Editorials

Prophylactic mastectomy: deliverance or delusion?

We don't know, so we need to start registering all cases now 

To prophesy the future we no longer need to examine the entrails of sacrificial animals. Mutant genes predisposing affected individuals to life threatening conditions such as vascular disease and malignancy have been identified. Although the multifactorial and environmental wild cards remain, the genetic card deck is gradually being laid face up on the table. But without effective interventions, knowledge of genetic risk may serve only to fuel anxiety and encourage the adoption of denial behaviour.

Germ line genetic mutations are responsible for only 5-10% of cases of breast cancer, but worried individuals form a disproportionately large part of the clinical workload. Almost half the cases of familial breast cancer and 75% of those with both ovarian and mammary malignancy are due to BRCA1 mutations, located on chromosome 17q21.¹ The 185delAG mutation is present in 1% of Ashkenazi Jewish women and in 21% of those developing breast cancer before the age of 40.² The other major breast cancer susceptibility gene is BRCA2, located on chromosome 13q12-q13, encoding a 3418 aminoacid protein of, at present, unknown function.³ The lifetime risk of cancer in women carrying a BRCA1 pathogenic mutation, previously estimated at 90%, ^{4 5} has been revised down to 56%.⁶

Breast surgeons will nevertheless be faced with an increasing number of well informed young women with pathological mutations. These consultations are as difficult for the doctor as for the patient since no proved preventive approaches exist. Though options such as tamoxifen will probably reduce the incidence, none will obliterate the risk.⁷ Intensive surveillance is an option but without proof of benefit.

Many women will want to resort to the more desperate measure of bilateral prophylactic mastectomy, believing that this will save their lives.⁸ For some this may prove to be a vain hope. Prophylactic mastectomy was performed on a large number of women in the United States for a range of ill defined indications. The Subcutaneous Mastectomy Data Evaluation Center collected information from 1500 treated women with varying indications for surgery and reported that 6% had unsuspected ductal carcinoma in situ or invasive disease.⁹ Hartmann et al carried out a retrospective cohort analysis of 950 women who underwent prophylactic mastectomy at the Mayo Clinic in 1980-93.¹⁰ The Gail model predicted 76 cancers during the mean 17 years of follow up whereas the actual number was 7. The original "high risk group" was not well characterised so that the risk of breast cancer may have been overestimated. In the absence of any evidence of benefit, it is now assumed that this same operation will be the answer to the genetically endangered maiden's prayer.

In the Sprague-Dawley rat/DMBA model system removal of ostensibly 100% of the mammary tissue had no effect on subsequent development of neoplasms.¹¹ Breast cancers evolved in all animals, possibly because of the difficulty in removing all subcutaneous mammary tissue. While it could be argued that the diffuse nature of rat breasts makes this a poor model, such problems may also occur in humans with sanctuaries from surgery located in the inferior aspect and the axillary tail.

Unless action is taken, another 10 years will see us in the same state of ignorance. While a randomised trial could compare subcutaneous and total mastectomy, in reality the current prejudices of both patients and doctors would probably inhibit accrual. Only a legally binding system of registering all women who have undergone any kind of prophylactic mastectomy could help determine the relative efficacy of the procedure in high risk individuals. At present no mechanism exists since these individuals do not have cancer and therefore are not reported to cancer registries and only some will have undergone counselling and testing in specialist cancer genetics units.¹² Moreover, the present patchy nature of the links between NHS clinical genetics and breast surgery units, with inequalities of service provision and waiting lists, means that many women are driven into the private sector.

Breast and plastic surgeons may not be depended on to report their cases as, even under optimal circumstances, they are likely to misremember. Pathologists, who have shown their ability to report cancer cases to registries accurately, constitute a more reliable source. Were all cases of prophylactic mastectomy to be reported to a central registry linked to cancer registries, individuals subsequently diagnosed with breast cancer could be identified. The price of inactivity will be high. Prophylactic mastectomy will be otherwise a lottery like procedure in which there will be no winners.

Ian S Fentiman, Professor of surgical oncology. 

Guy's Hospital, London SE1 9RT

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2. Fitzgerald MG, MacDonald DJ, Krainer M, Hoover E, O'Neil E, Unsal H, et al. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early onset breast cancer. N Engl J Med 1996; 334: 143-149[Abstract/Free Full Text].
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11. Wong JH, Jackson CF, Swanson JS, Palmquist MA, Oyama AA, Miller SG, et al. Analysis of the risk reduction of prophylactic partial mastectomy in Sprague-Dawley rats with 7,12-dimethylbenzanthracene-induced breast cancer. Surgery 1986; 99: 67-71[Medline].
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