Neurofibroma with adenosis in the mammary gland: a case report.

BACKGROUND: Neurofibroma of the breast is extremely rare, with only a few reported cases. Here, we report a case of solitary neurofibroma of the breast in a 95-year-old woman. CASE PRESENTATION: A 95-year-old woman presented with a palpable mass in the left breast. Mammography revealed a well-defined mass. A 1.6-cm round mass was found in the lower outer quadrant of the left breast on ultrasonography. The internal echo of the tumor was a mixture of relatively uniform hypoechoic areas with posterior enhancement and heterogeneous hyperechoic areas. She underwent a core needle biopsy. The pathological findings revealed a spindle cell lesion with no malignant findings. At 2 months follow-up, repeat breast ultrasonography showed that the mass had enlarged to be 2.7 cm in size. A repeat core needle biopsy, however, revealed no particularly new information. Because the tumor was growing and a definite diagnosis was not made, lumpectomy was performed. We found bland-spindled cells with shredded-carrot collagen bundles. Immunohistochemical antibody markers (S100, SOX10, and CD34) were positive for the spindle cells. Some of the tumors maintained the bilayer nature of luminal cells and myoepithelial cells, which might be the reason for internal heterogeneity on ultrasound. A histological diagnosis of neurofibroma with adenosis was made. At 6 months follow-up, no recurrent lesions were found. CONCLUSIONS: Ultrasound and pathological images revealed an extremely rare case of neurofibroma combined with adenosis. Tumor resection was performed because it was difficult to make a definitive diagnosis using needle biopsy. Even when a benign tumor is suspected, short-term follow-up is necessary, and if an enlargement is observed, early tumor resection is recommended.

Lipidomics-based tissue heterogeneity in specimens of luminal breast cancer revealed by clustering analysis of mass spectrometry imaging: A preliminary study.

Cancer tissues reflect a greater number of pathological characteristics of cancer compared to cancer cells, so the evaluation of cancer tissues can be effective in determining cancer treatment strategies. Mass spectrometry imaging (MSI) can evaluate cancer tissues and even identify molecules while preserving spatial information. Cluster analysis of cancer tissues' MSI data is currently used to evaluate the phenotype heterogeneity of the tissues. Interestingly, it has been reported that phenotype heterogeneity does not always coincide with genotype heterogeneity in HER2-positive breast cancer. We thus investigated the phenotype heterogeneity of luminal breast cancer, which is generally known to have few gene mutations. As a result, we identified phenotype heterogeneity based on lipidomics in luminal breast cancer tissues. Clusters were composed of phosphatidylcholine (PC), triglycerides (TG), phosphatidylethanolamine, sphingomyelin, and ceramide. It was found that mainly the proportion of PC and TG correlated with the proportion of cancer and stroma on HE images. Furthermore, the number of carbons in these lipid class varied from cluster to cluster. This was consistent with the fact that enzymes that synthesize long-chain fatty acids are increased through cancer metabolism. It was then thought that clusters containing PCs with high carbon counts might reflect high malignancy. These results indicate that lipidomics-based phenotype heterogeneity could potentially be used to classify cancer for which genetic analysis alone is insufficient for classification.

Evaluation of the Role of Axillary Lymph Node Fine-Needle Aspiration Cytology in Early Breast Cancer With or Without Neoadjuvant Chemotherapy.

PURPOSE: Fine-needle aspiration cytology (FNAC) of axillary lymph nodes (AxLNs) is performed to diagnose nodal metastasis in patients with breast cancer. Although the sensitivity of ultrasound-guided FNAC for identifying AxLN metastasis is in the range of 36%-99%, whether sentinel lymph node biopsy (SLNB) should be performed for neoadjuvant chemotherapy (NAC) patients with negative FNAC results is uncertain. This study aimed to determine the role of FNAC before NAC in the evaluation and management of AxLN in early breast cancer patients. METHODS: We retrospectively analyzed 3,810 clinically node-negative (a lymph node with no clinical metastasis without FNAC or radiological suspicion of metastasis with negative FNAC results) patients with breast cancer who underwent SLNB between 2008 and 2019. We compared the positivity rate of sentinel lymph nodes (SLNs) between patients who received and those who did not receive NAC with negative FNAC results or without FNAC and axillary recurrence rate in the neoadjuvant group with negative SLNB results. RESULTS: In the non-neoadjuvant (primary surgery) group, the positivity rate of SLNs in patients with negative FNAC results was higher than that in patients without FNAC (33.2% vs. 12.9%; p < 0.001). However, the SLN positivity rate of patients with negative FNAC results (false-negative rate for FNAC) in the neoadjuvant group was lower than that in the primary surgery group (3.0% vs. 33.2%; p < 0.001). After a median follow-up of 3 years, one axillary nodal recurrence was observed, which was a case from the neoadjuvant non-FNAC group. None of the patients in the neoadjuvant group with negative FNAC results had axillary recurrence. CONCLUSION: The false-negative rate for FNAC in the primary surgery group was high; however, SLNB was the proper axillary staging procedure for NAC patients who have clinically suspicious AxLN metastases on radiologic examination but negative FNAC results.

Arthralgia induced by endocrine therapy with or without cyclin-dependent kinase 4/6 inhibitors in breast cancer: A systematic review and meta-analysis.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have been approved for breast cancer (BC) treatment. Several trials suggested that arthralgia was reduced in patients treated with ET plus CDK4/6i compared with that in those with ET-alone. We aimed to compare arthralgia rates in BC patients treated with/without CDK4/6i. We reviewed randomized controlled phase II/III trials investigating CDK4/6i with ET in hormone receptor-positive and epidermal growth factor 2-negative BC. Publications were retrieved from PubMed from January 2014 to April 2021. We compared arthralgia rates between patients who were administered ET plus CDK4/6i (CDK4/6i group) and those treated with ET-alone (control group). We reviewed 12 trials that reported data on adverse effects for arthralgia. These trials included 17,440 patients (9255 in the CDK4/6i group and 8185 in the control group). The arthralgia rate in the CDK4/6i group was significantly lower than that in the control group (27.6% vs. 34.8%, p < .001), especially in early BC (28.8% vs. 37.3%, p < .001). These suggested that the arthralgia rate in patients treated with ET plus CDK4/6i was lower than that in patients treated with ET-alone and that CDK4/6i may decrease the arthralgia rate in BC patients treated with ET, especially in early BC.

Satisfaction survey on a preoperative explanation method using three-dimensional breast imaging for breast cancer patients considering breast-conserving surgery.

PURPOSE: Although one of the essential factors in surgical shared decision-making is the body image, the breast morphology after breast-conserving surgery is particularly difficult to explain in a uniform manner due to large individual differences. METHODS: Patients with breast cancer eligible for breast-conserving surgery (BCS) were recruited between June 2020 and October 2021. We surveyed the patients' satisfaction with our method of explaining the likely breast morphology after BCS using three-dimensional (3D) breast imaging in the form of a questionnaire. RESULTS: A total of 162 patients were enrolled, and 137 (84.6%) answered the questionnaire. One hundred and sixteen patients (84.6%) answered that they were very satisfied or satisfied with our explanation method, and 100 (73.0%) patients were very satisfied or satisfied with the 3D breast imaging. Some patients answered that 3D breast imaging helped them prepare for BCS, or on the contrary, made them choose mastectomy with breast reconstruction because the deformation likely with BCS was considered unacceptable. Only a few patients who underwent BCS felt that their postoperative morphology was more deformed than the preoperatively imagined one. CONCLUSION: Our results suggest that our preoperative explanation method using 3D breast imaging was useful for shared decision-making.

Time to Chemotherapy for Patients With Estrogen Receptor-Positive Breast Cancer and Cyclin-Dependent Kinase 4 and 6 Inhibitor Use.

PURPOSE: Safely postponing the use of chemotherapy is important for quality of life maintenance in patients with hormone receptor-positive advanced breast cancer. In previous studies, a combination of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and fulvestrant prolonged the time to chemotherapy (TTC). In this study, we used real-world data to evaluate TTC in the context of CDK4/6i therapy. METHODS: We performed a retrospective chart review of women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated at the Aichi Cancer Center Hospital. The patients were categorized into having received CDK4/6i therapy first (n = 41), second (n = 33), and none at all (n = 67). The change in TTC among the groups was examined. RESULTS: The median follow-up time was 13.8, 27.5, and 30.3 months in the CDK4/6i (first), CDK4/6i (second), and non-CDK4/6i groups, respectively. The median progression-free survival (PFS) with first-line therapy for metastasis was 30.0, 11.9, and 13.0 months, respectively (CDK4/6i [first] vs. non-CDK4/6i; p = 0.018, CDK4/6i [second] vs. non-CDK4/6i; p = 0.383). The median TTC was not reached in the CDK4/6i (first) group, was 39.1 months in the CDK4/6i (second) group, and was 44.2 months in the non-CDK4/6i group (CDK4/6i [first] vs. non-CDK4/6i; p = 0.880; CDK4/6i [second] vs. non-CDK4/6i; p = 0.407). The non-CDK4/6i group with TTC ≥ 60 months included more cases of secondary endocrine therapy resistance (p = 0.017), no perioperative chemotherapy (p = 0.021), and a longer disease-free interval (p = 0.093). CONCLUSION: Although PFS was significantly longer in the CDK4/6i (first) group than in the non-CDK4/6i group, TTC did not significantly differ among the three groups in real-world data. The non-CDK4/6i group showed a long TTC in patients with late recurrence and low risk at the primary lesion site, who benefited greatly from hormone monotherapy.

Impact of Tumor Progression on Survival During Neoadjuvant Chemotherapy in Breast Cancer: A Cohort Study.

BACKGROUND/AIM: Few patients with breast cancer experience tumor progression during neoadjuvant systemic therapy (NST), but their poor outcome is similar to that of patients who fail to achieve a pathological complete response (pCR). No previous reports have compared patients with pCR, non-pCR, and progression during NST to determine the survival outcomes. PATIENTS AND METHODS: This retrospective chart review of patients with stage I-III breast cancer was conducted between January 2001 and December 2018. pCR was defined as no invasive cancer or in situ residuals in the breast and lymph nodes (ypT0 ypN0). Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier methods. RESULTS: Of the 595 patients who received NST, 167 (28.1%) had pCR (pCR group), 404 (67.9%) did not attain pCR (non-pCR group), and 24 (4.0%) experienced tumor progression during NST (PD group). The median DFS was 6.0 months, 154.0 months, and not reached in the PD, non-pCR, and pCR groups, respectively. The PD group had significantly shorter DFS than patients without tumor progression in the pCR and non-pCR groups [hazard ratio (HR)=13.0, 95%CI=8.1-21.0, p<0.01]. The median OS was 13.6 months (95%CI=10.4-35.5) in the PD group and was not reached in the pCR and non-pCR (non-PD) groups. The OS was significantly poorer in the PD group than in the non-PD groups (HR=15.8, 95%CI=9.2-27.1, p<0.01). CONCLUSION: The PD group had the poorest survival outcome even after recurrence, thus warranting new treatment strategies.

Association between bevacizumab with cancer drug therapies and drug-induced interstitial lung disease in patients with solid tumor: A systematic review and meta-analysis of randomized clinical trials.

PURPOSE: This study aimed to determine interstitial lung disease (ILD) incidences in patients receiving cancer drug therapies with or without bevacizumab treatment. METHODS: Systematic searches of PubMed, Embase, and Cochrane Library were conducted in January 2021. The main inclusion criteria were randomized clinical trials that compared bevacizumab with standard treatment in patients with solid tumors. Cochrane Collaboration's Tool was used for assessing risk-of-bias. RESULTS: Thirteen records involving 7201 patients were included in the meta-analysis. There were 42 ILD events in bevacizumab groups and 72 in control groups. In bevacizumab groups, the odds ratio for ILD was 0.62 (95% CI 0.42-0.92; p = 0.02), which was a significantly lower incidence than the control. This tendency was shown in targeted therapy groups but not in the cytotoxic agent groups. CONCLUSION: Our data suggest that bevacizumab may reduce the incidence of ILD.

The frequency of low HER2 expression in breast cancer and a comparison of prognosis between patients with HER2-low and HER2-negative breast cancer by HR status.

PURPOSE: The DESTINY-Breast04 clinical trial is currently investigating whether trastuzumab deruxtecan (T-DXd) is effective in HER2-low as well as HER2-positive breast cancer. This highlights the interest in treatment strategies for patients with HER2-low breast cancer. The current study was therefore designed to determine the frequency of HER2-low among all breast cancers, and to compare the prognosis of HER2-low patients with that of HER2-negative patients. METHODS: We retrospectively reviewed the biological data from 4,918 of 4,977 primary breast cancer patients who attended our institute. We quantified the overall frequency of breast cancer patients with a new HER2-low subtype that was defined by an immunohistochemistry score of IHC1 + or IHC2 + /ISH-. We then compared the clinical characteristics and prognosis of HER2-low patients with that of patients who did not have HER2 amplification (HER2-0). RESULTS: Low HER2 expression was found in 3169 (64.4%) patients; 2860 (58.1%) were HR-positive and 309 (6.3%) were HR-negative. Among HER2-0 patients, 681 (13.9%) were HR-positive and 157 (3.2%) were HR-negative. The HER2-0 group tended to have more poor prognostic factors than the HER2-low group, irrespective of HR status. There were no statistically significant differences between the prognosis of HER2-low and HER2-0 patients, regardless of HR status. However, patients in the HER2-low group tended to have better prognosis than those in the HER2-0 group. CONCLUSION: HER2-low patients did not have a significantly different prognosis than HER2-0 patients, regardless of HR status. However, we should consider tailoring therapies for patients with HRE2-low early breast cancer according to their HR status.

The significance of biopsy scar excision at the time of skin- or nipple-sparing mastectomy with immediate breast reconstruction.

BACKGROUND: Neoplastic seeding (NS) can occur after tissue biopsy, which is a clinical issue especially in mastectomy with immediate reconstruction. This is because postoperative radiation is not usually given and local recurrence of preserved skin flap may increase. The purpose of this study is to investigate the importance of preoperative evaluation of NS and the validity of biopsy scar excision. PATIENTS AND METHODS: We retrospectively analysed 174 cases of mastectomy with immediate breast reconstruction. The primary endpoint is the frequency of clinical and pathological NS and the secondary endpoint is the problem of excision of needle biopsy site. RESULTS: Three cases (1.7%) had preoperative clinical findings of NS. Pathological examination revealed NS in all three cases. Biopsy scars could be excised in 115 cases among 171 cases without clinical NS. Pathological NS was found in 1 of 66 (1.5%) cases of which pathological examination was performed. Biopsy scars could not be excised in the remaining 56 cases: the biopsy scar could not be identified in 41 cases, and there was concern about a decrease in flap blood flow after excision in 15 cases. In 12 of these 15 cases, the scars were close to the skin incision; excision of these scars might have triggered skin necrosis between the incision and the biopsy scar excision site. No postoperative complications were observed. CONCLUSIONS: It is important to preoperatively evaluate clinical NS, and biopsy scars should be excised in clinical NS cases. Even in cases without clinical NS, biopsy scar excision should be considered. It is also important to perform a biopsy in consideration of the incision design for reconstructive surgery.

Impact of adjuvant endocrine therapy on prognosis in small hormone receptor-positive, HER2-negative early breast cancer.

BACKGROUND: The efficacy of adjuvant endocrine therapy for hormone receptor-positive breast cancer has been previously established. However, significant adverse events related to endocrine therapy cannot be ignored. T1 breast cancer is expected to have a good prognosis. Therefore, adjuvant endocrine therapy for T1a breast cancer patients is controversial. Thus, in this study, we examined the effect of endocrine therapy on the prognosis of T1N0 hormone receptor-positive, HER2-negative breast cancer patients in each tumor size group, and re-considered the application of endocrine therapy. METHODS: We retrospectively obtained clinical and pathological data from medical records of 7635 patients who underwent surgery for breast cancer at Aichi Cancer Hospital between January 2000 and December 2017. The primary end point of our analysis was disease-free survival (DFS). The secondary end points were distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS). The log-rank test, cumulative survival generated curves with Kaplan-Meier methods and the hazard ratio (HR) calculated with a Cox regression model were used to assess the effects of endocrine therapy on prognosis. RESULTS: The 5-year DFS was worse in the non-endocrine therapy (non-ET) group (78%) than the endocrine therapy (ET) group (95%) in the T1c population (p < 0.001, HR 0.25). However, there was no statistically significant difference in DFS between the ET and the non-ET groups in T1a (ET 96% vs non-ET 93%, p = 0.9314, HR 0.94) and T1b (ET 96% vs non-ET 93%, p = 0.1481HR 0.53) breast cancer. The OS, DDFS, and BCSS of the patients also showed that endocrine therapy was associated with improvement of the prognosis in the T1c group, but not in the T1a and T1b groups. CONCLUSIONS: Adjuvant endocrine therapy may be essential for T1c breast cancer patients. In contrast, this therapy should be discussed for T1a and T1b luminal breast cancer patients under some circumstances, such as suffering from adverse events.

A difficult-to-diagnose fibromatosis-like metaplastic carcinoma of the breast: a case report.

BACKGROUND: Fibromatosis-like metaplastic carcinoma (FLMCa), classified as a metaplastic carcinoma of the breast, is a very rare type of metaplastic carcinoma. We report a case of FLMCa that was difficult to diagnose. CASE PRESENTATION: The patient was a 56-year-old postmenopausal woman who presented with a left-sided breast mass. A 1.3-cm irregular mass was found in the lower outer quadrant of the left breast on breast ultrasonography. She underwent core needle biopsy and vacuum-assisted biopsy, but the pathological findings only revealed inflammatory cell infiltration and a high level of fibrosis, with no malignant findings. At 3 months follow-up, she underwent a repeat breast ultrasonography, which revealed an increase in the size of the mass to 1.8 cm, and a repeat core needle biopsy, which showed a few spindle cells and squamous cells positive for cytokeratin (CK)5/6 and AE1/AE3, leading to the suspicion of FLMCa. Since the amount of tissue was insufficient to establish a definitive diagnosis, she underwent a lumpectomy. We found low-grade and slightly atypical spindle cells and partly atypical spindle cell carcinoma and squamous cell carcinoma. CK5/6 and α-SMA were positive, thus confirming FLMCa. Because the margins on the edge of the nipple side and anterior side were "ink on tumor", she underwent a mastectomy and sentinel lymph node biopsy. After the surgery, she received adjuvant chemotherapy. At 3 years and 8 months of follow-up, no recurrent or metastatic lesions were identified in her body. CONCLUSIONS: FLMCa should be considered in the differential diagnosis when collagenous fibers are proliferating and malignancy is clinically suspected. Immunohistochemical analysis may be helpful in confirming this diagnosis.