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.
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.
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.
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.
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.
Fulvestrant is more effective for patients with non-visceral metastasis of recurrent breast cancer with than for those with visceral metastasis.
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.
Background The telomere G-tail, located at the terminal 3’-end, plays an important role in the maintenance of chromosome stability. Telomere G-tail length has been shown to be related to the presence of various cancers; however, the association between telomere G-tail length and breast cancer has remained unclear. Methods We measured the length of the leukocyte telomere G-tail using the hybridization protection assay, which has the advantages of being simple to perform, accurate and highly sensitive for G-tails as short as 20 nucleotides. The association between telomere G-tail length and presence of breast cancer was estimated by comparing breast cancer patients (n=70) and cancer-free individuals (n=83). We recruited cStage I-III breast cancer patients who underwent surgery between November 2016 and December 2017 at Hiroshima University Hospital. Cancer-free individuals included age-matched female individuals with no previous or current history of any cancer. Results The median telomere G-tail length was significantly shorter in breast cancer patients (11,886.70 ± 2,008.74 RLU/μg DNA) than in cancer-free individuals (13,336.00 ± 2,072.31 RLU/μg DNA; p < 0.01). Shortening of the telomere G-tail length was observed in the phase of ductal carcinoma in situ, and this trend was observed with or without shortening of the total telomere length. Spearman’s rank correlation analysis showed that there was no significant association between telomere G-tail length and total telomere length in breast cancer patients (ρ = -0.09; p = 0.48). In contrast, a significant correlation was found between telomere G-tail length and total telomere length in cancer-free individuals (ρ = 0.29; p = 0.01). Conclusions Our study indicated that leukocyte telomere G-tail length may serve as a novel potential biomarker for detection of breast cancer. Citation Format: Yumiko Koi, Yasuhiro Tsutani, Yukie Nishiyama, Shinsuke Sasada, Norio Masumoto, Takayuki Kadoya, Ryou-u Takahashi, Morihito Okada, Hidetoshi Tahara. Telomere G-tail length correlates with the presence of breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-04-01.
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