National Cancer Centre - Cancer Update

	Contents
1.	The race against breast cancer

2.	What's new in breast cancer research? The truth about Herceptin

3.	Radiotherapy in breast cancer treatment Nuts and bolts of mammography

4.	PET-CT in oncology Role of prophylactic mastectomy in breast cancer

5.	Breast conservation and breast reconstruction Genetics of breast cancer

6.	Risk assessment and chemoprevention Hormone receptors in breast cancer - from bench to bedside

	NCC Tumour Board Files

	Onco Quiz

	NCC Roundup

	Pharmacy Tips

	Breast Cancer Overview

	Staff Directory

	Contact

Breast conservation and breast reconstruction

Younger patients often see mastectomy as a mutilating procedure and opt for either breast conservation or breast reconstruction

Breast Conservation
Breast conservation involves a complete local excision of the tumour (including an axillary dissection for invasive cancers) and post-operative breast irradiation to achieve improved appearance with survival rates comparable to mastectomy.

Breast irradiation is generally well tolerated and reduces local recurrence rate by more than half. The breast appearance after treatment depends on the tumour site and volume of tissue excised relative to breast size.

Contraindications
Contraindications for breast conservation are: multicentric tumours, positive tumour margins after surgery, diffuse suspicious microcalcifications in the breast and contraindications to radiotherapy such as pregnancy and previous breast irradiation. Age is not a contraindication for breast conservation.

Breast Reconstruction
Breast reconstruction aims to recreate the breast after mastectomy. It may be performed during mastectomy (immediate) or later (delayed). The advantages of immediate reconstruction are:
(a) it involves one operation and hospital stay,
(b) it minimises the patient's trauma of losing the breast,
(c) it gives a superior cosmetic appearance.

Breast reconstruction uses either an implant or autologous tissue. Implant reconstruction, though an easier procedure is linked to problems such as infection, implant extrusion, capsular contracture, lack of symmetry with the other breast and a life span of 10-15 years. The problems will get worse with post-operative radiotherapy. Implant reconstruction is done when autologous tissue is not available.

Autologous reconstruction is done using a transverse rectus abdominis myocutaneous (TRAM) or latissimus dorsi (LD) flap. These flaps enable reconstructed breasts to look and feel natural, but leave a scar and weakness at the donor site.

Breast reconstruction has not been found to significantly delay adjuvant treatment, increase the risk of breast cancer recurrence or delay detection of local recurrence. A patient will need to discuss her suitability for breast conservation or breast reconstruction as well as the advantages and complications of each procedure with her surgeon before making an informed decision.

Dr Karen Yap
Associate Consultant
Surgical Oncology

Dr Ho Gay Hui
Consultant
Surgical Oncology

Read about psychosocial support and rehabilitation for breast cancer patients at http://www.nccs.com.sg/epub/cu/vol3_03/psy.sup.htm

Genetics of breast cancer

Identifying specific mutated genes helps to single out women at risk of developing cancers

Figure 1. Direct sequencing of exon 11 of the BRCA1 gene, showing the 2846insA frameshift mutation at codon 909, resulting in terminatino at codon 914.

Although most cancers are sporadic, hereditary breast carcinoma accounts for 5 to 10% of all breast cancers. BRCA1 and BRCA2 genes are two breast carcinoma susceptibility genes that account for most of these. Mutations in genes such as TP53, PTEN, LKB1 account for 1% of the rest. Mutations in BRCA1 and BRCA2 genes are transmitted in an autosomal dominant fashion. Women who carry a mutated BRCA1 gene have a 65% risk of developing breast cancer by age 70, while those who carry BRCA2-mutations have a 45% risk. This is in contrast to an estimated 5% lifetime risk in Singaporean women.

BRCA1 and BRCA2 genes are large genes found in chromosomes 17 and 13, respectively. BRCA1 consists of 22 coding exons, encoding 1863 amino acids and BRCA2 consists of 27 exons, encoding 3418 amino acids. Hundreds of different mutations are found in these genes, consequently all exons of both genes are screened for mutations. However, in families with known mutations, screening family members for the same mutation could help to identify people at high risk of developing breast and ovarian cancer.

What is the chance of finding such a mutation in an Asian family? A research protocol to assess the risks of breast and ovarian cancer among Asian women is being conducted at NCC. Computerised models are used to assess risk and genetic testing of BRCA1 and BRCA2 genes is done on a research basis.

Currently, using genetic and genomic strategies, NCC scientists are identifying more novel genes in breast cancer. For more information, contact Dr Ann Lee (email: dmslsg@nccs.com.sg) or Dr Peter Ang (email: dmoacs@nccs.com.sg).

Dr Ann Lee
Senior Scientist
Medical Sciences