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Minimizing Surgery for Young Breast Cancer Patients: Is It Safe?
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: The risk of local recurrence in young patients who underwent breast conserving therapy for early stage breast cancer was approximately 20% by 10 years. The risk was significantly reduced by the use of adjuvant systemic therapy.
Source: van der Leest M, et al. The safety of breast-conserving therapy in patients with breast cancer aged < 40 years. Cancer. 2007;109:1957-1964.
Over the past several decades breast-conserving surgery has become a standard approach, primarily because survival rates are demonstrably equivalent to modified mastectomy in patients with early stage breast cancer.1, 2 However, local recurrence rates may be higher, particularly in younger women who more frequently have primary tumors with negative prognostic features. Thus, in two studies that compared the risk of local recurrence after breast-conserving surgery in younger patients and older patients, there was a nine times greater risk observed in one3 and a five times greater risk observed in the second.4 These have raised concern about the this procedure as standard therapy in young patients, particularly in those with other known risks.
The current retrospective analysis from the Netherlands was designed to address those prognostic factors that would indicate higher risk of local recurrence in young women with early stage breast cancer. Using a data from the Eindhoven Cancer Registry and from the practice of two large radiotherapy departments in Southern Netherlands over a 14-year period (1988-2002) there were 1554 patients who were younger than 40 years at the time of breast cancer surgery. Of these, 774 underwent breast-conserving surgery and the great majority of these (96.5%) received postoperative radiotherapy. Seven hundred fifty-eight patients were evaluable for this analysis (ie, stage I or II breast cancer) and the median duration of follow-up was 8.5 years (range, 0.9 to 16.9 years). Study endpoints were local recurrence, regional recurrence, distant recurrence, contralateral breast cancer, or death.
Of the 758 evaluable patients, chemotherapy was administered to 218 (29%) and hormone therapy was administered to 25 (3%) and 86 patients (11%) received both. Early during the 14-year period of study, it was less common to prescribe chemotherapy for lymph node negative breast cancer, but this trend changed during the study interval. For example, from 1988 to 1992, 4% of lymph node negative patients received chemotherapy compared to 10% during the years 1993 to 1997, and 48% during the years 1998 through 2002. Patients with positive lymph nodes during these intervals received chemotherapy at a proportion of 71%, 96%, and 99% respectively.
Local recurrence was diagnosed in 95 patients without evidence for distant metastatic disease. Approximately one-half of these were detected by the physician upon routine clinical evaluation and the other half by the patient herself. Curiously, by multivariate Cox regression analysis, it appears that lymph node status was not an independent prognostic factor for local recurrence.
During the interval study, 22 of the 758 patients developed regional recurrence and 209 developed distant metastasis. Fifty-nine patients developed contralateral breast cancer and 174 patients have died. Thus, the 10-year actuarial rates of these end points were 3.5% (95% CI, 1.8-5.2%), 30.4% (95% CI, 26.6-34.2%), 9.6% (95% CI, 6.8-12.4%), and 26.9% (95% CI, 23.1-30.7%), respectively. The 10-year disease free survival (ie, survival without local, regional, or distant recurrence, and without contralateral breast cancer was 55.8%). In multivariate analysis, the significantly lower risk of contralateral breast cancer was identified in patients receiving adjuvant systemic treatment (hazard ratio = 0.46: 95% CI, 0.2-0.87).
The five- and 10-year actuarial local recurrence rates were 9% and 17.9% respectively in this series. Patients who received adjuvant systemic therapy had their risk reduced by more than 50%. These local recurrence rates for younger patients were lower than reported elsewhere (typically greater than 20% at 10 years3-7). However, these are difficult comparisons because of the variables in duration of study and local treatment trends, including the variable use of adjuvant chemotherapy.
It is notable that of the local recurrences observed in this study, the large majority occurred at, or near the site of the primary tumor, and only 7% developed elsewhere in the breast. This supports the notion that, at least in young women, local recurrences are not new primary tumors but more likely an indication of incompleted resected residual disease. These findings support the current practice of delivering a radiation "boost" to the local tumor bed upon completion of the standard radiotherapy course. Such has been demonstrated to reduce local recurrence rate in other studies including one conducted by the EORTC.8
In summary, the retrospective analysis of a fairly large series of young women with early-stage breast cancer suggest that the local recurrence rates are substantial, but can be significantly reduced by adjuvant chemotherapy and radiotherapy. The impact of a radiation "boost" to the tumor bed is also likely to be effective in reducing this untoward outcome.
1. van Dongen JA, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst. 2000;92:1143-1150.
2. Veronesi U, 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.
3. Voogd AC, et al. Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. J Clin Oncol. 2001;19:1688-1697.
4. Arriagada R, et al. Late local recurrences in a randomised trial comparing conservative treatment with total mastectomy in early breast cancer patients. Ann Oncol. 2003;14:1617-1622.
5. Elkhuizen PH, et al. Local recurrence after breast-conserving therapy for invasive breast cancer: high incidence in young patients and association with poor survival. Int J Radiat Oncol Biol Phys. 1998;40:859-867.
6. Jobsen JJ, et al. The value of a positive margin for invasive carcinoma in breast-conservative treatment in relation to local recurrence is limited to young women only. Int J Radiat Oncol Biol Phys. 2003;57:724-731.
7. Zhou P, et al. Factors affecting outcome for young women with early stage invasive breast cancer treated with breast-conserving therapy. Breast Cancer Res Treat. 2007;101:51-57.
8. Bartelink H, et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med. 2001;345:1378-1387.