Correspondence

Prophylactic Mastectomy in Women with a High Risk of Breast Cancer

N Engl J Med 1999; 340:1837-1839June 10, 1999

Article

To the Editor:

When Hartmann and colleagues (Jan. 14 issue)1 analyzed the outcomes of prophylactic mastectomies, they expressed the results as a relative risk reduction. They reported that prophylactic mastectomy reduces the incidence of breast cancer by about 90 percent among both moderate-risk and high-risk women. The relative risk reduction allows the reader to judge the magnitude of the association, but it does not express the clinical implications of the findings as clearly as the number of patients who would need to be treated to prevent a bad outcome (referred to as the number needed to treat).2 This distinction can make a difference in care, because it has been shown that results expressed as the relative risk reduction and those expressed as the number needed to treat have different influences on decisions about treatment.3,4

The number needed to treat makes clear the proportion of people who would be treated unnecessarily (Table 1Table 1Relative Risk Reduction and Number Needed to Treat for the Outcomes of Breast Cancer and Death in High-Risk and Moderate-Risk Women Who Underwent Prophylactic Mastectomy.) and highlights the differences between the moderate-risk and high-risk groups. Thus, it would be necessary to treat 6 women at high risk to prevent one case of breast cancer, but it would be necessary to treat 13 women at moderate risk to prevent one case. To prevent one death from breast cancer, it would be necessary to treat more women at moderate risk (42) than women at high risk (25).

Robert M. Hamm, Ph.D.
Frank Lawler, M.D.
Dewey Scheid, M.D.
University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104

4 References

1
Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999;340:77-84
Full Text | Web of Science | Medline

2
Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ 1995;310:452-454[Erratum, BMJ 1995;310:1056.]
CrossRef | Web of Science | Medline

3
Bucher HC, Weinbacher M, Gyr K. Influence of method of reporting study results on decision of physicians to prescribe drugs to lower cholesterol concentration. BMJ 1994;309:761-764
CrossRef | Web of Science | Medline

4
Forrow L, Taylor WC, Arnold RM. Absolutely relative: how research results are summarized can affect treatment decisions. Am J Med 1992;92:121-124
CrossRef | Web of Science | Medline

To the Editor:

In their informative analysis, Hartmann et al. note a dramatic reduction in cases of breast cancer among women who underwent prophylactic mastectomy. Most of the women, however, did not benefit from prophylactic mastectomy in terms of mortality associated with breast cancer. Among the 214 high-risk women, the estimated number of deaths from breast cancer that were averted ranged from 28.6 to 8.5. The higher estimate means that prophylactic mastectomy prevented one death from breast cancer for every 7.5 women who underwent the procedure and made no difference in terms of mortality associated with breast cancer for 87 percent of these women. The lower estimate means that prophylactic mastectomy prevented one death from breast cancer for every 25 women and made no difference in mortality for 96 percent. Similarly, among the 425 moderate-risk women, 10.4 deaths from breast cancer were averted; one death from breast cancer was prevented for every 41 women, but for 98 percent of these women, there was no benefit in terms of reduced mortality.

Providing data in relative terms (e.g., a 90 percent reduction in deaths from breast cancer) and in absolute terms (e.g., 1 in 25 women benefit) will help women who are contemplating prophylactic mastectomy make more informed decisions. Despite the marked reduction in the risk of breast cancer, we need to make it clear that prophylactic mastectomy would not save the vast majority of women from death due to breast cancer, because most women would not die of breast cancer even if they kept their breasts, and a few would die of breast cancer even if they had their breasts removed.

Virginia L. Ernster, Ph.D.
University of California, San Francisco, San Francisco, CA 94143

To the Editor:

The landmark report by Hartmann and colleagues provides sound evidence that bilateral prophylactic mastectomy can reduce the risk of breast cancer in women with a strong family history of the disease. For many women who consider undergoing this procedure, financial factors are a pivotal issue. We evaluated insurance coverage for prophylactic mastectomy in a university-based breast-care center in northern California.

We contacted the insurance carriers for our most recent 100 patients to determine the current policy on coverage for prophylactic bilateral mastectomy, with or without reconstruction, if the patient had one or more first-degree relatives with breast cancer or a known mutation in the BRCA gene (Table 1Table 1Insurance Coverage for Bilateral Prophylactic Mastectomy, with or without Reconstruction, among 100 Patients.). Our data show that the insurance carriers for more than half our patients may not cover bilateral prophylactic mastectomy. The lack of a universal policy for insurance coverage has made health care decisions like this one subject to arbitrary criteria.1

Recent federal legislation2 requires insurance companies to cover the cost of breast reconstruction for any woman who undergoes mastectomy, but it does not include a requirement to cover the cost of prophylactic mastectomy. As genetic testing becomes widespread, our health care system has a responsibility to provide all appropriate candidates with access to prophylactic mastectomy.

Henry Mark Kuerer, M.D., Ph.D.
E. Shelley Hwang, M.D.
Laura J. Esserman, M.D., M.B.A.
University of California, San Francisco, San Francisco, CA 94143

2 References

1
Rosenbaum S, Frankford DM, Moore B, Borzi P. Who should determine when health care is medically necessary? N Engl J Med 1999;340:229-232
Full Text | Web of Science | Medline

2
House of Representatives, 105th Congress. Omnibus appropriations bill for fiscal year 1999. Title IX — women's health and cancer rights. Conference report to accompany H.R. 4328, 452-54, 1998.

To the Editor:

Hartmann et al. report a 90 percent reduction in the risk of breast cancer among 639 women with a family history of breast cancer who underwent bilateral prophylactic mastectomy at the Mayo Clinic. In another study, women with breast hypertrophy who had undergone breast-reduction surgery were reported to have a 39 to 50 percent reduction in the risk of breast cancer; however, the protective effect was apparent only among women over the age of 40 years at the time of surgery.1,2 It would be interesting to know whether the protective effect noted by Hartmann et al. for the overall group of women in their study was found among those who were 40 years old or younger when the surgery was performed.

John D. Boice, Jr., Sc.D.
International Epidemiology Institute, Rockville, MD 20853

Jørgen H. Olsen, M.D.
Danish Cancer Society, Copenhagen, Denmark

2 References

1
Boice JD Jr, Friis S, McLaughlin JK, et al. Cancer following breast reduction surgery in Denmark. Cancer Causes Control 1997;8:253-258
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2
Baasch M, Nielsen SF, Engholm G, Lund K. Breast cancer incidence subsequent to surgical reduction of the female breast. Br J Cancer 1996;73:961-963
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Author/Editor Response

The authors reply:

To the Editor: Hamm et al. and Ernster raise two key questions. First, what is the appropriate end point in studies of cancer prevention: incidence, mortality, or both? Second, what is the best way to express an effect on these end points?

For trials of cancer treatment, mortality is an essential end point. For prevention studies, we believe incidence is a valid end point. For this disease, a significant reduction in incidence should subsequently translate into a reduction in mortality.

Measurements of relative risk are currently the standard for reporting the results of trials of screening, treatment, and prevention. The number needed to treat has some advantages but important limitations as well.1 This number is not static but changes with the duration of follow-up, if the intervention has a durable effect. Table 1Table 1Number Needed to Treat According to Years of Follow-up. shows the number needed to treat in our high-risk group at 5 years, 10 years, and 14 years (the current duration of follow-up).

The median age of the women in our cohort at the time of prophylactic surgery was 42 years. With 14 years of follow-up, their median age is now 56 years. If the protective effect of the procedure is durable, the number needed to treat will continue to decline as the women's remaining life expectancy declines. Expressing the results as the number needed to treat — 6 to prevent one case of breast cancer or 25 to prevent one death from breast cancer — conveys an effect over a period of 14 years, not an entire lifetime.

In our retrospective study, we included all women with any family history of breast cancer who had undergone bilateral prophylactic mastectomy between 1960 and 1993. Many of the women in our moderate-risk group would not now be considered to have a markedly elevated risk of breast cancer. Today, as we emphasized in our article, prophylactic mastectomy would generally be considered only for women with a family history that put them at high risk for breast cancer — namely, a history suggestive of an autosomal dominant predisposition to the disease.

With regard to Boice and Olsen's question about the degree of protection in the younger women, all seven of the breast cancers that occurred after prophylactic mastectomy were in women who were over the age of 40 years at the time of surgery.

We appreciate the comments of Kuerer et al. about inconsistencies in insurance coverage for prophylactic mastectomy. We have only anecdotal information to add to the data they have provided. It has been our experience that coverage for this procedure is by no means ensured and consistent.

Lynn C. Hartmann, M.D.
Daniel J. Schaid, Ph.D.
Thomas A. Sellers, Ph.D.
Mayo Clinic, Rochester, MN 55905

1 References

1
Rajkumar SV, Sampathkumar P, Gustafson AB. Number needed to treat is a simple measure of treatment efficacy for clinicians. J Gen Intern Med 1996;11:357-359
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Citing Articles (5)

Citing Articles

1
I. Bedrosian, C.-Y. Hu, G. J. Chang. (2010) Population-Based Study of Contralateral Prophylactic Mastectomy and Survival Outcomes of Breast Cancer Patients. JNCI Journal of the National Cancer Institute 102:6, 401-409
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2
Luis Landin. (2005) EVIDENCE-BASED APPROACH TO PROPHYLACTIC MASTECTOMY. Plastic and Reconstructive Surgery 116:4, 1173
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3
Scott L. Spear, Mary Ella Carter, Karl Schwarz. (2005) Prophylactic Mastectomy: Indications, Options, and Reconstructive Alternatives. Plastic and Reconstructive Surgery 115:3, 891-909
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4
Katja Goldflam, Kelly K. Hunt, Jeffrey E. Gershenwald, S. Eva Singletary, Nadeem Mirza, Henry M. Kuerer, Gildy V. Babiera, Frederick C. Ames, Merrick I. Ross, Barry W. Feig, Aysegul A. Sahin, Banu Arun, Funda Meric-Bernstam. (2004) Contralateral prophylactic mastectomy. Cancer 101:9, 1977-1986
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5
Liz Lostumbo, Nora E Carbine, Judi Wallace, Jeanette Ezzo, Kay Dickersin, Liz Lostumbo. 2004. Prophylactic mastectomy for the prevention of breast cancer. .
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