Correspondence
Radiation Therapy for in Situ or Localized Breast Cancer
N Engl J Med 1993; 329:1577-1579November 18, 1993
- Article
To the Editor:
In the study by Fisher et al. (June 3 issue)1 of lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer, more than 20 institutions enrolled 818 women, and the diagnosis of breast cancer was made by institutional pathologists. There was apparently no central pathology review. The ability of pathologists to categorize in a reproducible way proliferative lesions of the breast and the distinction between intraductal breast cancer and ductal hyperplasia are matters of concern2. We believe that misclassification of patients has not been excluded as a possible explanation for the benefit reported in the group treated with radiotherapy.
2 ReferencesD. Verhoeven, M.D., Ph.D.
E. Van Marck, M.D., Ph.D.
A.T. van Oosterom, M.D., Ph.D.
University Hospital of Antwerp, 2650 Edegem, Antwerp, Belgium1
Fisher B ,Costantino J ,Redmond C , et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993;328:1581-1586
Full Text | Web of Science | Medline2
Schnitt SJ ,Connolly JL ,Tavassoli FA , et al. Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardized criteria. Am J Surg Pathol 1992;16:1133-1143
CrossRef | Web of Science | Medline
To the Editor:
The study by Fisher et al. demonstrates the efficacy of radiation therapy for intraductal breast cancer in a generic sense. The study does not, however, indicate which subgroups of ductal carcinoma require in situ radiation therapy. Neither the article nor the accompanying editorial1 considers a large body of evidence that women with small and non-comedo types of ductal carcinoma in situ may be treated acceptably by surgical excision alone.
The benefit of radiation therapy in reducing the number of local recurrences after excisional biopsy for intraductal breast cancer has been documented repeatedly. This benefit appears to decrease with a longer follow-up period. In studies with a follow-up period of more than 5 years, recurrences appear to double between 5 and 8 years and are even more frequent after 10 years.
In an analysis of the influence of the histologic grade on local recurrence, Solin et al.2 noted a recurrence rate of 20 percent for high-grade intraductal breast cancers, as compared with a rate of 5 percent for low-grade lesions, after 87 months of follow-up. These results are similar to those of one of our studies,3 in which the recurrence rates were projected to be 28 percent for similarly defined high-grade intraductal cancers and 6 percent for low-grade cancers after 120 months of follow-up.
Fisher et al. reported a postirradiation local-recurrence rate of 7 percent after a mean follow-up period of 43 months. This is not substantially different from the results of surgery alone after a comparable follow-up period3.
Radiation may have a role in the treatment of some types of intraductal breast cancer, but whether it does anything more than delay recurrences of incompletely removed lesions remains to be demonstrated.
3 ReferencesMichael D. Lagios, M.D.
California Pacific Medical Center, San Francisco, CA 94120David L. Page, M.D.
Vanderbilt Medical School, Nashville, TN 372321
Swain SM . In situ or localized breast cancer -- how much treatment is needed? N Engl J Med 1993;328:1633-1634
Full Text | Web of Science | Medline2
Solin LJ ,Yeh I-T ,Kurtz J , et al. Ductal carcinoma in situ (intraductal carcinoma) of the breast treated with breast-conserving surgery and definitive irradiation: correlation of pathologic parameters with outcome of treatment. Cancer 1993;71:2532-2542
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Lagios MD ,Margolin FR ,Westdahl PR ,Rose MR . Mammographically detected duct carcinoma in situ: frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence. Cancer 1989;63:618-624
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To the Editor:
The studies by Fisher et al. and Veronesi et al. (June 3 issue)1 provide important evidence of reduced local recurrence of in situ or localized breast cancer in patients who received radiation therapy after tumor excision. However, despite the statistical significance of the differences, the absolute benefit was relatively small. After lumpectomy for intraductal breast cancer, radiation reduced the annual incidence of recurrences of intraductal breast cancer in the ipsilateral breast from 2.6 percent to 1.5 percent and of invasive cancer from 2.6 percent to 1.6 percent. Similarly, in the Milan study, the incidence of local recurrences was 8.8 percent for the patients treated with quadrantectomy without radiotherapy, as compared with 0.3 percent for those treated with postsurgical radiotherapy.
Neither report stressed that it is too early to evaluate the overall effects on survival of adding radiotherapy. If survival proved to be identical, regardless of the use of radiotherapy, then these studies would show that approximately 75 percent of patients with intraductal breast cancer and 90 percent of those with invasive tumors under 2.5 cm in diameter could be spared irradiation without compromising the ultimate outcome. This approach would be contrary to the unequivocal recommendations for radiation therapy made by both study groups and by Dr. Swain in her editorial. A more cautious interpretation is that radiation therapy after total excision of intraductal breast cancer or small invasive carcinomas reduces the risk of a local recurrence but that a survival advantage has not yet been demonstrated.
1 ReferencesClive L. Sinoff, M.B., B.Ch., F.C.P.(SA), F.R.C.P.(C)
Northeastern Ontario Regional Cancer Centre, Sudbury, ON P3E 5J1, Canada1
Veronesi U ,Luini A ,Del Vecchio M , et al. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med 1993;328:1587-1591
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Author/Editor Response
The authors reply:
To the Editor: The comment by Verhoeven et al. that there was no central pathology review is incorrect. Reference to such a review appears in our paper on page 1585 and in a footnote to Table 2. The pathologist was unaware of both the treatment received and the outcome. Since, as we stated, “discordant diagnoses were few and were distributed between the two groups,” misclassification cannot explain our findings.
Lagios and Page's inference that our paper is faulty because it includes no information about the relation of comedo necrosis or other clinical characteristics to outcome is inappropriate. We do not share their conviction that “a large body of evidence” indicates that small and noncomedo intraductal cancers can be treated by excision without irradiation. There are no data from a randomized trial to substantiate their claim.
With respect to the characteristics of the study patients, the tumor sizes listed in Table 2 of our paper require clarification. Those that were under 0.1 cm should have been more accurately labeled “no palpable mass.” All other tumor sizes listed in the table (i.e., 0.1-1.0 cm, 1.1-2.0 cm, and >2.0 cm) represent the sizes of palpable tumors reported by the investigators.
Dr. Sinoff minimizes the benefit of radiation therapy by choosing to present only the average annual incidence of intraductal cancer. When expressed as the cumulative incidence through five years of follow-up, the reduction after radiation was not trivial. Overall, the cumulative incidence of second tumors was reduced from 20.8 to 10.4 percent, noninvasive tumors from 10.4 to 7.5 percent, and invasive tumors from 10.4 to 2.9 percent. These reductions indicate that mastectomy is inappropriate treatment for localized intraductal carcinoma. Survival was not a primary end point of our study. Even if a survival difference is never demonstrated, the improved local disease control gained by eliminating mastectomies and the need for second ipsilateral-breast operations justifies the use of irradiation.
The view that five years of follow-up is insufficient to make our findings acceptable is reminiscent of the same criticism after our earlier reports1,2 indicating no benefit from radical mastectomy over simple mastectomy and from modified radical mastectomy over lumpectomy with or without radiation -- findings that prevail after more than 15 and 10 years, respectively. Although we cannot predict the outcome beyond five years, we consider the five-year results to be firm and more appropriate for therapeutic decision-making than retrospective anecdotal information, which currently dictates the choice of therapy for localized intraductal carcinoma.
2 ReferencesBernard Fisher, M.D.
Carol K. Redmond, Sc.D.
University of Pittsburgh, Pittsburgh, PA 15261Edwin Fisher, M.D.
Shadyside Hospital, Pittsburgh, PA 152321
Fisher B ,Montague E ,Redmond C , et al. Comparison of radical mastectomy with alternative treatments for primary breast cancer: a first report of results from a prospective randomized clinical trial. Cancer 1977;39:Suppl:2827-2839
CrossRef | Web of Science | Medline2
Fisher B ,Bauer M ,Margolese R , et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med 1985;312:665-673
Full Text | Web of Science | Medline
Author/Editor Response
In reporting the results of our study, we stated that survival rates at four years were similar in patients treated with and without radiotherapy after quadrantectomy. It is therefore likely that radiotherapy immediately after surgery has no survival advantage over radiotherapy at the time of a local recurrence. However, we believe that any strategy linked with a high risk of local recurrence, which is a dramatic event for the patient, should be avoided. Moreover, a local recurrence often leads to a mastectomy, thereby frustrating the objective of breast conservation.
For these reasons, we recommend radiotherapy after partial surgery for small breast carcinomas, at least in women less than 55 years of age. However, the rates of local recurrence after quadrantectomy remain lower than 10 to 12 percent in certain subgroups, and if the recurrences are successfully treated with radiotherapy, then immediate postsurgical radiotherapy in these subgroups may be avoided. This hypothesis applies only to breast quadrantectomy, which is not a disfiguring operation as Dr. Swain incorrectly states in her editorial, but involves a wider resection and requires more skill and competence than lump excision. Lumpectomy, on the other hand, if not supplemented by radiotherapy, leads to local recurrences in some 50 percent of patients, making it appear to be a sort of debulking operation that cannot be justified without radiotherapy.
Umberto Veronesi
Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy- Citing Articles (2)
Citing Articles
1
Isabelle de Mascarel, Françoise Bonichon, Gäetan MacGrogan, Christine Tunon de Lara, Antoine Avril, Véronique Picot, Michel Durand, Louis Mauriac, Monique Trojani, Jean-Michel Coindre. (2000) Application of the Van Nuys prognostic index in a retrospective series of 367 ductal carcinomas in situ of the breast examinated by serial macroscopic sectioning: Practical considerations. Breast Cancer Research and Treatment 61:2, 151-159
CrossRef2
Silverstein, Melvin J., Lagios, Michael D., Groshen, Susan, Waisman, James R., Lewinsky, Bernard S., Martino, Silvana, Gamagami, Parvis, Colburn, William J., . (1999) The Influence of Margin Width on Local Control of Ductal Carcinoma in Situ of the Breast. New England Journal of Medicine 340:19, 1455-1461
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