A Case of Metaplastic Squamous Cell Carcinoma of the Breast that Showed a Pathological Complete Response After Neoadjuvant Chemotherapy with Weekly Paclitaxel.

BACKGROUND Primary squamous cell carcinoma of the breast is a rare type of metaplastic breast carcinoma, characterized by resistance to conventional chemotherapy agents. We report a case of metaplastic squamous cell carcinoma of the breast in which a pathological complete response was achieved after neoadjuvant chemotherapy with weekly paclitaxel and in which the patient remained disease free for 15 years and 7 months. CASE REPORT A 40-year-old woman had a palpable 5-cm-diameter tumor in the right breast that was diagnosed as metaplastic squamous cell carcinoma of the breast based on core needle biopsy. The patient was initially treated with an adjuvant chemotherapy (AC) regimen consisting of doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) as neoadjuvant chemotherapy. Because the tumor grew rapidly and the skin redness increased after 1 cycle of the AC regimen, 12 cycles of weekly paclitaxel 80 mg/m² were subsequently administered. The tumor responded dramatically to paclitaxel. The patient underwent mastectomy with level II axillary lymph node dissection. No residual tumor cells were found, which indicated pathological complete response. The patient is currently disease free at 15 years and 7 months after the operation. CONCLUSIONS To our knowledge, there are no previous reports of metaplastic squamous cell carcinoma of the breast in which pathological complete response was achieved by treatment with neoadjuvant chemotherapy with weekly paclitaxel (80 mg/m²).

A new indication and surgical procedure to reduce fat necrosis after breast-conserving surgery using an inframammary adipofascial flap.

BACKGROUND: There is little information on the risk factors for fat necrosis after breast-conserving surgery using an inframammary adipofascial flap (IAF). METHODS: We conducted a retrospective cohort study from a single institution evaluating the risk factors for fat necrosis after breast-conserving surgery using an IAF (n = 41) performed from 2005 to 2020 for newly diagnosed stage 0-2 breast cancer or phyllodes tumor. RESULTS: Age (≥50 years of age vs. <50 years of age), mammographic density (fatty vs. other) and operation period (before vs. after revision of surgical procedure and patient indication) were significantly associated with fat necrosis (p = 0.006, p = 0.04 and p = 0.02, respectively). CONCLUSION: Our study suggested that the use of an IAF with crescent dermis and selection of appropriate cases for IAF after breast-conserving surgery may be useful for the purpose of reducing fat necrosis. Further study is needed.

Comparing the extent of breast cancer tumors through contrast-enhanced ultrasound vs B-mode, opposed with pathology: evergreen study.

BACKGROUND: To prove the efficacy of contrast-enhanced ultrasound (CEUS) in determining the extent of resection, more evidence about B-mode and CEUS as opposed to pathology is required. We compared maximum tumor width measured on B-mode/CEUS images with that determined pathologically. METHODS: In this retrospective multicenter study, 152 operable breast cancer patients who had undergone both B-mode and CEUS were analyzed. Maximum tumor width on B-mode and CEUS, and on the postoperative pathological examination (P), was measured by the participating investigators. In addition, maximum width was assessed in B-mode and CEUS image sets by independent reviewers blinded to all patient information. We analyzed differences in maximum width between CEUS, B-mode and P. RESULTS: The mean widths as measured by the participating investigators were 15 ± 7 mm (B-mode), 19 ± 8 mm (CEUS), and 17 ± 9 mm (P). The difference subtracted P from B-mode was - 3 ± 7 mm (p < 0.0001), and that from CEUS was 1 ± 6 mm (p = 0.0163). The mean widths as measured by the independent reviewers were 16 ± 7 mm (B-mode) and 18 ± 7 mm (CEUS). The difference subtracted P from B-mode was - 2 ± 8 mm (p = 0.0114), while that from CEUS was 1 ± 7 mm (p = 0.1921). CONCLUSIONS: Maximum lesion width measurement showed a tendency to increase in the order of B-mode, to P and CEUS. The difference in measurement between P and B-mode was significant, but there was no significant between CEUS and P. These results provide additional information of tendency patterns in measuring the maximum lesion width through enhancement on CEUS.

CD204-positive macrophages accumulate in breast cancer tumors with high levels of infiltrating lymphocytes and programmed death ligand-1 expression.

Although immunotherapy has been demonstrated to be promising in triple-negative (TN) breast cancer (BC), most BC cases are classified as non-TN. To enrich the responders for immunotherapy regardless of their subtypes, classification based on tumor-infiltrating lymphocyte (TIL) levels and programmed death ligand-1 (PD-L1) status may be useful. However, this classification has not been fully applied to BC. Furthermore, suppressive subsets in the local tumor microenvironment, such as tumor-associated macrophages (TAMs), which promote tumor progression, cannot be ignored to overcome immunotherapy resistance. The aims of the present study were to classify primary BC cases based on the TIL levels and PD-L1 status, and to identify suppressive immune subsets in each categorized group. A retrospective analysis of 73 patients with invasive BC was performed. The frequency of TILs was evaluated in HE-stained slides (10% cutoff), and PD-L1 levels (SP142; 1% cutoff), as well as immune subsets (CD3+, CD8+, FOXP3+, CD20+, CD68+ and CD204+ cells) were assessed using immunohistochemistry. It was revealed that 22% (16/73) of the tumors were categorized as TIL+PD-L1+, of which 69% (11/16) were TN type. By contrast, 66% (48/73) of the tumors were categorized as TIL-PD-L1-, of which 77% (37/48) were HR+ and HER2- types. The number of CD204+ M2-type macrophages was significantly associated with high histological grade (P=0.0246) and high Ki-67 (P=0.0152), whereas CD68+ macrophages were not associated with these factors. Furthermore, CD204+ macrophages and FOXP3+ Tregs accumulated in 88% (14/16) and 63% (10/16) of TIL+PD-L1+ tumors, respectively, compared with 20.8% (10/48) and 27.1% (13/48) of TIL-PD-L1- tumors. In conclusion, 22% of BC tumors were classified as TIL+PD-L1+ (69% were TN), which were enriched with suppressive immune subsets. These cell types may serve as potential novel immunotherapeutic targets.

Tenascin-C Induces Phenotypic Changes in Fibroblasts to Myofibroblasts with High Contractility through the Integrin αvß1/Transforming Growth Factor ß/SMAD Signaling Axis in Human Breast Cancer.

Tenascin-C (TNC) is strongly expressed by fibroblasts and cancer cells in breast cancer. To assess the effects of TNC on stromal formation, we examined phenotypic changes in human mammary fibroblasts treated with TNC. The addition of TNC significantly up-regulated α-smooth muscle actin (α-SMA) and calponin. TNC increased the number of α-SMA- and/or calponin-positive cells with well-developed stress fibers in immunofluorescence, which enhanced contractile ability in collagen gel contraction. The treatment with TNC also significantly up-regulated its own synthesis. Double immunofluorescence of human breast cancer tissues showed α-SMA- and/or calponin-positive myofibroblasts in the TNC-deposited stroma. Among several receptors for TNC, the protein levels of the αv and ß1 integrin subunits were significantly increased after the treatment. Immunofluorescence showed the augmented colocalization of αv and ß1 at focal adhesions. Immunoprecipitation using an anti-αv antibody revealed a significant increase in coprecipitated ß1 with TNC in lysates. The knockdown of αv and ß1 suppressed the up-regulation of α-SMA and calponin. The addition of TNC induced the phosphorylation of SMAD2/3, whereas SB-505124 and SIS3 blocked myofibroblast differentiation. Therefore, TNC enhances its own synthesis by forming a positive feedback loop and increases integrin αvß1 heterodimer levels to activate transforming growth factor-ß signaling, which is followed by a change to highly contractile myofibroblasts. TNC may essentially contribute to the stiffer stromal formation characteristic of breast cancer tissues.

Strategy for the accurate preoperative evaluation of the number of metastatic axillary lymph nodes in breast cancer.

BACKGROUND: After the ACOSOG Z0011 trial, it became important to evaluate the number of metastatic axillary lymph nodes (LNs) preoperatively. The purpose of this paper is to confirm whether the number of metastases can be accurately diagnosed by preoperative computed tomography (CT), ultrasound sonography (US), and US-guided fine-needle aspiration cytology (FNAC). METHODS: We retrospectively analyzed the axillary LNs finding of preoperative CT/US of 470 breast cancer patients. Metastasis was suspected based on the following findings: LNs with a long-axis diameter of ≥10 mm or a short-axis diameter of ≥5 mm on CT, and LNs with the absence of a fatty hilum, focal cortical thickness or a cortical thickness ≥2 mm on US. We also examined the results of FNAC making a rapid bedside diagnosis (bedside-FNAC) of 162 LNs that were suspected to metastatic based on the US findings. RESULTS: On CT, all cases with ≥3 LNs with a long-axis diameter of ≥10 mm and a short-axis diameter of ≥5 mm had metastasis. However, there was no relationship between the number of detected LNs and the number of metastases. On US, 75.7% of LNs with the absence of a fatty hilum and all LNs with cortical thickness ≥6 mm had metastasis. The accuracy of bedside-FNAC for suspicious LNs was 100%. CONCLUSIONS: Although we can pick up LNs that are likely to have metastasis on CT/US, it was impossible to accurately predict the number of metastases on CT/US. However, bedside-FNAC of suspicious LNs could accurately predict the number of metastases.

Impact of parametric imaging on contrast-enhanced ultrasound of breast cancer.

PURPOSE: To prospectively evaluate the usefulness of contrast-enhanced ultrasound (CEUS) using parametric imaging for breast cancer in a multicenter study. METHODS: A total of 65 patients with breast cancer were included in this study. CEUS was performed, and still images on peak time (S), accumulated images (A) and parametric images (P) were generated from the raw data. Four blind reviewers ranked the best visible images as first place, and determined second and third place consecutively. We compared the average ranking of each image. The maximal diameter of the tumor determined on ultrasonography and MRI was compared with the corresponding pathological maximal diameter for 48 of the 65 patients. The correlation between the diameter determined by two experts and two beginners was analyzed. RESULTS: The average rank of visibility was as follows: P, 1.44; A, 2.04; and S, 2.52. The correlation between each image and the pathology was as follows: P, r = 0.664; A, r = 0.630; S, r = 0.717; and MRI, r = 0.936. There were no significant differences among the correlation between the experts and beginners in each image. CONCLUSIONS: The use of parametric imaging improves the visibility of CEUS. The maximal diameter of the tumor determined on CEUS correlates substantially with the pathology.

Cosmetic evaluation methods adapted to asian patients after breast-conserving surgery and examination of the necessarily elements for cosmetic evaluation.

PURPOSE: Although various strategies have been reported, there are no defined criteria for cosmetic evaluation methods after breast-conserving surgery (BCS). Since Asians tend to have smaller breasts, indistinct inframammary folds, and conspicuous scars, differences in the cosmetic results are expected. So we examined two subjective methods and one objective method to determine the differences, and elements necessary for a cosmetic evaluation after BCS. METHODS: Frontal photographs of 190 Japanese were evaluated using the Harris scale (Harris) and the evaluation method proposed by the Japanese Breast Cancer Society Sawai group (Sawai group) as the subjective methods, and the Breast Cancer Conservation Treatment cosmetic results (BCCT.core) as the objective method, respectively. In order to examine the necessary elements for developing a new ideal method, 100 out of 190 were selected and assessed separately by six raters using both the Harris and modified Sawai group methods in the observer assessment. The correlation between the two methods was examined using the Spearman rank-correlation coefficient. RESULTS: The results of the BCCT.core and the other two methods were clearly different. In the observer assessment, the consensuses of the six raters were evaluated as follows: 27, 27, 26, and 20 cases were evaluated as "excellent," "good," "fair," and "poor," respectively. For the Spearman rank-correlation coefficient, values higher than 0.7 indicated a strong correlation, as seen by the values of 0.909 for the breast shape and 0.345 for the scar. The breast shape accounted for the most significant part of the evaluation, and the scar had very little correlation. CONCLUSION: In this study, we recognized a clear difference between the subjective and objective evaluation methods, and identified the necessary elements for cosmetic evaluation. We would like to continue developing an ideal cosmetic evaluation that is similar to subjective one and is independent from raters.

Abdominal advancement flap as oncoplastic breast conservation: report of seven cases and their cosmetic results.

An abdominal advancement flap (AAF) is a flap that pulls the elevated abdominal skin up and creates the shape of the inferior portion of the breast by making a neo-inframammary fold. Seven patients underwent remodeling using an AAF or a method combining an AAF with other volume displacement techniques after partial mastectomy. The excision volume ranged from 15% to 35%. AAF with only mobilization of the gland flaps was performed in two cases, with lateral mammoplasty in one case, with the round block technique (RBT) in one case, with a modified RBT in one case, and with medial mammoplasty in two cases. Although one patient treated with a RBT had a partial blood-flow insufficiency of the nipple-areola complex, it improved with conservative treatment. The cosmetic results were found to be excellent in three cases, good in three, and fair in one case.

Improved differential diagnosis of breast masses on ultrasonographic images with a computer-aided diagnosis scheme for determining histological classifications.

OBJECTIVES: A computer-aided diagnosis (CAD) scheme for determining histological classifications of breast masses is expected to be useful for clinicians in making a differential diagnosis. The purpose of this study was to evaluate the usefulness of using the CAD scheme on ultrasonographic images. METHODS: The database consisted of 390 breast ultrasonographic images with masses. Three experienced clinicians independently provided subjective ratings on the likelihood of malignancy for each of the 390 masses. Fifty benign masses (25 cysts and 25 fibroadenomas) and 50 malignant masses (25 noninvasive ductal carcinomas and 25 invasive ductal carcinomas) were selected as unknown cases for an observer study based on a stratified randomization method with the ratings. The likelihood of the histological classification in each unknown case was evaluated by the CAD scheme with image features that clinicians commonly use for describing masses. In the observer study, seven observers provided their confidence levels regarding the malignancy of the unknown case before and after viewing the likelihood of the histological classification. The usefulness of the CAD scheme was evaluated with a multireader multicase receiver operating characteristic (ROC) analysis. RESULTS: The areas under the ROC curves (AUCs) for all observers were improved by use of the CAD scheme. The average AUC increased from 0.716 without to 0.864 with the CAD scheme (P = .006). CONCLUSION: The presentation of the likelihood of the histological classification evaluated by the CAD scheme improved the clinicians' performance and therefore would be useful in making a differential diagnosis of masses on ultrasonographic images.

Oncoplastic technique combining an adipofascial flap with an extended glandular flap for the breast-conserving reconstruction of small dense breasts.

We introduce a method combining two oncoplastic techniques for breast-conserving reconstruction. The procedure is as follows: first, an extended glandular flap is made by undermining the breast from both the skin and the pectoralis fascia to the upper edge of the breast at the subclavicular area. After modeling the breast mound with the extended glandular flap, an inframammary adipofascial flap is made. The flap is reflected back to the breast area remodeled using the extended glandular flap. After reshaping the breast, the inframammary line is then re-shaped. This method is indicated for patients with breast cancer in the outer portion of the breast, who have small dense breasts, and have undergone a large excision of about 40% of their breast volume. We treated four patients, all of whom had either excellent or good cosmetic results with no fat necrosis.