Management of High-Risk Breast Lesions.

High-risk breast lesions (HRLs) are a group of heterogeneous lesions that can be associated with a synchronous or adjacent breast cancer and that confer an elevated lifetime risk of breast cancer. Management of HRLs after core needle biopsy may include close imaging and clinical follow-up or excisional biopsy to evaluate for cancer. This article reviews histologic features and clinical presentation of each of the HRLs, current evidence with regard to management, and guidelines from the American Society of Breast Surgeons and National Comprehensive Cancer Network. In addition, imaging surveillance and risk-reduction strategies for women with HRLs are discussed.

Overuse of Preoperative Staging of Patients Undergoing Neoadjuvant Chemotherapy for Breast Cancer.

BACKGROUND: Guidelines of the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO) discourage the use of imaging to stage newly diagnosed early breast cancer (stages 1 and 2). This study aimed to evaluate preoperative staging imaging rates among patients with stage 1 or 2 breast cancer treated with neoadjuvant chemotherapy (NAC). METHODS: From a prospectively maintained database, 303 patients with stage 1 or 2 breast cancer who had NAC from 2008 to 2016 were identified. The main outcome measures were the rate and outcomes of staging imaging performed. RESULTS: The mean age of the 303 patients with stage 1 or 2 breast cancer was 51 years (range, 26-87 years). Of these 303 patients, 278 (92.4%) had invasive ductal cancer. 90 (30.2%) had estrogen receptor (ER)-positive disease, 79 (26.5%) had triple-negative disease, and 127 (42.6%) had human epidermal growth factor receptor 2 (HER2)-positive disease. Staging positron emission tomography (PET) or computed tomography (CT) scan was performed for 258 patients (85.2%), brain imaging for 94 patients (31%), bone scans for 117 patients (38.6%), and all three for 48 patients (15.8%). As a result, 15 patients (4.9%) with a positive PET/CT scan were upstaged to stage 4 breast cancer. No difference was observed among the ER-positive (p = 1.000), HER2-positive (p = 0.259), or triple-negative (p = 0.369) receptor profiles of the patients upstaged to stage 4 disease. One patient (1.1%) had positive brain imaging. Five patients (4.3%) had a positive bone scan, and three of these patients (60%) had bone metastasis also shown on the PET/CT scan. CONCLUSION: Despite guideline recommendations, a high rate of preoperative staging imaging is completed for patients with clinical stage 1 or 2 breast cancer who receive NAC, with few positive results.

Comparison of 18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma.

UNLABELLED: Although guidelines such as those of the National Comprehensive Cancer Network consider (18)F-FDG PET/CT for systemic staging of newly diagnosed stage III breast cancer patients, factors in addition to stage may influence the utility of PET/CT. Because invasive lobular carcinoma (ILC) is less conspicuous than invasive ductal carcinoma (IDC) on (18)F-FDG PET, we hypothesized that tumor histology may be one such factor. We evaluated PET/CT systemic staging of patients newly diagnosed with ILC compared with IDC. METHODS: In this Institutional Review Board-approved retrospective study, our Hospital Information System was screened for ILC patients who underwent PET/CT in 2006-2013 before systemic or radiation therapy. Initial stage was determined from examination, mammography, ultrasound, MR, or surgery. PET/CT was performed to identify unsuspected distant metastases. A sequential cohort of stage III IDC patients was evaluated for comparison. Upstaging rates were compared using the Pearson χ(2) test. RESULTS: The study criteria were fulfilled by 146 ILC patients. PET/CT revealed unsuspected distant metastases in 12 (8%): 0 of 8 with initial stage I, 2 of 50 (4%) stage II, and 10 of 88 (11%) stage III. Upstaging to IV by PET/CT was confirmed by biopsy in all cases. Three of 12 upstaged patients were upstaged only by the CT component of the PET/CT, as the metastases were not (18)F-FDG-avid. In the comparison stage III IDC cohort, 22% (20/89) of patients were upstaged to IV by PET/CT. All 20 demonstrated (18)F-FDG-avid metastases. The relative risk of PET/CT revealing unsuspected distant metastases in stage III IDC patients was 1.98 times (95% confidence interval, 0.98-3.98) that of stage III ILC patients (P = 0.049). For (18)F-FDG-avid metastases, the relative risk of PET/CT revealing unsuspected (18)F-FDG-avid distant metastases in stage III IDC patients was 2.82 times (95% confidence interval, 1.26-6.34) that of stage III ILC patients (P = 0.007). CONCLUSION: (18)F-FDG PET/CT was more likely to reveal unsuspected distant metastases in stage III IDC patients than in stage III ILC patients. In addition, some ILC patients were upstaged by non-(18)F-FDG-avid lesions visible only on the CT images. Overall, the impact of PET/CT on systemic staging may be lower for ILC patients than for IDC patients.

Radioactive seed localization of nonpalpable breast lesions in an academic comprehensive cancer program community hospital setting.

Wire localized excision (WLE) has been a long-standing method for localization of nonpalpable breast lesions. Disadvantages of this method include difficulty locating the wire tip in relation to borders of the lesion, imprecise placement of the wire, and the need to place the wire shortly before scheduled surgery. These shortcomings may lead to a high positive margin rate requiring re-excision to obtain clear margins for breast cancer. Radioactive seed localized excision (RSLE) of nonpalpable breast lesions has been advocated as a safe and effective alternative to WLE. The primary endpoints of the study were to compare re-excision rates between WLE and RSLE of nonpalpable breast lesions and to determine if there were any differences in volume of tissue removed. One hundred three patients were included in a retrospective review of localized breast excisions done by a single surgeon. Forty-four patients underwent WLE between April 2007 and February 2009. Fifty-nine patients underwent RSLE between September 2009 and January 2012. Margins were considered to be clear if at least 1 mm of normal tissue was obtained from the circumferential periphery of the lesion in question. RSLE resulted in a re-excision rate of 17 versus 55 per cent re-excision rate for wire localization (P < 0.001). Excision volume was greater for patients having wire localization (P = 0.074). RSLE is an effective technique for excision of nonpalpable breast lesions in the community setting. This technique allows for accurate localization and appears to allow for smaller volume of tissue to be excised.

Guiding breast-conserving surgery in patients after neoadjuvant systemic therapy for breast cancer: a comparison of radioactive seed localization with the ROLL technique.

BACKGROUND: Radioguided occult lesion localization (ROLL) with technetium-99 m colloid (ROLL-(99m)Tc) is commonly used to perform breast-conserving surgery in patients with nonpalpable breast tumors. Radioactive seed localization is a relatively new technique that localizes the tumor with a radioactive iodine-125 ((125)I) seed. The feasibility and outcome of these techniques after neoadjuvant systemic treatment has not been widely investigated. METHODS: All patients treated with neoadjuvant systemic treatment between 2007 and 2010 in the Netherlands Cancer Institute who underwent breast-conserving surgery with the ROLL-(99m)Tc technique (n = 83) or with (125)I seed localization (n = 71) were analyzed. The weight of the resected specimen, the margins, and the percentage of patients requiring a second surgical intervention as a result of positive margins were assessed. RESULTS: Patient and tumor characteristics and systemic treatment regimens were comparable between both groups. The median weight of the resected specimen (53 vs. 48 g), the median smallest margin (3.5 vs. 3.0 mm), and the risk for additional surgery for incomplete resections (7 vs. 8 %) did not differ significantly between patients treated with the ROLL-(99m)Tc technique and (125)I seed localization. CONCLUSIONS: The ROLL-(99m)Tc technique and (125)I seed localization demonstrate comparable results when used to perform breast-conserving surgery after neoadjuvant systemic treatment. Because (125)I seed localization does not require additional radiological localization shortly before surgery, it simplifies surgery scheduling. Therefore, we prefer (125)I seed localization to perform breast-conserving surgery after neoadjuvant systemic treatment.

[Predictive value of (99)Tc(m)-MIBI scintimammography in evaluation of the efficacy of neoadjuvant chemotherapy in patients with operable breast cancer].

OBJECTIVE: To investigate the value of technetium-99m methoxyisobutylisonitrile ((99)Tc(m)-MIBI) imaging in predicting the efficacy of neoadjuvant chemotherapy (NCT) and prognosis in patients with operable breast cancer. METHODS: Sixty five patients with breast cancer underwent (99)Tc(m)-MIBI scintimammography before NCT, and static planar images were taken at 10 min and 180 min after scintimammography. The clearance rate was calculated in each patient, correlation between the clearance rate and efficacy of NCT, and the disease free survival rate were analyzed. RESULTS: The mean clearance rate of 65 patients was (17.4 ± 6.8)%. The efficacy of NCT was 86.2% (CR 4 cases, PR 52 cases, SD 8 cases, and PD 1 case), and the mean clearance rate of patients with good response or poor response of chemotherapy were (15.5 ± 5.0)% and (29.2 ± 3.2)%, respectively. There was a significant difference between the two groups. The average disease free survival rate in the group with low clearance rate was (75.8%, P = 0.046), significantly higher than that in the group with high clearance rate (53.1%). CONCLUSION: Scintimammography of (99)Tc(m)-MIBI may be used to evaluate the efficacy and prognosis of NCT for patients with operable breast cancer.

Ultrasound-guided laser-induced thermal therapy for small palpable invasive breast carcinomas: a feasibility study.

BACKGROUND: The next step in breast-conserving surgery for small breast carcinomas could be local ablation. In this study, the feasibility of ultrasound-guided laser-induced thermal therapy (LITT) is evaluated. METHODS: Patients with large-core needle biopsy-proven invasive, palpable breast carcinoma (clinically or=2 cm in size (P = .026). CONCLUSIONS: Successful LITT of invasive breast cancer seems to be feasible when confined to small (<2 cm) nonlobular carcinomas without surrounding extensive in-situ component and angioinvasion. However, to implement LITT in a curative setting, improvements in imaging to more reliably preoperatively assess tumor size and monitoring of fiber tip placement and treatment affect are essential.

[Value of fused 18F-FDG PET/CT images in predicting efficacy of neoadjuvant chemotherapy on breast cancer].

BACKGROUND & OBJECTIVE: Previous studies confirmed that fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging relates to clinical or pathologic responses of tumors to neoadjuvant therapy. This study was to evaluate the correlation of fused 18F-FDG PET/CT images to cell apoptosis of breast cancer after neoadjuvant chemotherapy, and explore its value in predicting the efficacy of neoadjuvant chemotherapy on breast cancer. METHODS: Forty-five patients with primary breast cancer, proven by core needle biopsy, underwent 3 cycles of neoadjuvant chemotherapy. PET/CT was performed before and after treatment, and the ratio of tumor area activity to non-tumor area activity (T/N) was calculated. The apoptosis index (AI) was determined using TUNEL technique. RESULTS: Of the 45 patients, 4(8.9%) achieved complete remission (CR), 29 (64.4%) achieved partial remission (PR), 10 (22.2%) presented stable disease (SD), and 2 (4.4%) presented progressive disease (PD) after neoadjuvant chemotherapy. The mean T/N ratio was decreased from 3.23+/-0.63 before chemotherapy to 2.31+/-0.49 after chemotherapy (P=0.006) by 6.4%-50.8%. The mean AI was increased from (2.81+/-0.76)% before chemotherapy to (17.31+/-6.85)% after chemotherapy (P<0.001) by 1.9%-41.3%. The T/N ratio reduction rate was positively correlated to AI change (r(s)=0.850, P<0.001). At a threshold of 20% decrease from baseline in T/N ratio, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in predicting clinical response were 90.9%, 83.3%, 93.8%, 76.9%, and 92.1%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy might effectively induce cell apoptosis in breast cancer and inhibit the glucose uptake. Fused PET/CT imaging is closely related to cell apoptosis status of breast cancer after neoadjuvant chemotherapy, and may be applied to predict the response of breast cancer to neoadjuvant chemotherapy.

99mTc-MIBI scintigraphy as a functional method for the evaluation of multidrug resistance in breast cancer patients.

PURPOSE: To evaluate the clinical application of (99m) Tc-methoxyisobutylisonitrile (MIBI) scintigraphy as a functional method for assessment of multidrug resistance (MDR) in breast cancer patients and the correlation of these results with P-glycoprotein (P-gp) overexpression and objective response to chemotherapy. PATIENTS AND METHODS: 22 women, 35-68 years old with breast cancer, suitable for neoadjuvant chemotherapy were included onto this study. Two or three cycles of neoadjuvant chemotherapy were administered (FEC in 15 and CMF in 7 patients). Planar and SPECT (99m) Tc-MIBI scintigraphy was carried out before and after neoadjuvant chemotherapy. Focal (99m) Tc-MIBI uptake in breast cancer lesions was used as a scintigraphic criterion of abnormality. Tumor/background uptake (T/B Index) was calculated. Immunohistochemistry was carried out after surgery for P-gp detection in all cases. The degree of expression was evaluated according to semiquantitative score analysis from 0 to 4. RESULTS: Planar imaging was true positive in 20 patients, false positive in 1 (with breast cancer and mastopathy), and false negative in 1 (with wide tumor necrosis and deep location in the breast). SPECT imaging was true positive in 21 patients and false positive in 1. In 3 patients with multifocal disease additional tumour masses were visualized using SPECT. Sensitivity was 95% (21/22) and 100% (22/22), respectively, for planar and SPECT detection of breast cancer. P-gp expression was positive in 40.8% of the patients and negative in 59.2%. Intense (99m) Tc-MIBI uptake was shown on the planar images in 21 patients independently of the P-gp expression. There was no significant relationship between T/B Index and P-gp detection. Objective response included 2 clinical complete remissions, partial response in 1 patient, minimal response in 12, and no change in 7. Some clinical results corresponded to (99m) Tc-MIBI scintigraphic data: after neoadjuvant chemotherapy T/B Index was reduced > or = 20% in 9 patients with objective response. CONCLUSION: SPECT is an important diagnostic approach for identification of breast cancer with deep location and satellite tumour spots in multifocal disease. T/B Index did not correlate with P-gp overexpression on baseline (99m) Tc-MIBI scan. Objective clinical results after neoadjuvant chemotherapy corresponded to scintigraphic results in 75% of the patients with minimal response.

[Excisional biopsy with wire localisation of non-palpable breast lesions: indications and limitations]. / Biopsia escissionale con repere metallico delle lesioni non palpabili della mammella: indicazioni e limiti.

Preoperative localisation of non-palpable breast lesions is necessary for excisional biopsies. This can be achieved with methods such as anchor wire, charcoal marking, or radio-guided localisation. The aim of the present study was to evaluate retrospectively our experience with the wire localisation technique. One hundred and eighty-two patients with non-palpable breast lesions (diameter: 0.4-1.5 cm) were operated on under local anaesthesia. Intraoperative X-rays were performed in all cases. No serious perioperative complications occurred. Three patients (2 with postoperative haematomas and 1 with wound infection) underwent conservative therapy. The lesions were benign in 67/182 patients (37%), ductal and/or lobular invasive cancer in 42 (23%), carcinoma in situ in 23 patients (12.5%) and ADH-ALH in 50 patients (27.5%). Our experience confirms that wire localisation biopsies constitute an excellent method for the excision of non-palpable breast lesions. This technique is characterised by high reliability (100% total excisions) and assures a prognostic evaluation of high-risk lesions such as ductal an/or lobular atypical hyperplasia.

Locally advanced breast carcinoma: accuracy of mammography versus clinical examination in the prediction of residual disease after chemotherapy.

PURPOSE: To determine the mammographic features of locally advanced breast carcinoma treated with neoadjuvant chemotherapy and to evaluate the accuracy of mammography in the prediction of residual carcinoma. MATERIALS AND METHODS: Of 90 women treated with hormonally synchronized cytotoxic therapy before mastectomy or lumpectomy for advanced breast carcinoma, 56 were selected because they had undergone mammography before and after neo-adjuvant therapy. Mammographic and clinical opinion on the presence of residual disease was compared with histologic results. RESULTS: Fifty-four (96%) of 56 women had a complete (n = 34 [61%]) or partial (n = 20 [36%]) clinical response. Thirteen (23%) of 56 women had no residual tumor. Sensitivity of mammography in the prediction of residual carcinoma was greater than that of clinical examination (79% vs 49%), but specificity was lower (77% vs 92%). In 24 women with inflammatory carcinoma, sensitivity of mammography was 78% while that of clinical examination was 39%; specificity was equal (83%). CONCLUSION: Mammography was more sensitive than clinical examination in the prediction of residual carcinoma; it was not accurate enough to obviate surgical biopsy.