Editor—I agree with Fentiman that all cases of prophylactic mastectomy should be centrally registered, but his proposals should go further to maximise the potential information from this group of women.1 The proposals should include compulsory testing of all women undergoing the operation for known mutations of the BRCA1 and BRCA2 genes; a central archive should be established for storing part of the mastectomy specimen, and a chemopreventive trial should be considered.
The first measure is crucial to allow research into the correlation between the BRCA1 or BRCA2 gene concerned, the nature of the mutation, and its position along the gene with the risk of breast cancer after mastectomy. This is important given that currently there are over 200 mutations for BRCA1,2 that different BRCA1 and BRCA2 mutations are associated with different risk of cancer,3 and that the penetrance of BRCA1 and BRCA2 genes may vary.4 This information may allow surgeons in the future to give an indication of the risk of breast cancer after mastectomy based on BRCA status and allow risk stratification.
Hartmann et al recently showed in a retrospective study that prophylactic mastectomy reduced the incidence of breast cancer in women at high risk on the basis of their family history. However, they did not test the women for mutations of the BRCA1 or BRAC2 gene and so were unable to assess the benefit of mastectomy for this risk factor.
A tissue bank would allow the prevalence of any new BRCA mutation to be investigated, and this could subsequently be linked to the risk of breast cancer after mastectomy. The library would also be useful for any future research into new genes that may have a role in the pathogenesis of familial breast cancer.
In the light of ongoing chemopreventive trials, consideration should also be given to establishing an international trial comparing mastectomy alone, mastectomy and chemoprevention with tamoxifen, and tamoxifen alone, given that some women may wish to avoid mastectomy. Hopefully, this trial would show the optimum preventive strategy. Furthermore, if the nature of the BRCA mutation was known the trial might allow the various prophylactic measures to be tailored on the basis of the mutation.
As with tamoxifen, the role of mastectomy in the prevention of breast cancer needs to be evaluated: all women may not benefit equally, and some may be spared the need for surgery and its inherent risks.
References
- 1.Fentiman IS. Prophylactic mastectomy: deliverance or delusion? BMJ. 1998;317:1402–1403. doi: 10.1136/bmj.317.7170.1402. . (21 November.) [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ardern-Jones A, Eeles R. Predictive gene testing for breast cancer. Trends Urol,Gynaecol Sexual Health 1997;Jan/Feb:19.
- 3.Gayther SA, Mangion J, Russell P, Seal S, Barfoot R, Ponder BA, et al. Variation of risks of breast cancer and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nature Genetics. 1997;15:103–105. doi: 10.1038/ng0197-103. [DOI] [PubMed] [Google Scholar]
- 4.Thorlacius S, Struewing JP, Hartge P, Olasdottir GH, Sigvaldason H, Tryggvadottir L, et al. Population-based study of breast cancer in carriers of BRCA2 mutation. Lancet. 1998;352:1337–1339. doi: 10.1016/s0140-6736(98)03300-5. [DOI] [PubMed] [Google Scholar]
- 5.Hartmann LC, Schaid DJ, Woods JE, Crotty TP, Myers JL, et al. Effficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med. 1999;340:77–84. doi: 10.1056/NEJM199901143400201. [DOI] [PubMed] [Google Scholar]