乳腺癌——筛查和治疗

在新加坡,乳腺癌是女性最常患的癌症。在所有诊断出癌症的女性中,超过25%是乳腺癌。从2010年到2014年,新加坡每年有超过1800名女性被诊断出患有乳腺癌。和大多数癌症一样,乳腺癌是癌性(恶性)肿瘤导致的。当乳腺细胞变得不正常且开始无序或不受控制地分裂后,就会产生这种情况。

诱因和风险

年龄越大,患乳腺癌的风险就越大。 M大多数诊断出乳腺癌的女性都在40岁及以上。男性也可能患乳腺癌,但是可能性很低,在所有乳腺癌患者中,男性只占不到1%。 5%到10%的乳腺癌和遗传因素有关,例如BRCA1和BRCA2基因。这些基因与乳腺癌有关,50%有乳腺癌或卵巢癌史的家族都有此种基因。患乳腺癌的风险还与以下因素有关:

女性受孕期的长短。 女性受孕期越长,其患癌症的可能性越大。
T女性第一次生育的年龄。 若女性生第一个孩子时不满30岁,其被诊断出乳腺癌的可能性较低。

症状

乳腺癌最常见的症状是乳腺肿块。其它症状包括乳头内陷或出血、乳肿、乳头溢液和腋窝淋巴腺肿大。

诊断

如果出现可疑的乳腺肿块, 需要进行乳房X光摄影检查和活组织检查。

治疗

手术通常是治疗乳腺癌的初始手段。如果乳房无法保留,需要进行乳房切除术。为了治疗剩余乳腺组织中残留的癌症细胞并防止癌症复发,手术后需要进行放疗和化疗。

What is Breast Cancer?

Breast cancer refers to a group of diseases where changes in the DNA of cells in breast tissue lead to uncontrolled growth. Such uncontrolled growth usually forms lumps that are either palpable (can be felt) or visible on X-Ray. Invasive breast cancers usually start in the ducts that carry milk to the nipple (ductal carcinoma) or glands that form milk (lobular carcinoma). Ductal carcinoma in-situ (DCIS) is a form of breast cancer that is a precursor to invasive cancer.

What are the Causes and Risk Factors of Breast Cancer?

Causes of Breast Cancer

Breast cancers are caused by DNA changes that lead to uncontrolled growth of cells in breast tissue. Most of these DNA changes are sporadic occurrences that cannot be predicted reliably. An inherited genetic predisposition may be found in less than 10% of all breast cancer cases.

Risk factors of Breast Cancer

Having certain risk factors increases your chances of developing breast cancers, but it does not mean you will get the disease.

Modifiable risk factors (risks you may be able to act on):
- High body weight
- Lack of exercise
- Alcohol
- Diet e.g. consuming excess processed food
- No childbearing or delayed childbearing
- No breastfeeding
- Hormone replacement therapy
- Oral contraceptives

Uncontrollable risk factors (risks you cannot act on):
- Age: More common after 40 years old
- Female gender
- Family history: having one first degree relative with breast cancer doubles the lifetime risk of breast cancer
- Genetic predisposition: Having gene mutations such as BRCA1, BRCA2, PALB, CHEK, ATM, PTEN, TP53
- Personal history of breast cancer
- Previous abnormal breast biopsy: Women whose biopsies indicate atypical ductal hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in-situ should undergo regular breast screening
- Early menarche (first menstruation) or late menopause
- Radiation to chest e.g. during lymphoma treatment

What are the Signs and Symptoms of Breast Cancer?

Breast lump (can be painless)
Swelling of lymph nodes in underarm
Bleeding or unusual discharge from the nipple
Dimpled or puckered skin over the breast
Persistent itch and rash around the nipple
Recent onset of pulled in or retracted nipple
Swollen and thickened skin over the breast

How to Screen for Breast Cancer?

Breast cancer screening allows cancer detection before it causes symptoms (like a lump that can be felt). Breast cancers found during screening exams are more likely to be smaller and at an earlier stage. The size of a breast cancer and extent of spread to neighbouring lymph nodes are some of the most important factors in predicting the prognosis (outlook) of a woman with this disease.

1. Mammogram

What is a mammogram?A mammogram is an X-ray examination of the breast. It is used to detect and diagnose breast disease in women who either have breast problems, such as a lump, pain, or nipple discharge, as well as for well women who have no breast complaints.The procedure allows detection of cancerous tumours that cannot be felt by hand, or lumps in the breast that are not yet cancerous but may grow into cancerous tumours.
What happens if your mammogram shows abnormal results?If a suspicious lump(s) is detected on a mammogram, an ultrasound of the breasts can be performed to supplement information from the mammogram to guide the next appropriate treatment step.
When should you go for a mammogram?Screening mammograms are recommended for healthy women aged 50 and above by major medical societies such as American College of Physicians and American Cancer Society. For healthy women aged between 40–49, the decision to perform a screening mammogram should be individualised.Women with known genetic mutations that increase their lifetime risk of developing breast and other cancers should have a discussion with a breast cancer specialist regarding the starting of screening measures at an earlier age as well as the role of preventive surgery.
What is the radiation impact from a mammogram?The dose of radiation from a standard mammogram is very small and safe for healthy women. It is estimated that one mammogram delivers the same amount of radiation from the background of a normal environment over two months.

2. Magnetic Resonance Imaging (MRI) of the Breast

MRI of the breast is a special screening procedure that takes images of the breast using strong magnetic fields and radio waves.It is occasionally used as a supplemental tool to mammograms, especially for women with dense breasts, when there is an abnormality on the mammogram that cannot be conclusively determined as a cancerous lump.

3. Breast self-examination

Regular self-examination is not a substitute for breast cancer screening with mammograms Regardless, women should be familiar with how their breasts normally look and feel and should report any changes to a health care provider right away.

Breast Cancer Diagnosis: How do I confirm if I have breast cancer?

Most masses seen on mammograms are benign (not cancerous). When a cancer is suspected, a needle biopsy of the breast mass is required to obtain tissue for microscopic analysis. Additional biopsy and placement of small marking clips inside the breast tissue (to locate the area of concern) may be required to confirm if enlarged/suspicious lymph nodes under the arm have been affected by the cancer. Upon confirmation of the breast cancer diagnosis, additional testing will be performed to understand the subtype, tumour grading, expression of hormone receptors (estrogen and progesterone) and HER2 protein. These factors will aid the breast cancer specialist in creating a management plan for the patient. Except for very small breast cancers, patients should undergo additional staging scans to determine the extent (or spread) of the cancer. Imaging that may be used include CT (computed tomography), bone scan, PET or MRI.

Breast Cancer Treatment at The Cancer Centre, Singapore

How Is Breast Cancer Treated?

At The Cancer Centre, treatment of breast cancers largely depend on the stage of the cancer, hormone receptors/HER2 expression, the patient’s wish and health comorbidities (presence of other existing disorders). Breast Cancer Treatment Based on Cancer Stage:

For very small cancers (typically less than 2–3cm) without suspicious lymph nodes involvement, upfront surgery is generally recommended.
For stage 2 or 3 breast cancers, patients will be counselled on the role of neoadjuvant therapy (drug treatment prior to surgery). This is usually chemotherapy +/- antiHER2 antibodies. This approach improves breast cancer survival and sometimes allows for breast-conserving surgery.
Patients with distant spread of cancer (to other parts of the body) found on staging scans are generally not recommended for breast surgery, unless in exceptional circumstances e.g. having open wounds from breast cancer.

Types of Breast Cancer Treatments

1. Surgery

As oncologists, we work very closely with breast surgeons and plastic surgeons to achieve the optimal oncological and cosmetic outcomes for our patients. Here are the different types of surgeries for treating breast cancer:

Breast-conserving surgery: Only the part of the breast containing the cancer is removed.
Mastectomy: Entire breast is removed.
Surgery to remove adjacent lymph nodes to assess for spread.
- Sentinel lymph nodes biopsy (SLNB)—For cases where no clinical involvement of lymph nodes in under arm is suspected. During surgery, a special mapping technique is used to identify the nearest lymph nodes that cancer drains into, that needs to be removed.
- Axillary lymph nodes dissection (ALND)— Removal of many lymph nodes in the underarm. Typically for cases with proven underarm nodes at diagnosis from needle biopsy or those with extensive involvement of sentinel lymph nodes.
Breast reconstruction surgery—This is an elective procedure that may be done during the treatment surgery or at a later stage using various methods including muscle flaps, fat or a prosthetic implant.

2. Drug Therapy

For early stage breast cancers: Neoadjuvant (prior to surgery) or adjuvant (after surgery) drug treatment may be offered to reduce the risk of cancer relapse and improve the chance of cure. Recent advancements has seen the use of genomic profiling, particularly in tumours without HER2 protein overexpression, to better select patients who will benefit from adjuvant chemotherapy, and to avoid using chemotherapy in patients with lower risks of recurrence. For metastatic breast cancers: Drug selection depends on hormone expression, HER2 protein overexpression and other newer molecular markers in order to optimise quality of life and survival.

Types of Drug Therapies

a) Chemotherapy

Chemotherapy refers to anti-cancer drugs that work in various ways to kill cancer cells. . There are many chemotherapy drugs that are effective for breast cancer. Most of them are in intravenous (IV) formulations but there are oral formulations as well. Depending on the breast cancer state, chemotherapy may sometimes be given together with surgery, or at other times given alone without surgery. Chemotherapy is given in varying cycles (schedules), typically as an injection every 1–4 weeks. Occasionally, chemotherapy is given in a metronomic schedule (continuous dosing of low doses) to improve tolerance towards the medication. The side effects of chemotherapy vary; not all drugs lead to hair loss, severe vomiting or major impairment in the immune system. Your oncologist will be able to manage and guide you through the chemotherapy side effects with supportive medications.

b). Hormonal Therapy

2 in 3 breast cancer patients have receptors that are stimulated by naturally occurring female hormones (estrogen and progesterone). For these women, hormonal therapy blocks the interaction between their female hormones and these receptors. Hormonal treatment can be used in the adjuvant setting (after surgery) for 5–10 years or for cases that have relapsed. Aromatase inhibitors and Fulvestrant are approved to be used in a post-menopausal setting, whereas Tamoxifen can be used in both pre and post-menopausal settings. These drugs have slightly different side effect profiles and patients who are intolerant to one drug may switch out to another drug for better tolerance.

c) Targeted Therapy

Some breast cancer cells have dominant gene mutations driving the growth of the cancer. Discovery and understanding of these mutations have led to the development of drugs that specifically block these mutations:

HER2: 20% of breast cancers have increased expression of HER2 protein on the cell surface, driving cancer growth. Major progress in drug development in this field led to approval of many new effective drugs: monoclonal antibodies, antibody-drug conjugates and small molecule tyrosine kinase inhibitors. The use of HER2 antibodies in early breast cancer has changed the outlook of an aggressive subtype of breast cancer into a disease with much higher cure rate.

CDK4/6 inhibitors: Blocking cyclin-dependent kinases (CDK) 4/6 in metastatic hormone positive breast cancers enhances the efficacy of hormonal therapy. This strategy is the new standard of care for the majority of newly diagnosed metastatic hormone positive breast cancer, with 42–46% prolongation of time to cancer progression. These effective drugs are available in oral form, greatly improving our patients’ quality of life.

PI3K: 30–40% of metastatic hormone positive breast cancers have mutation in PI3KCA protein. Blocking PI3KCA protein in patients who have failed prior hormonal treatment can significantly slow down cancer cell growth.

BRCA: Approximately 5% of all breast cancers are due to inherited BRCA gene mutations. BRCA gene mutations lead to defective processes of normal DNA repair of gene damage. When poly (ADP-ribose) polymerase (PARP) inhibitors are given to patients with BRCA positive breast cancer patients, cancer cells that already have trouble repairing DNA damage become totally unable to repair DNA damage via alternative PARP mechanism, leading to cancer cell death.

mTOR: Alteration in mTOR signalling pathway in metastatic hormone positive breast cancers lead to uncontrolled cancer cells growth. This pathway can be blocked in combination with hormonal therapy for patients who have failed prior hormonal therapy.

3. Radiotherapy

Radiotherapy is treatment with high-energy rays to destroy cancer cells. Adjuvant radiotherapy to reduce risk of local recurrence is recommended for women with:

Breast-conserving surgery
Tumour >5cm (even post total mastectomy)
Spread to lymph nodes

Conclusion

Breast cancer is the most common cancer in Singaporean females. However, breast cancer screening helps detect the cancer at an earlier stage and saves lives. There have also been major advancements in breast cancer treatment with a better selection of tools, more targeted drugs for improved efficacy and reduced side effects, more modern surgical and radiotherapy techniques and better supportive care. Visit The Cancer Centre in Singapore for breast cancer screening and treatment options.

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