When radical mastectomy was introduced by Halsted , the average patient presented for treatment with locally advanced disease, and a relatively extensive procedure was often necessary just to remove all gross cancer. This is no longer the case as most patients now present with much smaller, less locally advanced lesions. The emergence of breast-conserving therapy (BCT) has provided early-stage breast cancer patients with a chance to preserve a cosmetically acceptable breast and equivalent outcomes in terms of breast cancer survival.
Historically, Halsted  is credited with performing the first modern radical mastectomy in 1882 in the United States. This surgical procedure required the en bloc removal of the breast, pectoral muscles, and axillary lymph nodes. Radical mastectomy was the standard surgical procedure performed for breast cancer in the United States from the turn of the 20th century until the 1950s. The curative potential of this procedure was limited as a series of 1438 patients followed over 30 years showed that only 13% were free of disease, whereas 57% had succumbed to breast cancer . In an effort to improve locoregional and distant control several authors proposed using an extended radical mastectomy, which in addition to the en-bloc removal of the breast, pectoral muscles, and axillary lymph nodes required the resection of the internal mammary lymph nodes. A randomized trial, however, proved no benefit to the extended radical mastectomy [3,4]. Currently, radical mastectomy is rarely indicated or performed and in advanced cases, less-invasive surgery coupled with neoadjuvant chemotherapy is preferred.
The modified radical mastectomy (MRM) involves the removal of the breast, underlying pectoralis major fascia but not the muscle, and evaluation of selected axillary lymph nodes. MRM provides a better cosmetic and functional result than radical mastectomy. Two prospective randomized trials, single-institution data, and several retrospective studies all demonstrate no difference in disease-free or overall survival rates between radical mastectomy and MRM for early-stage breast cancer [5,6]. Until the early 1980s and the emergence of BCT, MRM was the standard treatment available to women for early-stage breast cancer. With the emergence of sentinel node biopsy simple mastectomies have become more frequently performed then MRM. As with MRM, a total or simple mastectomy requires the removal of the entire breast tissue without an axillary dissection. Similarly, with advent of immediate reconstruction at the time of mastectomy, ‘skin-sparing mastectomy’ (SSM) was developed as a technique to preserve the majority of the natural skin envelope of the breast in an effort to improve the cosmetic outcome of the procedure and allow for immediate reconstruction . The results of retrospective and prospective series have found that the local recurrence rates were comparable to those seen with standard mastectomies, ranging from 0 to 7% [8–10], and a meta-analysis of retrospective studies did not detect a significant difference in local recurrences between patients undergoing SSM with immediate reconstruction and patients undergoing conventional mastectomies without reconstruction . More recently, in carefully selected patients, nipple and areola sparing mastectomy (NSM) has been utilized to preserve the entire skin envelope, including the areola and nipple but removes the major ducts within the nipple along the entire breast parenchyma followed by immediate breast reconstruction. This approach appears to be particularly appealing for patients undergoing risk-reducing surgery but is more controversial for the treatment of cancer and has been reserved for patients with tumors less than 2 cm in size and more than 2 cm from the nipple with clinically negative lymph nodes [12,13]. No long-term clinical series or randomized trials have examined the safety of this approach; however, retrospective series indicate that the recurrence rates associated with NSM are comparable to the more traditional SSM and MRM [12,14]. SSM and NSM are contraindicated in patients with inflammatory breast cancer (IBC) because of the dermal lymphatic involvement. With the advent of research reporting on the quality of life improvements and psychological benefits associated with breast reconstruction, the number of women undergoing breast reconstruction has increased although the absolute number and proportion remain low [15,16]. Most patients when they choose to undergo breast reconstruction elect to have it carried out at the time of the mastectomy (immediate reconstruction) as opposed to a subsequent operation (delayed reconstruction) that may be more appropriate for patients with locally advanced breast cancer or IBC . Reconstructive options include prosthetic devices such as saline or silicone implants, which are technically simpler and associated with a more rapid recovery, or autologous tissue reconstruction using pedicled or free tissue flaps from the lower abdomen, the latissimus dorsi or the buttock area, which provide for a more natural and pleasing cosmetic result [18,19].
BCT involves an excision of the tumor mass with a negative surgical margin, an axillary evaluation, and postoperative irradiation. In the 1980s, six prospective randomized trials were conducted worldwide that showed no significant difference in locoregional relapse or overall survival between breast-conserving surgery and radiation versus MRM for early-stage invasive breast cancer. BCT has gained increasing acceptance as a treatment option for stages I and II and selected stage III breast cancers as a result of six prospective randomized trials as well as an overview of all completed trials that showed its therapeutic equivalence with mastectomy [20–26]. Patient selection for BCT is crucial for its success. The few absolute contraindications for BCT include the following:
- A history of prior therapeutic radiotherapy that would result in an excessively high total radiation dose to the chest wall.
- Persistently positive resection margins despite multiple attempts at re-excision.
- Multicentric disease with two or more tumors in separate quadrants of the breast.
- Diffuse malignant calcifications on mammography.
Radiation therapy is absolutely contraindicated in pregnancy; however, it may be possible to proceed with breast-conserving surgery in the third trimester and defer irradiation until after delivery [27,28]. Similarly, radiation-induced toxicities in patients with a history of connective tissue disease have kept them from undergoing BCT . Carefully matched retrospective case–control studies have, however, failed to show a statistically significant increase in radiation induced acute and late toxicities in all but patients with scleroderma and active systemic lupus erythematosus [30–33]. Tumor size itself is not a contraindication for BCT and is only a relative contraindication should an adequate resection to negative margins result in an unacceptable cosmetic result. In some cases preoperative or neoadjuvant chemotherapy can reduce the tumor size and allow for breast conservation as long as a metallic clip is placed prior to initiating therapy in order to accurately localize the tumor at the time of surgery [34,35]. Positive or unknown margins should prompt re-excision, as these patients are at higher risk for recurrence . Residual disease is discovered in about half of these patients depending on the histology with tumors containing an extensive intraductal component having the highest likelihood of residual tumor [37,38]. There is no standard definition for close margins, although most authorities recommend re-excision for margins less than 2 mm including the National Comprehensive Cancer Network that deems margins less than 1 mm to be inadequate except when at the chest or close to the skin [39,40]. In many cases radiation oncologists will choose to boost the lumpectomy bed in an effort to reduce the locoregional recurrence rate .
A commonly held belief is that young age that is usually defined as 40 or less years is a relative contraindication for BCT as it was associated with an increased risk of locoregional recurrence [42,43]. This may have been due to adverse pathologic features such as larger tumor size, higher grade, absence of estrogen receptors, and lymphovascular invasion as well as inherited genetic predispositions [44–46]. However, locoregional recurrences were also more commonly seen in young women with breast cancer following mastectomy [46,47]. When the long-term results of two large randomized trials as well as a large retrospective review of patients with breast cancer aged 20–49 years were reviewed, the choice of therapy was not associated with a noticeable difference in recurrence-free or cancer-specific survival [48–50]. Patients with an inherited predisposition for breast cancer, such as BRCA1 and BRCA2 mutation carriers, who are diagnosed and treated for breast cancer are not only at increased risk for a contralateral cancer following their diagnosis and treatment but may also be at increased risk for an in breast recurrence or ipsilateral new primary breast tumors [51–53]. Systemic chemotherapy and risk reducing salpingo-oophorectomies seem to reduce the frequency of ipsilateral breast tumor recurrences and contralateral breast cancers in this patient population but the decision to pursue BCT needs to be thoroughly discussed with the assistance of specialized genetic counselors [52,54].
In addition to providing an optimal oncologic outcome, one of the goals of BCT is to achieve a cosmetically acceptable result. Many factors play a role in the final appearance of the breast among which the amount of resected breast tissue and postoperative radiation therapy play a determining role [55,56]. Oncoplastic surgical techniques aim to provide wide surgical margins all the while preserving the appearance and shape of the breast [57,58▪].
Despite the consistent evidence showing the therapeutic equivalence of BCT and mastectomy, BCT continues to still be underutilized with more than a quarter of patients with early-stage breast cancer still choosing mastectomy . Possible explanations include patient preference over concerns about locoregional cancer recurrence and the effects of radiation therapy [60,61]. Preoperative breast MRI has also been used preoperatively in an effort to define the extent of disease and help achieve clear surgical margins, however, there is no evidence that such an approach results in a lower rate of positive margins and reoperation , in fact some evidence suggests that mastectomy rates increase when MRI results are used to direct surgical planning .
Conventional radiation therapy after breast-conserving surgery delivers 45–50 Gy to the entire breast over 4–5 weeks resulting in a reduction in locoregional recurrence, distant recurrences, and death [64▪▪]. In an effort to increase the convenience of radiation therapy and decrease the cost and strain on resources associated with conventional radiation therapy, accelerated irradiation schedules have grown in popularity and a recent meta-analysis of four randomized trials concluded that the shorter fractionation schedule was equivalent to conventional radiation therapy in terms of locoregional recurrences, overall survival, breast cosmesis, early and late toxicities . The accelerated scheduled has not, however, been sufficiently examined in patients under the age of 50 years, with positive lymph nodes, or close margins. Similarly, accelerated partial breast irradiation (APBI) techniques were developed in order to deliver focused radiation therapy to a limited volume of tissue over a shorter period using higher doses of radiation in order to decrease the toxicity associated with conventional radiation therapy and decrease healthcare costs, although increasing patient convenience . APBI can be delivered using conformal external beam radiation therapy such intensity modulated radiation therapy or brachytherapy using interstitial catheters surrounding the lumpectomy site, intracavitary balloon catheter placed into the lumpectomy site or intraoperative radiation therapy using a spherical radiation device or portable linear accelerator [67–69]. Although the initial outcomes are promising when comparing APBI to conventional radiation therapy, follow-up is limited and the patients were highly selected with small unifocal tumors with wide negative margins and without adverse histologic features . In addition a recent population-based cohort study of women with invasive breast cancer who were 67 years or older revealed that APBI was associated with a higher incidence of subsequent mastectomy at 5 years and of postoperative infectious and noninfectious complications [71▪▪].
Axillary staging remains one of the most important prognostic indicators in women with early-stage breast cancer. Axillary lymph node dissection (ALND) has traditionally been the linchpin for axillary evaluation and is still the standard of care in patients with clinically palpable/positive axillary nodes. The purported benefits of ALND beyond its prognostic role include local regional control and survival benefits. The impact of ALND on survival remains, however, unclear with available data showing conflicting results. In the National Surgical Adjuvant Breast and Bowel Project trial B-04, women assigned to a modified radical mastectomy did not fare any better at 10–25 years of follow-up than the women who underwent a simple mastectomy with nodal irradiation or a simple mastectomy and ALND when lymphadenopathy occurred . Similarly, in a meta-analysis of three randomized trials comparing axillary dissection versus no dissection in clinically node negative early-stage breast cancer patients, ALND did not confer a survival advantage, although the rate of axillary recurrences was increased in the absence of dissection . ALND may also result in nerve injury, lymphedema, shoulder dysfunction and injury/thrombosis of the axillary vein . Sentinel lymph node biopsy (SLNB) has been developed as a method of accurately evaluating the axilla with less morbidity than ALND with several studies showing significantly lower arm morbidity and lymphedema rates in patients undergoing SLNB [75,76]. Using injection of vital blue dye and/or radiolabeled colloid around the area of the tumor or intradermally, sentinel lymph nodes (SLNs) can be consistently identified in about 96% of cases with a false-negative rate of less than 5–10% in experienced hands [77,78]. Using a combination of radiocolloid and blue dye may result in a significantly higher success rate for SLN identification as well as a lower false-negative rate . The outcome of patients undergoing SLNB followed by ALND if the SLN was positive was similar to that of patients who underwent ALND in terms of regional control and overall survival . More recently the role of completion ALND in patients with micrometastases or macrometastases in less than three SLNs has been questioned as the SLN is found to be the sole site of metastasis in up to 60% of patients overall and 90% of patients with micrometastases . In the American College Of Surgeons Oncology Group (ACOSOG) Z-0011 trial patients with clinically node negative breast cancer undergoing BCT were randomized to completion ALND versus observation if they had less than three positive SLNs. The overall survival and local regional recurrence rates were similar between the two groups [82▪▪]. However, these results cannot be extrapolated to patients who undergo PBI and the trial failed to meet its enrollment goal of 1900 patients due to slow accrual . Predictive nomograms have also been developed to estimate the risk of additional positive nodes in patients with SLN metastases in an effort to spare them from a potentially morbid ALND. A retrospective analysis examining the performance of four different nomograms did not show them to be sufficiently accurate and reliable [83,84]. Clinical circumstances in which SLNB is controversial include locally advanced breast cancer or IBC due to an unusually high false-negative rate presumably because of partially obstructed subdermal lymphatics. The size of the primary tumor is not in itself a contraindication as long as the axilla is clinically negative [85,86]. Similar concerns regarding the accuracy and false-negative rates for SLNB in patients following neoadjuvant chemotherapy have been reported and the National Comprehensive Cancer Network (NCCN) guidelines recommend that SLNB be performed prior to initiating chemotherapy [87,88▪]. The American Society of Clinical Oncology (ASCO) guidelines recommended against SLNB in patients with a previous axillary surgery, although there are increasing reports of successful SLNB in patients with local regional breast recurrence following a previous SLNB and/or ALND [89,90]. Supravital dyes such as isosulfan blue are contraindicated in pregnant patients, although the available data suggest that the radiation dose to the fetus is minimal using radiocolloid during SLNB [91,92]. Even though the NCCN guidelines report that radiocolloid use in pregnancy is well tolerated, the 2005 ASCO guidelines recommend against SLNB in pregnant patients. For patients with ductal carcinoma in situ a SLNB is not required in most cases except when there is evidence of microinvasion on the biopsy, a strong suspicion for invasive disease on imaging or exam or in the event of a mastectomy as the performance of a SLNB following a mastectomy may not always be successful [93,94].
The treatment for breast cancer has evolved over the past few decades from the Halsted radical mastectomy to breast-conserving surgery in most patients with early-stage breast cancer. This approach has been able to offer such patients a cosmetically acceptable result all the while preserving their excellent oncologic outcome. For patients who undergo a mastectomy many patients opt for immediate reconstruction and preservation of the skin envelope thereby improving their cosmetic outcome. Similarly, the trend in axillary staging has been toward a more limited approach in an effort to minimize the long-term morbidities associated with a traditional ALND whose therapeutic value has been increasingly questioned.
Conflicts of interest
The author has no relevant conflicts of interest or sources of funding to disclose.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 89).
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