Correspondence
Breast-Conserving Surgery for Breast Cancer
N Engl J Med 2003; 348:657-660February 13, 2003
- Article
To the Editor:
As a primary care physician who performs breast-cancer screening as a large part of my preventive care practice, I was interested in the data on breast-conserving surgery for breast cancer reported by Veronesi et al. (Oct. 17 issue).1 Such 20-year survival data from randomized, prospective trials will be helpful when I counsel women who have recently received a diagnosis of breast cancer.
The authors' conclusion that breast-conserving surgery is the treatment of choice is not supported by their data. The observation that the 20-year survival rate among the women who underwent radical mastectomy was the same as that in the group of women treated with breast-conserving surgery plus irradiation is well supported. The data also support the observation that the rate of local recurrence was higher in the group treated with breast-conserving surgery plus irradiation. Given that the mortality rate was the same in both groups and that the rate of local recurrence was lower in the radical-mastectomy group, why is breast-conserving surgery plus irradiation the “treatment of choice”? Shouldn't these issues be discussed with the patient, who may reasonably choose a more aggressive therapy for the benefit of a lower risk of local recurrence? The conclusions stated by Fisher et al. on the basis of their study (also reported in the Oct. 17 issue)2 are supported by the data: “Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained.”
2 ReferencesDavid H. Sharkis, M.D.
Central Ohio Primary Care, Columbus, OH 432351
Veronesi U ,Cascinelli N ,Mariani L , et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227-1232
Full Text | Web of Science | Medline2
Fisher B ,Anderson S ,Bryant J , et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:1233-1241
Full Text | Web of Science | Medline
To the Editor:
According to the report by Fisher et al. on the 20-year follow-up data from the B-06 trial of the National Surgical Adjuvant Breast and Bowel Project, the addition of radiotherapy to lumpectomy resulted in a statistically significant proportional reduction of 18 percent in the number of deaths in women with recurrent or contralateral breast cancer (crude rate, 42 percent in the lumpectomy-alone group and 35 percent in the lumpectomy-plus-radiotherapy group) among the patients who were actually treated with lumpectomy (i.e., excluding patients randomly assigned to the two lumpectomy groups who underwent mastectomy because they had positive specimen margins). Although the crude rate of death was higher in the lumpectomy-alone group (53 percent) than in the lumpectomy-plus-irradiation group (50 percent), this difference was not significant.
However, in a previous report, the authors noted that there was a statistically significant difference in rates of distant-disease–free survival between the treatment groups among patients with uninvolved axillary nodes but not among patients with positive nodes.1 Such a difference was also found in a similar trial conducted in Ontario, Canada, which included only patients with negative axillary nodes.2 These findings support the hypothesis that improved initial local–regional tumor control may be most beneficial in patients with the lowest risk of subclinical systemic metastases (or the smallest systemic tumor burden) at the time of diagnosis.3,4 Therefore, it would be of great importance for the authors to give the same results shown in Figure 3 and the text of their article for the node-positive and node-negative groups separately.
4 ReferencesAbram Recht, M.D.
Harvard Medical School, Boston, MA 02115
arecht@caregroup.harvard. edu 1
Fisher B ,Anderson S ,Redmond CK ,Wolmark N ,Wickerham DL ,Cronin WM . Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1995;333:1456-1461
Full Text | Web of Science | Medline2
Clark RM ,Whelan T ,Levine M , et al. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. J Natl Cancer Inst 1996;88:1659-1664
CrossRef | Web of Science | Medline3
Hellman S . Karnofsky Memorial Lecture: natural history of small breast cancers. J Clin Oncol 1994;12:2229-2234
Web of Science | Medline4
Recht A . Local control and survival for patients with early-stage breast cancer. Breast J 1998;4:372-378
CrossRef
To the Editor:
In the study reported by Veronesi et al., the significantly higher local-recurrence rate in the group treated with quadrantectomy plus irradiation than in the group treated with radical mastectomy is disturbing, especially since the tumors were 2 cm or less in diameter. An increased incidence of local recurrences, in addition to the adverse effects of irradiation, may be a source of increased anxiety and may adversely affect the quality of life. Whether larger tumors will be associated with a higher local-recurrence rate if treated with quadrantectomy plus irradiation, leading to a lower survival rate, is open to speculation.
In the study reported by Fisher et al., tumors in the ipsilateral breast after lumpectomy (with or without irradiation) were not considered local recurrences. It is possible that the lumpectomy-plus-irradiation group had a higher local-recurrence rate than the mastectomy group, if new ipsilateral breast tumors are counted as recurrences. Also, although the overall survival rate was similar in all treatment groups, lumpectomy followed by irradiation was associated with a lower rate of death related to breast cancer than was lumpectomy alone.
These two studies and others1,2 raise some serious issues. Mastectomy may be superior to conservative surgery plus irradiation for local control. Conceptually, better local care may improve survival. Is lumpectomy without irradiation appropriate, since the survival rate for lumpectomy alone is similar to the rates for lumpectomy plus irradiation and for mastectomy? Differences in the quality of life need to be assessed for patients who undergo conservative surgery and those who undergo mastectomy. Finally, with the advent of reconstructive breast surgery, how important is breast-conserving surgery?
2 ReferencesGuru Sonpavde, M.D.
Maricopa County Medical Center, Phoenix, AZ 85008
gsonpavde@att.net 1
Overgaard N ,Hansen PS ,Overgaard J , et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med 1997;337:949-955
Full Text | Web of Science | Medline2
Ragaz J ,Jackson SM ,Le N , et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997;337:956-962
Full Text | Web of Science | Medline
Author/Editor Response
In the group of patients treated with breast-conserving surgery, we defined local recurrences as all new reappearances of malignant disease in the ipsilateral breast. However, we clarified that most of the reappearances occurred in quadrants other than the one in which the primary carcinoma originated and were therefore considered new primary ipsilateral carcinomas. The number of true local recurrences (i.e., those appearing in the area where the primary carcinoma originated) was similar to the number of local recurrences in the mastectomy group (10 in the breast-conserving group and 8 in the mastectomy group). Moreover, the number of ipsilateral new primary carcinomas (20) was lower than the number of carcinomas in the contralateral breast (29 in the breast-conserving group and 34 in the mastectomy group).
These results indicate that leaving both breasts (after breast conservation) instead of one (after mastectomy) exposes the woman to an additional risk of a new carcinoma in the conserved breast. This risk, however, is somewhat lower than the risk in the contralateral breast. This is a calculated risk common to all conservative surgical procedures. One might, of course, perform a mastectomy to eliminate this risk, but to be consistent, it should be a bilateral mastectomy. What may appear surprising is that in spite of the additional new cancers in the ipsilateral breast in the breast-conserving group, the survival rates were similar in the two groups. The likely reason is that in patients who underwent quadrantectomy, the follow-up was generally accurate, with great attention to the surgically treated breast, so that new carcinomas were discovered very early, with a very high rate of curability.
We believe that our study, as well as the study by Fisher et al., strongly supports the breast-conserving approach. We also agree that radiotherapy after breast-conserving surgery does not improve survival1; studies are in progress to identify subgroups of patients in whom radiotherapy might be avoided. However, the future advent of full-dose intraoperative radiotherapy after breast-conserving surgery2 will greatly reduce the current burden of radiotherapy for patients.
2 ReferencesUmberto Veronesi, M.D.
European Institute of Oncology, 20141 Milan, Italy
umberto.veronesi@ieo. it Luigi Mariani, M.D.
Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy1
Veronesi U ,Marubini E ,Mariani L , et al. Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol 2001;12:997-1003
CrossRef | Web of Science | Medline2
Veronesi U ,Orecchia R ,Luini A , et al. A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated. Eur J Cancer 2001;37:2178-2183
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Recht seeks information to support Hellman's “spectrum hypothesis” and his own contention that the use of radiotherapy after lumpectomy will improve distant-disease–free survival and overall survival in patients with breast cancer and negative axillary nodes (i.e., those with “the smallest systemic tumor burden”).1,2
In our initial report,3 we noted that irradiation after lumpectomy provided a small advantage in distant-disease–free survival among node-negative patients. However, throughout 20 years of follow-up (Figure 1Figure 1
Distant-Disease–free Survival (Panel A) and Overall Survival (Panel B) among Node-Negative Women with Breast Cancer Who Were Treated with Lumpectomy Alone (N=361) or Lumpectomy Followed by Irradiation (N=375).), we observed no statistically significant difference in distant-disease–free survival or overall survival between node-negative patients who were treated with lumpectomy alone and those who were treated with lumpectomy and irradiation. The rate of death related to breast cancer also did not differ significantly between the two groups (P=0.41). Recht points out that Clark et al. noted a reduction in distant failure associated with radiotherapy after lumpectomy but failed to demonstrate an improvement in survival.4 Recht fails to mention, however, that Clark et al. noted that a lead-time bias might have been responsible for the former finding, an observation that we suggested as influencing our initial finding.5 Dr. Sonpavde fails to appreciate that in the initial design of the B-06 study, it was decided that tumor recurrences in the ipsilateral breast would not be considered local recurrences because after total mastectomy, it was impossible to have recurrence in the ipsilateral breast, thus making a comparison of such events among the treatment groups meaningless. In all subsequent National Surgical Adjuvant Breast and Bowel Project studies, tumor recurrences in the ipsilateral breast were counted as local recurrences. In those trials, irradiation and systemic therapy were administered, the former to prevent local disease and the latter to prevent both local and systemic disease. The rate of local recurrence was lower when both therapies were used. Thus, there is ample reason to conclude that radiotherapy should be administered after lumpectomy.
Our study was not designed to address any of Dr. Sonpavde's hypothetical concerns, such as those related to the quality of life and reconstructive breast surgery. Our aims were to evaluate the clinical efficacy of breast conservation and to assess the credibility of our alternative hypothesis.6 Both have been achieved.
6 ReferencesBernard Fisher, M.D.
Stewart Anderson, Ph.D.
John Bryant, Ph.D.
National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA 15212-5234
bernard.fisher@nsabp. org 1
Hellman S . Karnofsky Memorial Lecture: natural history of small breast cancers. J Clin Oncol 1994;12:2229-2234
Web of Science | Medline2
Recht A . Local control and survival in early stage breast cancer. Breast J 1998;4:372-378
CrossRef3
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 | Medline4
Clark RM ,Whelan T ,Levine M , et al. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. J Natl Cancer Inst 1996;88:1659-1664
CrossRef | Web of Science | Medline5
Fisher B ,Redmond C ,Poisson R , et al. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989;320:822-828[Erratum, N Engl J Med 1994;330:1467.]
Full Text | Web of Science | Medline6
Fisher B . Laboratory and clinical research in breast cancer -- a personal adventure: the David A. Karnofsky Memorial Lecture. Cancer Res 1980;40:3863-3874
Web of Science | Medline
