ELSEVIER

l Editorial

Int. J. Radiation Oncology Biol. Phys., Vol. 34, No. 5, 1173- 1174, 1996 pp. Copyright 0 1996 Elsevier Science Inc.

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IMPROVING LOCAL CONTROL IN BREAST CONSERVING THERAPY: TO CLIP OR NOT TO CLIP?

MONICA MORROW, M.D.

Lynn Sage Comprehensive Breast Program, Northwestern University Medical School, Chicago, IL 60611

Local control in the breast after lumpectomy and radio- therapy is dependent on a number of factors. In this issue of the International Journal of Radiation Oncology Biol- ogy Physics, Fein et al. (2) test the hypothesis that a precise definition of the tumor bed with surgical clips will improve local control by allowing an accurate delineation of the boost volume. Somewhat surprisingly, this was not found to be the case, and in fact, a significantly higher rate of breast failure was observed in the patients with clips. Because it is unlikely that surgical clips are carcino- genic, other explanations for this finding must be sought.

Local recurrence may be secondary to extensive resid- ual disease in the breast, which cannot be controlled with radiotherapy, or may be a manifestation of biologically aggressive breast carcinoma (5 ) . The second type of re- currence will not be impacted upon by the extent of the surgical resection, the dose of irradiation, or the precision with which the boost is delivered. It would be of interest to know whether any of the 52 recurrences reported by Fein et al. (2) occurred in the setting of concurrent nodal or distant failure, and whether survival differed between the patients with and without clips. Although no signifi- cant differences in tumor size, nodal status, or receptor status were present between patients with and without clips, significantly fewer patients with clips received adju- vant systemic therapy. In addition to reducing the risk of distant recurrence, the use of both chemotherapy and tamoxifen has been shown to reduce the incidence of breast recurrence after excision and irradiation. In the National Surgical Adjuvant Breast Project (NSABP) pro- tocol B06, node positive patients received chemotherapy and node negative patients did not. After 8 years of fol- low-up, local failure rates were 6% in the node positive patients and 12% in the node negative patients (3). Simi- lar findings were observed in NSABP protocol B 13 where node negative, receptor negative patients were random- ized to receive chemotherapy or no treatment, as well as in NSABP protocol B 14 in which node negative, receptor

positive patients were randomized to receive tamoxifen or placebo (3). In both of these studies, local failure rates in patients receiving systemic therapy were approximately half those of patients not receiving such therapy. The failure to receive adjuvant therapy was identified by Fein et al. (2) as a factor that significantly influenced breast recurrence and might account for some of the differences observed between patients with and without clips.

The other significant predictor of breast recurrence in this study was a particular surgeon. At first glance, this information does not seem to be too useful for those who do not interact with this individual. However, the surgeon in question failed to ink specimen margins in one half of the cases, and the high breast recurrence rates observed in these patients serve to emphasize the importance of accurate margin assessment in determining the extent of surgery necessary for local control. Microscopic residual carcinoma is present in between 30% and 48% of patients with clinically localized carcinoma who undergo tumor excision with negative margins ( 1, 10, 12). In patients with positive or unknown margins, residual tumor is pres- ent in 42% to 69% of cases (4, 7, lo), and macroscopic residual disease is more likely than in cases with negative margins. The likelihood of residual carcinoma does not differ between cases with positive and unknown margins, and in 90% of cases is located within 4 cm of the index tumor (6). A gross determination of margin status by the surgeon or the pathologist is inadequate to identify microscopic residual disease, and cases in which margins have not been inked should be re-excised. The routine inking of breast biopsy specimens will avoid the need for re-excision in many cases. We have demonstrated that the routine use of magnification mammography to define the extent of the primary tumor coupled with an attempt to remove a gross margin of 0.5- 1 .O cm of normal breast tissue around the tumor at the time of diagnostic biopsy results in negative margins in 95% of cases without compromising cosmesis in patients with benign disease (7, 8).

Accepted for publication 16 January 1996.

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The excess of local failures in the patients with clips in this study may be due to the large number of cases with unknown margins and the potential for a heavy tu- mor burden unlikely to be controlled by irradiation. Schmidt-Ullrich et al. (9) and Solin et al. ( 11) have reported no differences in the incidence of breast failure for patients with positive, close, or negative margins when the radiation dose was adjusted on the basis of the margin status. The series of Solin et al. ( 11) is of particular interest because it includes 346 patients with unknown margins subject to the same uncertainties regarding the extent of residual tumor burden as the patients in the report of Fein et al. (2)) yet no increase in local failure was noted. These discrepant results may be due to differ- ences in the amount of tissue resected, the total radiation dose. or the boost volume between studies. However, the current study strongly suggests that the use of clips to

Volume 34. Number 5. 1996

mark the biopsy site will not compensate for an inade- quate surgical resection when standard radiation doses are utilized.

In the end. is there any role for placing clips in the tumor bed? Fein et al. ( 2 ) fail to demonstrate a benefit for the technique, even after excluding the patients of the surgeon with the unusually high local failure rate from analysis. However, given the lack of consensus about whether a boost significantly decreases the rate of local recurrence, it is not surprising that a study that looks at a refinement to improve the delivery of the boost fails to show a benefit. In the absence of the very large, very expensive randomized trial. which would be needed to answer this fairly small question, placing clips to ensure that the boost dose actually covers the tumor bed seems to be a reasonable thing to do.

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