Preoperative Neutrophil-to-Lymphocyte Ratio in Postmenopausal Breast Cancer Patients.

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR) has been recognized as a marker of systemic inflammation with a prognostic impact in patients with various cancers, including breast cancer. The aim of this study was to investigate the relationships between the preoperative NLR and breast cancer prognosis in the patients before and after menopausal age, and its relationship with other prognostic factors. METHODS: A total of 1868 patients with clinical Stage I-III primary breast cancer were enrolled. The associations between clinicopathological factors and the preoperative NLR were analyzed, and relapse-free survival (RFS) and overall survival (OS) were estimated. RESULTS: Statistical analyses stratified by the menopausal status revealed that a high NLR was significantly associated with worse RFS (P < 0.001) and OS (P = 0.001) in postmenopausal patients, but not in premenopausal patients. Although the postmenopausal patients with relapsed cancer tended to have higher NLR levels than those without relapse (P = 0.079), NLR levels of premenopausal patients with relapsed cancer were significantly lower than that of relapse-free patients (P = 0.024). In postmenopausal patients, a high NLR was only associated with worse RFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (P < 0.001), in those managed without adjuvant chemotherapy (P = 0.003); this association was not observed in patients who received adjuvant chemotherapy. CONCLUSIONS: The preoperative NLR can be a useful prognostic marker, especially in postmenopausal breast cancer patients. The relationships between the NLR and breast cancer prognosis may be more evident when patients are assessed according to their menopausal status.

Predicting the presence of breast cancer using circulating small RNAs, including those in the extracellular vesicles.

Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA-based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer-free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR-21-5p (3' addition C), miR-23a-3p and tRF-Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early-stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF-7 and MDA-MB-231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection.

Diagnostic performance of peripheral leukocyte telomere G-tail length for detecting breast cancer.

The telomere G-tail (G-tail) plays an essential role in maintaining chromosome stability. In this study, we assessed the leukocyte G-tail length of breast cancer (BC) patients and cancer-free individuals and evaluated the association between the G-tail length and the presence of BC. A significant shortening of the median G-tail length was observed in BC patients compared with cancer-free individuals and was found in the early phase of BC. Our study indicated that the leukocyte G-tail length might be a potential biomarker for BC detection.

A dramatic response to an immune checkpoint inhibitor plus chemotherapy in a patient with metastatic metaplastic carcinoma of the breast: A case report.

We present a unique case of metastatic metaplastic breast carcinoma responding dramatically to immunochemotherapy. A 46-year-old Japanese woman with primary metaplastic carcinoma of the breast, which was immunohistochemically confirmed to be triple-negative breast cancer, underwent radical surgery, followed by adjuvant chemotherapy with an anthracycline and a taxane. Since multiple lung metastases were detected two months post-chemotherapy and the primary site was shown to be PD-L1-positive, the immune checkpoint inhibitor (ICI) pembrolizumab plus gemcitabine/carboplatin was initiated. While the treatment was discontinued after 15 days due to suspected drug-induced pneumonitis, the lung metastases significantly shrank with no development of new lesions for three months. The patient remained alive as of approximately 15 months after the recurrence date. This case highlights the potential of immunochemotherapy in treating metaplastic breast carcinomas.

Bilateral breast metastases from anaplastic lymphoma kinase-positive lung cancer in a male: a case report.

BACKGROUND: Distant metastases from lung cancer are commonly found in the brain, bone, and liver. Metastases to the breast from non-mammary malignancies are extremely rare, and their clinical presentations remain unclear. CASE PRESENTATION: We herein report a case of bilateral breast metastases from anaplastic lymphoma kinase-positive advanced lung cancer in a 51-year-old Japanese male patient. During the course of systemic treatment for advanced lung cancer, computed tomography revealed bilateral breast enlargement without contrast enhancement, a finding consistent with gynecomastia. While other metastatic lesions responded to chemotherapy, both breast masses grew vertically like nodules. The breast masses were immunohistochemically diagnosed as metastases from lung cancer and were removed surgically. Simultaneous bilateral breast metastases from malignancies of other organs, like ones in this case, have rarely been described. CONCLUSIONS: It is important to keep in mind that breast metastases from nonmammary malignancies are a possible explanation for unusual breast findings in a patient with a history of malignancies.

Mutation spectra of the BRCA1/2 genes in human breast and ovarian cancer and germline.

Annotating genomic sequence alterations is sometimes a difficult decision, particularly in missense variants with uncertain pathogenic significance and also in those presumed as germline pathogenic variants. We here suggest that mutation spectrum may also be useful for judging them. From the public databases, 982 BRCA1/1861 BRCA2 germline missense variants and 294 BRCA1/420 BRCA2 somatic missense variants were obtained. We then compared their mutation spectra, i.e., the frequencies of two transition- and four transversion-type mutations, in each category. Intriguingly, in BRCA1 variants, A:T to C:G transversion, which was relatively frequent in the germline, was extremely rare in somatic, particularly breast cancer, cells (p = .03). Conversely, A:T to T:A transversion was most infrequent in the germline, but not rare in somatic cells. Thus, BRCA1 variants with A:T to T:A transversion may be suspected as somatic, and those with A:T to C:G as being in the germline. These tendencies of mutation spectrum may also suggest the biological and chemical origins of the base alterations. On the other hand, unfortunately, variants of uncertain significance (VUS) were not distinguishable by mutation spectrum. Our findings warrant further and more detailed studies.

A case of BIA-ALCL in which postoperative chest wall recurrence was highly suspected: the third reported case of BIA-ALCL in Japan.

BACKGROUND: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare malignancy. Many cases of BIA-ALCL are identified based on the presence of late-onset effusion and/or masses. Importantly, the United States Food and Drug Administration noted that in all cases diagnosed in patients with textured implants, the patients either had a history of mixed implantation of smooth and textured devices or no clinical history was supplied for review. In Japan, the first case of BIA-ALCL was reported in 2019, and we encountered the third case in Japan in December 2021. There have been a total of five cases of BIA-ALCL previously reported at Japanese academic conferences (Japan Oncoplastic Breast Surgery Society. http://jopbs.umin.jp/medical/index.html ), of which only the first case has been published. Unlike the first case, this patient had clinical features that were highly suggestive of the postoperative chest wall recurrence of breast cancer, with a mass and rash on the skin. CASE PRESENTATION: The patient was a 45-year-old woman who had undergone breast reconstruction after breast cancer surgery of the right breast 8 years previously. The patient presented with a mass and skin rash inside the inframammary area, and we suspected a damaged silicone breast implant (SBI) or chest wall recurrence. We examined the mass by a core needle biopsy and made a pathological diagnosis of BIA-ALCL. Imaging findings suggested internal thoracic lymph node swelling and lymphoma infiltration beyond the capsule but no metastatic lesions (cStage III). After en bloc resection of the SBI and lymphoma, adjuvant systemic therapy was performed. CONCLUSION: We encountered the third case of BIA-ALCL in Japan. This was a case with clinically advanced stage of disease; however, the BIA-ALCL was found to be in remission.

Assessment of the expression of microRNAs­221­3p, ­146a­5p, ­16­5p and BCL2 in oncocytic carcinoma of the breast: A case report.

Oncocytic carcinoma of the breast is rare and its molecular profiles remain poorly understood. MicroRNAs (miRNAs/miRs) have been identified as contributors to carcinogenesis at the post-transcriptional level; thus, an aberrant expression of miRNAs has attracted attention as a potential biomarker of numerous diseases, including cancer. The present study reports the case of a 76-year-old woman diagnosed with oncocytic carcinoma of the breast. Considering the distinctive feature of oncocytic carcinoma of the breast, which is the presence of granular eosinophilic cytoplasm containing numerous mitochondria, the present study hypothesized that the expression of mitochondria-related miRNAs could be altered in oncocytic carcinomas. Aberrant expression levels of the miRNAs previously reported as mitochondria-related miRNAs, such as miR-221-3p, -146a-5p and -16-5p, were revealed in tissue from specimens of oncocytic carcinoma of the breast, compared with that of a more typical type of invasive ductal carcinoma of the breast. The present study highlights the changes in miRNA expression in oncocytic carcinoma of the breast, suggesting its potential as a biomarker for diagnosis.

Endobronchial ultrasound-guided transbronchial needle aspiration facilitating diagnosis of sarcoidosis in a breast cancer patient with multiple lymphadenopathy: a case report.

BACKGROUND: Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology. Cell-mediated immunity disorder is often found in sarcoidosis patients, and an association between malignant tumors and sarcoidosis has been suggested. Sarcoidosis and malignant disease can occur simultaneously or sequentially, leading to misdiagnosis and mistreatment. Sarcoidosis is diagnosed clinically, radiologically, and histologically. We report herein a case of sarcoidosis diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration from the mediastinal lymph nodes of a breast cancer patient. CASE PRESENTATION: The patient was a 70-year-old Asian woman who presented with right breast tumor. A 20-mm movable mass was identified in the inferolateral quadrant of the right breast, and mammography revealed a spiculated mass with calcification. Ultrasonography revealed a mass with internal hypoechogenicity, and biopsy revealed estrogen receptor-positive, human epidermal growth factor receptor 2-positive invasive ductal carcinoma. Positron emission tomography/computed tomography showed multiple lymphadenopathy including mediastinal lymph nodes, with fluorodeoxyglucose accumulation in those nodes suggesting breast cancer metastases. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymph node revealed noncaseous epithelioid granuloma. Due to a history of uveitis and elevated soluble interleukin 2 receptor, lymphadenopathy due to sarcoidosis and stage IIA breast cancer were diagnosed. Right partial mastectomy and axillary lymph node dissection were performed after preoperative chemotherapy. No exacerbation of sarcoidosis symptoms has been observed during treatment. CONCLUSION: We report a case of breast cancer in which sarcoidosis could be diagnosed based on endobronchial ultrasound-guided transbronchial needle aspiration, a history of uveitis, and elevated soluble interleukin 2 receptor despite fluorodeoxyglucose positron emission tomography/computed tomography suggesting multiple lymph node metastases. This report emphasizes the importance of differential diagnosis of lymph node involvements in cancer patients.

Impact of serum vitamin D on the response and prognosis in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Several studies have recently reported that the relationships between serum vitamin D and the prognosis or the pathological response to neoadjuvant chemotherapy (NAC) in breast cancer. However, there are no data regarding the clinical impacts of the vitamin D in Japanese breast cancer patients so far. PATIENTS AND METHODS: In the present study, a total of 250 patients with clinical Stage I-III primary breast cancer who were treated with NAC and subsequently underwent definitive surgery were included. Serum 25-hydroxvitamin D (25(OH)D) levels were evaluated using blood samples obtained before NAC. RESULTS: The serum 25(OH)D was positively associated with age, and the serum 25(OH)D was significantly higher in postmenopausal women than that in pre/peri-menopausal women. Serum 25(OH)D level was not associated with the achievement of pathological complete response (pCR) in this cohort. The low 25(OH)D levels were significantly associated with shorter time to distant recurrence (TTDR). According to the univariate analysis, high clinical stage before NAC (cStage III) and low serum 25(OH)D level were significantly associated with the shorter TTDR, and pCR was significantly associated with the longer TTDR. According to a multivariate analysis, low serum 25(OH)D level were independent poor prognostic factors for TTDR. CONCLUSIONS: The low 25(OH)D levels were significantly associated with poorer prognosis in Japanese women with operable breast cancer patients treated with NAC.

Association between CA 15­3 and progression of interstitial lung disease in a case of coexisting systemic sclerosis and recurrent breast cancer: A case report.

Carbohydrate antigen 15-3 (CA 15-3) is known as a specific tumor marker for breast cancer, the main use of which is monitoring therapy in patients with advanced breast cancer. Either systemic sclerosis (SSc)-interstitial lung disease (ILD) or pulmonary arterial hypertension is currently the leading cause of disease-related morbidity and mortality in patients with scleroderma. Although CA 15-3 has been investigated as a biomarker in SSc-ILD, its role remains unclear. The current report presented a case of recurrent breast cancer diagnosed with SSc-ILD during treatment. The patient, at 63 years old, experienced shortness of breath with minimal exertion after four cycles of perutuzumab, trastuzumab and weekly paclitaxel. Computed tomography (CT) revealed ground-glass opacities and linear shadows in the peripheral lower lobes of both lungs. Although the development of lung involvement associated with breast cancer, such as carcinomatous lymphangitis, was initially suspected, because of the increase in CA 15-3, skin biopsies were taken from the left index finger base and extension side of the left elbow, which demonstrated increased thickness of the dermis, leading to a diagnosis of SSc-ILD. The findings in this case suggested the importance of considering a differential diagnosis, including ILD, concurrently while screening for the progression of recurrent breast cancer when encountering patients with breast cancer and elevated levels of CA 15-3.

The clinical usefulness of the CTS5 in the prediction of late distant recurrence in postmenopausal women with estrogen receptor-positive early breast cancer.

BACKGROUND: Clinical Treatment Score post-5 years (CTS5) is a promising prognostic tool to evaluate late distant recurrence (DR) risk for breast cancer after 5-year adjuvant endocrine therapy. PATIENTS AND METHODS: Among 560 postmenopausal women with pathological stage I-III estrogen receptor-positive (ER+) primary breast cancer, 383 women who had received 5-year adjuvant endocrine therapy without any recurrence at 5 years after surgery were included in this study. The CTS5 was calculated for each patient using a previously published formula, and the patients were stratified by their CTS5 values into the low-, intermediate- and high-CTS5 risk groups. RESULTS: According to the CTS5, 205 (53.5%), 106 (27.7%) and 72 (18.8%) patients were classified into the low-, intermediate-, and high-CTS5 risk groups, respectively. A higher ER expression level was significantly associated with the low CTS5. The increased administration of adjuvant chemotherapy was significantly associated with a high CTS5. The occurrence of DR was higher in the intermediate and high CTS5 groups than in the low CTS5 group. The DRFS in the low CTS5 risk group was significantly better than that in the intermediate- or high-risk groups. In the ER-high or HER2-negative (HER2-) group, the DRFS in the low-risk group was significantly better than that of the intermediate- or high-risk groups. However, in the low-ER or HER2-positive group, there was no significant difference in DRFS among the three risk groups. CONCLUSIONS: In postmenopausal women with ER+ breast cancer, low CTS5 was considered to be associated with a very low risk of late DR. Thus, extended endocrine therapy may be unnecessary for patients with low CTS5 scores. Extended endocrine therapy should be offered for patients with intermediate or high CTS5 scores, especially those with high-ER and HER2- breast cancer.

Spontaneous regression of breast cancer with immune response: a case report.

BACKGROUND: Spontaneous regression (SR) is a rare phenomenon in which a cancer disappears or remits without treatment. We report a case of breast cancer that showed spontaneous tumor regression in the surgical specimen after core needle biopsy. CASE PRESENTATION: A 59-year-old woman came to our hospital complaining of a painful lump in the right breast. In the upper-outer quadrant of the right breast, a tumor with an unclear boundary, 30 mm in diameter, was palpable. In pathological findings from needle biopsy, the tumor was diagnosed as solid-type invasive ductal breast carcinoma. Partial coagulation necrosis was generated in estrogen receptor-negative, HER2-negative, and AE1/AE3-positive ductal carcinoma without infiltration of lymphocytes. Surgery for right breast cancer was then performed. Histological examination of the surgical specimen revealed the tumor was invasive ductal carcinoma with lymphocyte infiltration, coagulation necrosis, and fibrous tissue with hemosiderin. The tumor formed a solid nest, 3 mm in diameter, suggesting the possibility of SR. CONCLUSIONS: Immune responses, infection, hormones, surgical stress, and ischemia have been reported as mechanisms of SR. The findings in this case strongly suggest that SR of breast cancer is associated with anti-tumor immune responses.

Asymptomatic solitary metastasis to the stomach from breast cancer: A case report.

Distant metastases from breast cancer are frequently found in bones, lungs and the liver. Metastasis to the stomach is rare, and its clinical presentation remains unclear. The present report describes a case of isolated gastric metastasis from breast cancer identified by contrast-enhanced computed tomography (CT). A 45-year-old female patient underwent right mastectomy and axillary lymph node dissection after preoperative chemotherapy for right invasive lobular breast carcinoma T4bN2M0, stage IIIB. Postoperative radiotherapy and endocrine therapy with tamoxifen for 5 years were performed. CT for postoperative follow-up at 52 years old revealed thickening of the stomach wall. Although the patient was asymptomatic, erosive mucosa was observed on the gastric body during gastroscopy. The gastric lesion was immunohistochemically diagnosed as metastatic luminal disease from the breast cancer. Positron emission tomography/CT revealed no abnormal accumulation suggesting metastasis to other organs. Palbociclib and fulvestrant treatment were initiated for gastric metastasis. Invasive lobular breast carcinoma results in gastrointestinal metastasis, including the stomach, more frequently than invasive ductal breast carcinoma. However, most gastric metastases occur simultaneously with systemic metastases. Solitary metastasis to the stomach without symptoms as in this case has rarely been reported. The possibility of gastric metastasis should be considered among the differential diagnoses, even in the absence of symptoms, when gastrointestinal abnormalities are seen on CT in patients with a history of breast cancer.

Impact of Visceral Metastasis on Efficacy of Fulvestrant in Patients with Hormone Receptor-positive Recurrent Breast Cancer.

BACKGROUND: Previous studies have suggested that the presence of visceral metastasis is a parameter useful in predicting the treatment efficacy of fulvestrant in patients with advanced breast cancer. PATIENTS AND METHODS: We retrospectively examined the association between treatment efficacy and presence of visceral metastasis in 75 patients with hormone receptor-positive recurrent breast cancer who were treated with fulvestrant or no more than five lines of other endocrine monotherapy after recurrence. RESULTS: Nineteen patients received fulvestrant, 10 of whom had visceral metastasis. The median time to progression was 4 months for the overall study population; it was significantly longer for patients with non-visceral metastasis (5.4 months; 95% confidence interval=3.7-11.2 months) than for those with visceral metastasis (3.3 months; 95% confidence interval, 0.4-5.3 months; p=0.01). No differences in time to progression were found between the groups of patients with visceral metastasis and non-visceral metastasis who underwent other endocrine therapies. CONCLUSION: Fulvestrant is more effective for patients with non-visceral metastasis of recurrent breast cancer with than for those with visceral metastasis.