National Cancer Centre - Cancer Update

Breast cancer is the most common type of cancer affecting women. About 1000 new cases of breast cancer are diagnosed annually.

One out of 100 new cases of breast cancer occur among men. According to the Singapore Cancer Registry, 3,574 cases were diagnosed between 1993-97. Overall incidence of breast cancer in Singapore still lags behind the West. However, nearly half of the affected women here are below 50 years of age and the incidence rate in the 40 to 50 years of age cohort mirror that in the West.

Etiology & Risk Factors
The is no single underlying cause of breast cancer. Many factors have been linked to an increased risk of developing breast cancer including genetic, environmental, hormonal, and nutritional influences. Despite all of the available data on breast cancer risk factors, 75% of affected women do not have an identifiable risk factor. 5-10% of breast cancer cases are familial and some are linked to an abnormal gene.
(Read article on Genetics of breast cancer). Estrogens are believed to be associated with this disease. Well-known risk factors are:

Signs and Symptoms
Early stage breast cancers usually show no symptoms. Hence, the role of mammography in screening asymptomatic women cannot be overemphasised. The following symptoms can result from breast cancer or non-cancerous conditions, so their appearance should be further evaluated:

Screening and diagnosis
A woman with a symptom, e.g. a newly discovered lump in her breast needs an evaluation for diagnosis right away. She should not wait for the periodic routine screening mammogram. Women with no symptoms would benefit from screening. Currently, mammography is an established screening tool. Women above 50 years old will benefit from one to two yearly screening mammograms.

Women in their forties will benefit less from screening mammography due to several factors. This has led to the controversy on recommending routine screening for this age group. Women of all ages should have pertinent information on risks and benefits prior to screening. Like all tests, mammograms can be falsely negative or falsely positive.

In some clinical situations, ultrasonography gives more information. Women with a strong family of breast cancer mammography are advised to go for screening earlier. MRI and spectrometric protein patterns in blood are evolving screening tools.

*Breast self-exam is encouraged even though survival benefit has not been proven. Breast self-exam may detect interval cancers between screenings.

**Mammography before age 40 and referral for risk evaluation is recommended for women with:

Diagnosis
A diagnostic evaluation that includes a diagnostic mammogram, ultrasound, and sometimes a biopsy rather might be necessary in the following circumstances:

Definite diagnosis of breast cancer requires a biopsy. Biopsy using Trucut needle or by excision (sometimes under mammography or ultrasonic guidance) are all appropriate methods depending on availability and clinical circumstances. Fine needle aspiration has a role as well.

If breast cancer is diagnosed, further pathological tests are necessary to find out whether the cancer is hormone responsive. Usefulness of numerous other tests is not yet validated and their use should be limited to research studies.

Most breast cancer patients first undergo blood tests and X-rays to define the extent of their disease. To determine if the cancer has spread to other organs – such as liver, lungs or bones – blood tests, liver scans, chest X-rays or bone scans are done. However extensive staging tests are unnecessary for patients with no symptoms of advanced disease.

(Source: AJCC Cancer Staging Manual, 6 th edition (2002) published be Springer-Verlag New York, www.springer-ny.com)

Treatment
Management of breast cancer may include one or a combination of the following and is best done at a multidisciplinary centre and is achieved after careful staging and prognostication:

Localised breast cancer (early stage disease)
Treating localised breast cancer involves control of breast tumour, followed by additional (adjuvant) therapies to curb the spread to the rest of the body (which cannot be seen but the risk can be estimated). AJCC staging system for breast cancer was revised in 2002 (see above Table). Stage grouping is based on the tumour size and its local extent, T stage, and lymph node involvement, N stage. Determining N stage now incorporates the number, sites and extent of lymph nodes.

Currently, local treatment of breast cancer is either a mastectomy or a lumpectomy and axillary lymph node dissection. Role of sentinel lymph node biopsy to reduce need for axillary lymph node dissection is evolving. Patients with locally advanced cancer benefit from chemo or hormonal therapy prior to surgery. Such neo adjuvant treatment reduces tumour size and extent of surgery.

After lumpectomy radiation therapy is always required. Often, after mastectomy, radiation is needed, if the tumour was large, involved skin or many lymph nodes.

After surgery, some patients might have a relapse. Relapses recur from small tumours undetected by existing technology. However, the risk of relapse can be estimated using tumour (T) and lymph node (N) staging system and other prognostic factors determined at diagnosis. Tumour size and grade, number of axillary lymph nodes involved and hormone receptor expression (ER and PR) by cancer cells are commonly use. Others such as HER2/neu, p53, Ki-67, cathepsin D and gene expression by microarrays are being investigated.

Women who have a tumour with high risk of relapse are offered additional (adjuvant) chemotherapy or hormonal therapy or both to reduce the risk of relapse and to prolong lifespan. Chemotherapy is a combination of drugs given once every two to four weeks for four to eight cycles. Patients whose tumours express hormonal receptors benefit from hormonal drugs, which are given after completing chemotherapy. Chemotherapy or hormonal therapy is customised based on tumour-related factors and patients’ preferences.

Post-treatment follow-up
After the initial treatment, which can last several months for some patients, regular follow up is crucial. The goal is to detect a local or regional recurrence that can be cured. A simple physical examination is all that is necessary to detect recurrences. Self-examination is crucial too, since many recurrences are detected earlier by patients. History helps to detect symptoms of a distal recurrence, which that needs evaluated and treated to relieve symptoms. Annual follow-up mammogram is important as new breast cancers can develop.

Relapsed/Metastatic disease treatment
Patients with a relapse of the disease usually first undergo tests to define extent of their disease. Treatment is based on factors like hormonal responsiveness, bone or other organ involvement. Other factors such as age, general health, family support, ability to endure treatment, prior treatment and patient’s wishes are considered. Like the initial treatment that involves many specialists, in treating advanced disease, a team of specialists is involved too. Doctors from medical oncology, radiation oncology, palliative care oncology, surgical oncology, supporting staff of nurses, social workers, and physiotherapists work together to give the best care to the patient.

As metastatic breast cancer is not curable, judicious use of different modalities of treatment is important. Tumours that are hormonally responsive are initially treated with drugs that act on the hormonal receptors or decrease hormone synthesis by ovaries and other tissues. Ovarian function can also be blocked using radiation or by surgery. These hormonal treatments avoid the side effects of chemotherapy and in some patients can relieve symptoms; it can shrink or stabilise the disease for months to years.

In hormone refractory tumours, chemotherapy provides palliation, prevents complications and prolongs life span. Patients whose tumours express HER2 can derive significant benefit from Herceptin, a monoclonal antibody. (Read our story on The truth about Herceptin)

For patients whose bones with metastatic cancer, a new class of drugs, bisphosphonates can reduce rates of fractures and other complications. Other useful modalities such as radiation and surgery help to manage the disease.