Local Control, Aggressive Surgery, and Overall Survival for Breast Cancer
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- Liakakos, T. & Lykoudis, E.G. Ann Surg Oncol (2008) 15: 1544. doi:10.1245/s10434-007-9739-3
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To the Editor:
In a recent issue of the journal, Morrogh and colleagues1 highlighted the effect of a recent landmark study2 on women who will receive a new diagnosis of breast cancer and on society. Reports have emphasized the increased risk of local recurrence after breast conservation therapy (BCT), particularly among young patients and those who underwent surgery with inadequate disease-free margins3,4 before the publication of the Early Breast Cancer Trialists Collaborative Group early-stage breast cancer meta-analysis.2 But this meta-analysis also revealed an increased risk of death among patients who experience local recurrence.
Can these data affect the patients’ preferences and the surgeons’ decision making? Is more extensive surgery—perhaps unilateral mastectomy, previously the standard procedure—more beneficial than the currently preferred breast-conserving surgery (BCS)?
Evidence from a current analysis of the Surveillance, Epidemiology, and End Results Program (SEER) database for breast cancer patients treated in the United States between 1998 and 2003 is clear. The report of Tuttle et al.5 demonstrates that patients with unilateral breast cancer are increasingly choosing to undergo contralateral prophylactic mastectomy (CPM). The rate of CPM greatly increased, from 4.2% in 1998 to 11.0% in 2003. In this population-based study, the rate of BCS increased while the rate of unilateral mastectomy decreased.
Given that the increase in CPM was based on descriptive studies with conflicting results about overall survival,6 it is possible that the recent strong evidence from randomized trials for poor survival with BCS will abandon this approach in favor of unilateral mastectomy and CPM. What will be the risks of such a new trend?
Although patients’ psychological satisfaction and lowered anxiety about local recurrence and death are better among women who undergo aggressive surgery, a relatively high risk of complications after plastic and reconstructive surgery7 and the increased costs to insurance and public health should be considered.
The increase in the rate of BCS in the United States—from 56.1% in 1998 to 59.7% in 2003, according to SEER data5—is modest considering the randomized trial–based evidence and recommendations8 for routine BCS in early-stage breast cancer. This BCS rate is expected to be reduced in the years after 2003, after the publication of another meta-analysis.
In an era of personalized medicine, with clinical use of molecular profiling and genetic tests as diagnostic or prognostic tools,9,10 a generalized call to perform aggressive surgery in all patients within our criteria is not an advance, but rather taking several steps back.
Stratification of patients according to the prediction of local and contralateral recurrence and subsequent decision on the extent of surgery is currently the most rational approach. Unilateral or bilateral mastectomy now seems to be an alternative only for BRCA mutation carriers.11 Data suggest a far higher risk of in-breast recurrence and contralateral breast recurrence among BRCA carriers than in non-BRCA carriers after BCS or unilateral mastectomy for breast cancer.12 This increased risk of recurrence of at-risk residual breast tissue is due to BRCA-deficient cells. Women with inherited BRCA mutations are at high risk of developing breast and ovarian cancer and urgently need primary surgical13,14 or nonsurgical preventive intervention to be protected from cancer.15
Another example of risk stratification and a genetic test–based individualized approach in the primary prevention of breast cancer is the management of women with inherited CDH1 mutations. These women face a 40% risk of breast cancer and benefit from intensified breast surveillance.16 But the first priority is gastric cancer prevention because such women face a 70% to 80% risk of developing hereditary diffuse gastric cancer.16,17 Given that overall, prognosis of gastric cancer in the West is poor,18–20 with the exception being early-stage gastric tumors,21,22 primary prevention is of major clinical importance.23 Despite advances in adequate D2 surgery24–27 and adjuvant postoperative chemoradiation28,29 or perioperative adjuvant chemotherapy,30–33 survival rates in the United States still remain poor.34
Guided extent of surgery based on individualized recurrence-risk prediction is currently a scientifically rational approach with benefits for society, public health, and patients. Therapy with the current, clinically used trastuzumab and aromatase inhibitors in the treatment of early-stage breast cancer should be considered.35 These agents, along with modern chemotherapy, may affect and reduce local and contralateral tumor recurrence. Therefore, while we await new data on recurrence, careful design of treatment strategy and decisions about the appropriate extent of surgery should be made on an individual basis by an experienced team.