Use of axillary ultrasound to guide breast cancer management in the genomic assay era.

INTRODUCTION: Chemotherapy is conventionally offered to non-stage IV breast cancer patients with metastatic nodes. However, the RxPONDER trial showed that chemotherapy can be omitted in selected patients with 1-3 metastatic nodes if the 21-gene assay recurrence score is ≤25. We aimed to investigate if axillary ultrasound can identify this group of patients with limited nodal burden so that they can undergo upfront surgery followed by gene assay testing, to potentially avoid chemotherapy. METHODS: T1-3, node positive, hormone receptor-positive and HER2-negative breast cancer patients ≥50 years old with axillary lymph node dissection (ALND) were reviewed from 2 centres. Patients with neoadjuvant chemotherapy and bilateral cancers were excluded. Number of ultrasound-detected abnormal axillary nodes, demographic and histological parameters were correlated with the number of metastatic nodes found on ALND. RESULTS: 138 patients were included, 59 (42.8%) and 79 (57.2%) patients had 1-3 and >3 metastatic nodes on ALND respectively. On logistic regression and ROC analysis, the number of ultrasound-detected abnormal nodes was significant (p < 0.001) for predicting limited nodal burden (ROC AUC = 0.7135). Probabilities of <4 metastatic nodes with ultrasound cut-offs of 5, 6 and 8 abnormal nodes were 0.057, 0.026 and 0.005 respectively, with 100% specificity. CONCLUSION: A cut-off of ≤5 ultrasound-detected abnormal nodes can distinguish between patients with limited versus high nodal burden, with high specificity. Hence, incorporating the number of abnormal ultrasound-detected nodes into clinical practice may prove useful in guiding between upfront surgery and gene assay testing or neoadjuvant chemotherapy in this group of patients.

Injection mammoplasty: Normal imaging appearances, complications, and implications for mammographic screening.

BACKGROUND: The normal imaging appearances of the common agents used in injection mammoplasty and the challenges of mammography screening will be reviewed. METHODS: The local database from a tertiary hospital was accessed for imaging cases of injection mammoplasty. RESULTS: Free silicone is seen as multiple high-density opacities on mammograms. Silicone deposits can often be seen within axillary nodes due to lymphatic migration. Sonographically, a snowstorm appearance is seen when the silicone is diffusely distributed. On MRI, free silicone is hypointense on T1-weighted and hyperintense on T2-weighted images, with no contrast enhancement. Mammograms have a limited role in screening due to the high density of silicone. MRI is often required in these patients.Polyacrylamide gel and hyaluronic acid are seen as multiple collections on mammography. Polyacrylamide gel collections are of the same density as cysts, while hyaluronic acid collections are of higher density but less dense than silicone. On ultrasound, both can appear anechoic or show variable internal echoes. MRI demonstrates fluid signal with hypointense T1-weighted and hyperintense T2-weighted signal. Mammographic screening is possible if the injected material is located predominantly in the retro-glandular space without obscuring the breast parenchyma.On mammograms, autologous fat locules appear as lucent masses. Rim calcification can be seen if fat necrosis had developed. On ultrasound, focal fat collections can demonstrate varying levels of internal echogenicity, depending on the stage of fat necrosis. Mammographic screening is usually possible for patients after autologous fat injection as fat is hypodense compared to breast parenchyma. However, the dystrophic calcification associated with fat necrosis may mimic abnormal breast calcification. In such cases, MRI can be utilized as a problem-solving tool. CONCLUSION: It is important for the radiologist to recognize the type of injected material on the various imaging modalities and recommend the best modality for screening.

The Characteristics of Real-time Transvaginal Sono-elastography in Endometrial Cancer.

Background: Endometrial cancer is the most common gynecological cancer among women in developed countries. Sono-elastography is an extended ultrasonographic technique that has been shown to be useful in a wide range of conditions ranging from breast, prostate, and thyroid nodules to chronic liver disease and musculoskeletal conditions. The aim of this study is to compare the sonoelastographic features of endometrial malignancy and normal endometrium. Methods: This case-control observational study was conducted at a single institution. Participants with histologically proven endometrial cancer according to the results from microcurettage or hysteroscopic biopsy and scheduled for total hysterectomy were included as cases, while asymptomatic women scheduled for routine screening ultrasound examination were recruited as controls. Both cases and controls underwent conventional B-mode transvaginal ultrasonography and strain elastography. Demographic, ultrasonographic, and histopathologic findings were analyzed. Results: A total of 29 endometrial cancer patients (cases) and 28 normal females (controls) were included in the analysis. There was no significant difference in the mean age between the two groups, but the mean body weight was significantly higher in the case group (P < 0.001). The strain ratio and elastographic thickness ratio of the endometrium were statistically significantly different between the case and the control group (P ≤ 0.05) due to increased endometrial stiffness in cancer patients as compared to the normal group. Conclusion: Our results suggest that endometrial cancer can result in increased stiffness that is detectable by transvaginal sonoelastography. Sonoelastography may serve as an adjunct to conventional ultrasound in evaluating the endometrium of women with abnormal uterine bleeding.

Sonographic visibility of the UltraCorTM TwirlTM tissue marker.

BACKGROUND: Tissue markers are inserted into the breast after percutaneous biopsy to mark the site of the lesion to facilitate potential re-localisation. Tissue markers are increasingly developed with improved sonographic visibility due to benefits conferred by ultrasound-guided localisation. OBJECTIVES: We aim to study the sonographic visibility of the recently-introduced UltracorTM TwirlTM tissue marker and feasibility of its pre-operative localisation under ultrasound guidance. METHODS: All patients who underwent insertion of the UltracorTM TwirlTM tissue marker in our institution from July 2017 to December 2018 were reviewed. Retrospective data including sonographic visibility, evidence of migration and rate of successful surgical excision were collected. RESULTS: All tissue markers were visible on subsequent ultrasound with 198 (85.0%) well-visualised with high degree of confidence while 35 (15.0%) were moderately well-visualised with moderate level of confidence. None of the tissue markers were poorly visualised and none demonstrated migration. No statistical difference in sonographic visibility is seen based on interval duration between deployment and subsequent ultrasound assessment or depth of tissue marker. CONCLUSION: UltracorTM TwirlTM demonstrates consistent sonographic visibility, identifiable with a high or moderate level of confidence with no associated migration. Its use in pre-operative localisation with ultrasound guidance is therefore both reliable and feasible.

Usefulness of supplementary ultrasound surveillance in the detection of a second breast cancer in patients with ductal carcinoma in situ.

INTRODUCTION: Supplementary ultrasound surveillance in breast cancer patients can detect additional cancers but is associated with unnecessary biopsies and follow-ups. We aim to determine, in patients with ductal carcinoma in situ (DCIS), the prevalence and factors associated with second breast cancers and the usefulness of supplementary ultrasound surveillance. This is the first study which focused on the usefulness of ultrasound surveillance in DCIS patients. METHODS: DCIS patients were retrospectively analyzed to determine the prevalence and factors associated with second breast cancers. The prevalence of patients with benign biopsies, additional ultrasound follow-ups and second breast cancers, resulting from ultrasound surveillance, were calculated. RESULTS: Three hundred and thirty- two patients were included. 25 (7.5%) patients developed second breast cancers after a mean follow-up of 77.7 months. Breast conservation (P= .0218), involved margins after lumpectomy (P = .0003) and shortened hormonal therapy (P= 0.0369) were associated with second cancers. Of the 314 patients who had ultrasound surveillance, ipsilateral, and contralateral ultrasounds yielded 1.7%/1.3% cancer detection, 5.8%/6.7% benign biopsies and 10.4%/15.3% additional follow-ups. Patients with involved margins after lumpectomy have ipsilateral cancer detection, benign biopsies and additional follow-ups of 4.5%, 4.5%, and 9.1% respectively. A total of 85.4% patients had mammographically dense breasts. CONCLUSION: In DCIS patients, the rate of second breast cancers was 7.5%. Breast conservation, involved margins after lumpectomy and shortened hormonal therapy were associated with second cancers. Patients with involved margins after lumpectomy have the highest cancer detection rate and minimal unnecessary biopsies and follow-ups. Hence, ipsilateral breast ultrasound surveillance could be personalized for this high-risk group with mammographically dense breasts.

Would Removal of All Ultrasound Abnormal Metastatic Lymph Nodes Without Sentinel Lymph Node Biopsy Be Accurate in Patients with Breast Cancer with Neoadjuvant Chemotherapy?

LESSONS LEARNED: Removal of sonographically abnormal (up to 3) metastatic clipped nodes, without sentinel lymph node biopsy, could accurately predict axillary status in breast cancer patients receiving neoadjuvant chemotherapy. ypT and the first clipped node status were statistically significant factors for nodal pathologic complete response. This novel approach requires validation in larger studies. BACKGROUND: In patients who have node-positive breast cancer, neoadjuvant chemotherapy could result in nodal pathologic complete response (pCR) and avoid an axillary lymph node dissection (ALND). Axillary staging, in such cases, can be performed using targeted axillary dissection (TAD) with a low false negative rate. However, identification of sentinel lymph nodes (SLNs) after chemotherapy can be difficult, and currently, it is the standard to remove only one clipped node in TAD. We aimed to determine if removal of all sonographically abnormal metastatic clipped nodes, without SLN biopsy, could accurately predict the axillary status post neoadjuvant chemotherapy. METHODS: Patients with breast cancer with one to three sonographically abnormal metastatic axillary nodes were prospectively recruited. Each abnormal node had histology and clip insertion before neoadjuvant chemotherapy. After chemotherapy, the patients underwent removal of clipped nodes using the Skin Mark clipped Axillary nodes Removal Technique (SMART) and ALND. RESULTS: Fourteen patients were recruited, having a total of 21 sonographically abnormal metastatic nodes, with nine, three, and two patients having 1, 2, and 3 malignant nodes clipped, respectively. Mean age was 55.5 years; 92.9% and 57.1% of patients had invasive ductal carcinoma and grade III tumors, respectively; and 35.7% patients achieved nodal pCR. The first clipped node predicted the axillary status with a false negative rate of 7.1%. Adding to this another second clipped node, the false negative rate was 0%. Pathologic tumor staging after neoadjuvant chemotherapy (ypT) (p = .0390) and the first clipped node pathological response status (p = .0030) were statistically significant predictors for nodal pCR. CONCLUSION: Removal of sonographically abnormal metastatic clipped nodes using SMART, without sentinel lymph node biopsy, could accurately predict axillary status. This finding needs validation in larger studies.

Initial results of a novel technique of clipped node localization in breast cancer patients postneoadjuvant chemotherapy: Skin Mark clipped Axillary nodes Removal Technique (SMART trial).

PURPOSE: Removal of clipped nodes can improve sentinel node biopsy accuracy in breast cancer patients post neoadjuvant chemotherapy (NACT). However, the current methods of clipped node localization have limitations. We evaluated the feasibility of a novel clipped node localization and removal technique by preoperative skin marking of clipped nodes and removal by the Skin Mark clipped Axillary nodes Removal Technique (SMART), with the secondary aim of assessing the ultrasound visibility of the various clips in the axillary nodes after NACT. METHODS: Invasive breast cancer patients with histologically metastatic axillary nodes, going for NACT, and ≤3 sonographically abnormal axillary nodes were recruited. All abnormal nodes had clips inserted. Patients with M1 disease were excluded. Post-NACT, patients underwent SMART and axillary lymph node dissection. Specimen radiography and pathological analyses were performed to confirm the clipped node presence. Success, complication rates of SMART, and ultrasound visibility of the various clips were assessed. RESULTS: Twenty-five clipped nodes in 14 patients underwent SMART without complications. The UltraCor Twirl, hydroMARK, UltraClip Dual Trigger, and UltraClip were removed in 13/13 (100%), 7/9 (77.8%), 1/2 (50.0%), and 0/1 (0%), respectively (P = .0103) with UltraCor Twirl having the best ultrasound visibility and removal rate. Removal of three clipped nodes in the same patient (P = .0010) and deeply seated clipped nodes (P = .0167) were associated with SMART failure. CONCLUSION: Skin Mark clipped Axillary nodes Removal Technique is feasible for removing clipped nodes post-NACT, with 100% observed success rate, using the UltraCor Twirl marker in patients with <3 not deeply seated clipped nodes. Larger studies are needed for validation.

Determining Whether High Nodal Burden in Early Breast Cancer Patients Can Be Predicted Preoperatively to Avoid Sentinel Lymph Node Biopsy.

PURPOSE: The Z0011 trial showed that axillary lymph node dissection (ALND) can be safely avoided in breast cancer patients with low nodal burden (LNB). ALND can be performed in patients with high nodal burden (HNB). We aimed to determine whether HNB in early breast cancer patients can be predicted preoperatively to avoid sentinel lymph node biopsy (SLNB). METHODS: Early invasive breast cancer patients (cT1-2cN0) were retrospectively reviewed. We excluded patients with neoadjuvant chemotherapy and incomplete data. The patients were divided into the following groups based on surgical histology: no positive (N0), LNB, and HNB, defined as 0, 1-2, and ≥ 3 metastatic lymph nodes (LNs), respectively. Of the patients with metastatic nodal disease, only those with ALND were included in the analysis. Clinical, radiological, and histological parameters were evaluated using logistic regression analysis as predictors of HNB versus LNB and N0 combined. RESULTS: Of the 1,298 included patients, 832 (64.1%), 286 (22.0%), and 180 (13.9%) had N0, LNB, and HNB, respectively. Univariate logistic regression analysis revealed that sonographic features of breast tumor size (p < 0.0001), number of abnormal LNs (p < 0.0001), cortical thickness (p = 0.0002), effacement of the fatty hilum (p < 0.0001), and needle biopsy being performed (p < 0.0001) were indicators of HNB. Breast tumor grade (p = 0.0001) and human epidermal growth factor receptor 2 status (p = 0.0262) were also statistically significant. Among these significant features, multivariable stepwise logistic regression showed that the number of abnormal LNs is the sole independent predictor of HNB (p < 0.0001, area under the curve = 0.774). The positive predictive value of HNB in patients with ≥ 4 abnormal LNs was 92.9%. CONCLUSION: The detection of ≥ 4 abnormal LNs on ultrasound can help to identify HNB patients who require upfront ALND and thus avoid SLNB.

Breast Microcalcifications as the Only Imaging Manifestation of Metastatic Serous Peritoneal Adenocarcinoma in the Breast.

We present a case of a 65 year old female with newly diagnosed primary peritoneal serous carcinoma who was found to have indeterminate segmental microcalcifications in the right upper outer quadrant with a mildly enlarged right axillary node on mammogram. There was no associated breast mass on ultrasound. Core biopsy of the right axillary lymph node and right upper outer quadrant breast microcalcifications confirmed the presence of breast metastases at both sites from primary peritoneal serous carcinoma. This case highlights the importance of histopathological correlation of any breast and axillary abnormalities in patient with primary extramammary malignancy. Imaging features of metastatic lesions to the breast are also reviewed.

Young breast cancer in a specialised breast unit in Singapore: clinical, radiological and pathological factors.

INTRODUCTION: Whilst only 5.5% to 7% of breast cancer occurs in women less than 40 years of age in the West, the incidence has been reported in up to 18% in Asian population. This study seeks to evaluate our unit's experience in breast cancer in young women. MATERIALS AND METHODS: A retrospective review of our database identified women with newly diagnosed breast cancer from January 2006 to February 2011. Patient demographics, clinical presentation, imaging and pathological findings and treatment received were determined. RESULTS: Out of a total of 1160 women with breast cancer, 135 (11.6%) were under 40 years of age and made up our study population. The most common presentation was a self-detected breast lump. Most patients did not have a positive family history. Mammography demonstrated abnormal findings in 78% of patients. Ultrasound was very sensitive in the evaluation of a breast lump and demonstrated abnormal findings in 95%. Out of 129 women, 40 (31%) underwent breast-conserving surgery of which 5 (12.5%) proceeded to mastectomy due to involved margins. Also, 89 out of 129 women (69%) underwent mastectomy of which 19 (21.3%) had immediate reconstruction. Of a total of 121 primary resections, 94% were invasive ductal carcinoma while 15.5% were pure ductal in-situ carcinomas. The majority (61.2%) showed high grade disease. CONCLUSION: Most young breast cancer patients present with a self-detected breast lump and do not have a positive family history. A strong clinical index of suspicion and appropriate breast imaging workup are useful for the early and accurate diagnosis of breast cancer in young women.

Radiologic features of polyacrylamide gel mammoplasty.

OBJECTIVE: The objective of our study was to describe the imaging features of polyacrylamide gel breast implants in women with and those without complications from mammoplasty. CONCLUSION: Although polyacrylamide gel implants may mimic conventional implants on both sonography and MRI in women who do not have complications from mammoplasty, polyacrylamide gel implants have some distinguishing features. The imaging appearance of polyacrylamide gel implants is related to the technique of injection and whether there are any associated complications. The implants are usually in a retroglandular location. Mammography, sonography, and MRI can be used to evaluate short-term complications, although MRI appears to be the most sensitive. Common short-term complications include extravasation of polyacrylamide gel and secondary infection, which may be related to lactation. The long-term complications of polyacrylamide gel mammoplasty are unknown. Knowledge of the appearances of polyacrylamide gel implants in women with and those without complications from mammoplasty is useful in the radiologic evaluation of such patients.

Primary malignant mixed mullerian tumor of the uterus: findings on sonography, CT, and gadolinium-enhanced MRI.

OBJECTIVE: The purpose of our study was to evaluate the sonographic, contrast-enhanced CT, and gadolinium-enhanced MRI findings of primary malignant mixed müllerian tumors (MMMTs) of the uterus. CONCLUSION: Uterine MMMT most commonly presents as an intracavitary mass with coexistent dilatation of the endometrial canal. Tumors tend to appear hyperechoic on sonography, heterogeneously hypodense and ill defined on contrast-enhanced CT, and heterogeneously hyperintense on T2-weighted MR images with signal abnormalities indicating subacute hemorrhage on T1-weighted MR images. Myometrial invasion is common and has a predilection for the uterine fundus.