The discipline of breast surgery, like many specialties, has moved toward a minimally invasive approach to local therapy. Radical surgery had previously been the standard; however, surgical approaches continue to evolve as we gather more data about the oncologic safety of less invasive procedures. In addition, we are placing more emphasis on targeted therapy, and surgery is an integrated portion of patient care. Most patients are diagnosed with image-guided biopsies instead of surgical excision, allowing for better surgical planning and fewer procedures.1 Furthermore, most patients are being diagnosed at earlier stages due to the increased use of screening mammography, and therefore most are candidates for breast conservation. For women with early-stage breast cancer, the sentinel lymph node biopsy procedure is widely accepted and its application is growing, which spares more women the morbidity of axillary lymph node dissection.
In some cases, we may still recommend or women may choose to undergo mastectomy, but we are improving our ability to provide cosmetically acceptable procedures with oncologically acceptable outcomes. Most women are candidates for immediate reconstruction and skin-sparing mastectomy. We are still exploring our ability to preserve the nipple-areola complex.
Breast-conserving surgery is the treatment of choice for early-stage primary breast cancers.2 For this surgery, the goal is to remove the tumor with clear margins while preserving the cosmesis of the breast.3 This surgery is followed by radiation therapy to minimize the risk of local recurrence within the breast. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 study found that postlumpectomy radiation decreased the rate of local recurrence from 39% to 14%.4
The American College of Radiology and the American College of Surgeons issued guidelines for the selection of patients for breast-conserving surgery. They recommended5:
• Patients with unifocal disease are appropriate candidates.
• Diffuse calcifications may contraindicate breast-conserving surgery. En bloc removal of calcifications is preferred, but limited resection and close imaging followup are possible when the radiologist is confident that calcifications are benign.
• Previous therapeutic radiation to the chest is a contraindication to breast-conserving surgery.
• Radiation is traditionally contraindicated in pregnant women, but breast conservation can be offered to women using a thoughtful, multidisciplinary approach when delivering radiation postpartum does not cause too long a delay.6
• Inability to achieve negative margins on a lumpectomy specimen may result in increased risk of local recurrence, delay in adjuvant therapy, and a change in cosmetic outcome.
• Certain connective tissue disorders may be associated with increased morbidity after delivery of radiation.
• Tumors should be less than 5 cm, because clinical trials of breast-conserving surgery involved T1 and T2 lesions. Tumor size in comparison with breast size is also a consideration, both for ability to deliver adequate radiation and cosmesis.
Patients with larger tumors may become candidates for breast-conserving surgery with the use of neoadjuvant or preoperative chemo therapy, endocrine therapy, and/or targeted therapy. In the NSABP B-18 trial, patients with larger unifocal tumors were found to have improved ability to undergo breast-conserving surgery (68% vs 60%) with no statistically significant difference in local recurrence or survival at a median follow- up of 6 years.7,8
Previously, women with tumors involving the nipple-areola complex or the subareolar area were recommended to undergo mastectomy. We now understand that women with disease confined to that area who can achieve negative margins may be candidates for central lumpectomy. This course of action has been shown to be oncologically safe.9 These women can go on to have elective nipple-areola complex reconstruction after completion of radiation therapy.
For women who prefer or are required to undergo mastectomy, advances in surgical technique afford them an oncologically safe procedure with greater attention paid to patient satisfaction and cosmetic outcome. Mastectomies can often be performed using a skin-sparing technique that preserves as much of the patient’s own skin as possible as well as the inframammary fold. The technique provides a natural envelope, which can be filled with implant or autogenous tissue during the reconstruction. This technique allows for a closer match to the contralateral breast when reconstruction is performed. With careful attention to flap thickness and removal of breast parenchyma, the rates of local recurrence are shown to be equivalent to that of standard mastectomy.10,11 Women who will definitely or may require postmastectomy radiation therapy (PMRT) are still recommended to undergo mastectomy, with most needing a delay in reconstruction. Women who may require PMRT, however, may be afforded the benefit of skin-sparing mastectomy and reconstruction with the use of tissue expanders. These women still derive the benefit of skin preservation as well as the psychological benefit of waking from surgery with a breast mound, without compromising the delivery of radiation therapy.12 The area of reconstruction in the setting of PMRT is still controversial, and most radiation oncologists and reconstruction surgeons would prefer a delayed approach in this setting.
Skin-sparing mastectomy has traditionally included removal of the nippleareola complex, but in appropriate candidates, preservation of the nipple-areola complex can be oncologically sound and provide excellent cosmetic results. There is growing interest in the safety of this procedure, particularly as the numbers of prophylactic mastectomy for risk reduction grow. In recent studies, rates of local recurrence have not been significantly different from those for mastectomy or skin-sparing mastectomy.13 Patients with small peripheral tumors, as well as those seeking prophylactic mastectomy, may undergo this procedure, potentially resulting in increased patient satisfaction and necessitating fewer reconstructive procedures. The best outcomes are seen in women with breasts that are nonptotic and small to medium in size, with no previous history of radiation to the breast, and with no prior periareolar incisions. With selection of appropriate candidates, attention to nipple/areolar anatomy, and appropriate use of intraoperative pathology and preoperative breast imaging, the rate of nipple necrosis is low and cosmetic outcomes are excellent.14,15 The oncologic safety of this procedure will be better determined when more of the current studies have long-term follow-up data available or when a randomized trial comparing the technique with traditional mastectomy techniques is undertaken.
Management of axillary lymph nodes
Lymphatic mapping and sentinel lymph node biopsy were introduced more than 15 years ago and are now the standard axillary evaluation for women with clinically node-negative, earlystage breast cancer in the United States. These procedures, their indications, and their outcomes have generated great research interest. The sentinel lymph node dissection procedure carries significantly less morbidity than the axillary lymph node dissection procedure.16 The de creased rates of wound infections, seromas, paresthesias, and incidence of lymphedema17 improves quality of life in women with early-stage breast cancer. This is particularly important as the number of breast cancer survivors increases worldwide. Current researchseeks to expand the indications for sentinel lymph node dissection.
Patients who are clinically node negative and who undergo neoadjuvant chemotherapy are able to undergo axillary evaluation by sentinel lymph node biopsy before or after the administration of chemotherapy with accurate results.18,19 Further investigation is ongoing to determine whether women who are initially node positive with excellent clinical response to neoadjuvant chemotherapy may be candidates for sentinel lymph node biopsy and, if pathologically node negative, this may obviate the need for completion of node dissection.20 It has been shown to be safe for pregnant women to undergo mapping and sentinel lymph node biopsy.21 As the indications for the procedure expand, more women may be spared the morbidity of axillary lymph node dissection. The routine recommendation for complete axillary dissection in women with positive sentinel nodes or clinically positive nodes will continue to evolve toward axillary observation or axillary radiation as we gain better understanding of tumor biology.
Minimally invasive ablation
Nonsurgical removal or ablation of breast tumors is a field of growing interest. Difficulties in assessing margins, confirming complete destruction, and standardizing postprocedure imaging still prohibit acceptance of these techniques. Surgical removal of the primary breast tumor remains the gold standard. These techniques, however, may be useful for benign lesions as well as for palliative ablation of lesions for women with metastatic disease or women who are not candidates for surgery.
Many women undergo percutaneous biopsy of a breast mass to rule out malignancy or help in the planning of local therapy. Percutaneous biopsy techniques under mammography or ultrasound can also be employed to excise benign and malignant breast lesions.22 The most likely indication for this technique will be for benign lesions, because margin assessment is not possible. There are also anatomic restrictions in that the lesion should not be too close to the skin, chest wall, or nipple-areolar complex.
The effectiveness of radiofrequency ablation (RFA) in treatment of primary breast tumors has also been investigated. Tumors are visualized with ultrasound or magnetic resonance imaging (MRI), and then a high-frequency alternating current creates frictional heating and ablates the lesion. This technique has shown promise in patients with small tumors (<2 cm), although good results depend on the imaging giving an appropriate estimation of tumor size. This treatment is not appropriate for poorly defined, extensive, multifocal, or multicentric tumors. In addition, the tumor must be an adequate distance (1 cm) from the chest wall and skin to avoid burns.23 Other studies suggest that the use of RFA after lumpectomy may reduce the need for reexcision for inadequate margins.24 This procedure could also be used for palliative ablation of tumors in women with metastatic disease or women who are deemed to be poor candidates for surgery.
Focused ultrasound ablation
This technique also uses thermal tumor ablation. A 1.5-MHz ultrasound source ablates the lesion, and high-resolution imaging monitors tumor destruction. No probe insertion is necessary. Thus far, the results are quite variable in regard to degree of tumor necrosis, ranging from 20% to 100%.25 Assessment of margins is also a concern. Tumors treated by focused ultrasound ablation must be more than 1 cm from the skin and chest wall to prevent thermal injury. Palliative therapy is a possible indication for this procedure, as is the treatment of tumors 2 cm or benign lesions.25
Less research has been done on the technique of laser ablation for early-stage breast cancer. This technique involves delivery of energy to the target via a fiberoptic probe inserted using imaging guidance. Ultrasound, mammography, and MRI have been used successfully in this treatment. Although not extensively studied, this technique may be effective for treatment of small primary breast tumors and appears to be well tolerated.26
With cryosurgery, a freezing probe is used to destruct cells by membrane rupture during successive freeze-thaw cycles. Using image guidance, the growth of the zone of freezing can be monitored. This technique is successful at destroying the center of the lesion, but the periphery often contains viable cells, so the zone of ablation needs to be larger than the tumor. The US Food and Drug Administration has approved this technique for the destruction of fibroadenomas. Invasive tumors up to 1.5 cm without an extensive intraductal component also appear to be adequately treated by cryosurgery.27
The management of breast disease has undergone a transformation from surgery as the mainstay of therapy into a multidisciplinary approach to treatment involving surgeons, radiation oncologists, medical oncologists, reconstruction surgeons, pathologists, and radiologists. Further, more emphasis is being placed on the psychological and cosmetic outcome of surgery. More women are candidates for breast conservation surgery, either up front or with neoadjuvant therapy. Most wo men who undergo mastectomy have the benefit of a skin-sparing technique and the option of immediate reconstruction. Sentinel lymph node biopsy can be performed in women with early-stage breast cancer to avoid the morbidity of axillary lymph node dissection, and indications for sentinel lymph node biopsy continue to grow. Treat ment will evolve further as we emphasize the use of targeted therapies tailored to an individual patient’s breast cancer. In the future, minimally invasive techniques may be used to treat residual disease after successful treatment with targeted therapy. As we continue to de monstrate oncologic safety and equivalent outcomes to more invasive techniques, these approaches will continue to grow in acceptance. !
1. Smith DN, Christian R, Meyer JE. Large-core needle biopsy of nonpalpable breast cancers. The impact on subsequent surgical excisions. Arch Surg. 1997;132:256-260.
2. Mamounas, E. NSABP breast cancer clinical trials: recent results and future directions. CMR. 2003;1:309-326.
3. Newman LA, Kuerer HM. Advances in breast conservation therapy. J Clin Oncol. 2005; 23:1685-1697.
4. 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.
5. Morrow M, Strom EA, Bassett LW, et al; for American College of Radiology; American College of Surgeons; Society of Surgical Oncology; College of American Pathology. Standard for breast conservation therapy in the management of invasive breast carcinoma. CA Cancer J Clin. 2002;52:277-300.
6. Rosenkranz KM, Lucci A. Surgical treatment of pregnancy associated breast cancer. Breast Dis. 2006;23:87-93.
7. Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15:2483-2493.
8. Wolmark N, Wang J, Mamounas E, et al. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001; 30:96-102.
9. Kawase K, DiMaio D, Tucker SL, et al. Paget’s disease of the breast: there is a role for breastconserving therapy. Ann Surg Oncol. 2005; 12:391-397.
10. Carlson GW, Styblo TM, Lyles RH, et al. The use of skin sparing mastectomy in the treatment of breast cancer: the Emory experience. Surg Oncol. 2003;12:265-269.
11. Kroll SS, Khoo A, Singletary SE, et al. Local recurrence risk after skin-sparing and conventional mastectomy: a 6-year follow-up. Plast Reconstr Surg. 1999;104:421-425.
12. Kronowitz SJ, Robb GL. Radiation therapy and breast reconstruction: a critical review of the literature. Plast Reconstr Surg. 2009;124:395-408.
13. Gerber B, Krause A, Dieterich M, et al. The oncological safety of skin sparing mastectomy with conservation of the nipple-areola complex and autologous reconstruction: an extended follow- up study. Ann Surg. 2009;249:461-468.
14. Vlajcic Z, Zic R, Stanec S, et al. Nipple-areola complex preservation: predictive factors of neoplastic nipple-areola complex invasion. Ann Plast Surg. 2005;55:240-244.
15. Petit JY, Veronesi U, Orecchia R, et al. Nipple sparing mastectomy with nipple areola intraoperative radiotherapy: one thousand and one cases of a five years experience at the European Institute of Oncology of Milan (EIO). Breast Cancer Res Treat. 2009;117:333-338.
16. Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC trial. J Natl Cancer Inst. 2006;98:599-609.
17. Lucci A, McCall LM, Beitsch PD, et al. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011. J Clin Oncol. 2007;25:3657-3663.
18. Mamounas EP. Sentinel lymph node biopsy after neoadjuvant systemic therapy. Surg Clin North Am. 2003;83:931-942.
19. Breslin TM, Cohen L, Sahin A, et al. Sentinel lymph node biopsy is accurate after neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2000;18:3480-3486.
20. Surgery to remove the sentinel lymph node and axillary lymph nodes after chemotherapy in treating women with stage II, stage IIIA, or stage IIIB breast cancer. ClinicalTrials.gov identifier: ACOSOG-Z1071. www.clinicaltrials.gov/ct2/show/NCT00881361?term=ACOSOGZ1071&rank=1. Updated January 6, 2010. Accessed January 7, 2010.
21. Keleher A, Wendt R 3rd, Delpassand E, et al. The safety of lymphatic mapping in pregnant breast cancer patients using Tc-99m sulfur colloid. Breast J. 2004;10:492-495.
22. Fine RE, Whitworth PW, Kim JA, et al. Lowrisk palpable breast masses removed using a vacuum- assisted hand-held device. Am J Surg. 2003;186:362-367.
23. Fornage BD, Sneige N, Ross MI, et al. Small (< or = 2-cm) breast cancer treated with US-guided radiofrequency ablation: feasibility study. Radiology. 2004;231:215-224.
24. Klimberg VS, Kepple J, Shafirstein G, et al. eRFA: excision followed by RFA—a new technique to improve local control in breast cancer. Ann Surg Oncol. 2006;13:1422-1433.
25. Schmitz AC, Gianfelice D, Daniel BL, et al. Image-guided focused ultrasound ablation of breast cancer: current status, challenges, and future directions. Eur Radiol. 2008;18:1431-1441.
26. Dowlatshahi K, Francescatti DS, Bloom KJ, et al. Image-guided surgery of small breast cancers. Am J Surg. 2001;182:419-425.
27. Vlastos G, Kinkel K, Pelte MF, et al. MRI-guided cryotherapy as a treatment option for early stage breast cancer: preliminary results. Breast Cancer Res Treat. 2004;88(suppl):S168.