Breast Cancer Diagnosis & Treatment in Singapore

Breast Cancer Treatment: Chemotherapy

Chemotherapy are drugs used to kill malignant cancer cells. These medications target tumour cell vulnerabilities compared to normal cells.  The Achilles heel of cancer cells are that they need various mechanisms to grow faster, repair themselves,  utilise certain nutritional pathways, increase their blood flow, reduce cell death signals and evade immunity. Chemotherapy and other kinds of anti-cancer  therapy hinges on these and other mechanisms to attack and kill the cancer cell.

Breast cancer treatments in Singapore encompass a variety of modalities such as surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy or immunotherapy.

(A) Adjuvant setting (after surgery when there is no evidence of disease spread to other sites): This is to reduce the risk of recurrence and improve the overall survival by treating any cancer cells that may still be present but just cannot be picked up by blood or radiological test

(B) Neoadjuvant setting (before definitive surgery): This has some advantages, particularly for larger tumours. We are able to downstage the cancers, making them smaller, so that there is an option of breast conservation for some suitable patients. In addition, being able to assess the tumour response to drug treatment allows some adjustment to therapy for some groups of breast cancer patients. Patients who already have large locally advanced breast cancers affecting the skin, chest wall,  or with large lymph nodes should have chemotherapy first to maximise the chance of clearance at surgery. Sometimes, a course of further chemotherapy may still be offered after surgery in certain subtypes of breast cancer and your doctor will discuss this with you

(C) Advanced setting: This is used as a first-line treatment strategy in certain situations when the breast cancer has already spread to distant organs and sites (stage IV disease)

Typically, chemotherapy regimens may take between three and six months, and are administered in ‘cycles’. Administering the medications with a rest of one to three weeks allows the patient’s own cells to recover before the next drug administration. Some cytotoxic cancer drug treatment is given as a short infusion, while some may take several hours. Almost all treatment is usually given in a comfortable outpatient setting in our clinic.

Side effects of chemotherapy vary depending on the drug type and regimen. However, these side effects can be generally well managed. We have a scalp cooling machine that can help to reduce the risk of hair loss but it works for only certain chemotherapy drugs. Please feel free to discuss this with your doctor or specialist to see if you are suitable to use it.

Sometimes in early stage cancers, the necessity of chemotherapy may not be very clear. In these cases, there are certain genomic tests done on your tumour tissue that can help in assessing the risk for recurrence and help you make a decision about chemotherapy. Your treating doctor will be able to help you understand when you need these tests.

Hormone Therapy

Anti-cancer hormone therapy , also called endocrine therapy, uses drugs to target the estrogen (oestrogen) signalling that hormone-sensitive breast cancer cells need to drive their growth and multiplication.

Breast cancers that utilise this signalling pathway primarily are identified on the tumour cell staining as estrogen receptor positive (ER positive) and / or progesterone receptor positive (PR positive). This test uses an antibody test, staining the tumour cells with colour. The intensity and percentage of cells stained may be reflected in the pathology report.

There are many studies involving many cancer patients which have shown improved survival for women with hormone sensitive breast cancer taking these drugs for a period of time. Common oral medicines that are prescribed include tamoxifen for women before and after menopause and aromatase inhibitors such as anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara) for postmenopausal women. These drugs are used in both early and advanced stages of breast cancer. There are also other hormone therapy used in the advanced cancer setting such as fulvestrant (Faslodex) which comes in the form of intra-muscular injections. Some types of hormonal therapy work by suppressing the ovaries from making hormones, either through surgery, radiotherapy or through medications. In general, the side effects of the hormonal therapy drugs vary depending on the type, but are usually well tolerated and easily managed.

To treat advanced breast cancer, the latest developments are a group of drugs known as CDK4/6 inhibitors (namely palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) targeting the enzymes CDK4 and CDK 6 which are important in cell division. These oral drugs are used in combination with the hormonal therapy described above (aromatase inhibitors, tamoxifen, fulvestrant). These drugs have side effects which are tolerable and generally manageable. Your treating doctor will provide you with an in-depth discussion of the relevant side effects so you can better understand them.

Targeted Treatments

Cellular growth and metabolism requires multiple signalling pathways. Cancer cells may sometimes hijack these signals to gain an advantage over normal cells, resulting in tumour cell proliferation.

One of the established targeted pathways for breast cancer is the HER2 (also known as erbB2) signalling pathway. About 20 to 25% of breast cancer cells amplify the HER2 gene in the cancer cell which then results in an excess of the HER2 growth promoting protein being expressed on it. This is like hyperactivating the cellular growth engine. These tumours are known as HER2-positive breast cancers. Such tumours are known to behave more aggressively, and tend to spread early to lymph nodes and other organs, including the brain.

Trastuzumab (Herceptin) is a monoclonal antibody directed against the HER2 protein. It was approved in 1998 to block this particular signalling pathway. It is usually given intravenously but there is now a subcutaneous formulation resulting in easier administration. When given with chemotherapy, it has resulted in high tumour response rates and better success rates in both the early and advanced stage settings.

Since then other HER2 targeting drugs have been approved, including ado-trastuzumab (T-DM1 or Kadcyla) and pertuzumab (Perjeta); both given intravenously and neratinib (Nerlynx) and lapatinib (Tykerb) both given orally. These drugs are used in different settings and stages of your breast cancer treatment and your treating doctor will be able to determine which is the best drug suited for you.

The side effects of anti-HER2 agents are generally mild but some can be more serious. For example trastuzumab, pertuzumab or ado-trastuzumab can cause heart weakening or heart failure and monitoring of the cardiac function is important during treatment.

Other targeted therapeutic agents against other pathways have also been developed for use in advanced breast cancer. These include the following:

(1) PARP inhibitors (olaparib[Lynparza], talazoparib[ Talzenna]): oral drugs approved for use in advanced breast cancers that are HER2-negative. These  people should also carry a germline BRCA gene mutation (an inherited mutation in the BRCA gene that helps in DNA repair)

(2) PIK3CA inihibitor (alpelisib[Piqray]): this is an oral drug used in combination with the hormonal therapy drug fulvestrant (Faslodex) in hormone receptor-positive HER2-negative advanced breast cancers which carry a PIK3CA mutation. The PI3K/AKT/mTOR pathway is a signalling pathway for cellular growth and metabolism. Inhibition of this pathway can result in tumour suppression.  About 30-40% of breast cancers have been found to have this PIK3CA gene mutation.

(3) mTOR inhibitors (everolimus [Affinitor]: an oral drug used in combination with exemestane (Aromasin) in hormone receptor-positive HER2-negative advanced breast cancers. By inhibiting the protein mTOR, it inhibits or slows down cell proliferation. It can also limit the growth of new blood vessels into tumours depriving it of nutrients.

All these targeted therapies have their own distinctive side effect profiles and your doctor will be able to help you decide which is best suited for your condition.

Immunotherapy drugs harness the body’s own immune system to recognise and kill cancer cells. This class of drugs when used in conjunction with chemotherapy have been found to be most effective in the subtype of triple-negative breast cancers (estrogen and progesterone receptors negative, HER2 negative).

Radiation Therapy

Radiation therapy (or radiotherapy) uses high-energy X-rays (radiation) to treat breast cancer. Post-surgery radiotherapy is recommended after lumpectomy (breast conservation surgery) or in certain cases after a  mastectomy when the risk of locoregional recurrence is high (such as if there are large tumours or heavy lymph node  disease). Radiation therapy is typically given over a period of several weeks and through detailed planning of the radiation field, avoids the main organs as far as possible. 

Radiotherapy is also a modality used in advanced cancer to treat certain conditions such as bone pains or if there is nerve compression in the spinal cord. Brain metastases from breast cancer would also often need radiotherapy. Focal radiation to selected tumour sites, called stereotactic radiotherapy, may be utilised in some situations to minimize side effects of treatment.

What are the Signs and Symptoms of Breast Cancer?

Breast cancer is the top cancer in women both in the developed and the developing world.  Over the past 40 years, the incidence of breast cancer in Singapore has more than doubled from 25 to 65 per 100,000 women. It accounts for about 1 in 3 cancers in women locally, with rates beginning to increase after the age of 40yo. However, young onset breast cancer occurring in women in their 20s and 30s can still happen and the number of reported cases is increasing in this age group. Notably, men can also get breast cancer but it is far less common.

The most common sign of breast cancer is a lump which is most commonly painless, but can be tender or painful too. Other signs include nipple retraction,  nipple discharge, swollen lymph nodes in the underarm area (can occur even before feeling a breast mass), swelling of all or part of the breast, skin redness over the breast which can resemble inflammation and/or skin dimpling which looks like an orange peel (peau d’orange). 

The key is early detection because when found at an early stage, it is highly curable and treatment can be minimized. When found at stage 0, chemotherapy can even be avoided.

What are the Types of Breast Cancer?

Breast cancer typically starts when abnormal cells in the breast start to grow uncontrollably forming a tumour. Most often it arises from the milk ducts of the breast (ductal cancers) or less commonly from the glands that make the milk (lobular cancers). There are other kinds of breast cancers such as malignant phyllodes tumours, or tumours which start in other kinds of tissue residing in the breast such as lymphomas (lymphatic tissue) or sarcomas (connective tissue, blood vessels). Paget’s disease is a rare form of breast cancer which arises in and around the nipple.

The subtypes of breast cancer based on the appearance of the tissue obtained upon biopsy include invasive ductal cancers which comprise about 80%, with the frequency of invasive lobular cancers being much lower (about 10%). Breast cancers can also occur very early such as  ductal carcinoma in-situ (DCIS) tumours.  DCIS are stage 0 cancers and do not have the ability to spread to distant sites away from the breast. They have an extremely good prognosis.

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