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Examining the Evidence


Q Which preventive strategy is the “best buy” for women with BRCA1/2 mutations?

October 2006 · Vol. 18, No. 10

<huc>A</huc> In this Markov model, surgical options—bilateral salpingo-oophorectomy alone or with bilateral mastectomy—were more cost-effective than chemoprevention (tamoxifen for breast cancer or oral contraceptives for ovarian cancer) or surveillance. For BRCA mutation carriers 35 years of age, the 2 surgeries combined had an incremental cost-effectiveness ratio over oophorectomy alone of $2,352 per life-year for BRCA1 and $100 per life-year for BRCA2. After adjustment for quality of life, oophorectomy was the most cost-effective strategy for women with BRCA1 mutations, and had an incremental cost-effectiveness ratio of $2,281 per life-year for women with BRCA2 mutations.

Expert Commentary

The significance of hereditary predisposition to cancer is now widely understood. Although this predisposition is responsible for only 5% to 10% of the breast and ovarian cancers that occur each year, it offers the potential for prevention and early diagnosis. This study further validates the utility of risk-reducing surgery—not just from an individual patient’s point of view, but also from a public health and healthcare financing perspective.

Newer data shed light on age-specific incidence

This study benefited from fairly recent data on the age-specific incidence of breast and ovarian cancer in women with germline mutations.1 Thus, the 2 surgical options and chemoprevention could be more accurately compared with surveillance to determine the most economical and effective approach. Surveillance consisted of annual mammography; breast ultrasonography if necessary; clinical breast examination; and semiannual gynecologic examinations that included pelvic examination, ultrasonography, and CA-125 studies.

Strengths and weaknesses of the study

Anderson and colleagues are to be commended for a well-planned and well-executed study. All modeling studies are limited by their assumptions, as the authors observed, and it appears they went to great lengths to optimize their parameters.

I would take issue with only 2 points. First, the authors stated that “BRCA-positive women who develop cancer would have the same conditional probability of death as women with cancer in the general population.” Several groups have reported better survival among women with BRCA mutations who develop advanced ovarian cancer than among matched controls whose disease occurred on a sporadic basis.2,3

The authors also assumed that women at age 35 who were given estrogen therapy until age 50 after prophylactic oophorectomy had no heightened risk for breast cancer, other than the risk already conferred by BRCA1 or BRCA2 mutations. However, in a report cited by the authors, Rebbeck et al4 described a decrease in the risk of breast cancer among these women—a decrease that hormone therapy did not alter.

Younger women benefited most

Not surprisingly, cost-effectiveness varied with age, with younger women benefiting the most from the preventive strategies.

A dislike of prophylactic mastectomy

Because women are reluctant to undergo prophylactic mastectomy, even when a BRCA1 or BRCA2 mutation is present, the findings were adjusted for quality of life, which negated the greater cost-effectiveness of surgical strategies that included mastectomy.

Choice of preventive option should involve both patient and physician

Ultimately, a risk-reducing surgical strategy should be chosen by the patient after a thorough review with her physician of the options and their risks and benefits. However, as this report concludes, “Any primary prevention strategy would be cost-effective or cost-saving compared with surveillance.”

REFERENCES

1. King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302:643-646.

2. Rubin SC, Benjamin I, Behbakht K, et al. Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA. N Engl J Med. 1996;335:1413-1416.

3. Cass I, Baldwin RL, Varkey T, Moslehi R, Narod SA, Karlan BY. Improved survival in women with BRCA-associated ovarian carcinoma. Cancer. 2003;97:2187-2195.

4. Rebbeck TR, Levin AM, Eisen A, et al. Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst. 1999;91:1475-1479.

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