breast cancer is the most frequently diagnosed nondermatological malignancy in women and ranks second only to lung in cancer - related deaths . while the incidence has increased over the past decade , ( figures 1(a ) and 1(b ) ) the mortality rate of breast cancer has gradually declined [ 2 , 3 ] ( figure 2 ) .
this improved survival may stem from earlier detection as well as improved therapies [ 2 , 3 ] .  
surgical resection was one of the first effective treatments for breast cancer and continues to play a critical role in the treatment of this disease .
a multidisciplinary approach is now standard of care , involving a coordinated effort with the surgeon working in concert with the medical and radiation oncologist to achieve the best possible outcome for each individual .
improvements in both the quality and quantity of life for victims of breast cancer can be attributed to the advances made in each of these disciplines . as with all cancers ,
it is these early - stage cancers in which the most significant improvements in the operative management has occurred .
adoption of breast conservation surgery has allowed an increased focus on the cosmetic outcome , during a time that has also witnessed improved survival .
this represents a clear victory for breast cancer patients , which needs to be extended to breast cancer of all stages .
the greek physician galen is considered to be one of the earliest advocates of surgical treatment , recommending wide excision of breast tumors nearly 2000 years ago .
galen , like his predecessor hippocrates , also recognized that breast cancer should be considered a systemic disease .
hippocrates proposed that cancers were the result of an imbalance of the four basic humours - blood , phlegm , and yellow and black bile .
he attributed an excess of black bile for postmenopausal women having a greater incidence of breast cancer , as premenopausal women were relieved of this excess black bile with regular menstruation .
although primitive , this concept can be extended to the current breast cancer treatment paradigm : systemic control of the disease at a molecular level , with local control by surgical intervention . while we now know that 
black bile  does not result in breast cancer , the most effective breast cancer management embodies this concept of breast cancer as a systemic disease .
these procedures consisted of amputation followed by cauterization , performed as rapidly as possible to minimize hemorrhage .
unfortunately , patients surviving the initial surgical procedure would all too frequently die of fulminant sepsis . in the late 19th to early 20th century ,
some of the most dramatic changes in surgical therapy for breast cancer were pioneered by william steward halstead .
his approach to the mastectomy helped change the surgical therapy of the breast from a simple amputation to a formal procedure .
his technique , now termed the  radical mastectomy ,  involved en bloc resection of the breast , the pectoralis muscle , and the axillary contents .
this procedure was as effective at initial local tumor control as any early technique , with the significant advancement of a dramatically decreased rates of recurrence that plagued halstead 's predecessors . during halstead 's era , prior to any understanding or capacity for early diagnosis , initial presentation of profoundly advanced tumors was the norm . accepting halstead 's basic principles ,
this evolved into dissection of the neck , abdomen , and even the mediastinum to remove diseased lymph nodes . around the same period ,
early methods for surgical staging were developed , yielding a basic classification of patients with tumors in which radical mastectomy was potentially curative and those with disseminated cancer not appropriate for attempted resection .
however , it would not be until the 1940s when evidence from preoperative staging brought the futility of what had become  superradical mastectomies  into question .
initial deviation from the tenets of halstead began in the late 1930s with an initial push for preservation of the nondiseased breast tissue during cancer resection .
shortly thereafter , postoperative radiotherapy was added for control of local tumor recurrence , laying the groundwork for breast conservation therapy ( bct ) as we know it today .
although bct was not significantly implemented in clinical practice until the 1980s , the stage was set for the current surgical treatment of breast tumors utilizing either bct or mastectomy .
optimal management of a patient with breast cancer includes establishing a pathologic diagnosis prior to any definitive operative intervention .
formal surgical excision in the operating room is rarely required to establish the diagnosis of breast cancer , as there are many alternative techniques to obtain tissue for diagnosis .
for example , much pathologic information can be gained from small , 1 - 2  mm  core 
the diagnosis of breast cancer is confirmed by histological evaluation , and the tumor is assessed for grade as well as human epidermal growth factor receptor 2 ( her2 ) , estrogen , and progesterone receptor status .
this information is critical for optimal decision making regarding treatment options , most importantly allowing for coordination of care for those patients that will benefit from neoadjuvant chemotherapy prior to operative intervention .
after the diagnosis of breast cancer is established , patients are evaluated to determine the extent of the disease .
standard of care includes bilateral mammography to identify any suspicious areas in either breast that will impact surgical management .
laboratory values that will assist in treatment recommendations include complete blood count , liver function tests , and alkaline phosphatase .
there are not established tumor markers for breast cancers , although cancer antigen ( ca ) 15 - 3 and ca 27 - 29 may be helpful when elevated .
additional imaging studies to evaluate for metastatic disease are obtained depending on signs and symptoms of the patient , as well as the clinical stage at presentation .
a bone scan is indicated if the patient has localized bony pain or elevated alkaline phosphatase , chest imaging is indicated for pulmonary symptoms , and abdominal imaging by computerized tomography is indicated for abnormal liver functional tests or abdominal symptoms .
a review of the acquired data , including pathology , laboratory assessment , and imaging , allows the multidisciplinary team to make recommendations for definitive management of the patient with breast cancer .
those patients with evidence of advanced disease are typically managed medically with preoperative chemotherapy , prior to any definitive surgical management .
surgical treatment should allow the patient to be involved in the decision - making process , with the surgeon providing information about all surgical options available .
local excision alone is at times acceptable , usually in the setting of elderly or otherwise debilitated patients without adjuvant radiation .
this decision must be carefully weighed and based on evaluation of tumor aggressiveness and comorbid conditions of the patient .
first , tumors must be resectable with a pathologically clear margin , that is , a surrounding margin of breast parenchyma without disease .
secondly , patients undergoing partial mastectomy typically receive whole breast irradiation to achieve local control in the breast .
tumor size must be sufficiently small relative to the entire breast , such that the appearance of the breast is cosmetically acceptable following partial mastectomy .
pregnancy and a history of previous chest irradiation do not allow bct , as they are contraindications to the requisite postoperative radiotherapy .
positive margins after bct require a repeat attempt at excision or completion mastectomy to achieve clear margins .
findings of involved margins with partial mastectomy significantly increase the chance of disease recurrence .  
mastectomy is indicated for the curative resection of tumors ( i.e. , absence of metastatic disease ) not amenable to bct , and for those patients that do not want to consider conservation even though they meet criteria .
the modern version of this procedure is termed the  modified radical mastectomy ,  which entails removal of the breast , its underlying pectoralis fascia , and axillary contents , performed for more extensive disease .
in addition to resection of the primary tumor , all invasive breast cancers require assessment of axillary lymph nodes for tumor invasion .
the ipsilateral axillary lymph nodes are theoretically the first site that breast cancer is expected to spread , with the sentinel nodes representing the first group of nodes at risk for invasion .
assessment of the axillary nodes includes sentinel lymph node biopsy ( slnb ) during lumpectomy , or at the time of mastectomy .
injection of a dye and/or radio - isotope into the breast allows the surgeon to identify the first (  sentinel  ) lymph node draining the tumor basin .
involvement of axillary nodes is considered regional disease ( not metastatic ) and is usually followed by complete axillary node resection .
furthermore , negative findings after a properly performed slnb allow a patient to avoid the potential for significant morbidity after axillary dissection .
an all too common and often debilitating complication of this procedure is upper extremity lymphedema . in situ breast cancer
this early neoplasm can be derived from a duct or lobule and is , therefore , referred to as lobule carcinoma in situ ( lcis ) or ductal carcinoma in situ ( dcis ) .
lcis of the breast requires special consideration , as it is considered a marker for the future development of invasive breast cancer .
the risk of developing invasive cancer is low , and if it occurs , histology tends to be favorable . for this group of women , lcis is managed by appropriate monitoring without additional intervention .
the potential adverse reactions of these medications must be considered and balanced with the presumed risk reduction .
in contrast to lcis , the diagnosis of dcis requires treatment for local control at the time of diagnosis . with the development of techniques for the earlier diagnosis of breast cancer
, dcis is the only diagnosis in approximately 15% of newly diagnosed breast cancer patients .
this finding must be addressed , as the survival rates for treated dcis are near 100% , but the development of invasive disease occurs in up to 30% of patients with untreated dcis .
although dcis is often found in conjunction with an invasive carcinoma , treatment for the invasive component takes precedence and dictates both surgical and medical management .
in contrast to management of invasive disease , those patients with dcis usually do not require axillary dissection , as axillary nodal involvement in patients with pure dcis is unusual .
as a small number will have axillary involvement , sentinel node evaluation should be performed if mastectomy is the chosen operation for local control .
starting in the mid - twentieth century , most notably in the lab of bernard fisher , early chemotherapeutic agents were being analyzed for use in the preoperative setting .
the use of neoadjuvant chemotherapy ( nact ) prior to an attempted surgical resection represents a dramatic improvement in breast cancer therapy , addressing the systemic aspect of this disease .
locally advanced breast cancer entails large tumors or those that invade the chest wall or skin ( t4 ) or have spread to the axillary nodes ( n2 or n3 ) .
an excellent response to chemotherapy merits reassessment of the patient to ensure a concomitant clinical and radiological response .
eradication of all tumor after neoadjuvant chemotherapy is termed pathological complete response ( pcr ) , strictly defined as the absence of invasive cancer from the breast and axilla on pathological assessment in response to chemotherapy . while achieving pcr has been found to increase long - term survival , a wide range of local recurrence rates ( 2.622.6% ) after bct following neo - adjuvant therapy has been noted .
one recent study indicates that her2 positive and positive axillary lymphadenopathy may predict this recurrence after pcr . while high risk populations certainly merit close postoperative surveillance for recurrent disease .
appropriately placing those patients achieving excellent response to chemotherapy into the algorithm for the surgical management of breast cancer requires further assessment . improved methods are needed to predict those tumors best amenable to downstaging to bct , as certain patients may in fact be better candidates for mastectomy .
molecular tests such as the 21 gene ( oncotype dx ) and 70 gene ( mammaprint ) assay , that provide tumor - specific scores reflecting risk of recurrence , may become useful in this scenario .
the effectiveness of nact for locally advanced disease eventually led to the use of pre - operative treatment in an attempt to  downstage  even more advanced cancer to a scope amenable to treatment by mastectomy .
a recent extension of these principles is the use of chemotherapy to downstage tumors , in order to avoid mastectomy altogether in lieu of bct .
nact is indicated for tumors meeting all criteria for breast conservation ( see above ) except for tumor size .
an excellent response in this scenario has now allowed the option for bct in a patient who would have required a mastectomy .
most of the recent advances in the surgical management of breast cancer follow the basic template of ever more conservative surgical resections .
the first involves operative breast cancer therapy with a concomitant focus on breast reconstruction , known as oncoplastic breast surgery .
this trend represents another advancement made possible by the refinements in the use of postoperative radiation , the same concept that led to the advent of bct .
oncoplastic surgery entails the use of plastic surgery techniques to restore cosmesis and natural symmetry , ideally during cancer resection .
plastic surgery techniques utilized include breast augmentation and reduction , flaps , implants , and expanders , on both the diseased and the normal breast if necessary to achieve the desired symmetry .
indications are still widely debated , but appropriate candidates are those that have sufficient residual breast after the oncological resection to facilitate the necessary reconstruction .
one of the most recent advances in surgical therapy involves management of the positive sentinel lymph node biopsy ( slnb ) .
substantial morbidity , not unlike that which was seen in the days of halstead , all too often follows .
however , a recent study has demonstrated that high - risk patients with small tumors ( t1-t2 ) and limited lymph node spread , who are able to receive radiotherapy , do not benefit further from complete axillary lymph node removal .
simply stated , survival for small breast tumors with limited spread does not improve after axillary dissection in older individuals or those with significant medical problems .
this early work has found that this subset of patients suffer more from the complications of the procedure than benefit .
the adjuvant radiotherapy therapy given for this early - invasive disease seems to provide most of the survival benefit . a recent trend including surgery as cancer prevention has gained wide acceptance .
contralateral prophylactic mastectomy ( cpm ) has been found to decrease the risk of development of a cancer in the disease - free breast in women at high risk . those women harboring a brca mutation or a strong family history of breast cancer
may be considered candidates for prophylactic bilateral mastectomy . as mentioned previously , with the diagnosis of lcis ,
the risk of developing an invasive breast cancer is equal in both breasts , such that bilateral mastectomy may be necessary for true risk reduction .
many women , in an otherwise low - risk category , also opt for cpm after a newly diagnosed breast cancer .
while recent data suggests an increased overall as well as disease - free survival after cpm , the debate is ongoing regarding the appropriate indications for cpm .
similarly , the quest to identify the population benefiting the most from this intervention must be equally rigorous .
the most successful operative management of metastasis is prophylactic : appropriate screening for detection of suspicious lesions of the breast , followed by appropriate local control to minimize the potential for metastatic dissemination .
this is reflected in recent trends showing improved survival of breast cancer patients , as screening and early intervention has translated into improved outcomes .
after the diagnosis and completion of treatment of a primary breast cancer , surveillance for recurrence or metastatic spread ensues .
followup entails focused clinical and laboratory assessment , and mammography to detect new or recurrent lesions . the discovery of metastatic disease at any point merits a complete reevaluation . traditionally , surgical intervention was avoided in the patient harboring metastatic disease , due to a perceived lack of benefit . only those patients with extremely limited metastatic lesions were considered for therapeutic resection . for the most part , patients found to have metastatic disease were deferred to induction chemotherapy in the hopes of an excellent response and prolongation of life .
most traditional use of surgical intervention in the setting of metastatic disease was for palliative purposes , at either the primary tumor site or any distant metastatic lesions .
for example , resection of the primary tumor was considered for persistent infection , bleeding , or general difficulty maintaining cleanliness .
however , many recent studies have been able to challenge this practice of avoiding intervention on the primary tumor in the setting of metastatic disease .
early studies indicate that resection of a primary breast lesion may increase survival in the setting of limited metastasis .
this effect probably stems from more effective and specific chemotherapy , but randomized trials are needed to define both the optimal candidates and indications for this intervention .
however , the significance of the early findings of reduced need for chemotherapy , improved quality of life , and even long - term cures with the concomitant resection of ( limited ) metastatic lesions can not be overstated .
operative intervention for metastasic lesions is typically palliative , involving the treatment of a symptomatic mass .
this may entail bypassing an obstructing metastatic lesion in the bowels , utilizing a normal segment of bowel to allow free flow of intestinal contents .
however , aggressive resection of metastatic lesions for curative intent has gained favor in recent years .
the best studied is the resection of metastatic lesions to the lung , in which long - term success and even some cures have been reported .
the patients most amenable to metastasectomy are those with limited metastatic burden ( oligometastases ) with hormonally responsive tumors .
it is a well - known fact that the most common site of breast cancer metastasis is the bone , with breast cancer being the leading cause of bone metastasis of any cancer in women .
however , it has recently been demonstrated that the basic breast cancer subtypes ( luminal a , luminal b , her-2 positive , and basal ) differentially target certain sites for metastasis .
for example , the her-2 positive and triple negative subtypes have been shown to preferentially metastasize to the brain over the other subtypes .
while this represents an interesting finding , further investigation is needed to translate this data into clinical practice .
for example , knowledge of the presence of a basal phenotype in a high risk patient may merit more aggressive , organ - specific followup .
surgical resection of breast cancer is absolutely curative if performed while the primary tumor is contained .
escape of tumor cells from the primary lesion completely changes therapeutic management , expectations , as well as outcomes .
interestingly , some early stage tumors , all of which were previously assumed to be self - contained , have been shown to harbor the capacity for systemic tumor dissemination . while there is no method to accurately predict which tumors have this devastating capacity ,
certain factors such as large tumors , younger age at diagnosis , vascular invasion , and nodal involvement have been found to be associated with a high risk of developing distal metastasis after appropriate treatment [ 22 , 23 ] .
the best treatment option currently available is effective loco - regional control of the primary tumor .
most studies have found that obtaining at least a 2 millimeter margin for invasive and in situ breast cancer best minimizes the chance of local recurrence [ 24 , 25 ] .
this threshold has consistently led to reduced local recurrence rates , while balancing the potential for an overly aggressive resection .
effective local control removes the nidus for both local and distant recurrence , emphasizing the management of the primary tumor on the systemic aspect of the disease .
this effect is exemplified by the significant increase in distant metastasis rates and subsequent survival with the development of a local recurrence of a resected breast tumor [ 2226 ] .
further evidence that breast cancer , even at its early stages , can be a systemic disease can be found in animal studies and early analysis in cancer patients . utilizing pcr and immunohistochemistry ,
increased cancer - related cells have been demonstrated in the systemic circulation due to surgical manipulation [ 2730 ] .
needle biopsies of primary tumors have even been found to result in increased rates of nodal metastasis [ 31 , 32 ] .
tumor cells that break off from the primary site and enter the systemic circulation are referred to as circulating tumor cells ( ctcs ) . while the ctcs were first described over a century ago ,
current methods allow for the enrichment of ctcs by antibody - mediated targeting of the epithelial cell adhesion marker ( epcam ) . while the clinical usefulness of ctc assessment is controversial , some consider that greater than five ctcs is the breaking point for a poor prognosis in breast cancer [ 33 , 34 ] .
detection of ctc has been used to demonstrate significant shedding of putative tumor cells into the systemic circulation during surgical manipulation . while this shedding is known to occur in both breast and lung cancers , the functional result and ability of these cells to successfully migrate and seed distant sites is not known .
furthermore , some hypothesize that the tissue trauma resultant from needle or operative manipulation may lead to the expression of an invasive or metastatic phenotype
. this alteration may lead to cancer progression or the release of ctcs , respectively .
pathways implicated in these effects are normal and appropriate wound healing responses , such as those involved in inflammation and angiogenesis . with the continued technological improvement for the detection of ctcs , determining the clinical relevance of these effects may become possible .
the assessment of ctcs could one day provide the basis for highly specific real - time biopsies , yielding a strong potential for the modification of surgical techniques and traditional indications .
the capacity to harvest and analyze ctcs could become a key feature of individual tumor profiling , allowing for patient - specific therapies to further reduce the current complication profile of today 's interventions [ 8 , 40 ] .
even so , recent advances represent significant steps away from the extensive resections performed by halstead and his predecessors . while these early attempts successfully decreased local recurrence rates , advances in the treatment of breast cancer as a systemic disease
were needed to facilitate long - term cures . continued improvements in early diagnosis via breast imaging , advanced prognostic tests , patient - specific molecular diagnosis , and the development of targeted chemotherapeutic agents
, breast cancer therapy will become more focused , increasing efficacy and reducing complications of all the treatment disciplines .
this will move the bar closer to the ultimate goal of transforming breast cancer into an easily targeted , readily manageable disease .
 surgical resection was the first effective treatment for breast cancer and remains the most important treatment modality for curative intent . 
 refinements in operative techniques along with the use of adjuvant radiotherapy and advanced chemotherapeutic agents have facilitated increasingly focused breast cancer operations . 
 surgical management of breast cancer has shifted from extensive and highly morbid procedures , to the modern concept obtaining the best possible cosmetic result in tandem with the appropriate oncological resection . 
 an ever - growing comprehension of breast cancer biology has led to substantial advances in molecular diagnosis and targeted therapies . 
 an emerging frontier involves the breast cancer microenvironment , as a thorough understanding , while currently lacking , represents a critical opportunity for diagnosis and treatment . 
 collectively , these improvements will continue to push all therapeutic interventions , including operative , toward the goal of becoming more focused , targeted , and less morbid . 