Predicting and Preventing Positive Surgical Margins and Local Failures in Breast-Conserving Surgery
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- Ziogas, D., Ignatiadou, E. & Fatouros, M. Ann Surg Oncol (2009) 16: 544. doi:10.1245/s10434-008-0254-y
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To the Editor
Standard treatment of early-stage breast cancer includes breast-conserving surgery (BCS).1 Despite advances with radiation and adjuvant empirical cytotoxic and targeted systemic treatment, tumor-free surgical margins continue to play an important role in preventing local recurrence, and thus it is considered essential in designing treatment strategies.2,3
Prediction of surgical margins in both first surgical resection and reexcision is a helpful tool to prevent positive margins and to select the appropriate extent of surgery. Therefore, the report by Kurniawan and colleagues for the potential prediction of surgical margins will attract the attention of surgeons.4 On the basis of a population-based breast-screening program in Melbourne, Australia, these authors evaluated clinicopathologic data on 2160 women diagnosed with ductal carcinoma-in-situ or invasive cancer and treated with BCS.
Kurniawan et al. conclude that after BCS, patients with mammographic microcalcifications, larger tumor size, and multifocal tumors are more likely to have involved margins. Patients with involved margins, large tumor size, and/or a ductal carcinoma-in-situ component are more likely to have residual disease at reexcision. This information may influence decision on the extent of surgery. However, in an absence of randomized trials, as well as the unknown effect of modern adjuvant targeted agents including trastuzumab and aromatase inhibitors, which are used after completion of this study (2005), is difficult to draw robust conclusions.
Although BCS has become a standard of care, caution suggests that we remember the high rates of local ipsilateral and contralateral breast cancer recurrence in specific subgroups.5 Given the recent evidence that locoregional failure may worsen not only recurrence-free survival but also overall survival, a surprising increase of the rate of more aggressive surgery has been observed in the United States.6,7
This increase in the rate of contralateral prophylactic mastectomy or bilateral mastectomy in the United States, which eliminates the risk of positive surgical margins, may suggest surgical overtreatment.7 Basic and clinical evidence increasingly suggests that either the group with the highest risk of recurrence in the ipsilateral breast or the group with a new contralateral cancer is the group of patients who carry mutations in the BRCA1 or BRCA2 genes.8–12 There is no other specific group with an established high risk of local failures to proceed with aggressive breast cancer surgery despite advances in global gene expression research.13
Mutations in the breast cancer BRCA susceptibility genes are involved in carcinogenesis of hereditary breast cancer and can be identified by genetic testing. This testing drives decision making for primary prevention of in healthy women with familial susceptibility to breast cancer. Women with positive BRCA testing benefit from prophylactic surgery, either with bilateral mastectomy or with bilateral salpingo-oophorectomy, which appears to be more effective than intensive screening, including magnetic resonance imaging.14–16 Beyond women with inherited BRCA mutations, carriers of germ-line mutations in the CDH1 gene also face a high risk, approximately 40%, for developing lobular breast cancer.17 Because women with CDH1 mutations face a higher risk of gastric cancer, approximately 70%, preventive interventions include primarily prophylactic gastrectomy for the prevention of poor-prognosis gastric cancer, and secondary protection from breast cancer.17–24
Current advances in the identification of human genetic variation, namely single-nucleotide polymorphisms and copy-number variations that might be responsible for differences in local recurrence risk among patients with breast cancer, might be useful in a clinical setting. Novel research models and clinical algorithms for personalized surgical and adjuvant treatments are proposed not only for breast cancer, but also for other solid tumors.25–27 However, breast cancer is a highly heterogeneous and complex disease with various treatment responses, and there are serious obstacles to overcome before we can reach a practical level of personalized medicine.28–30
Despite major progress in the multimodality treatment, every effort should be made for tumor-free surgical margins. However, beyond appropriate margins, careful selection of women for BCS is required that takes into consideration conventional clinicopathologic factors, family history, impact of effectiveness of modern adjuvant systemic treatment on locoregional tumor control, and BRCA testing.