As noted above, careful physical examination and documentation of findings is an important first step in the evaluation of a mass found by the patient or a physician. Breast imaging is also a critical component for most patients, especially those over 30 years of age. For some patients, the characteristics of the mass on exam may be typical for a cystic mass. If so and the mass is symptomatic (i.e., painful), the most expeditious management may be to aspirate the cyst with a syringe and needle in the clinic, guided by palpation. For indeterminate masses, breast imaging, especially ultrasound (US), can distinguish between solid and cystic masses. Asymptomatic simple cysts can be followed without intervention; complex cysts (e.g., with internal echoes or nodules) and solid masses will most often need to be biopsied, usually a needle biopsy with imaging guidance.

Mobile, lobulated masses in young women (teens and 20s) are usually fibroadenomas (FA; see below under benign disease). If there is uncertainty, the US or a needle biopsy can be used to confirm this.

Perhaps the most important point to make about evaluation of nipple discharges is that non-spontaneous nipple discharges (i.e., elicited by pressure on the breast tissue) are not pathologic and should not lead to any evaluation whatsoever. Spontaneous nipple discharges, on the other hand, are reason for concern, either because they may indicate significant pathology or because they may be bothersome to the patient. Nipple discharge fluid that most often indicates a neoplastic process, in addition to being spontaneous, is either visibly bloody or clear and copious in amounts. However, testing for occult blood using testing kits that are intended for fecal material should be discouraged. This is not the intended purpose of these tests and often leads to unnecessary testing and/or surgery. Furthermore, sending nipple fluid for cytological examination is also fraught with hazard; false-negative and false-positive tests are both frequent, and this will generally not resolve the diagnosis [1, 2]. The use of ductograms (or galactograms) is controversial but may delineate a mass lesion in a duct system and may localize a lesion that might be missed by “blind” excision of the central ducts leading to the orifice from which the discharge was observed [3]. Excision of the central ducts behind the nipple may well result in stopping the discharge but could leave a peripheral malignant or premalignant lesion in place. Some have advocated duct endoscopy to evaluate nipple discharges [4–6]. Nipple discharges are usually caused by duct ectasia, by intraductal papillomas, and, rarely, by ductal carcinoma in situ (DCIS) or invasive ductal cancer (IDC). Duct ectasia usually causes clear, yellowish, greenish, or brown discharge, and excision of dilated or ectatic ducts usually only has the benefit of resolving the annoying symptom. Management of papillary lesions, especially when diagnosed by core needle biopsy, is controversial, but papillomas with atypia have about a 30% chance of being malignant on excision [7–14]. And like atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) , atypia associated with a papillary lesion increases the risk of developing breast cancer long term.

Breast pain , whether generalized or localized, is rarely the presenting symptom of a cancer, but about 10% of patients with a new cancer may have associated pain. Most breast pain is attributable to a “wastebasket” of diagnoses under the heading of fibrocystic change. The first responsibility of the surgeon evaluating a patient for breast pain is to rule out cancer or other serious diseases. This can be done by careful physical exam and routine imaging, mammography, and/or US, depending on the age of the patient. Rarely is a “blind” biopsy going to be productive. Recommendations for pain relief are mostly empiric and include non-steroidal anti-inflammatory drugs (NSAIDs), ice packs, local heat, good support, and reassurance. Anecdotally, severe pain from fibrocystic disease (FCD) has been ameliorated by treatment with selective estrogen receptor modulators (SERMs, e.g., tamoxifen), bromocriptine, or danazol [15–17]. However, because of the potential side effects, we would only rarely resort to these measures unless the patient was also at increased risk for breast cancer and over the age of 35. Pain can also be caused by breast cysts, and these can be aspirated with almost instant relief. Mastitis and breast abscesses (see below) can also cause severe acute breast pain.

Scaling lesions of the nipple may be a manifestation of eczema or a form of ductal carcinoma in situ known as Paget’s disease. Essentially, Paget’s represents DCIS emerging from the nipple milk ducts into the epidermis of the nipple (intraepidermal adenocarcinoma). It generally presents with a scaly crusted appearance that may spread out onto the surrounding areola. Evaluation should include thorough physical examination and mammography for associated masses. The only reliable way to make this diagnosis and distinguish it from more benign conditions is to biopsy the nipple. Generally, a small wedge of nipple tissue can be excised under local anesthesia and closed with a few small sutures. Foci of invasive cancer or DCIS in the breast parenchyma are associated with Paget’s in a majority of cases [18–20]. This may have a profound effect on treatment decisions. For isolated Paget’s of the nipple, excision of the nippl e with a small amount of underlying breast tissue is generally sufficient for breast conservation treatment (BCT) . Whether or not to add radiation therapy will depend on patient age, margins, and grade, similar to DCIS in general (see below) [21]. For those patients with additional sites of cancer within the breast parenchyma, total mastectomy with lymph node sampling is usually recommended, unless the focus of invasion is directly under the nipple. However, just as in patients with two separate sites of cancer and depending on breast size, two segmental resections may be feasible and acceptable.

The most important “take-away” from this section is that all palpable and imaging-detected abnormalities that require biopsy should first be considered for a needle biopsy , either fine-needle aspiration (FNA) or core needle biopsy (preferred) rather than surgical, incisional, or excisional biopsy. This is considered a quality indicator and is recommended by the Commission on Cancer as part of the “Choosing Wisely” program of the American Board of Internal Medicine Foundation [32–35]. Needle biopsy usually establishes a definitive diagnosis with the least morbidity, avoids excision with positive margins requiring reoperation, and also avoids the need for a second surgical procedure for nodal staging. Core needle biopsy is more likely to distinguish invasive cancer from in situ cancer than FNA and also provides more tissue for breast biomarkers, including estrogen receptors, progesterone receptors, human epidermal growth factor receptor 2 (ER, PR, HER-2), and Ki67 or other ancillary testing. This information should be provided by pathology for any needle biopsy showing invasive cancer, since these may be important for decisions about which patients may need adjuvant or neoadjuvant systemic therapy (more on this later). For core biopsies showing DCIS, we do not generally ask for these markers, since the phenotype of an invasive cancer, if present, in the definitive surgical resection has greater significance [36]. We therefore only perform biomarkers in cases of pure DCIS on surgical specimens, not on needle core biopsy. The exception to this would be patients who, for reasons of comorbidity or on a clinical trial, might be considered for primary or neoadjuvant hormonal therapy as initial treatment.

The so-called fibrocystic change really refers to a clinical entity characterized by intermittent breast pain and nodularity or dense breast tissue without a definite or discrete mass. This is not really a disease, since it is so common and is associated with a variety of histopathologic findings if biopsied. This most commonly occurs in late pre- and perimenopausal women. Pain may be cyclical or constant. In general, surgery is not indicated for this complaint, unless associated with a definite imaging abnormality or a palpable discrete mass. This can make it difficult to detect breast cancer and may cause significant patient anxiety. Recommendations for relief of symptoms include local ice, heat, or NSAIDS. Although many recommend avoidance of caffeine for these patients, there is little evidence that this is a causative agent [48–51].

In contrast to fibrocystic change, which may include collections of small cysts , larger cysts may present as discrete masses detected on palpation or on mammogram. These may be painful or asymptomatic. If cysts are painful, the most expeditious management is aspiration with a needle (20 gauge is usually sufficient), under either ultrasound guidance or by palpation (“digital” guidance). If there is uncertainty as to whether a mass detected by palpation or mammography is cystic, ultrasound can be used to distinguish solid from cystic lesions. If the cyst is “simple” (no internal echoes or mural nodules) and not symptomatic, nothing further needs to be done. If it is painful or “complex” by ultrasound, then aspiration or biopsy should be undertaken to rule out a neoplasm. If the aspirated fluid is not bloody, then it does NOT need to be sent for any testing (e.g., cytology), as this will rarely yield a malignant diagnosis and is expensive. If the cyst does not recur, then nothing further needs to be done. If the cyst recurs, it should be managed according to symptoms. Cysts can be aspirated again if symptomatic or excised if repeated aspirations do not resolve the patient’s concerns.

Papillary lesions of the lactiferous ducts may present as a nipple discharge, sometimes bloody or blood tinged, or as a mass found on imaging or physical exam. These are usually centrally located, but can be some distance from the nipple-areolar complex. For this reason, many advocate galactograms as part of the workup for nipple discharge, but this is controversial [3]. Excision, possibly with guidance from the galactogram, is usually indicated for ductal lesions with nipple discharge. If a papillary lesion is diagnosed on needle biopsy, the question of whether to surgically excise the lesion depends on whether or not there is associated atypia on pathology. A number of reports indicate that a core needle diagnosis of a papillary lesion with atypia is associated with a 20–30% likelihood of coexisting DCIS or invasive cancer on complete excision. However, for benign papillary lesions without atypia, excisional biopsy will diagnose a cancer in less than 10% of cases and may not be necessary [9–11, 38].

Fibroadenomas (FAs) are benign fibroepithelial masses (see pathology section) that usually present as smooth, lobulated mobile masses, most often in young women (teens and 20s). They may be asymptomatic or mildly painful. If asymptomatic and less than 2 cm in greatest diameter, they can be followed clinically. For FAs that have grown relatively rapidly, attained a size greater than 2 cm, or if they are painful, excision, usually under local anesthesia, is indicated. A wide margin is not required. If there is any doubt about the diagnosis, ultrasound and/or needle biopsy can be used to confirm the clinical impression. If the size of the mass increases over time, exceeds 2 cm, or becomes painful, excision should be considered. These tumors are sometimes found on routine screening, and if the imaging is typical for fibroadenoma, they can be followed, or if there is some concern that the lesion is atypical or enlarging, needle biopsy can be done for reassurance. Because fibroadenomas are usually very mobile, they can usually be reached through a circumareolar incision, resulting in minimal deformity. Even very large fibroadenomas (sometimes referred to as “giant”) can be excised readily, and the breast size and shape will gradually return to normal. Occasional recommendations to undergo mastectomy for very large fibroadenomas are inappropriate, as these benign tumors compress the surrounding breast tissue, which then fills in the space left behind. An alternative to surgical excision is cryotherapy ablation, using US guidance [52–55]. This leaves minimal scar, but the tumor may take some time to regress after freezing.

One should be cautious about apparent FAs that are very large or have grown rapidly, as these may be phyllodes tumors. Needle biopsy will sometimes raise this issue but often is not definitive, with a diagnosis of “fibroepithelial lesion, cannot rule out phyllodes.” These require excision to make a definitive diagnosis. Excision should include a margin of normal breast tissue if possible. If it turns out that the tumor is a benign phyllodes, then excision with a negative margin should be adequate treatment [56–59]. Most phyllodes tumors are benign but can recur locally; some (about 10–25%) are malignant [60, 61], and these can be locally aggressive and may even metastasize, usually hematogenously. Some have recommended excision with at least a 1 cm margin for phyllodes tumors, although the most important factor is achieving a histologically negative margin. For high-grade phyllodes tumors treated with breast-conserving surgery, radiation to the breast may improve local control [62–64]. If wide excision with a negative margin is not feasible, total mastectomy may be necessary. However, since phyllodes tumors rarely spread via lymphatics, surgical staging of regional nodes is unnecessary [61, 63].

Dilated lactiferous ducts may be detected on mammogram or may present clinically as spontaneous or elicited nipple discharge. The nipple discharge may be clear or serous, yellow, brown, or green, among other colors. If the discharge only occurs with squeezing or manipulation of the breast, it is generally considered non-pathologic and should be ignored. If it is spontaneous, additional workup, such as galactography or, in some centers, mammary duct endoscopy, may be warranted [65]. Ectatic ducts may also be the underlying cause of breast abscesses, particularly retroareolar/central infections (see below). Dilated ducts appearing as a new finding on mammogram are considered by some to be a possible sign of a cancer and should be evaluated further, with US and/or galactograms.

We will not consider postpartum mastitis here, since this is not usually a surgical disease and is generally treated conservatively with antibiotics [66, 67]. Diffuse mastitis otherwise is unusual but can be quite painful and may even be associated with systemic sepsis. This can occasionally occur as a complication of breast lymphedema associated with lymph node dissection and breast irradiation. This should be evaluated with breast imaging to rule out an underlying mass or abscess and needs to be distinguished from inflammatory breast cancer , which can have a similar appearance. If there is not a mass or abscess, treatment with antibiotics, usually to cover gram-positive bacteria, should be prescribed. If the process does not improve, a punch biopsy of the erythematous skin may be necessary to rule out inflammatory breast cancer, which can present without a mass.

Breast abscesses , which are usually evident clinically, present as painful fluctuant masses under or adjacent to the areola, with associated cellulitis surrounding the mass. The patient may also report purulent drainage from the nipple. Until recently, these were generally managed with surgical incision and drainage (I&D) under anesthesia, followed by wound care and gradual healing. At advanced stages, these are often fluctuant clinically, or they may show as fluid-filled spaces on ultrasound. The management of breast abscesses has changed in recent years, from routine I&D in the operating room to ultrasound-guided needle aspiration and antibiotics . The latter strategy is successful in most cases [68–70]. If the abscess recurs or has loculated or complex fluid that is too thick for aspiration, I&D may be necessary. Surgical drainage may also be preferred in patients with signs and symptoms of systemic sepsis, particularly in diabetic patients. In the past, it was routinely recommended that once the acute process had resolved, central duct excision should be performed to reduce the risk of subsequent recurrences [71, 72]. However, this has become more controversial, and some have suggested that duct excision should only be performed if multiple episodes occur. It should be pointed out that multiple other entities, such as infected sebaceous cysts, hidradenitis of the axilla, or inframammary fold area, are managed differently (managed in the same manner as in other parts of the body) as they are not the same as breast abscesses arising in milk ducts.

This may be one of the most mysterious diseases of the breast, with a myriad of presentations and no clear-cut etiology or best treatment. This may present as a discrete mass, which may be painful, a chronic abscess with or without spontaneous drainage to the skin, or a diffuse mass effect involving large areas of the breast. The cause is not clear, and recommended treatments range from antibiotics to steroids to methotrexate to I&D to excision of discrete masses to total mastectomy. The only clear recommendation is to start conservatively and reserve more radical treatments for diffuse disease that does not respond to other therapies [73–75].

Blunt trauma to the breast , such as from a seatbelt or airbag in a motor vehicle accident, may result in a mass lesion in the breast, which may be a hematoma or an area of fat necrosis. This can cause considerable pain, with ecchymosis and a palpable mass. Although these may take a considerable time to resolve, surgery is rarely indicated unless a hematoma becomes secondarily infected, requiring drainage. If there is uncertainty about the diagnosis, breast imaging, with mammograms and ultrasound, can usually clarify the problem.

A diagnosis of radial scar usually results from image-guided needle biopsy of a clinically occult lesion seen on mammography. The common recommendation for this result has long been to surgically excise the area, because an underlying cancer can be missed [39–42]. However, this may only be the case if the mammographic finding was a spiculated density that looks very much like cancer. More recently, data have suggested that when radial scar is strictly a microscopic finding associated with a needle biopsy for other types of abnormalities, such as microcalcifications, the likelihood of missing a cancer is quite low and surgical excision may not be indicated [40–42, 76].

Atypical ductal or lobular hyperplasia has clearly been shown to be a risk factor for subsequent development of breast cancer long term [37, 77]. It may be appropriate, based on these diagnoses, especially if combined with other risk factors such as positive family history, to recommend chemoprevention with estrogen receptor modulators or aromatase inhibitors [78–81]. When these diagnoses, or lobular carcinoma in situ (which is NOT really cancer), are made with core needle biopsy, it is generally recommended that the lesion be entirely excised to rule out coexisting cancer, which may be found in up to 30% of cases [82, 83]. However, it has been suggested that if the biopsy is done with a large bore needle and vacuum-assisted equipment, especially if all of the calcifications on mammogram have been removed, that surgical excision may not be required.

For patients with a biopsy-proven diagnosis of breast cancer, in addition to a complete history, review of systems, and physical examination, a complete set of current bilateral mammograms (within the last 3–6 months) should be available. Ultrasound of the breast may or may not be needed but sometimes can help delineate the extent of disease in the breast when breast density or other factors (such as invasive lobular cancer) make this difficult to determine on mammography. Routine breast MRI has been advocated by some for women with a new diagnosis of breast cancer, based on the likelihood of a change in management based on MRI findings [84–92]. A significant proportion of women (up to 25%) will have additional sites or extent of disease defined by MRI, and 3–5% of women will have otherwise undetected contralateral cancers found on MRI. However, other retrospective studies and at least two randomized trials have not shown that MRI decreases the need for re-excision or the rate of local recurrence after BCT [93–97]. It has been argued that although MRI does detect unsuspected additional lesions in the affected or the contralateral breast, the very low ipsilateral breast tumor recurrence (IBTR) and contralateral recurrence rates indicate that radiation to the affected breast, along with better systemic therapy, makes the discovery of these lesions irrelevant. Indeed, some have suggested that the routine use of MRI may unnecessarily delay the start of treatment and may increase the likelihood of total mastectomy. An intermediate stance holds that MRI should be used selectively for younger patients, patients with very dense breasts, patients with invasive lobular cancer (which can be very indistinct on other imaging), patients who will undergo primary or neoadjuvant systemic therapy, and in patients for whom accelerated partial breast irradiation is anticipated.

One of the greatest drivers of excessive healthcare costs in the United States of America (USA) has been the profligate use of complex advanced imaging looking for systemic metastases in patients with early-stage cancers. For patients with breast cancer up to Stage II, and perhaps Stage IIIA, and with no symptoms to indicate the presence of metastases, the addition of studies such as CT scans, PET scans, or bone scans has clearly been shown to be of little or no benefit [98]. These expensive tests rarely turn up unsuspected metastatic cancer and often lead to additional unnecessary tests to clarify the results of the first unnecessary test. The recommendation NOT to perform these tests has been laid out clearly in guidelines from professional societies, such as the American Society of Clinical Oncology, and listed in the “Choosing Wisely” list maintained by the American Board of Internal Medicine Foundation at www.​choosingwisely.​org.

For women with locally or regionally advanced breast cancer (i.e., AJCC Stage III), CT scans of the chest, abdomen, and pelvis would be appropriate. PET-CT scans may be more convenient but are more expensive, are not always definitive for breast cancer metastases, and may not be covered by insurance. Alternative would be CT scans of the chest abdomen and pelvis, plus a nuclear medicine bone scan. For women with symptoms that suggest the presence of metastatic disease, regardless of stage, focused imaging may be justified (e.g., plain X-rays and bone scan for severe bone pain of recent onset, chest X-ray and chest CT for dyspnea or chronic cough of recent onset, head CT or MRI for neurologic symptoms or severe headache).

In general, primary surgery has been the standard approach to breast cancer treatment, followed by adjuvant systemic therapy and radiation. However, in the past three decades or so, it has been demonstrated that neoadjuvant systemic therapy can be used to make locally advanced inoperable breast cancers more amenable to surgical resection and can convert patients from total mastectomy to breast conservation [99–107]. Depending on the phenotype of the cancer, and possibly the molecular profile, primary systemic therapy may be either cytotoxic chemotherapy or hormonal therapy. Neoadjuvant systemic therapy should be considered for any patient with a tumor ≥2 cm and/or with positive nodes, and the use of neoadjuvant chemotherapy (NCT) is particularly likely to be useful for tumors that are triple negative (TNBC, i.e., negative for estrogen and progesterone receptors and HER-2) and those that are HER-2 amplified. Potential advantages, in addition to reducing the scope of surgery for the breast primary, are (1) allowing time for genetic counseling and plastic surgery consultations without delaying treatment; (2) assessing the response to therapy, which may result in changes in treatment, either pre- or postoperatively; and (3) reducing the scope of surgery to axillary lymph nodes, avoiding the need for full axillary node dissection.

Surgical extirpation of the breast primary most simply comes down to breast conservation treatment (BCT—partial or segmental mastectomy, often called “lumpectomy”) versus simple or total mastectomy. A number of factors have been suggested to be contraindications to BCT, but some of these have been disputed or even dispelled in the past two decades [108, 109]. Listed in Table 3.1 are factors that no longer should be considered contraindications to BCT. Extensive intraductal component (EIC, defined as DCIS comprising more than 25% of the tumor area) was found to predict a higher likelihood of ipsilateral breast tumor recurrence, but only if negative margins were not routinely obtained [110–113]. More recent series have not found this to be an issue, if margins are negative and treatment includes irradiation to the breast [114–116]. Young age does indeed portend a higher risk of local recurrence, but total mastectomy and BCT still have equal outcomes [117–125]. Large tumor size has now been shown to be overcome by neoadjuvant systemic therapy, either chemotherapy or hormonal therapy, depending on the biologic features of the tumor [99–107, 126]. Even multicentric disease or large areas of DCIS have now given way to multiple lumpectomies in selected cases or to oncoplastic resections and rearrangement of breast tissue, which allow for removal of large segments of breast tissue and acceptable to excellent cosmetic outcomes [127–135]. Cancers presenting during pregnancy, while once considered indications for termination of the pregnancy and/or total mastectomy, can be safely treated with neoadjuvant chemotherapy, with minimal risk to the fetus, and breast-conserving surgery near or after delivery and radiation after delivery. The remaining relative and absolute or true indications for total mastectomy over BCT are listed in Tables 3.2 and 3.3. By far the most frequent of these should be patient choice, for reasons that are as varied as the patients themselves (e.g., fear of recurrence, not wanting to have further mammograms, strong family history [with or without a documented germline mutation]).

This aspect of breast cancer management has undergone major changes in the past two decades. For patients with clinically negative axillary lymph nodes , sentinel node biopsy has largely supplanted axillary lymph node dissection (ALND, usually removal of level I and II nodes) for providing staging information about the presence or absence of microscopic cancer in the nodes [136–139]. Sentinel lymph node (SLN) biopsy has been shown to result in equivalent outcomes to routine axillary node dissection in randomized trials. This has greatly decreased the morbidity of surgical management, particularly the incidence of lymphedema of the upper extremity [140]. This procedure is performed by injection into the breast of a radiotracer that can be taken up by the lymphatics and/or a colored dye that also helps to identify the sentinel nodes visually. We generally inject 1 microcurie of ⁹⁹Technetium sulfur colloid into the breast, while the patient is in the pre-op holding area, split between retroareolar injection and injection intradermally overlying the tumor site, in a total volume of 0.5 cc. Some have advocated and practiced injection after induction of anesthesia in the operating room [141, 142]. The advantage of this is that the patient does not experience the pain associated with the injection. However, those that favor the later injection have generally been using much larger volumes (4–5 cc), which is certainly more painful. We have found that with careful explanation and sometimes administration of mild sedation or after a regional block if being administered prior to mastectomy, the patients generally tolerate the injection well, and this allows more time for the tracer to reach the nodes. However, the later injection has been reported to work equally well. After induction of anesthesia and prepping, we then inject 3–5 cc of isosulfan blue, part retroareolar and part peri-tumoral, and massage the breast for 3–5 min before making an incision in the axilla and searching for the “hot” and blue nodes. Some centers use only one dye or tracer to identify the SLN, but dual dye techniques may improve the yield and accuracy, especially after neoadjuvant chemotherapy (see below). A variety of other radioactive, nonradioactive, and colored dyes have also been used to map the SLN for excision. It is also possible to find and remove the sentinel node through the mastectomy incision if a total mastectomy is being performed.

After the surgeon removes the nodes that are identified by a gamma probe and/or visual inspection, they are carefully examined by the pathologist, either immediately (intraoperative consultation) or by permanent section, depending on the situation. Randomized trials have demonstrated the accuracy of this approach, with false-negative rates in the range of 10% and no difference in patient outcomes compared to ALND [136–139]. If the sentinel nodes are negative, then no further surgery for regional nodes is needed. Initially, finding positive sentinel nodes would lead to a completion axillary node dissection. More recently, however, several studies have questioned whether the remaining lymph nodes need to be removed. For patients undergoing BCT followed by radiation and with one or two positive SLNs, the Z1011 trial found that completion ALND was not beneficial [143, 144]. The AMAROS trial in the United Kingdom found that for patients undergoing total mastectomy who had positive SLN, axillary radiation was as effective as ALND with less morbidity [145]. Some studies have now shown that if axillary US is negative for suspicious nodes in the axilla, then surgical staging is unlikely to find significant disease in axillary nodes that would lead to changes in patient treatment [146, 147]. In fact, decisions about systemic adjuvant therapy are now driven more by molecular characterization of breast cancers than by anatomic/pathologic staging.

Whether or not to perform SLN biopsy for patients with DCIS has been controversial [148]. Although positive SLN has been reported in about 5% of patients with “pure” DCIS, this does not appear to impact prognosis significantly and generally is not recommended. However, in certain circumstances, SLN may be appropriate for patients with a core biopsy diagnosis of DCIS. Patients undergoing total mastectomy because of the extent of disease or by patient choice should be considered for SLN biopsy because of the possibility of finding invasive cancer in the mastectomy specimen, which can occur in 20–25% of patients. If this occurs, one cannot go back to map the SLN after the breast has been removed. Similarly, imaging findings (e.g., a mass or extensive disease, especially if high grade) or pathology findings suspicious for invasion increase the likelihood of DCIS being upstaged to invasive cancer and should lead to consideration of a SLN biopsy.

This is a particularly controversial area, particular in an era when MRI and US often detect abnormal nodes that may not be appreciated on physical exam. Regardless of the method of detection, abnormal nodes should generally be sampled by either FNA or core biopsy to document involvement prior to treatment. Whether the patient is considered to be a candidate for neoadjuvant therapy or primary surgery, pathologic confirmation of node involvement impacts the options for management. In the case of those who are not candidates for chemotherapy, then an axillary dissection will generally be appropriate for patients with clinically and pathologically positive nodes. On the other hand, neoadjuvant chemotherapy will often be chosen for women with positive nodes, and the management of the regional nodes for those patients is an evolving issue. With pathologic complete response rates for some subsets of patients (TNBC and HER-2 overexpressing cancers, in particular) ranging from 40 to 70%, the potential to avoid full axillary dissection even in patients presenting with positive nodes has become a reality. Although some still advocate SLN biopsy prior to receiving NCT, finding a positive SLN in this setting may obligate the surgeon to complete an ALND after treatment. Therefore, a number of studies have examined the accuracy of SLN biopsy in patients presenting with positive nodes after NCT. False-negative rates (FNR) of 10–15% have raised concerns that this could result in understaging and undertreatment, but these rates are little different from the FNR for primary SLN biopsy with no prior treatment. Furthermore, a number of maneuvers can reduce the rate of missing residual cancer in nodes, including the use of two dyes (radionuclide and colored dye), removing three or more nodes (if they exist), and marking the positive node with a clip and then confirming removal of the clipped node by specimen mammography [149–156]. In 80% of patients, the clipped node will be one of the nodes that maps with one of the dyes, but in the other 20%, the formerly positive clipped node will be different from the mapped nodes [157, 158]. Finding and removing the clipped node can be facilitated by also marking with India ink or a radioactive seed. With the combination of these techniques, the false-negative rate for post-NCT SLN biopsy for patients with initially positive nodes can be reduced to low single digits [157, 158]. Exceptions to this approach in our institution would be patients with multiple (three or more) nodes that are abnormal prior to therapy or those whose nodes remain abnormal clinically or on imaging at the end of treatment. These patients should generally have a standard axillary node dissection.

The subsequent management of the axilla in patients presenting with positive nodes and receiving NCT is also evolving. For patients whose SLN and clipped node are negative after NCT, most would agree that axillary dissection is unnecessary, but at this time addition of regional nodal irradiation would be considered standard for these patients. In the face of retrospective data suggesting that such patients are at low risk for regional recurrence [159], a clinical trial is currently underway which randomizes patients with documented pathologically positive nodes whose nodes are negative after NCT to regional nodal irradiation versus no irradiation after total mastectomy or breast-only irradiation for patients undergoing BCT [160–162]. Conversely, for patients with persistent cancer in the axilla, the current standard would be to complete an ALND and to add regional nodal irradiation. For these patients, a current clinical trial is randomizing patients with positive SLN after NCT to ALND + regional nodal irradiation versus omitting the ALND. Hopefully, these trials will be completed and provide answers to the questions that remain regarding the management of regional nodes in patients receiving NCT.