced stage of breast cancer, in which the cancer spreads from the breast to different components of the body. Metastasis or metastatic refers to the process in which cancer spreads to different parts of the body.³ 

Anatomy of the breast 

The breast is composed of fatty tissue known as adipose tissue. Breasts are seen in both males and females, but females have greater amounts of adipose tissue than males.⁴

The female breast has ten to twelve lobes which can be split into small lobules. The lobes and lobules are linked by milk ducts.⁴ Sex hormone estrogen greatly influences the breast, and its decline during menopause leads to reduced glandular tissue. When this happens, the active parts of the breasts shrink and are slowly replaced by adipose tissue. The breasts are attached to the chest wall by ligaments and rest on the pectoralis major muscle.⁵

Stages of breast cancer

Breast cancer is of five stages, stage 0 to stage 4. Stage 1st is the earliest, and Stage four is the last stage of breast cancer. Stage 0 is the lowest stage, which means the cancer has not spread to other organs, and Stage 4 represents that the cancer has spread to various other parts of the body. However, cancer experience may differ from person to person, but cancer with the same stage is treated similarly.⁶

Types of breast cancer

Breast cancer can be categorised as invasive and noninvasive breast cancer based on the cancer site. Non-invasive breast cancer is further divided into ductal carcinoma in situ and lobular carcinoma in situ. The most frequent form of noninvasive breast cancer is the ductal carcinoma in situ, which accounts for 90% of breast cancer cases.⁷

Metastatic breast cancer

Metastasis can be of two types:

1. Local metastasis
2. Distant metastasis

Local metastasis occurs if the cancer extends to the adjacent body parts, like the axillary lymph nodes, and distant metastasis occurs when the cancer has extended beyond the body part, far from the cancer cell mass known as the primary tumour. Even if breast cancer spreads to different parts of the body, it can still be known as breast cancer.⁸

Early metastatic breast cancer

What are the common sites of metastasis?

The most frequent sites of metastasis include

• Bone including spine
• Liver
• Lungs
• Brain
• Distant lymph nodes

Signs and symptoms of breast cancer

• Presence of a new mass or lump in the breasts or the armpits
• Swelling and thickening in the breast region
• Changes in the skin around the breast region are causing irritation 
• Redness around the nipple or breast area
• Pain or pulling in the nipple region 
• Changes in the size and shape of the breast
• Unusual nipple discharge, such as blood, pus, etc⁹
• Shortness of breath
• Pain in the bone, abdomen or chest
• Persistent headache¹⁰

Signs and symptoms of metastatic breast cancer according to the site of involvement

Metastatic breast cancer is when cancer cells start to spread from the breast to other parts of the body through the bloodstream or lymphatic system. The symptoms can vary depending on the organs affected: 

Bone metastasis 

• Swelling
• Fracture
• Unexpected, continuing bone pain

Brain metastasis

• Nausea or vomiting
• Vision and speech issues
• Changes in behaviour
• Headache
• Convulsions
• Issues with memory

Liver metastasis

• Pain in the abdomen; nausea or vomiting
• Itchy skin or rash
• Yellowing of skin and sclera (jaundice)
• Elevated liver enzymes in blood

Lung metastasis

• Chest pain
• Cough 
• Shortness of breath
• Abnormalities in chest X-ray¹¹

Diagnosis of metastatic breast cancer

Diagnosis of breast cancer starts with a general physical examination followed by mentioned below test according to the patient's needs:

1. Blood tests
   • Complete blood count (CBC): includes levels of RBC, WBC, and platelets 
   • Liver function tests (LFT)
   • Alkaline phosphatase: elevated levels can indicate the spread of cancer to the liver or bone
   • Comprehensive metabolic panel: measures fourteen distinct substances in the blood. Some of them include fat (lipids), sugar, electrolytes, enzymes, proteins, etc
2. Imaging techniques
   • CT( Computed tomography) scan
   • Magnetic resonance imaging (MRI)
   •  X-ray of bone 
   • Scanning of bone 
   • Breast mammogram 
   • Positron emission tomography (PET)
   • Ultrasound
   • Biopsy: fine needle aspiration( FNAC), incisional biopsy and excisional biopsy
3. Hormone receptor status
4. Biomarker testing
5. PCR- Polymerase chain reaction
6. NGS- Next generation sequencing
7. Liquid biopsy⁸

Molecular subtypes in metastatic breast cancer

Breast cancer has several subtypes depending on the presence or absence of certain receptors (proteins) on the surface of the cancer cells. These receptors influence how cancer grows and how it can be treated. 

1. Hormone receptor positive/ HER 2 negative: presence of estrogen and progesterone
2. Human epidermal growth factor receptor 2 (HER 2) positive: hormone receptor can be positive or negative
3. Triple negative breast cancer: absence of estrogen, progesterone and HER2^12,13

Treatment of metastatic breast cancer

Even though treatment for Metastatic Breast Cancer (MBC) has improved, it is still considered a non-curable disease. Treatment of MBC can be of two types

1. Standard chemotherapy
2. Targeted therapy

Treatment of metastatic breast cancer frequently involves chemotherapy (e.g., anthracyclines, taxanes, and 5-fluorouracil), with more recently developed drugs such as epothilones and ixabepilone providing improved outcomes for patients who have already received treatment. Targeted therapies such as hormone therapy (e.g., tamoxifen, letrozole) block estrogen or decrease its production, while drugs that target HER-2, such as trastuzumab, enhance outcomes in HER-2-positive cancers. More recently developed HER-2 drugs, such as trastuzumab-MCC-DM1 and pertuzumab, are also demonstrating improved outcomes.¹⁰ 

Self-breast examination

Breast self-examination helps to detect any changes in breast size, presence of a lump, abnormal nipple discharge, etc. This will help diagnose cancer in its early stages.

Risk factors of breast carcinoma

• Family history: the presence of a family history of breast cancer increases higher chances of developing breast cancer 
• Gender: females are more commonly prone to breast cancer than males
• Mutations
• Previous history of breast cancer: There is a chance of breast cancer recurrence
• Heavy breast
• Diethylstilbestrol exposure
• Obesity in post menopausal stage
• Alcohol consumption
• Hormone replacement therapies⁹

FAQs

Can breast cancer be genetic?

Yes, genetics is one of the causes of developing breast cancer.

Is breast cancer treatable?

Breast cancer can be treated if it is diagnosed in the early stage, but there are chances of recurrence. 

Is it possible to detect breast cancer by oneself?

Yes, breast cancer can be detected by yourself through self-breast examination, but professional advice should be taken before confirming it.

Can a woman in her postmenopausal state get breast cancer?

Post menopausal women with a heavy weight can be at risk of developing breast cancer.

Summary 

As breast cancer is the leading cause of death, early detection and providing the right treatment are crucial. Educating family members of individuals with breast cancer about the risk of breast cancer among other families helps in early identification. Providing nutritional support to individual with breast cancer helps in their overall health outcome, and their quality of life can be improved