CLINICAL OPTIONS FOR WOMEN AT HIGH RISK FOR BREAST CANCER

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• 作者：Lynn C. Hartmann ; MD^a ; Thomas A. Sellers ; PhD^a ; Daniel J. Schaid ; PhD^a ; Susan Nayfield ; MD ; MSc^b ; Clive S. Grant ; MD^a ; Julie A. Bjoraker ; MD^a ; John Woods ; MD^a ; Fergus Couch ; PhD^a
• 刊名：Surgical Clinics
• 出版年：1999
• 出版时间：1 October 1999
• 年：1999
• 卷：79
• 期：5
• 页码：1189-1206
• 全文大小：998 K

文摘

For women at high genetic risk of breast cancer, three management options are generally considered: cancer surveillance, prophylactic surgery (mastectomy or oophorectomy), and chemoprevention. This article examines the available data for all three options with particular attention to a study of prophylactic mastectomy performed at the Mayo Clinic.

A woman is considered to be at high genetic risk if her family history suggests an autosomal dominant predisposition to breast cancer. Features of such a family history include multiple relatives with breast cancer, early age at diagnosis and, in some families, ovarian cancer. At present, inherited mutations in several genes are known to manifest in hereditary patterns of breast cancer: BRCA1, BRCA2, p53 (Li-Fraumeni syndrome), PTEN (Cowden syndrome), and hMLH1 and hMSH2 (Muir Torre syndrome). Mutations in these genes may account for 40 % to 50 % of hereditary breast cancer in this country. Clearly other susceptibility genes exist. Mutation-specific recommendations cannot be made based on the available scientific literature. In this review, women with high genetic risk include women with mutations in one of the known susceptibility genes, women from families that are known to possess such a mutation although the woman has not undergone testing herself, and women from families with a hereditary pattern of breast cancer where testing was not performed or was inconclusive.

An example of a woman at high risk can best illustrate the clinical challenges. In the pedigree in , individual 3:7 is 30 years old and has not had cancer. There are numerous cases of breast and ovarian cancer in this family. In fact, approximately one half the women in the family have developed either breast or ovarian cancer. This pattern of inheritance is autosomal dominant, in that the cancers appear in every generation, and there is maternal (2:5 ?3:6) and paternal (2:1 ?3:1) transmission. In this family, the average age of diagnosis of breast cancer is 35. Patient 3:7 has very nodular breasts on examination and dense breast tissue on mammography. She has opted to pursue genetic testing and is found to be a carrier of the BRCA1 mutation present in this family. Her options for management include cancer surveillance, chemoprevention, and prophylactic surgery. What data support these options?