Multimodality Imaging of Benign and Malignant Diseases of the Nipple-Areolar Complex.

The nipple-areolar complex (NAC), a unique anatomic structure of the breast, encompasses the terminal intramammary ducts and skin appendages. Several benign and malignant diseases can arise within the NAC. As several conditions have overlapping symptoms and imaging findings, understanding the distinctive nipple anatomy, as well as the clinical and imaging features of each NAC disease process, is essential. A multimodality imaging approach is optimal in the presence or absence of clinical symptoms. The authors review the ductal anatomy and anomalies, including congenital abnormalities and nipple retraction. They then discuss the causes of nipple discharge and highlight best practices for the imaging workup of pathologic nipple discharge, a common condition that can pose a diagnostic challenge and may be the presenting symptom of breast cancer. The imaging modalities used to evaluate and differentiate benign conditions (eg, dermatologic conditions, epidermal inclusion cyst, mammary ductal ectasia, periductal mastitis, and nonpuerperal abscess), benign tumors (eg, papilloma, nipple adenoma, and syringomatous tumor of the nipple), and malignant conditions (eg, breast cancer and Paget disease of the breast) are reviewed. Breast MRI is the current preferred imaging modality used to evaluate for NAC involvement by breast cancer and select suitable candidates for nipple-sparing mastectomy. Different biopsy techniques (US -guided biopsy and stereotactic biopsy) for sampling NAC masses and calcifications are described. This multimodality imaging approach ensures an accurate diagnosis, enabling optimal clinical management and patient outcomes. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Diffusion Tensor Imaging for Characterizing Changes in Triple-Negative Breast Cancer During Neoadjuvant Systemic Therapy.

BACKGROUND: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST). PURPOSE: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST. STUDY TYPE: Prospective. POPULATION: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). FIELD STRENGTH/SEQUENCE: 3.0 T/reduced field of view single-shot echo-planar DTI sequence. ASSESSMENT: Three MRI scans were acquired longitudinally (pre-treatment, after 2 cycles of NAST, and after 4 cycles of NAST). Eleven histogram features were extracted from DTI parameter maps of tumors, a peritumoral region (PTR), and FGT in the ipsilateral breast. DTI parameters included apparent diffusion coefficients and relative diffusion anisotropies. pCR status was determined at surgery. STATISTICAL TESTS: Longitudinal changes of DTI features were tested for discrimination of pCR using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC). A P value <0.05 was considered statistically significant. RESULTS: 47% of patients (40/86) had pCR. DTI parameters assessed after 2 and 4 cycles of NAST were significantly different between pCR and non-pCR patients when compared between tumors, PTRs, and FGTs. The median surface/average anisotropy of the PTR, measured after 2 and 4 cycles of NAST, increased in pCR patients and decreased in non-pCR patients (AUC: 0.78; 0.027 ± 0.043 vs. -0.017 ± 0.042 mm2 /s). DATA CONCLUSION: Quantitative DTI features from breast tumors and the peritumoral tissue may be useful for predicting the response to NAST in TNBC. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Predicting pathological complete response to neoadjuvant systemic therapy for triple-negative breast cancers using deep learning on multiparametric MRIs.

We trained and validated a deep learning model that can predict the treatment response to neoadjuvant systemic therapy (NAST) for patients with triple negative breast cancer (TNBC). Dynamic contrast enhanced (DCE) MRI and diffusion-weighted imaging (DWI) of the pre-treatment (baseline) and after four cycles (C4) of doxorubicin/cyclophosphamide treatment were used as inputs to the model for prediction of pathologic complete response (pCR). Based on the standard pCR definition that includes disease status in either breast or axilla, the model achieved areas under the receiver operating characteristic curves (AUCs) of 0.96 ± 0.05, 0.78 ± 0.09, 0.88 ± 0.02, and 0.76 ± 0.03, for the training, validation, testing, and prospective testing groups, respectively. For the pCR status of breast only, the retrained model achieved prediction AUCs of 0.97 ± 0.04, 0.82 ± 0.10, 0.86 ± 0.03, and 0.83 ± 0.02, for the training, validation, testing, and prospective testing groups, respectively. Thus, the developed deep learning model is highly promising for predicting the treatment response to NAST of TNBC.Clinical Relevance- Deep learning based on serial and multiparametric MRIs can potentially distinguish TNBC patients with pCR from non-pCR at the early stage of neoadjuvant systemic therapy, potentially enabling more personalized treatment of TNBC patients.

Triple-Negative Breast Cancer: Histopathologic Features, Genomics, and Treatment.

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive group of tumors that are defined by the absence of estrogen and progesterone receptors and lack of ERBB2 (formerly HER2 or HER2/neu) overexpression. TNBC accounts for 8%-13% of breast cancers. In addition, it accounts for a higher proportion of breast cancers in younger women compared with those in older women, and it disproportionately affects non-Hispanic Black women. TNBC has high metastatic potential, and the risk of recurrence is highest during the 5 years after it is diagnosed. TNBC exhibits benign morphologic imaging features more frequently than do other breast cancer subtypes. Mammography can be suboptimal for early detection of TNBC owing to factors that include the fast growth of this cancer, increased mammographic density in young women, and lack of the typical features of malignancy at imaging. US is superior to mammography for TNBC detection, but benign-appearing features can lead to misdiagnosis. Breast MRI is the most sensitive modality for TNBC detection. Most cases of TNBC are treated with neoadjuvant chemotherapy, followed by surgery and radiation. MRI is the modality of choice for evaluating the response to neoadjuvant chemotherapy. Survival rates for individuals with TNBC are lower than those for persons with hormone receptor-positive and human epidermal growth factor receptor 2-positive cancers. The 5-year survival rates for patients with localized, regional, and distant disease at diagnosis are 91.3%, 65.8%, and 12.0%, respectively. The early success of immunotherapy has raised hope regarding the development of personalized strategies to treat TNBC. Imaging and tumor biomarkers are likely to play a crucial role in the prediction of TNBC treatment response and TNBC patient survival in the future. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Assessment of Response to Neoadjuvant Systemic Treatment in Triple-Negative Breast Cancer Using Functional Tumor Volumes from Longitudinal Dynamic Contrast-Enhanced MRI.

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles (C2) and 4 cycles (C4) of NAST as predictors of response in TNBC. A group of 100 patients with stage I-III TNBC who underwent DCE MRI at baseline, C2, and C4 were included in this study. Tumors were segmented on DCE images of 1 min and 2.5 min post-injection. FTVs were measured using the optimized percentage enhancement (PE) and signal enhancement ratio (SER) thresholds. The Mann-Whitney test was used to compare the performance of the FTVs at C2 and C4. Of the 100 patients, 49 (49%) had a pathologic complete response (pCR) and 51 (51%) had a non-pCR. The maximum area under the receiving operating characteristic curve (AUC) for predicting the treatment response was 0.84 (p < 0.001) for FTV at C4 followed by FTV at C2 (AUC = 0.82, p < 0.001). The FTV measured at baseline was not able to discriminate pCR from non-pCR. FTVs measured on DCE MRI at C2, as well as at C4, of NAST can potentially predict pCR and non-pCR in TNBC patients.

Prediction of pathologic complete response to neoadjuvant systemic therapy in triple negative breast cancer using deep learning on multiparametric MRI.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Neoadjuvant systemic therapy (NAST) followed by surgery are currently standard of care for TNBC with 50-60% of patients achieving pathologic complete response (pCR). We investigated ability of deep learning (DL) on dynamic contrast enhanced (DCE) MRI and diffusion weighted imaging acquired early during NAST to predict TNBC patients' pCR status in the breast. During the development phase using the images of 130 TNBC patients, the DL model achieved areas under the receiver operating characteristic curves (AUCs) of 0.97 ± 0.04 and 0.82 ± 0.10 for the training and the validation, respectively. The model achieved an AUC of 0.86 ± 0.03 when evaluated in the independent testing group of 32 patients. In an additional prospective blinded testing group of 48 patients, the model achieved an AUC of 0.83 ± 0.02. These results demonstrated that DL based on multiparametric MRI can potentially differentiate TNBC patients with pCR or non-pCR in the breast early during NAST.

Overview of incidental breast lesions.

Screening mammography identifies early-stage breast cancers and is associated with reduced breast cancer mortality. An unintended consequence of breast screening is the detection and diagnosis of multiple incidental benign and malignant breast lesions, including the heterogenous group of incidental benign (B3) lesions with uncertain biological outcomes and malignant potential, for which management remains controversial. Recent shifts toward more conservative management approaches, including the identification of patients who can undergo observation after vacuum-assisted excision, has gained interest. This commentary provides an overview of incidental B3 lesions and summarizes the current management paradigms for them.

MRI for Evaluation of Complications of Breast Augmentation.

Breast augmentation is one of the most common aesthetic procedures performed in the United States. Several techniques of breast augmentation have been developed, including the implantation of breast prostheses and the injection of autologous fat and other materials. The most common method of breast augmentation is to implant a prosthesis. There are different types of breast implants that vary in shape, composition, and the number of lumina. The rupture of breast implants is the leading cause of implant removal. The rupture rate increases substantially with the increasing age of the implant. Most implant ruptures are asymptomatic. Implant complications can be grouped into two categories: local complications in the breast and adjacent soft tissue, and systemic complications associated with rheumatologic or neurologic symptoms. The onset of local complications may be early (infection and periprosthetic collections including seromas, hematomas, or abscesses) or late (capsular contraction, implant rupture, gel bleed, or breast implant-associated anaplastic large cell lymphoma). Although mammography is the imaging modality for breast cancer screening, noncontrast breast MRI is the imaging modality of choice for evaluation of the integrity of breast implants and the complications of breast augmentation, for equivocal findings at conventional imaging, and as a supplement to mammography in patients with free injectable materials. The fifth edition of the Breast Imaging Reporting and Data System (BI-RADS) provides a systematic outline for MRI evaluation of patients with breast implants. Silicone- and water-selective sequences provide useful supplemental information to confirm intracapsular and extracapsular rupture. Breast MRI for evaluation of implant integrity does not require intravenous contrast material. The use of MRI contrast material in patients with breast augmentation is indicated when infection or malignancy is suspected. Radiologists should have a thorough understanding of the different techniques for breast augmentation, normal imaging features, and complications specific to breast augmentation. An invited commentary by Ojeda-Fournier is available online. ©RSNA, 2022.

BI-RADS Ultrasound Lexicon Descriptors and Stromal Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer.

PURPOSE: Increased levels of stromal tumor-infiltrating lymphocytes (sTILs) have recently been considered a favorable independent prognostic and predictive biomarker in triple-negative breast cancer (TNBC). The purpose of this study was to determine the relationship between BI-RADS (Breast Imaging Reporting and Data System) ultrasound lexicon descriptors and sTILs in TNBC. MATERIALS AND METHODS: Patients with stage I-III TNBC were evaluated within a single-institution neoadjuvant clinical trial. Two fellowship-trained breast radiologists used the BI-RADS ultrasound lexicon to assess pretreatment tumor shape, margin, echo pattern, orientation, posterior features, and vascularity. sTILs were defined as low <20 or high ≥20 on the pretreatment biopsy. Fisher's exact tests were used to assess the association between lexicon descriptors and sTIL levels. RESULTS: The 284 patients (mean age 52 years, range 24-79 years) were comprised of 68% (193/284) with low-sTIL tumors and 32% (91/284) with high-sTIL tumors. TNBC tumors with high sTILs were more likely to have the following features: (1) oval/round shape than irregular shape (p = 0.003), (2) circumscribed or microlobulated margins than spiculated, indistinct, or angular margins (p = 0.0005); (3) complex cystic and solid pattern than heterogeneous pattern (p = 0.006); and (4) posterior enhancement than shadowing (p = 0.002). There was no significant association between sTILs and descriptors for orientation and vascularity (p = 0.06 and p = 0.49, respectively). CONCLUSION: BI-RADS ultrasound descriptors of the pretreatment appearance of a TNBC tumor can be useful in discriminating between tumors with low and high sTIL levels. Therefore, there is a potential use of ultrasound tumor characteristics to complement sTILs when used as stratification factors in treatment algorithms for TNBC.

The Challenging Image-Guided Preoperative Breast Localization: A Modality-Based Approach.

Breast conservation surgery (BCS) is the standard of care for treating patients with early-stage breast cancer and those with locally advanced breast cancer who achieve an excellent response to neoadjuvant chemotherapy. The radiologist is responsible for accurately localizing nonpalpable lesions to facilitate successful BCS. In this article, we present a practical modality-based guide on approaching challenging pre-operative localizations and incorporate examples of challenging localizations performed under sonographic, mammographic, and MRI guidance, as well as under multiple modalities. Aspects of preprocedure planning, modality selection, patient communication, and procedural and positional techniques are highlighted. Clip and device migration is also considered. Further, an overview is provided of the most widely used wire and nonwire localization devices in the United States. Accurate pre-operative localization of breast lesions is essential to achieve successful surgical outcomes. Certain modality-based techniques can be adopted to successfully complete challenging cases.

Bracketing with Multiple Radioactive Seeds to Achieve Negative Margins in Breast Conservation Surgery: Multiple Seeds in Breast Surgery.

INTRODUCTION: Breast conservation surgery (BCS) is the treatment of choice for unifocal, early-stage breast cancer. The ability to offer BCS to a wider subset of patients, including those with multifocal/multicentric cancer as well as extensive ductal carcinoma in situ, has emerged over time, especially in those undergoing joint oncoplastic reconstruction and those treated with neoadjuvant therapy. However, localization techniques using multiple radioactive seeds for bracketing in this patient subset have not been validated. MATERIALS AND METHODS: A single-institution retrospective review was conducted of all patients with breast cancer who underwent BCS, guided by multiple bracketed iodine I 125 radioactive seeds between January 2014 and April 2017. RESULTS: Bracketing of breast cancer using 2 or more radioactive seeds was performed in 157 breasts in 156 patients. Negative margins were achieved in 124 of 157 (79%) breasts, including 33 cases (21%) that underwent targeted margin reexcision at the time of surgery after intraoperative, multidisciplinary margin assessment. Thirty-three cases (21%) resulted in close or positive margins, of which 11 (7%) and 10 (6.4%) underwent completion mastectomy or repeat lumpectomy, respectively. Twelve patients (7.6%) did not undergo reexcision. En bloc resection was successful in 134 of 157 (85.4%) lumpectomies. Eighty-nine percent of the procedures were coupled with oncoplastic reconstruction. CONCLUSION: Bracketing techniques using multiple radioactive seeds expands the indications for breast conservation therapy in patients who would have traditionally required mastectomy. Intraoperative margin assessment improves surgical and pathologic success. Larger defects created by multifocal resection are optimally managed in concert with oncoplastic reconstruction to minimize asymmetries and aesthetic defects.

Mimickers of breast malignancy: imaging findings, pathologic concordance and clinical management.

Many benign breast entities have a clinical and imaging presentation that can mimic breast cancer. The purpose of this review is to illustrate the wide spectrum of imaging features that can be associated with benign breast diseases with an emphasis on the suspicious imaging findings associated with these benign conditions that can mimic cancer. As radiologic-pathologic correlation can be particularly challenging in these cases, the radiologist's familiarity with these benign entities and their imaging features is essential to ensure that a benign pathology result is accepted as concordant when appropriate and that a suitable management plan is formulated.

Breast Cancer Staging: Updates in the AJCC Cancer Staging Manual, 8th Edition, and Current Challenges for Radiologists, From the AJR Special Series on Cancer Staging.

The standardization of the AJCC TNM staging system for breast cancer allows physicians to evaluate patients with breast cancer using standard language and criteria, assess treatment response, and compare patient outcomes. Previous editions of the AJCC Cancer Staging Manual relied on the anatomic TNM method of staging that incorporates imaging and uses population-level survival data to predict patient outcomes. Recent advances in therapy based on biomarker status and multigene panels have improved treatment strategies. In the newest edition of the AJCC Cancer Staging Manual (8th edition, adopted on January 1, 2018), breast cancer staging integrates anatomic staging with tumor grade, biomarker data regarding hormone receptor status, oncogene expression, and gene expression profiling to assign a prognostic stage. This article reviews the 8th edition of the AJCC breast cancer staging system with a focus on anatomic staging and the challenges that anatomic staging poses for radiologists. We highlight key imaging findings that impact patient treatment and discuss the role of imaging in evaluating response to neoadjuvant therapy. Finally, we discuss biomarkers and multigene panels and how these impact prognostic stage. The review will help radiologists identify critical findings that affect breast cancer staging and understand ongoing limitations of imaging in staging.

Ultrasound Evaluation of the Axilla in the Breast Imaging Setting.

ABSTRACT: Ultrasound evaluation of the axilla plays a critical role in the setting of newly diagnosed breast cancer as surgical management evolves toward more targeted axillary nodal resection. Regional nodal involvement by metastatic carcinoma is one of most important prognostic factors in breast cancer and guides local, regional, and systemic treatment. Ultrasound also evaluates response to neoadjuvant chemotherapy. This article will review ultrasound techniques and the anatomy and the morphology of axillary lymph nodes. Lymph node staging in breast cancer will also be discussed. Ultrasound-guided interventions and localizations and emerging technologies of elastography and contrast-enhanced ultrasound will be discussed. In addition, this article will discuss the role of ultrasound as it applies to management of the axilla since the American College of Surgeons Oncology Group Z011 and Z1071 trials. Finally, other causes of benign and malignant axillary lymphadenopathy, not related to breast cancer, are discussed.

68Ga-DOTATATE Uptake in Primary Breast Cancer.

ABSTRACT: 68Ga-DOTA peptides have revolutionized the imaging of neuroendocrine tumors because the agents are specific to somatostatin receptors. However, other tumors, including breast cancer, have been shown to express somatostatin receptors. We present the case of a 74-year-old woman with primary cardiac paraganglioma, who was found to have 68Ga-DOTATATE activity in the breast on staging PET/CT. Subsequent breast imaging workup and biopsy confirmed primary invasive lobular breast cancer, which was not 18F-FDG-avid on prior FDG PET/CT. Our case is in alignment with prior studies that suggest that 68Ga-DOTA peptides may play a future role in imaging breast cancer patients.