Breast Cancer

Breast cancer has become the most common cancer among women in Hong Kong since 1994.

• In Hong Kong, female breast cancer cases had increased by 5 times from 1,152 in 1993 to 5,565 in 2021. On average, about 15 women are diagnosed with breast cancer every day. 
• The median age of breast cancer patients was 58 in Hong Kong. Compared with other countries, the median age at diagnosis was lower in Hong Kong (median age at diagnosis in Australia: 61; United States: 62).

Lifetime breast cancer risk for females is 1 in every 13. In 2021, 47.7% of the women diagnosed with breast cancer were aged 40-59. The older the age, the greater the risk. 

What is breast cancer? 

When cells divide and replicate at an uncontrolled rate, they affect healthy cell tissues and spread to other organs, which leads to the formation of tumours/ cancers.

• Cancer cells affect the healthy breast tissues, which then spread into the lymph nodes, and have risk of spreading to organs like the lungs, bone marrow and the brain. Organs that are severely affected by cancer cells may have failure in function.   
• Early discovery and proactive treatment can prolong life expectancy. 

• Gender: Though mostly associated with women, men can also be diagnosed with breast cancer
• Age: The risk increases with age
• Genetics: Having a mother-daughter, sibling or direct relation with a patient increases risk of occurrence. Research has shown that 5-10% of breast cancer cases are genetically linked
• Menstruation cycle: First menstruation before 12 years of age, and post-menopause after 55 years of age
• Diet: Long-term consumption of high amounts of animal fat 
• Living habits: Smoking, alcoholism and lack of exercise
• Fertility: Have not been pregnant, or being pregnant after 35 years of age 
• Medication: Long-term use of contraceptives or having received hormone replacement therapy for more than 5 years 
• Cancer history: Previous experiences of Hodgkin’s lymphoma, adenocarcinoma of the lungs, colorectal cancer or being diagnosed with cancer during childhood

1. Breasts 
   • The appearance of lumps, big or small 
   • Changes of shape and/or size 
   • Dot-like indentations on the skin 
   • Vein expansion or appearance of peau d’orange (Peau d’orange is an area of skin resembling the colour and texture of an orange peel)
2. Nipples 
   • Discharge or bleeding 
   • Indentation  
3. Armpits 
   • Swelling in the armpit or axillary lymph nodes 

Triple Assessment: 

• Mammography 

A mammogram is an X-ray of the breasts that can identify a tumour at an early stage before a lump is detectable. The breasts will be placed on the machine, which composed two metal plates which will press the tissues in between for 10 to 15 seconds. Mammogram can reveal breast tissues and ducts, including micro-calcification, breast cysts (commonly seen during menstruation), undetectable lumps and other key indicators. 

• Ultrasound scan 

Ultrasound scan uses sound waves to generate a digital picture of the breast area. It can examine breast lumps and lymph nodes in the armpit. If the radiologist finds any abnormalities during the mammogram, further ultrasound scan can show whether the breast lump is solid or a fluid-filled cyst. 

• Pathological tests 

A breast biopsy is needed to confirm the diagnosis of breast cancer. A breast biopsy involves the removal of a small piece of breast tissue from the suspected area for testing. The tissue sample will be examined under a microscope to check for any cancer cells. You may have pain, bleeding or bruises at the biopsy site after the procedure, but the wound will heal within a few days. 

Further Investigations: 

• Liver ultrasound:  
  • To detect any spread to the liver. 
• Bone scan: 
  • To check for any bony metastasis. 
• MRI breasts: 
  • MRI breasts can reveal any diseases at other sites of the breast (multifocal disease).
• CT/PET-CT scan: 
  • To confirm distant metastasis, such as spreading to the liver, brain, bones or lungs.

The most common types are:  

• Ductal carcinoma in situ (DCIS)
  • DCIS accounts for about 20% of all diagnosed breast cancers. 
  • DCIS means that some cells in the lining of the ducts of the breast tissue have started to turn into cancer cells. These cells are all contained inside the ducts. They have not started to spread into the surrounding breast tissue. 
  • Although DCIS is a pre-invasive breast cancer, it can develop into more invasive cancers if left untreated.  
• Invasive ductal carcinoma (IDC) 
  • The most common type of breast cancer, accounting for 80% of invasive breast cancers. 
  • IDC begins in the ducts, before breaking through the ductal walls to reach the fatty tissue.  
  • If left untreated, it can invade other parts of the body via the lymphatic and circulatory system. IDC can be identified by mammogram.  
• Invasive lobular carcinoma (ILC) 
  • Accounts for about 10% of all cancers originating in the breast.  
  • ILC starts in the lobules (or, milk glands) and can spread to other parts of the body.  
  • ILC is rather difficult to spot on mammogram. An MRI scan may be helpful to check any disease in other parts of the breast.  
• Inflammatory breast cancer (IBC)
  • Accounts for about 1% - 3% of all breast cancers.  
  • It affects the skin tissue and blocks the lymph channels. The breast might become swollen, red, firm or hard, and may be susceptible to infection.
• Paget’s disease
  • An extremely rare type of breast cancer which accounts for 1% of all breast cancers.   
  • It usually appears as a red, scaly rash of the skin over the nipple and areola. You may feel itchy, painful or burning discomfort. 
  • Paget’s disease is a sign that there might be breast cancer in the tissues behind the nipple. It is possible for someone to have Paget’s of the breast with no underlying cancer but this is less common. 

Differentiation by receptors:  

• Hormone receptor-positive (HR+) breast cancer（~70-80%）
  • Either oestrogen receptor (ER) or progesterone receptor (PR) is positive. 
• HER2-positive (HER2+) breast cancer（~20%）
  • HER2 is found on the surface of normal breast cells. It is a protein that affects the growth of some cancerous cells. When higher levels of HER2 protein are found in a breast cancer, it is referred to as ‘HER2-positive breast cancer’. The extra HER2 receptors stimulate cancerous cells, causing them to split and grow.
  • HER2+ breast cancers tend to be more aggressive and invasive. Researchers identified that patients with HER2+ breast cancer have lower survival rates than patients with HER2 breast cancer.
  • Besides surgery and chemotherapy, anti-HER2 targeted therapy is usually given to decrease the risk of recurrence. 
• Triple-negative breast cancer (TNBC)（~10%）
  • ER, PR and HER2 protein receptors are all negative. 
  • Though rare, it is the most lethal type of breast cancer and is very aggressive. 
  • TNBC is more likely to affect younger people. It is more likely to spread and recur than other types of breast cancer. 

• Stage 0: 
  • Stage zero (0) implies that cancer only exists in the ducts of the breast tissue and has not spread to the surrounding tissue of the breast. It is also called non-invasive or in situ cancer (Tis, N0, M0).
• Stage I
  • IA: The tumour is small, invasive, and has not spread to the lymph nodes 
  • IB: Cancer has spread to the lymph nodes, and is between 0.2 mm and 2 mm in size. There is either no evidence of a tumour in the breast or the tumour in the breast measures 20 mm or smaller. 
• Stage II
  • IIA: Any 1 of these conditions: 
    • There is no evidence of a tumour in the breast, but the cancer has spread to 1 to 3 axillary lymph nodes. It has not spread to distant parts of the body. (T0, N1, M0). 
    • The tumour measures 20 mm or below, and has spread to 1 to 3 axillary lymph nodes (T1, N1, M0). 
    • The tumour is larger than 20 mm but not larger than 50 mm and has not spread to the axillary lymph nodes (T2, N0, M0). 
  • IIB: Either of these conditions: 
    • The tumour is larger than 20 mm but below 50 mm, and has spread to 1 to 3 axillary lymph nodes. 
    • The tumour is larger than 50 mm but has not spread to the axillary lymph nodes. 
• Stage III
  • IIIA: The cancer of any size has spread to 4 to 9 axillary lymph nodes or to internal mammary lymph nodes. It has not spread to other parts of the body (T0, T1, T2, or T3; N2; M0). Stage IIIA may also be a tumour that is larger than 50 mm and has spread to 1 to 3 axillary lymph nodes. 
  • IIIB: The tumour has spread to the chest wall or caused swelling or ulceration of the breast, or is diagnosed as inflammatory breast cancer. It may or may not have spread to up to 9 axillary or internal mammary lymph nodes. It has not spread to other parts of the body. 
  • IIIC: A tumour of any size that has spread to 10 or more axillary lymph nodes, the internal mammary lymph nodes, and/or the lymph nodes under the collarbone. It has not spread to other parts of the body. 
• Stage IV (metastatic)
  • The tumour can be any size and has spread to other organs, such as the bones, lungs, brain, liver, distant lymph nodes, or chest wall (any T, any N, M1). 

In cancer care, doctors from different teams including surgeons, oncologists, radiologists and pathologists work together to design a patient’s overall treatment plan, which incorporates different types of treatments. 

The biology and behaviour of breast cancer affects the treatment plan. Some tumours are smaller but develop quickly, while some may be larger and develop slowly. Treatment options and recommendations are personalized depending on several factors, including

• The tumour’s subtype, such as hormone receptor status (ER, PR), HER2 status, and nodal status  
• The stage of the tumour 
• Genomic markers, such as Oncotype DX™ or MammaPrint™, if appropriate  
• The patient’s age, general health, menopausal status, and preferences 
• The presence of known mutations in inherited breast cancer genes, such as BRCA1 or BRCA2

Surgical treatment 

There are two main types of surgery: 

1) Lumpectomy 

• The surgeon removes only the breast tumour and its surrounding tissues; patients should require radiotherapy afterwards to reduce the risk of recurrence. This approach is most suitable for smaller lumps located further from the nipple while less undesirable effects are seen on the cosmesis. 

2) Mastectomy (removal of whole breast) 

• When the breast tumours are too large or distinctly located, the whole breast has to be removed surgically. 
• For patients undergoing mastectomy, the patient may choose to undergo breast prosthesis or breast reconstruction surgery. The reconstruction surgery generally uses abdominal fat or back muscle to restore the contour and shape of the breast. It is recommended to seek further advice from experienced plastic surgeons and nurse specialists before and after breast surgery. 

In either procedure, the lymph nodes in the armpit of the affected side have to be sampled or removed for further microscopic examination. Nowadays, suitable patients with lymph node involvement clinically would be offered sentinel lymph node biopsy. If no tumour cells are detected in the sentinel lymph node, patients could be spared from axillary dissection. This will reduce the risk of post-operative lymphoedema of the upper limbs. 

Other treatment methods 

Radiotherapy 

• Radiotherapy is needed for patients who have lumpectomy. This applies to all patients with invasive breast cancer and most patients with in-situ cancer.
• Radiotherapy is also recommended in patients with more advanced disease even after mastectomy, e.g. large tumour, having lymph node involvement or cancer cells involving the surgical margin. 
• Before starting radiotherapy treatment, the patient needs to visit a radiotherapy centre. The planning procedure usually takes 45 - 60 minutes. The oncologist or radiation therapist will first mark the breast tissue on your chest wall. You will then have a planning CT which covers the neck and the chest. Radiation therapists will then put marks on your skin to guide on directions of the radiotherapy beams. These marks are small and you need to beware not to wash them off during the radiotherapy period. In some radiotherapy centres, these marks are permanently tattooed.
• Radiotherapy is usually given 5 fractions in week over 3 to weeks, so total around 15 to 30 treatments. Nowadays, hypofractionated treatment of 3 to 4 weeks has also been proved to be equally effective than long duration of radiotherapy.
• Even shorter schedules have been studied and are in use in some centers, including accelerated partial breast radiation therapy for 5 days. 
• Common side effects of radiotherapy include: 
  • Erythema or desquamation of the irradiated skin area 
  • Nerve pain, pinching feelings and numbness of upper limbs
  • Tiredness
  • Long term side effects that happened months or years after treatment: lung inflammation (chronic radiation pneumonitis), heart problems (for left sided breast radiotherapy)  

Chemotherapy 

• The decision to offer and administer chemotherapy, as well as the most appropriate combination, will be made by the oncologists after discussion with the patients. Several factors are taken into consideration, including the stage and size of the tumour, or any involvement of the axillary lymph nodes. In addition, the tumour biological characteristics like ER/ PR/ HER2 status are taken into considerations. 
• Chemotherapy drugs can be administered orally or through intravenous injection, depending on the type of chemotherapy. 
• Common side effects of chemotherapy include: 
  • Increased risk of infection 
  • Hair loss or thinning
  • Mouth sores 
  • Nausea and vomiting
  • Fatigue 
  • Change in appetite 
  • Change in bowel habit 

Hormonal treatment 

• Oestrogen and progesterone can stimulate the growth of some breast cancer cells. Hormonal therapy lowers the levels or blocks the effects of oestrogen and progesterone in the patient’s body to inhibit the growth of breast cancer cells.
• Hormonal therapy is used in patients with breast cancer carrying either oestrogen receptors (ER), progesterone receptors (PR), or both. 
• The treatment usually consists of oral tablets being taken for up to 10 years. 
• The different therapies available to reduce the level of female hormones include:
  • Tamoxifen 
    • Applicable to: Pre- or post-menopausal women
    • Administration method: Taken orally 
    • Treatment duration: Once per day for 5-10 years 
  • Aromatase inhibitors 
    • Generic name: Anastrozole, Letrozole or Exemestane
    • Trade name: Arimidex, Femara or Aromasin
    • Applicable to: Post-menopausal women with early breast cancer or metastatic cancer
    • Administration method: Taken orally
    • Treatment duration: Once per day for several months or even years, depending on your situation. 
  • Anti-ovarian treatments
    • Generic name: Goserelin or Leuprorelin
    • Applicable to: Pre-menopausal women
    • Administration method: Intravenous or subcutaneous injection
    • Treatment duration: Every 1-3 months

Targeted therapy 

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. These treatments are very focused and work differently from chemotherapy. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells. 

Targeted therapies for early-stage breast cancer are mainly applicable for: 

• HER2-positive breast cancer 
• Breast cancer with high risk of recurrence

HER2-targeted therapy 

• Trastuzumab 
  • Administration method: Intravenous or subcutaneous injection  
  • Treatment duration: Every three weeks for one year 
  • Currently, patients with stage I to stage III breast cancer (see Stages) should receive a trastuzumab-based regimen, often including a combination of trastuzumab with chemotherapy, followed by a total of 1 year of adjuvant trastuzumab.  
  • Side effects: 
    • Heart problems
      • Usually at a low risk, prevalence 2-5%
      • Higher risk in patients who bears other risk factors for heart diseases, or those who are on chemotherapy (e.g. Adriamycin), which also increases the risk of heart problems.  
      • Your heart will be regularly checked with echocardiogram or MUGA scan during treatment.
    • Infusional reaction 
      • Usually mild and subside with pre-medication before infusion 

• Pertuzumab 
  • Administration method: Intravenous  
  • Treatment duration: Every three weeks over a year 
  • This drug is approved for stage II and stage III breast cancer in combination with trastuzumab and chemotherapy.  
  • Phesgo (combination of pertuzumab and trastuzumab in a single dose), a novel preparation, can be given by subcutaneous injection. 

• Neratinib 
  • Administration method: Oral medication 
  • Treatment duration: One year 
  • Neratinib may be used to treat women with early-stage hormone receptor-positive, HER2-positive breast cancer after they have completed a year of trastuzumab therapy. 

• Ado-trastuzumab emtansine or T-DM1  
  • Administration method: Intravenous  
  • Duration: every 3 weeks for total 14 cycles 
  • Ado-trastuzumab emtansine or T-DM1 is approved for patients with early-stage breast cancer who have had treatment with trastuzumab and chemotherapy with either paclitaxel or docetaxel followed by surgery, and who had cancer remaining (or present) at the time of surgery. 
  • T-DM1 is a combination of trastuzumab linked to a very small amount of a strong chemotherapy. This allows the drug to deliver chemotherapy into the cancer cell while lessening the chemotherapy received by healthy cells, which usually means that it causes fewer side effects than standard chemotherapy.  

Other types of targeted therapy for patients with high risk of recurrence 

• Olaparib
  • Administration method: Oral medication, taken twice a day
  • Treatment duration: One year
  • Olaparib is a kind of PARP inhibitor. PARP, which stands for stands for poly-ADP ribose polymerase, is a protein that helps damaged cancer cells to repair themselves. As a cancer treatment, PARP inhibitors stop the PARP from doing its repair work in cancer cells and the cell dies.
  • Olaparib can be used for one year after chemotherapy and surgery in early-stage, HER2-negative breast cancer in people with an inherited BRCA1 or BRCA2 gene mutation and a high risk of breast cancer recurrence (e.g. involvement of axillary lymph node, tumor > 2cm or pathological residual cancer cells after neoadjuvant chemotherapy).  

• Abemaciclib
  • Administration method: Oral medication, taken twice a day
  • Treatment duration: two years in combination with hormonal therapy (tamoxifen or an aromatase inhibitor)
  • Abemaciclib is an oral medication called CDK 4/6 inhibitor. CDK 4 and CDK 6 are proteins that stimulate cancer cells to divide and grow. Abemaciclib blocks these proteins to slow or stop the growth of the breast cancer.
  • Abemaciclib can be used in combination with hormonal therapy for patients with hormone receptor-positive, HER2-negative, early breast cancer with high risk of recurrence, defined as having > 4 positive axillary lymph nodes, or as having 1-3 positive axillary lymph nodes and one or more of the following features: histologic grade 3 disease, tumor size > 5 cm, or Ki-67 index > 20%. 

Advanced breast cancer, or metastatic breast cancer means that the breast cancer is not operable and has spread to other parts of the body. Treatments cannot completely cure metastatic breast cancer, but they can control it, sometimes for many years. 

The treatments offered for stage IV breast cancer depend on the hormone-receptor status and the HER2 status of the cancer cells. They will also depend on where the cancer has spread to, whether it is causing any symptoms, and your overall health. 

Hormonal receptor-positive, HER2-negative breast cancer (HR+/HER2-)

A. Hormonal therapy

• Hormonal therapy, also called endocrine therapy, is an effective treatment for breast cancer with ER+ or PR+. 
• Options for hormonal therapy include: 
  • Tamoxifen  
    • Administration: taken daily orally 
    • Mechanism: Tamoxifen is a drug that blocks oestrogen from binding to breast cancer cells. This will inhibit the growth of cancer cells. 
    • Common side effects: hot flushes, vaginal discharge or bleeding; Very rare risks include a cancer of the lining of the uterus, cataracts, and blood clots.  
    • This treatment is an option for both premenopausal and postmenopausal women and for men. 
  • Aromatase inhibitors (AI): anastrozole, exemestane, and letrozole 
    • Administration: taken orally daily
    • Mechanism: AIs decrease the amount of oestrogen produced by tissues other than the ovaries by blocking the aromatase enzyme. This enzyme changes androgen hormones into estrogen when the ovaries stop producing estrogen after menopause.  
    • Side effects: joint stiffness, sometimes with joint aches, hot flushes, vaginal dryness, an increased risk of osteoporosis and broken bones, and increased cholesterol levels.  
    • Used for post-menopausal women. Both premenopausal women and men can take AIs as long as they have ovarian suppression (see below). Women who have not gone through menopause should not take AIs without the injectable medication to block ovarian function, as they do not block the effects of estrogen made by the ovaries.  
  • Ovarian suppression  
    • Gonadotropin or luteinizing releasing hormone (GnRH or LHRH), examples include goserelin or leuprolide
    • Administration: subcutaneously in monthly dose  
    • Mechanism: Stop the ovaries from producing oestrogen, causing temporary menopause 
    • Ovarian suppression is commonly used as a part of treatment for hormone receptor-positive metastatic breast cancer in women who have not been through menopause. It is used with tamoxifen, an AI or fulvestrant.  
    • Other methods of ovarian suppression: surgery to remove both ovaries, radiotherapy to the pelvis to stop the ovarian function.
  • Fulvestrant 
    • Administration: monthly injection into muscles (2 injections are given every 2 weeks for the first 3 doses and then continued monthly) 
    • Mechanism: Fulvestrant is a selective oestrogen receptor downregulator (SERD) that blocks the ability of oestrogen to attach to oestrogen receptors (ER).  
    • Fulvestrant is only for women who have been through menopause or who are also receiving a shot to stop their ovarian function 

B. Targeted therapy for HR+/HER2- advanced breast cancer 

• CDK4/6 inhibitors: Palbociclib/ Ribociclib/ Abemaciclib 
  • What is CDK4/6 inhibitors? 
    • CDK4/6 inhibitors interrupt the process through which breast cancer cells divide and multiply. To do this, they target specific proteins known as the cyclin-dependent kinases 4 and 6, abbreviated as CDK4/6. 
    • The CDK4/6 proteins, found both in healthy cells and cancer cells, control how quickly cells grow and divide. In metastatic breast cancer, these proteins can become overactive and cause the cells to grow and divide uncontrollably. CDK4/6 inhibitors interrupt these proteins in order to slow or even stop the cancer cells from growing. 
    • CDK4/6 inhibitors are used to treat metastatic breast cancers that are HR+/ HER2-. 
  • Examples of CDK4/6 inhibitors  
    • Palbociclib and Ribociclib
      • Oral medication: taken once a day, 3 weeks on and 1 week off 
    • Abemaciclib
      • Oral medication: taken twice a day, continuous dose 
  • Side effects of CDK4/6 inhibitors 
    • nausea
    • diarrhea
    • fatigue
    • low white blood cell counts (also called neutropenia)
    • anaemia (low red blood cell counts)
    • low platelet counts 
  • Specific side effects: 
    • Abemaciclib: Diarrhea (It can be severe in about 10 percent of patients)
    • Ribociclib: Ribociclib can cause a heart problem known as QT interval prolongation. (The QT interval is a measurement made on an electrocardiogram, or EKG, which is used to record the electrical activity of the heart.) This can lead to a fast or irregular heartbeat, which may be life-threatening but it is very rare. Patients taking ribociclib need to have an EKG every couple of weeks during the first few cycles of treatment. 

Other targeted agents for HR+/HER2- advanced breast cancer 

• Everolimus
  • Administration: taken orally, once a day 
  • Everolimus is used with the AI exemestane for ER-positive, HER2-negative metastatic breast cancer that has grown despite treatment with another AI.  
  • Side effects: mouth sores, rash, diarrhea, and, rarely, an inflammation of the lungs called interstitial pneumonitis. 

• Alpelisib
  • Administration: taken orally, once a day 
  • Alpelisib is an option along with the hormonal therapy fulvestrant for some people with hormone receptor-positive, HER2-negative metastatic breast cancer that has a PIK3CA gene mutation  
  • Side effects: diarrhea, rash, fatigue, decreased in blood cell count, nausea and vomiting, mouth sores, increased serum sugar level, deranged liver function 

• Trastuzumab deruxtecan or T-DXD 
  • Administration: intravenously, given every 3 weeks 
  • T-DXD can be considered for patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH‑) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy.
  • Side effects: Nausea/ vomiting, tiredness, hair loss, loss of appetite, liver function impairment, low risk of interstitial lung disease (ILD), which causes scarring of the lungs, making it difficult to breathe or causing coughing.  

• Sacituzumab govitecan
  • Administration: Intravenously, given on day 1 and 8 every 21 days per cycle
  • Sacituzumab govitecan is an antibody-drug conjugate, which is a complex molecule composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. It is an option for patients with unresectable locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
  • Common side effects: neutropenia, diarrhea, nausea and vomiting, and allergic reaction.  

HER2-positive breast cancer (HER2+) 

• In general, for a person with HER2+ metastatic breast cancer, there is almost always a HER2-targeted therapy being used along with another systemic therapy.
• Anti-HER2 targeted therapy includes: 
  • Trastuzumab 
    • Trastuzumab can be given in combination with chemotherapy (e.g. taxanes based) or hormonal therapy. 
    • Administration: every 3 weeks with intravenous infusion or subcutaneous injection 
    • Side effects: risk of heart problems in 2% to 5% of patients. Requires cardiac monitoring every 3 months. 
  • Pertuzumab 
    • Pertuzumab is given in combination with trastuzumab and chemotherapy (docetaxel, paclitaxel) as first-line therapy for HER2+ metastatic breast cancer as this combination can improve the survival of the patients.
    • Administration: intravenous medication, given every 3 weeks 
    • Side effects: occasionally causes diarrhea and rash. 
  • Ado-trastuzumab emtansine or T-DM1
    • T-DM1 is a combination of trastuzumab linked to very small amount of a strong chemotherapy. This allows the drug to deliver chemotherapy into the cancer cell while lessening the chemotherapy received by healthy cells.  
    • Administration: given intravenously every 3 weeks 
    • This is approved for the treatment of metastatic breast cancer for patients who have previously received trastuzumab and chemotherapy with either paclitaxel or docetaxel. 
    • Side effects: small risk of heart problems and liver abnormalities  
  • Trastuzumab deruxtecan or T-DXD
    • Administration: intravenously, given every 3 weeks 
    • This HER2-targeted treatment is a combination of a drug that is similar to trastuzumab, linked to a small amount of a strong chemotherapy. The trastuzumab biosimilar carries the chemotherapy to the HER2-positive cancer cells so it can kill the cancer cells and limit damage to healthy cells.  
    • It is used for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens. 
    • Side effects: Nausea/ vomiting, tiredness, hair loss, loss of appetite, liver function impairment, low risk of interstitial lung disease (ILD), which causes scarring of the lungs, making it difficult to breathe or causing coughing. 
  • Lapatinib  
    • Administration: oral medication, taken once a day 
    • Lapatinib is usually used together with other medications (e.g. capecitabine or letrozole) when first-line or second-line treatment are no longer effective in limiting the cancer’s growth.  
    • Lapatinib and capecitabine (Xeloda) may be given to treat metastatic HER2-positive breast cancer when other types of chemotherapy or trastuzumab (Herceptin) no longer work. 
    • Side effects: diarrhea, liver function impairment 
  • Neratinib
    • Administration: oral medication, taken once  
    • Neratinib, in combination with capecitabine chemotherapy can be considered for the treatment of advanced or metastatic HER2-positive breast cancer in patients who have already received 2 or more HER2-targeted therapies. 
    • Side effects: diarrhea, liver function impairment 
  • Tucatinib
    • Administration: oral medication, taken twice a day
    • Tucatinib, in combination with trastuzumab and capecitabine, is an option for patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.
    • Side effects: Diarrhea, rashes, pain, swelling or blisters on the palms, mouth sores, decreased appetite, nausea and vomiting, tiredness, liver function impairment 

Triple-negative breast cancer (HR-/HER2-) 

Chemotherapy

• Chemotherapy is the major treatment modality for triple-negative breast cancer. With recent advances in novel medications, immunotherapy can be used together with chemotherapy in some patients with metastatic triple-negative breast cancer. 
• Though having many new medications developed in recent years, chemotherapy still plays an important role in the treatment of metastatic breast cancer (all types).  
• Chemotherapy for metastatic breast cancer can be given on many different schedules. It may be given once a week, once every 2 weeks (also called dose-dense), once every 3 weeks, or once every 4 weeks. Weekly schedules often include weeks off as a break.   
• In general, chemotherapy is often given continuously as long as it is working against the cancer and the patient isn’t experiencing too many side effects.  
• The best chemotherapy option for each patient depends on several factors, including the previous treatment received, potential side effects, the patient’s overall health, and the patient’s preferences. 
• The following single drugs may be used:  
  • Doxorubicin/ epirubicin  
  • Paclitaxel/ docetaxel/ nab-paclitaxel  
  • Pegylated liposomal doxorubicin  
  • Capecitabine  
  • Gemcitabine
  • Vinorelbine  
  • Cyclophosphamide  
  • Carboplatin/ cisplatin  
• The following combinations of chemotherapy drugs may be used for advanced breast cancer:  
  • FAC – cyclophosphamide, doxorubicin and 5-fluorouracil  
  • FEC – cyclophosphamide, epirubicin and 5-fluorouracil  
  • AC – doxorubicin and cyclophosphamide  
  • EC – epirubicin and cyclophosphamide  
  • Docetaxel and capecitabine
  • Gemcitabine and paclitaxel  
  • Gemcitabine and carboplatin  
  • Vinorelbine and carboplatin
• Side effects of chemotherapy will depend on the type of drug, the combinations, the dose, how it is given and the patient’s overall health. Some common side effects of chemotherapy are:  
  • low blood cell counts  
  • infection
  • nausea and vomiting
  • sore mouth and throat  
  • hair loss  
  • diarrhea  
  • constipation
  • fatigue  
  • loss of appetite  
  • treatment-induced menopause  
  • cognitive changes  
  • nervous system damage  
  • fertility problems  

Immunotherapy 

• Immunotherapy is designed to boost the body's natural defenses to fight the cancer. The most commonly used immunotherapy for breast cancer is immune checkpoint inhibitors. 
• Examples of immunotherapy: Pembrolizumab, Dostarlimab 
• Pembrolizumab
  • A combination of pembrolizumab with chemotherapy (paclitaxel protein-bound, or paclitaxel, or gemcitabine plus carboplatin) for patients with locally recurrent unresectable or metastatic triple-negative breast cancer whose tumours express PD-L1 (CPS ≥10).  
  • Compared with chemotherapy alone, adding pembrolizumab on top of chemotherapy improved the progression-free survival in patients with advanced triple-negative breast cancer whose tumours express PD-L1 (CPS ≥ 10).  
• Dostarlimab 
  • A type of immunotherapy for recurrent or metastatic breast cancers that have DNA mismatch repair deficiency (dMMR) and have progressed on previous treatment. 
• Side effects:  
  • One big concern about immune checkpoint inhibitor medicines is that they may allow the immune system to attack healthy cells and organs. As the medicines essentially take the brakes off the immune system, T cells may start attacking cells other than cancer cells. Some serious side effects include problems with the lungs, liver, intestines, pancreas, and kidneys.  

Targeted therapy 

• Sacituzumab govitecan:
  • For treatments of patients with metastatic triple-negative breast cancer who have already received at least two treatments, including 1 treatment for metastatic disease.  
  • Sacituzumab govitecan is an antibody-drug conjugate, whereas the antibody attaches to a cancer cell then delivers the anticancer drug it carries to disintegrate the cancer cell.  
  • Administration: given by vein, or intravenously, on days 1 and 8 of every 21-day cycle. 
  • Common side effects: neutropenia, diarrhea, nausea and vomiting, and allergic reaction.  

Others

For patients with BRCA1 or BRCA2 gene mutation  

• For patients with metastatic breast cancer who have a BRCA1 or BRCA2 gene mutation, oral PARP inhibitor may be an option.  
• Olaparib/ Talazoparib
  • Administration: oral medication 
  • This is a type of PARP inhibitor which destroys cancer cells by preventing them from fixing damage.  
  • Common side effects: fatigue, nausea and vomiting, headaches, diarrhea, decreased appetite, hair loss and lower levels of certain blood cells. 

Most breast cancers are first spotted by the patients themselves. Since the cure rate is much higher in early breast cancers, women should stay aware and self-examine their breasts monthly. 

Healthy lifestyles will help to lower its risk. 

• Regular exercise 
• Eat more fresh vegetables and fruits while avoid food with high fat content
• No alcohol consumption or smoking 

The role of mass breast cancer screening in Asian population remains controversial. Up till now, there is no convincing evidence to recommend routine check-ups for all women. However, women with higher risk (e.g. strong family history of breast cancer) should consult their doctors for advice. 

Hong Kong Cancer Registry, 2020, Breast cancer 

The Hong Kong Anti-Cancer Society: Breast cancer (Chinese only) 

Smart Patient (by Hospital Authority): Breast cancer 

American Society of Clinical Oncology (ASCO): Breast cancer 

Canadian Cancer Society: Breast cancer 

Special thanks to Mr. Joshua Tang, Ms. Jasmine Wing-Fong Wu (Class M23), medical student of Li Ka Shing Faculty of Medicine, the University of Hong Kong, and Dr. Wendy Wing-Lok Chan, Department of Clinical Oncology, the University of Hong Kong for authoring and editing this article. 

Last updated on 18th Dec, 2023.