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NEJM
In a 1976 lecture to the Society of Surgical Oncology, the late Jerome Urban lamented the loss of a rational approach to the treatment of breast cancer, which he thought had been replaced "by an emotional appeal to the patient's vanity. A great cry has been raised in the public media to save the breast, despite the long-term consequences."1 In this issue of the Journal, Fisher and colleagues2 and Veronesi and colleagues3 describe the long-term outcomes of two pivotal randomized trials comparing breast-conserving surgery and mastectomy. These studies document how far our understanding of breast cancer has evolved since Urban's lecture. Breast cancer has a long natural history, and conclusions drawn from short-term follow-up studies may give an inaccurate picture of the ultimate outcome. The failure to observe a survival advantage of mastectomy after 20 years should convince even the most determined skeptics that mastectomy is not superior to breast conservation for the treatment of breast cancer. In addition to the belief that a more extensive operation for cancer must be a better operation for cancer, the potential for local failure in the preserved breast has been a cause for concern. These two reports provide reassurance that at 20 years the incidence of recurrence in the ipsilateral breast is low: 8.8 percent in the study by Veronesi et al.3 and 14.3 percent in the trial by Fisher et al.2 In both studies, the incidence of recurrences in the node-positive women who received adjuvant chemotherapy was approximately half the incidence in their node-negative counterparts who did not receive systemic therapy. Today, the widespread use of adjuvant systemic therapy for both node-negative and node-positive breast cancer, coupled with improvements in the mammographic and pathological evaluation of patients undergoing breast-conserving surgery, has resulted in a decreased incidence of local failure, and 10-year actuarial rates of recurrence that are less than 5 percent4,5 are not uncommon. Despite these low rates of local failure in women who were selected for breast-conserving surgery on the basis of physical examination and mammography, it has been suggested that both ultrasonographic studies of the whole breast6 and magnetic resonance imaging7 should be part of the preoperative evaluation. These recommendations are based on the identification of unsuspected foci of carcinoma in 16 percent to 37 percent of women6,7 who undergo these studies. The possibility that small foci of carcinoma can be present in apparently normal breast tissue has been recognized since the 1970s. Pathological studies of breast-tissue specimens from women with localized tumors have shown occult carcinoma in similar proportions of women.8 In fact, these pathological studies formed the cornerstone of the argument that breast-conserving therapy was inappropriate. The B-06 trial conducted by Fisher et al.2 demonstrates that these foci of tumor are clinically significant. Among patients treated with lumpectomy alone, the incidence of a recurrence in the ipsilateral breast was 39.2 percent, whereas it was 14.3 percent when the treatment was lumpectomy plus irradiation of the breast. Subjecting women to mastectomy because we now have an imaging technique that is sensitive enough to detect microscopical foci of tumor is not a step forward. Instead, we may be able to use such techniques to identify women who require radiation therapy only in the quadrant in which the primary tumor is located or those who do not require radiation therapy at all. The risk of local failure in the preserved breast will never be entirely eliminated. Some local failures reflect biologically aggressive disease and are similar to recurrences in the chest wall that occur after mastectomy. Local failures that occur many years after the initial diagnosis are often new primary tumors, indicating that irradiation of the whole breast does not provide long-term protection against cancer. This phenomenon is apparent in the study by Veronesi et al.3: the rate of new ipsilateral tumors at a distance from the site of the original primary tumor was similar to the rate of new contralateral tumors (0.42 and 0.66 per 100 woman-years of observation, respectively). Twenty years of experience have shown us that local recurrences due to inappropriate selection of patients or inadequate therapy can be largely eliminated with the use of high-quality diagnostic mammography, excision with negative margins, and postoperative irradiation. The focus on local recurrence has distracted us from a more serious problem with breast-conserving therapy. Despite a large body of mature scientific data from randomized trials, which is unequaled in the literature on the local treatment of cancer, many women today are not offered the option of breast-conserving therapy. My colleagues and I9 found that in a national sample of 16,643 women with stage I or II breast cancer who were treated in 1994, only 42.6 percent were treated with a breast-conserving approach. There was a significant correlation between treatment with mastectomy and factors associated with a poor prognosis, such as the size of the tumor, nodal status, and histologic grade. The preferential use of mastectomy for women who have a poor prognosis strongly suggests that 20 years later breast-conserving therapy is still not accepted as equivalent to mastectomy, but is instead viewed as a less aggressive therapy appropriate only for women with a good prognosis. What proportion of women with breast cancer should receive breast-conserving therapy? The answer depends on the particular population of women, but a reasonable goal is that every woman should be informed of the availability of breast-conserving therapy and of the suitability of the procedure in her particular case. In a study of 231 women with breast cancer who were seen for a second opinion between 1996 and 1999, Clauson et al.10 reported that 29 percent of the women had been offered only the option of a mastectomy during the initial consultation. The women in this study were from a metropolitan area, 70 percent had more than a high-school education, 62 percent reported an annual family income of more than $30,000, and more than 90 percent had health insurance. If a substantial proportion of educated and insured women do not receive complete information about options for treatment, the problem may be even more serious in disadvantaged populations. Efforts to expand eligibility for breast-conserving therapy and to reduce the associated morbidity are well under way. Preoperative chemotherapy and endocrine therapy have been shown to be safe and effective ways to shrink tumors that are too large for a lumpectomy with a good cosmetic result. Accelerated fractionation schedules and brachytherapy are being studied as alternatives to six weeks of external-beam irradiation. However, if we do not apply what we have learned from the pioneering work of Fisher and Veronesi and their colleagues to the treatment of the women with breast cancer we see today, we will have made little or no progress over the past 20 years in the search for a rational approach to the local treatment of breast cancer. It is time to declare the case against breast-conserving therapy closed and focus our efforts on new strategies for the prevention and cure of breast cancer.
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