Breast Cancer Treatment-Related Imaging and the Postoperative Breast

Combined Clinical and Imaging Workup of Breast Abnormalities

Once the referring physician finds a suspicious breast mass or receives a suspicious mammographic report, the patient undergoes a thorough history and a focused breast examination. Usually a breast cancer specialist (most likely a general surgeon with an interest in breast cancer, a dedicated breast surgeon, or a surgical oncologist) then estimates the patient’s risk of having breast cancer, seeks patterns of familial breast cancer, reviews the imaging and pathology, and helps the patient to make an informed decision on immediate intervention or the need to gather more information.

Most patients then undergo a thorough diagnostic imaging workup. Patients with suspicious palpable abnormalities undergo ultrasound, with or without mammography, depending on age, family history, and level of concern over the finding. For example, ultrasound would likely be the sole imaging modality in an 18-year-old woman with a new breast lump and no family history of breast cancer. On the other hand, ultrasound and mammography would likely be used for a 25-year-old woman with a new palpable lesion and an extensive family history of breast cancer in young relatives. The final decision to incorporate mammography into a very young patient’s workup is a shared responsibility of the clinician directing the breast workup, the radiologist performing the initial imaging (ultrasound in this case), and the patient. Breast magnetic resonance imaging (MRI) is used sparingly during the initial evaluation of a palpable finding, unless there is an extensive breast or ovarian cancer family history, in which case it serves a dual role as both a diagnostic tool on the affected breast and a screening tool on the contralateral breast.

For patients with nonpalpable findings on screening mammography, workup always includes diagnostic mammography, with or without ultrasound. For suspicious calcifications alone, the radiologist usually obtains magnification mammograms, often not needing ultrasound. An exception might be extensive pleomorphic microcalcifications, in which ultrasound might discover masses suggesting invasive cancer within the calcifications, prompting biopsy. However, if there is an image-detected mass, area of architectural distortion, or palpable mass, the radiologist usually uses both mammography and ultrasound to evaluate the abnormality, estimate its size, and later direct the biopsy. Breast MRI may be valuable in selected cases, as discussed in Chapter 7 . Ideally, the radiologist correlates all physical and imaging findings in the report to form a composite picture of all potential abnormalities and their level of suspicion using mammography, ultrasound, and MRI.

Using the combined report, the directing clinician and radiologist plan percutaneous or open biopsy to sample all areas of concern. This sequence varies from patient to patient. This may be as simple as FNA in a young woman with a single area of fibrocystic nodularity and a normal ultrasound or as complex as numerous core biopsies or surgical biopsies in one or both breasts using palpation or image guidance for localization.

Although there are no hard and fast rules about what defines a suspicious palpable abnormality, generally cancers are firm or hard; asymmetric compared with the opposite breast; irregular in shape; and feel as if they are rising up out of the breast tissue, rather than spreading out in the substance of the breast. Physical examination, ultrasound/mammography, and FNA are generally considered the minimum intervention for a suspicious palpable finding and in combination are referred to as the triple test. For suspicious palpable findings in which all components of the triple test are negative, the risk of malignancy is considered approximately 3% or less. Even if all components of the triple test are normal, it is extremely important to inform the patient that there is a low, but measurable, false-negative rate for the triple test and that surgical excision can be performed to completely exclude the possibility of malignancy. This discussion is ideally documented in the medical record. Patients with likely benign palpable findings, unremarkable imaging, and normal percutaneous sampling with FNA (ie, a negative triple test) usually undergo a single follow-up visit 3 to 6 months later with the referring physician for follow-up physical examination and evaluation. Patients who undergo image-guided core biopsy usually undergo repeat imaging at 12 months to assess stability of any residual findings. Progressive findings on repeat palpation or breast imaging at follow-up prompt surgical excision.

For suspicious image-detected nonpalpable lesions, image-guided FNA, percutaneous core biopsy, or wire-localized excisional biopsy is generally considered the minimum intervention. Percutaneous needle core biopsy has become the more common choice. Here, too, it is important to inform the patient of the limitations of percutaneous core biopsy—specifically, that there is a small false-negative rate with needle biopsy. Wire-localized surgical biopsy is usually recommended to exclude malignancy if percutaneous biopsy is indeterminate or discordant with imaging findings or cannot be done. For an anxious patient, wire-localized surgical excision may be a better option initially; the surgeon will usually document this discussion in the medical record. For some patients with lesions close to the chest wall or nipple, wire-localized excisional biopsy may be the safer initial approach.

Breast Cancer Diagnosis and Treatment

Breast cancer treatment planning usually involves surgery, systemic therapy, and radiation therapy. The goals are removing all the cancer from the breast, optimizing chances for locoregional control, and eradicating occult foci of metastatic disease with systemic treatment (eg, hormone therapy, chemotherapy) as indicated. The team of breast imagers, surgeons, medical oncologists, pathologists, radiation oncologists, and breast reconstruction surgeons plan the sequencing of these events. The pathology report is a key component on which treatment is based. The report details tumor histology; size; estrogen, progesterone, and her2neu receptor status; and lymph node involvement. Traditionally, breast tumors are staged using the TNM (tumor, lymph node, metastasis) Classification on Breast Cancer from the American Joint Committee on Cancer (in the 7th edition as of September 2015; Table 8.1 ). The treatment plan is based on this classification, imaging, physical findings, the patient’s wishes, and discussions between the patient and the treating team. A clinical decision algorithm is also available from the National Comprehensive Cancer Network (NCCN) regarding the full spectrum of care.

Locoregional control of breast cancer means eradication of tumor in the breast and treatment to prevent IBTR. If done by surgery first, locoregional control is achieved by either mastectomy or lumpectomy (cancer removal with a margin of normal tissue), and usually is followed by whole-breast or partial breast irradiation. As shown by Protocol B-06 conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP; ), both approaches (lumpectomy with or without breast irradiation and total mastectomy) yield identical disease-free, distant-disease–free and overall survival rates in women with tumors 4 cm or smaller in diameter whether the axillary lymph nodes were positive or negative for metastatic disease. Furthermore, 12 and 20 years of follow-up of subgroups in NSABP B-06 showed that the cumulative incidence of a recurrence of tumor in the ipsilateral breast was significantly higher in the group treated with lumpectomy alone (12 years, 35%; 20 years, 39.2%) compared with the group treated with lumpectomy and breast irradiation (12 years, 10%; 20 years, 14.3%), indicating that lumpectomy followed by breast irradiation is appropriate therapy for women with stage I or II breast cancer ( ).

The radiologist helps the team select candidates for breast-conserving surgery or mastectomy by estimating the location and extent of disease with imaging. The critical information is lesion location, size, and extent of disease. This allows the surgeon to form a 3D representation of normal versus malignant tissue, develop a mental image of the tumor within the breast, estimate the amount of additional tissue needed to obtain tumor-free margins, and plan the incision (surgical approach) with the goal of maximizing the probability of tumor removal and maintaining the best cosmetic result. For example, the patient would be recommended for mastectomy if it is not possible to remove an extensive multicentric invasive breast cancer completely with microscopically clear margins. Still, increasingly there is interest in removing multiple lesions from the same breast while preserving the breast. This is being evaluated by an ongoing prospective trial evaluating outcomes in women with multifocal or multicentric disease treated with breast conservation therapy.

Multifocal disease refers to cancers in the same breast quadrant; multicentric disease refers to cancers in separate quadrants. As a straightforward example, a 3-mm satellite cancer close to the primary tumor is almost always amenable to surgical resection using breast-conserving techniques with an acceptable cosmetic outcome. In contradistinction, a pair of 3- to 4-cm cancers on opposite sides of the breast is usually treated with mastectomy. There are no hard and fast rules for excising multiple lesions with breast conservation; clinical judgment and experience must be used. For this reason, the surgeon requests information regarding the number and size of cancers, as well as their geographic relationship to each other. If too many foci of invasive cancer or extensive ductal carcinoma in situ (DCIS) is present, the patient is not a candidate for breast-conserving surgery because the surgeon may not be able to excise all the cancer with an acceptable cosmetic result and because of concern over an elevated risk of IBTR.

Patients undergo mastectomy if the entire cancer cannot be excised with a good cosmetic result (as just discussed), if the woman has contraindications to radiotherapy, or if it is her preference. Mastectomy candidates usually are offered immediate or staged ipsilateral breast reconstruction with an autologous tissue flap or a tissue expander, unless there are medical contraindications to reconstruction (eg, multiple comorbidities). Because the contralateral breast may be much larger than the operated cancerous breast after surgery, patients often are offered reduction mammoplasty on the contralateral side for a symmetric postoperative appearance. Characteristic appearances of reduction mammoplasty and breast reconstruction are discussed in Chapter 9 .

Breast-conservation patients usually undergo postsurgical whole-breast irradiation to achieve control of residual microscopic disease. Relative contraindications to radiation therapy include pregnancy, previous radiation therapy, and collagen vascular disease such as scleroderma ( Box 8.1 ). Axillary nodal involvement is not a contraindication. Six randomized trials of lumpectomy and radiation therapy showed that the frequency of local recurrence and overall survival (OS) rates are generally comparable to mastectomy. However, IBTRs are reported in 5% of patients at 5 years and in 10% to 15% at 10 years after completion of therapy. Treatment failures (ie, IBTR) usually undergo salvage mastectomy. A trial of women undergoing lumpectomy plus radiation versus mastectomy showed that 9% to 14 % of the lumpectomy plus radiation therapy group had IBTR. With salvage mastectomy, overall and disease-free survival in this group was the same as the mastectomy group at 20 years ( ).

Invasive IBTR usually occurs in the lumpectomy site or quadrant within the first 7 years but rarely earlier than 18 months after treatment. IBTR after 7 years will more likely occur in any quadrant, not necessarily at the original site, and is usually considered a new cancer. IBTR near the original lumpectomy site is associated more frequently with systemic relapse than IBTR in other quadrants, which more often reflect a new primary tumor. It is considered more likely in women who have invasive ductal cancer with an extensive intraductal component, residual disease in the breast, extensive DCIS, lymphatic or vascular invasion, or multicentricity, and is more common in younger women ( Box 8.2 ).

Adjuvant systemic therapy is often used after surgery to achieve radical cure. The types of systemic therapy include chemotherapy, endocrine therapy, and anti-HER2 therapy (trastuzumab, etc.). Chemotherapy alone or in these combinations is selected based on the clinician’s estimates of the likely risks of breast cancer relapse and death, and the likely benefit of adjuvant therapy. Since 2000, it has been recognized that breast cancer is a heterogeneous collection of genetically distinct disease entities, known as intrinsic subtypes. Genetic features or molecular expression status largely affects the therapeutic response and tumor behavior. Generally, tumors with the expression of hormone receptors (eg, estrogen receptor [ER], progesterone receptor [PgR]) and HER2 receptor can respond well to endocrine therapy and anti-HER2 therapy, respectively. Otherwise, chemotherapy may be required to treat the residual disease. However, the indication for chemotherapy for early breast cancers is complex, because no single biomarker predicts chemotherapy response. Particularly in ER-positive breast cancer, the widespread use of adjuvant chemotherapy has resulted in overtreatment in many patients with chemotherapy, although it has contributed to improved prognosis. Various methods thus are being developed to predict chemotherapy response to stratify breast cancer patients’ management, particularly those with ER-positive disease. Adjuvant! Online is an Internet-based tool to provide guidance regarding prognosis and the potential benefit of different chemotherapy protocols by using classic parameters, such as age, histology, lymphatic or vascular invasion, tumor size, nodal stage, ER status, and therapy used ( ). Gene expression profiling (such as Oncotype DX, MammaPrint, and PAM50) has also been developed, and is becoming useful in managing subsets of early stage breast cancer. These gene signatures are the subject of two large randomized trials, one in the United States (the TAILORx trial for Oncotype DX) and the one in Europe (the MINDACT trial for MammaPrint). Oncotype DX (Genomic Health, Redwood City, CA) is a reverse transcriptase polymerase chain reaction (RT-PCR) assay of 21 selected genes in paraffin-embedded tumor tissue. A validated study showed that Oncotype DX quantifies the likelihood of distant recurrence in patients with node-negative, ER-positive breast cancer treated with tamoxifen alone ( ), suggesting Oncotype Dx helps in identifying subgroups who will benefit from adding chemotherapy. MammaPrint (Agendia, Amsterdam, the Netherlands) is a complementary DNA microarray analysis of 70 selected genes in tumor tissue established at the Netherlands Cancer Institute. A prospective clinical study, RASTER, for patients with cT1-3N0M0 breast cancer showed that the MammaPrint is useful in identifying patients who may safely forgo chemotherapy compared with standard clinicopathologic classification ( ). PAM50 (ARUP, Salt Lake City, UT) is a quantitative RT-PCR assay for selected 50 genes that offers intrinsic molecular subtyping and generates a risk of recurrence (ROR) score. Recent studies suggest that the PAM50 ROR score has a significant prognostic value for patients with ER-positive early breast cancer treated with endocrine therapy alone ( ; ; ).

propose the indications of systemic adjuvant therapy based on the presence of hormone receptors and HER2 receptor and also use histology and stage of disease. In addition, a gene signature assay (Oncotype Dx) is also recommended to be considered in patients with tumors >0.5 cm, HER2-negative disease, and either N0 or N1mi (micrometastasis) disease. In 2011, the St. Gallen International Breast Cancer Conference determined the clinicopathologic surrogate definition of intrinsic subtypes (updated in 2013) by using immunohistochemical results of Ki67 index in addition to the status of hormone receptors and HER2 receptor ( ; Table 8.2 ). They recommend systemic treatment according to the subtypes. In this definition, the degrees of Ki67 index and of PgR expression, and the categories of recurrence risk based on gene signature assays if available, are used to stratify ER-positive HER2-negative early breast cancers into “luminal A-like” in which endocrine therapy alone is recommended for most or “luminal B-like (HER2 negative)” in which endocrine therapy with chemotherapy is recommended for most.

Preoperative NAC, combination chemotherapy given before definitive surgical treatment (lumpectomy or mastectomy), is now a standard option for locally advanced or bulky breast cancers. Locally advanced breast cancer usually includes tumors greater than 5 cm (T3-4); inflammatory breast cancers (T4d); those with spread to other tissues around the breast such as the skin, muscle, or ribs (T4a or b); or those with spread to regional lymph nodes (N2-3), which have no distant metastasis. Thus locally advanced breast cancer mostly belongs to stage III or higher disease. Three distinct benefits of NAC compared with postoperative chemotherapy include enhancing the feasibility of breast-conserving surgery, enabling surgical resection of initially inoperable tumors, and assessing for tumor chemosensitivity. NAC provides tumor shrinkage, decreases tumor burden, and allows some patients to undergo lumpectomy and radiation rather than mastectomy for local control. It also allows some patients with initially inoperable tumors to receive potentially curative surgery. After NAC, surgical resection of the original tumor site establishes the type and extent of residual tumor. This information is important for predicting prognosis. A complete pathologic response (no residual cancer in the original tumor bed by histology) is a good prognostic indicator. Surgical lumpectomy with negative margins also helps to determine whether breast-conserving therapy may be the final surgical step as the patient’s best option.

The indication for NAC is now extended to early-stage breast cancer. The NSABP B-18 trial ( ; ) of 1523 women with operable stage I–II breast cancer (T1-3N0M0) showed that NAC with AC (doxorubicin and cyclophosphamide) provided equivalent outcome in disease-free survival (DFS) and OS compared with adjuvant chemotherapy with AC, and that more patients who received NAC than adjuvant chemotherapy underwent breast-conserving surgery. In the neoadjuvant group, the primary tumor response to chemotherapy correlated with outcome, suggesting an advantage of NAC as a predictive factor of outcome. Patients who achieved a pathologic complete response had significantly superior DFS and OS compared with patients who did not. The advantages of NAC found in NSABP B18 have led to greater use of NAC for women with operable breast cancer, especially when they desire a lumpectomy but have large tumors ineligible for conventional conservative surgery at presentation.

Evaluation of Axillary Lymph Nodes

The treatment of invasive breast cancer historically involved removal of ipsilateral axillary lymph nodes. This was natural, because most women receiving treatment for breast cancer 100 years ago had nodal involvement. With earlier detection of breast cancer, nodal involvement is no longer the norm. In fact, approximately 65% to 70% of women with newly diagnosed invasive breast cancer have normal lymph nodes and therefore will not derive any benefit from ALND.

ALND is a complete en bloc removal of the level I and II lymph nodes ( Table 8.3 ), and is problematic from the standpoint of side effects. It exposes patients to the risk of major complications such as lymphedema, shoulder dysfunction, and sensory changes in and around the axilla. To address this problem, routine level I/level II ALND has evolved to use the SLNB as an initial screen for nodal involvement in patients who are clinically node negative or there are no palpable suspicious axillary lymph nodes on physical examination.

SLNB was initially described for patients with penile cancer, but did not attract much attention until it was broadly adopted for use in melanoma patients. In patients with breast cancer, SLNB was first used in 1993, and its proof of concept was established in the 1990s ( ). SLNB is performed by injecting a tracer material, either a radionuclide, blue dye, or both, into the breast either preoperatively or perioperatively and by looking for evidence of the tracer in one or more sentinel nodes ( Box 8.3 ). SLNB alone does not eliminate, but does significantly decrease, the risk of developing the common complication of lymphedema. The reported sensitivity of SLNB ranges from 88% to 100%, whereas the specificity has been consistently very high, at almost 100% using hematoxylin and eosin (H&E) assessment ( ).

NSABP trial B-32 was a randomized controlled phase 3 trial designed to answer the question if SLNB had the same OS, disease-free survival (DFS) and regional control as ALND when the SLN was negative. The trial involved clinically node-negative patients with operable breast cancer stratified by age, tumor size, and surgical treatment (lumpectomy versus mastectomy) who were randomly assigned to ALND versus SLNB. If the SLN was positive, patients went on to completion ALND. Survival results showed no significant difference in OS, DFS, and regional control between SLN-positive patients undergoing ALND versus SLN-negative patients who had no further axillary surgery, suggesting that SLNB without ALND is appropriate when the SLN is negative ( ).

However, a second central pathology review of paraffin blocks of SLNs that were initially read as negative showed an overall case conversion rate to “positive” of 10.3% of cases ( ). Despite the discovery that initially negative SLN cases had occult metastases in up to 10.3% of cases, the entire group of patients with “negative” SLNB with no further treatment had the same OS and DFS as patients undergoing ALND. The occult metastases in the initially negative-SLNB–only group were ≤1 mm in size. This discovery brought into question the significance of tiny metastases and, specifically, if survival was associated with tiny metastases or isolated tumor cells, and if there was need for ALND in the setting of H&E-negative but immunohistochemistry (IHC)-positive SLN. In their follow-up study at 5 years, revealed that log-rank tests showed patients with occult metastases had a significant difference in OS ( P = 0.03), DFS ( P = 0.02), and distant disease-free interval (DDF; P = 0.04) but suggested that the magnitude of the difference in outcome at 5 years was 1.2 percentage points and was small enough to not indicate clinical benefit for ALND.

The ACOSOG Z0010 prospective trial studied the significance and the survival of women with immunohistochemistry (IHC)-detected micrometastases when the SLN was negative by H&E staining. Women had clinical T12N0M0 breast cancer and received breast-conserving therapy and SLN dissection ( ). If the SLN was negative by H&E staining, the patient had no ALND. OS and DFS were compared between women who were SLN negative by both H&E and IHC staining versus women who were SLN negative by H&E but were positive by IHC. ACOSOG Z0010 revealed that 10.5% of H&E-negative SLNs contained IHC-positive occult metastases. However, the IHC-negative and IHC-positive patients had no difference in OS at a median of 6.3 years. The NSABP B-32 and ACOSOG Z0010 trials suggested that SLNB showing H&E-negative SLNs was acceptable without ALND even when micrometastatic disease was presumed to be present in approximately 10% of patients.

However, the next question to be answered was if women with limited positive SLNs by H&E and no ALND had the same survival as women with positive SLNs undergoing ALND. The ACOSOG Z0011 phase 3 noninferiority trial asked if patients with limited SLN metastatic breast cancer could undergo SLNB and have the same survival as women with limited SLN metastatic breast cancer undergoing ALND ( ). In this trial, inclusion criteria included women with clinical T1-T2 invasive breast cancer, no palpable adenopathy, and no more than two SLNs containing metastases identified by frozen section, touch preparation, or H&E staining on permanent section after SLNB. All women underwent SLNB and were randomized to SLNB alone or ALND. All patients underwent lumpectomy with postoperative whole-breast radiotherapy. Exclusion criteria were those with three or more involved SLN or planned mastectomy. Of 420 patients randomized to ALND, 106 (27.4%) had additional positive nodes removed beyond the SLN. At a median follow-up of 6.3 years, ALND did not significantly affect OS or DFS in women treated with lumpectomy, systemic therapy, and tangential WB-XRT compared with the use of SLND alone ( ). Because of ACOSOG Z0011 inclusion criteria, it is important for radiologists to report suspicious-appearing lymph nodes on imaging, particularly if there are three or more suspicious lymph nodes (which would exclude patients for SLND alone).

The American Society of Breast Surgeons (ASBS) suggests that SLNB may be appropriate for T1-T2 invasive breast cancer with a clinically negative axilla, DCIS sufficient to require mastectomy or DCIS with suspected/proved microinvasion, and patients with clinically negative axillary nodes following NAC ( Box 8.4 ). Patients with multicentric cancers, T3 disease, or pregnancy are also indicated as possible candidates for SLNB. ALND has largely been replaced by SLNB for patients with clinical node-negative breast cancer but is still required for a significant proportion of patients ( Box 8.5 [ASBS ALND indications]).

The role of the radiologist is to understand the rationale for SLNB and to facilitate its performance. First, tracer is not to be injected into the biopsy cavity or the tumor; tracer injected into a biopsy site cavity is likely to remain in the cavity rather than be transported into the lymphatics. The most common tracers are technetium-99 sulfur colloid and lymphazurin blue dye; some also use methylene blue dye.

Preoperative lymphoscintigraphy is used in some facilities to assist preoperative localization of SLNs in the axilla or in extraaxillary sites ( Fig. 8.1 ). Most commonly these extraaxillary sites are in the supraclavicular, infraclavicular, or internal mammary regions. If tracer does not identify an axillary SLN, the surgeon may choose to harvest an SLN from one of these other sites. Some facilities do not remove an internal mammary SLN or other nonaxillary SLN because of the very low frequency of isolated positive biopsies (usually <3%) and the relatively few cases that would result in meaningful changes in prognosis or therapy. Perhaps not surprisingly, institutions that harvest both axillary and internal mammary SLNs have demonstrated a poorer prognosis when lymph nodes at both sites are involved.

Although there are differences of opinion as to the optimal location of tracer injection, as well as optimal tracer modality, there is general agreement from randomized studies that the technique is sensitive and specific enough to obviate the need for a full ALND in patients whose sentinel nodes test negative for tumor. Generally, the SLN is harvested at the time of surgery and tested with touch preparation or frozen section intraoperatively. If there are tumor cells in more than two SLNs, the surgeon proceeds to a completion level I/level II ALND. Nonvisualization of the SLN on lymphoscintigraphy does not preclude SLN identification by the surgeon in the operating room. The SLN may be within thick adipose tissue that can only be identified by the gamma probe in the operating room. The yield for SLN identification in the operating room when it cannot be visualized on lymphoscintigraphy can be increased if blue dye is also used.

Intraoperative evaluation of SLNs occasionally yields false-positive findings. False-negative findings are more common. This can precipitate return of the patient to the operating room weeks after the original SLNB for completion ALND if indicated.

Based on current American Joint Committee on Cancer guidelines, nodal staging is based on the maximal size of the single largest tumor deposit in am SLN (if the SLN is the only involved node) as well as the number of involved lymph nodes. The descriptive category for the smallest extent of disease, isolated tumor cells, means that no single tumor deposit in an axillary node is larger than 0.2 mm. Patients with isolated tumor cells are considered to have normal nodes and are usually not treated with a completion ALND. Proceeding from SLNB alone to the wider axillary node clearance typically requires micrometastatic (>0.2- to 2-mm tumor cell cluster in an SLN) or macrometastatic (>2-mm focus) disease within three or more SLN. In patients with only one or two positive SLNs, ACOSOG Z0011 suggests that no further axillary lymph node surgery may be necessary if they receive adjuvant radiotherapy. In addition, there are new trials evaluating the need for nodal clearance after SLN after NAC. Management of the axilla is performed independent of the decision to pursue lumpectomy or mastectomy.

Not all patients are candidates for SLNB. For example, patients who present with clinically involved axillary nodes may proceed directly to ALND if NAC is not pursued. However, it is important to exercise caution in declaring an axillary lymph node as clinically positive. With the increased frequency of percutaneous core biopsy, more and more patients are presenting to breast cancer specialists with enlarged reactive nodes. A recent study by experienced breast surgeons demonstrated that clinical examination in this setting often overestimates the probability that lymph nodes are involved, which in turn could overestimate the number of patients who proceed directly to ALND. Although SLNB has been widely adopted as a precursor to a full ALND for most patients, many have sought to use imaging studies to determine the need for ALND. Toward this end, investigators have assessed the preoperative appearance of nodes on mammography, ultrasound, MRI, and even positron emission tomography (PET). Among these, only PET with a high standardized uptake value may provide near-definitive proof of nodal involvement preoperatively in the absence of percutaneous sampling. Here, too, one must be careful to distinguish between a reactive node versus an uninvolved node.

One preoperative axillary imaging method that has gained a following is axillary lymph node ultrasound with percutaneous FNA of suspicious nodes ( Fig. 8.2 ). Although this test is not a routine part of the initial breast imaging evaluation, there is a new appreciation for preoperative evaluation of ipsilateral axillary lymph nodes in the setting of breast cancer. Axillary ultrasound is particularly helpful when the results of clinical examination of the axilla are suspicious for cancer. Several studies have recently been published using ultrasound-guided FNA or core biopsy to document nodal involvement preoperatively, thus allowing the surgeon to bypass if needed in appropriate clinical settings. This can obviate several known issues with intraoperative assessment of SLNs, such as the time needed to harvest one or more nodes, the intraoperative time needed for pathology to evaluate the node and, most important, the potential for false-negative touch preparation or frozen section at the time of surgery, which may lead to reoperation at a later date. It is possible to mark the biopsied positive lymph nodes by either a metallic marker or by tattoo at the time of biopsy if the nodes are positive to identify them at surgery, as needed.

Clinical and Breast Imaging Factors in Determining Appropriate Local Therapy: Lumpectomy or Mastectomy

The therapeutic options for local control of a breast malignancy are lumpectomy (almost always followed by radiotherapy) and mastectomy. Lumpectomy (followed by whole-breast radiotherapy) was introduced approximately 40 years ago and offers equivalent survival to mastectomy. Mastectomy has a slightly lower risk of local recurrence than lumpectomy and obviates the need for radiotherapy in most patients. The use of postmastectomy radiotherapy is controversial in premenopausal women with one to three involved nodes (see the meta-analysis of randomized studies with and without radiotherapy by the Early Breast Cancer Trialists’ Collaborative Group [EBCTCG] [ EBCTCG, 2011]), but it is a common recommendation for women with tumors larger than 5 cm or with four or more involved nodes. The equivalence in OS between lumpectomy with radiotherapy and mastectomy was shown in Protocol B-06 conducted by the NSABP and the Milan I trial conducted in Italy.

The breast imager plays a critical role in aiding the surgeon to make the right therapeutic choice by showing how much cancer is in the breast. There is virtually no disagreement that patients with a unifocal DCIS or invasive cancer may be treated with breast conservation therapy if the entire tumor can be removed with a good cosmetic result and if there are no relative contraindications to radiation therapy (ie, pregnancy, collagen vascular disease, poorly defined or multicentric disease or prior radiotherapy involving the breast).

The controversy regarding the best surgical approach concerns patients with multifocal disease. Some physicians believe that mastectomy is the proper choice for such patients. This preference may be because of results from the original clinical trials comparing lumpectomy with mastectomy, which involved almost exclusively women with unifocal breast cancers. Hence, the safety of breast conservation with respect to local recurrence, distant metastasis, and survival is not as well documented in women with multifocal disease. Still, surgeons are increasingly offering breast conservation to patients with multifocal disease. Thus there is no hard and fast rule regarding how many satellite lesions, or what distance between lesions, constitutes an absolute indication for mastectomy. It is the physician’s clinical judgment to avoid predisposing the patient to IBTR; recent data suggest that an IBTR may increase the risk of distant metastasis and death from breast cancer.

Whether the surgeon offers lumpectomy to patients with unifocal disease alone or to patients with multifocal disease, tumor-free margins are a must. For example, offering a woman breast conservation may be reasonable if she has multifocal invasive carcinoma with subcentimeter lesions 3 mm apart and margins that are tumor free by several millimeters. On the other hand, breast conservation may not be offered if a patient has multifocal high-grade DCIS scattered over an area of 5 to 6 cm with only a 1-mm margin; in this example, one would be concerned about additional multifocal disease just beyond the surgical margin.

The definition of tumor-free margin has varied among institutions, with some accepting the NSABP model of nontransection and others requiring a 2-mm or greater tumor-free margin. However, a recent consensus guideline from the Society of Surgical Oncology (SSO) and the American Society of Radiation Oncology (ASTRO) has recommended that a negative margin be defined as “no tumor on ink” based on a review of multiple studies. Generally, the margin status must be carefully considered in patients with multifocal disease. Ideally, these patients should have the multiple lesions resected in continuity to gain the best histologic understanding of size, extent, and relationship of lesions to one another, and of the true margins.

Some surgeons offer breast conservation to patients with known multicentric disease, but the less controversial route is with mastectomy as initial treatment. As stated previously, no prospective, randomized study to date has evaluated the safety and effectiveness of breast conservation therapy in the setting of multifocal or multicentric disease. Retrospective studies have been published suggesting that this approach may be safe by demonstrating comparable local recurrence rates in multifocal as well as unifocal disease, whereas others suggest higher IBTR rates. These studies are not powered to draw definitive conclusions but do suggest that further investigation is warranted. There is currently a prospective trial following patients with multifocal or multicentric disease treated with breast conservation therapy to determine the rate of IBTR in this population.

Preoperative Imaging

Mammography, ultrasound, and MRI for tumor extent are important tools for selecting appropriate breast conservation therapy candidates and planning surgery ( Table 8.4 ). Mammography is the mainstay for determining extent of disease. It identifies diffuse or multicentric disease by finding suspicious breast masses and pleomorphic calcifications ( Fig. 8.3 ). Mammography also can identify benign, extensive, and innumerable bilateral calcifications that could hide early tumor recurrence. Such calcifications are a relative contraindication to breast conservation therapy. Furthermore, mammography finds DCIS that is invisible to MRI. Specifically, approximately 25% of DCIS cases are false-negative on MRI and are discovered only by visualizing pleomorphic calcifications on the mammogram.

On the other hand, MRI has been especially useful in predicting tumor extent before the first surgical procedure ( Fig. 8.4 ). Some investigators have claimed particular effectiveness of MRI in women with invasive lobular carcinoma or showing tumor invasion into the pectoralis muscle or chest wall ( Fig. 8.5 ). With respect to invasive lobular carcinoma, several studies have suggested that MRI may be more effective in detecting the extent of disease than physical examination, mammography, and ultrasound. However, false-negative studies in these series have led to mixed opinions regarding the routine use of MRI in staging invasive lobular carcinoma.

Chest wall tumor invasion on MRI was shown by obliteration of the fat plane between the tumor and the pectoralis muscle, with muscle enhancement, and was proven in five of five cases at surgery ( ). No muscle involvement was seen at surgery when muscle enhancement was absent in 14 of 14 cases.

MRI also helps exclude candidates for APBI when it finds more than one focus of cancer. reported a 95% tumor detection rate with MRI and a change in surgical management in 26% (69/267) of patients requiring wider/separate excision or mastectomy, with pathologic verification in 71% (49/69).

Overall, these studies show that MRI may be helpful in surgical planning, but they also indicate that MRI prompts a number of unnecessary biopsies because of a relative lack of specificity. MRI also has false-negative results in invasive lobular carcinoma and DCIS. Other data show that MRI may be associated with treatment delay and an increased mastectomy rate and does not decrease the number of fewer positive margins at surgery. The use of pretreatment MRI before definitive breast cancer surgery remains controversial, particularly if one anticipates whole-breast radiotherapy. The literature on this subject is extensive.

When imaging is complete, additional dialog with the breast imaging team or additional review of imaging studies may be necessary to help the surgeon, medical oncologist, or radiation oncologist properly counsel the patient regarding appropriate treatment options. This involves a review of the original workup to ensure that all potential abnormalities on physical examination have been evaluated and that the breast imaging workup has been completed (such as up-to-date contralateral mammography as well as additional ultrasound or mammographic imaging for lesions previously considered of secondary concern). The thorough combination of abnormalities identified by palpation or on breast imaging helps ensure that any suspicious foci of tumor are evaluated and incorporated into the treatment plan.

According to , systemic staging using imaging modalities such as chest diagnostic computed tomography (CT), abdominal (±pelvic) CT or MRI, and bone scan (or sodium fluoride PET/CT), is usually recommended for patients with clinically advanced cancer (clinical stage III or IV), and those with clinical stage I and II who have signs or symptoms of distant metastases. ¹⁸ F-FDG PET/CT is considered as an optional study for those with clinical stage III or IV disease ( Fig. 8.6 ).

Normal Postoperative Imaging Changes After Breast Biopsy or Lumpectomy

To perform a local excision for diagnostic or therapeutic purposes, the surgeon makes a skin incision, removes the mass or wire-localized abnormality, and then closes the subcutaneous tissues and skin. More tissue is excised when removing a cancer to obtain a margin of normal tissue. Usually, the surgeon allows the surgical cavity to fill in with fluid and granulation tissue.

As a rule, mammograms are not often obtained immediately after diagnostic surgical excisional biopsy. However, in the rare cases when a mammogram is obtained within a few days of surgery, mammography shows a round or oval mass in the postoperative site representing a seroma or hematoma, with or without air. This mass represents the biopsy cavity, filled with fluid that should resolve over time ( Fig. 8.7 ). The adjacent breast tissue shows thickening of trabeculae in subcutaneous fat and increased density caused by local edema or hemorrhage. Skin thickening at the incision is usually present. On MRI the biopsy site is filled with blood or seroma. The fluid in the biopsy cavity is high signal intensity on T2-weighted noncontrast fat-suppressed images ( Fig. e8.1 ).

Over the subsequent weeks, the postoperative site resorbs the air and fluid collection; the collection is replaced by fibrosis and scarring, with residual focal skin thickening and breast edema. On MRI, the immediate postbiopsy cavity is a fluid-filled structure with surrounding normal healing tissue enhancement for up to 18 months after the biopsy. The biopsy cavity shows high signal intensity, architectural distortion, and a scar that can simulate cancer ( Fig. 8.8 ; Box 8.6 ). The biopsy site usually contains fluid from the seroma, which will be bright on T2-weighted images on MRI. Rim enhancement around the biopsy site is normal even if there is no residual tumor and is caused by healing. In the ipsilateral axilla, reactive lymph nodes may develop that cannot be distinguished from metastatic disease ( Fig. 8.9 ). MRI after surgery may reveal cancer at the margin edge by showing clumped enhancement or an eccentric residual mass. Although immediate postbiopsy MRI for cancer staging may depict cancer at the biopsy margin, it is more often used to look for cancer elsewhere in the breast away from the biopsy site.

Normal postoperative findings on mammography include architectural distortion, increased density, and parenchymal scarring in at least 50% of patients ( Box 8.7 ). These findings diminish in severity over time ( Fig. 8.10 ). After 3 to 5 years, the findings should be stable on subsequent mammograms. On the mammogram, in 50% to 55% of cases, the biopsy cavity resolves so completely that it leaves no scar or distortion in the underlying breast parenchyma, and only comparison with prebiopsy mammograms indicates that breast tissue is missing. In other cases, the scar appears as a chronic architectural distortion or a spiculated mass more evident on one projection than the other.

The remaining 45% to 50% of patients continue to have variable mammographic findings ranging from spiculated masslike scars to slight architectural distortion ( Fig. 8.11 ). In still other, more rare cases, seroma cavities persist, appearing as a round or oval mass as shown in Fig. 8.7 .

Postbiopsy scars often have a spiculated masslike appearance that can simulate cancer. Spiculated masses should be viewed with suspicion unless one knows that a biopsy was performed in that location. For this reason, it is important to document the date and location in the breast of previous biopsies on the breast history sheet. Some facilities also place a linear metallic scar marker directly on the skin’s biopsy scar before taking the mammogram to show the previous biopsy site. On the mammogram, the linear metallic scar marker on the skin will be near the underlying scar. The skin scar may not be immediately adjacent to the scar inside the breast because the skin is compressed away from the underlying breast parenchyma during the mammogram, but the skin scar is always in close proximity to the postbiopsy scar. If a spiculated mass is seen far from the metallic scar marker, the mass might be cancer rather than a scar. The radiologist reviews the preoperative mammograms to see where the biopsy occurred and correlates the prebiopsy and current mammograms to make this determination ( Fig. 8.e8.2 ).

Fat necrosis is common after a breast biopsy and usually appears as a radiolucent lipid-filled mass. Mammography is pathognomonic for fat necrosis if it shows lipid cysts or typical calcified eggshell-type rims around a radiolucent center ( Fig. 8.12 ). The fat necrosis, lipid cyst, and calcifications usually form in the scar, so these findings should be located near any linear metallic scar markers on the skin. As shown in Chapter 3 , calcifications around an oil cyst or fat necrosis can be seen easily with tomosynthesis (see Fig. 3.32 ).

On ultrasound, the immediate postoperative site shows a seroma or hematoma, breast edema, and focal skin thickening. The fluid collection occasionally contains air. More commonly, the seroma is completely filled with fluid, sometimes containing septa or debris that has varying appearances on ultrasound ( Figs. 8.13 and 8.14 ). Usually the incision can be traced from the biopsy cavity up to the skin and is shown as a linear scar that disturbs the normal breast architecture ( Box 8.8 ).