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Table.  

Author Year Dataset Findings
Khan and colleagues[3] 2002 National Cancer Data Base, 1990-1993N = 16,023 Mortality HR = 0.61 for resection (95% CI = 0.58-0.65)
Rapiti and colleagues[4] 2006 Geneva Cancer Registry, 1977-1996N = 300 Mortality HR = 0.6 for resection (95% CI = 0.4-1.0)
Babiera and colleagues[5] 2006 University of Texas M.D. Anderson Cancer Center,1997-2002N = 224 Overall survival RR = 0.5 (95% CI = 0.21-1.19)
Cady and colleagues[6] 2008 Massachusetts General Hospital and Brigham and Women's Hospital,1970-2002N = 622 Survival advantage for patients undergoing surgery, but most of survival advantage explained by selection bias in matched-pair analyses

Outcome for Patients Undergoing Primary Breast Surgery for Stage IV Breast Cancer

CI = confidence interval; HR = hazard ratio; RR = relative risk

Breast Surgery for Stage IV Breast Cancer

Authors: Lisa A. Newman, MD, MPHFaculty and Disclosures

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Question
A 42-year-old premenopausal woman presented with locally advanced right breast infiltrating ductal carcinoma, estrogen/progesterone receptor (ER/PR) negative, HER2 3+, with an osteolytic lesion measured at L3. No response was noted after 3 cycles of doxorubicin plus cyclophosphamide (AC), but there is good partial response after 6 cycles of docetaxel, carboplatin, and trastuzumab (TCH). Primary tumor size has decreased from 9x9 cm to 5x5 cm. Is surgery or radiotherapy to the primary tumor advised at this stage?

Response from Lisa A. Newman, MD, MPH
Professor of Surgery, University of Michigan, Ann Arbor, Michigan; Director, Breast Care Center, University of Michigan, Ann Arbor, Michigan

If this patient's primary breast tumor and metastatic disease are both responding to systemic therapy, then it indeed seems appropriate to proceed with definitive breast management. Depending on the patient's breast size and personal wishes, potential management options include either lumpectomy and breast radiation or mastectomy. Optimal management of the axilla has not been addressed in published studies of surgery for Stage IV breast cancer, but it seems reasonable to perform axillary dissection very selectively (ie, in cases of overt, clinically evident nodal metastases.

Most patients with invasive breast cancer require primary breast and axillary surgery for definitive locoregional control of disease, as well as for staging information. Systemic therapies (delivered pre- and/or postoperatively) provide substantial survival advantages by eradicating occult, micrometastatic disease in distant organs. Application of multimodality therapy to patients with Stage I-III disease results in long-term control of disease for most patients. In contrast, survival of patients with established Stage IV disease (defined by documented, clinically evident metastatic disease in distant organs) is less favorable, and these patients are generally referred for primary palliative management. Breast surgery for Stage IV breast cancer is therefore usually limited to resections that aim to control ulcerated or fungating tumors that are resistant to nonoperative measures.

This conventional approach to metastatic disease has been challenged recently, largely due to 2 arguments. First, systemic therapies for breast cancer have advanced, and survival with metastatic breast cancer has indeed improved over the past few decades.[1,2] This improved outcome has led to renewed interest in durable locoregional disease control. A second argument in favor of breast surgery for metastatic disease is related to its potential therapeutic value: resection of the primary breast lesion may improve outcome by minimizing the total body tumor burden and also by removing a source of ongoing tumor seeding. Conversely, however, others have speculated that resection of the primary breast tumor could disrupt the immunologic balance achieved by the small fraction of patients with metastatic disease that remains indolent for a prolonged interval. From the perspective of cancer research, aggressive attention to the primary tumors of patients with Stage IV disease could expand tissue bank resources.

As illustrated in the Table , several investigators, using very different datasets, have shown that primary breast surgery for Stage IV breast cancer is associated with a survival advantage. The outstanding question in all these studies, however, is whether significant selection bias may be contributing to these outcome patterns. Factors associated with improved outcome after breast surgery include age, limited site metastases (especially if osseous-only), and evidence of response to preoperative systemic therapy.

Definitive answers regarding this controversial issue will likely require a large, multicenter phase 3 clinical trial. In the absence of such high-level data, an aggressive approach to primary breast surgery with curative intent in selected, physically fit patients whose metastatic disease appears to be well-controlled with systemic therapy is at least a reasonable option for consideration. The pros and cons of surgery and the limited data supporting an outcome benefit should be presented in detail to the patients under consideration; the discussion should include perspectives offered by the multidisciplinary treatment team.

This activity is supported by an independent educational grant from Susan G. Komen for the Cure.

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