The Effect of Manual Lymph Drainage and Compression Bandaging for Stage 2 Breast Cancer-Related Lymphedema: A Randomized Controlled Trial.

Aim: To explore the effect of manual lymph drainage (MLD), compression bandaging (CB), or combined decongestive therapy (CDT), including MLD and CB, on stage 2 breast cancer-related lymphedema (BCRL). Methods: Sixty women with stage 2 BCRL were enrolled. They were randomly divided into the MLD group, the CB group or the CDT group. Each group, respectively, received MLD alone, CB alone, or CDT composed of MLD and CB, for 2 weeks. The volume and the local tissue water (LTW) of affected arms were measured before and after treatment. Arm circumferences were measured at 4 cm interval starting from the wrist to the shoulder with a tape measure. LTW was detected using the (tissue dielectric constant, TDC) method and was expressed as TDC value in two sites on the ventral midpoint of upper arm and forearm. Results: The volume of affected arms in each group after 2-weeks' treatment was lower than their baseline and the difference was statistically significant (p < 0.05). But there was no significant difference in volume change among three groups. The TDC value of the upper arm and forearm in the group CB and the group CDT decreased distinctly compared with baseline (p < 0.05). But the TDC value of the upper arm and forearm after MLD did not change (p > 0.05). Compared with the group MLD and the group CDT, the reduction of the TDC value in the group CB was more significant (p < 0.05). Conclusions: MLD or CB alone could effectively reduce the volume of affected arms for patients with stage 2 BCRL, and CB also could reduce the LTW more significantly. CDT did not seem to show an extra advantage. Therefore, CB may be the first choice for stage 2 BCRL. But for patients who are unwilling or intolerant to CB, MLD can be selected.

Rationale and design of a phase II trial of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for N0/N1mi, HER2 + early breast cancer (PHAEDRA).

BACKGROUND: The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated. METHODS: This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1-7, then 4 mg bid on days 8-21) or the first 2 cycles (4 mg tid on days 1-7, then 4 mg bid on days 8-42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea. DISCUSSION: This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.

Tissue Dielectric Constant Combined With Arm Volume Measurement as Complementary Methods in Detection and Assessment of Breast Cancer-Related Lymphedema.

Background: To investigate the role of tissue dielectric constant (TDC) in the detection and assessment of breast cancer-related lymphedema (BCRL) and to determine whether the TDC could potentially be used as a complementary method for arm volume measurement. Methods: Sixty-nine patients with BCRL were enrolled in this study. Local tissue water was assessed bilaterally by using the TDC method in four sites: upper arm, forearm, hand, and lateral thorax. Arm circumferences were measured at the 4-cm interval, starting from the shoulder to the wrist by using a tape measure. The arm volume was calculated by a standard formula. Patients' demographic information and clinical characteristics were also recorded. Results: Fifty-one of the 69 patients were diagnosed with clinical lymphedema. Using a TDC ratio of 1.2 or a diagnostic reference standard of ≥2 cm arm circumference, the sensitivity of these two methods was found to be identical at 73.9%. The TDC values in four sites on the affected side were significantly higher (p < 0.05) relative to the unaffected side. The inter-side TDC ratio of upper arm and forearm was substantially higher than that of lateral thorax and hand (p < 0.05). The TDC ratio of upper arm, forearm, and hand, especially of the upper arm and forearm, was positively correlated with inter-limb volume difference and stage of lymphedema. Conclusion: The TDC method elucidated a meaningful clinical correlation to the arm volume measurement. Applying those two methods together showed promise in the detection and assessment of BCRL. The forearm and upper arm were reliable examination sites for TDC measurements in the clinic.

T1a triple negative breast cancer has the worst prognosis among all the small tumor (<1 cm) of TNBC and HER2-rich subtypes.

BACKGROUND: Triple negative breast cancer (TNBC), accounting for 15% of all breast cancer cases, was usually considered as the most aggressive subtype. The present study evaluated the prognosis of T1a TNBC and the impact of tumor size on T1 TNBC survival in large-scale population. METHODS: This retrospective study enrolled T1a/T1b/T1c TNBC and HER2+/hormone receptor (HoR)- patients diagnosed between 2010 to 2012 from the Surveillance, Epidemiology, and End Results database. The following information was extracted for further analyses: demographic variables including age at diagnosis, race, marital status, laterality, histological grade, T/N stage, American Joint Committee on Cancer (AJCC) stage, radiation therapy, survival and cause of death. Kaplan-Meier method and Cox regression were engaged for breast cancer specific survival (BCSS) and overall survival (OS) analyses. RESULTS: In all, the present study enrolled 6,953 TNBC and 2,648 HER2+/HoR- patients. T1a TNBC which generally omitted adjuvant chemotherapy had worse prognosis than T1a HER2+/HoR- [BCSS: hazard ratio (HR) 3.23, 95% confidence interval (CI): 1.05-9.09, P=0.03; OS: HR 2.63, 95% CI: 1.25-5.56, P=0.01] and T1b HER2+/HoR- (BCSS: HR 5.26, 95% CI: 1.61-16.7, P=0.006; OS: HR 3.03, 95% CI: 1.27-7.14, P=0.013) tumors which both were recommended by the National Comprehensive Cancer Network (NCCN) guideline to have chemotherapy. T1a TNBC also showed a trend with poorer prognosis than T1b TNBC, but did not reach statistical significance. CONCLUSIONS: T1a TNBC had the worst prognosis among all small tumors (<1 cm) of TNBC and HER2+/HoR- subtypes, indicating the necessity of more intensive adjuvant treatment.

Omitting radiotherapy is safe in breast cancer patients ≥ 70 years old after breast-conserving surgery without axillary lymph node operation.

To verify whether omitting radiotherapy from breast cancer treatment for patients ≥ 70 years old following breast-conserving surgery (BCS) without axillary lymph node dissection is safe. Previous studies have shown that omitting breast radiotherapy after BCS and axillary lymph node dissection is safe for elderly breast cancer patients. We aimed to evaluate the safety of BCS without axillary surgery or breast radiotherapy (BCSNR) in elderly patients with breast cancer and clinically negative axillary lymph nodes. We performed a retrospective analysis of 481 patients with breast cancer, aged ≥ 70 years, between 2010 and 2016. Of these, 302 patients underwent BCSNR and 179 underwent other, larger scope operations. Local recurrence rate, ipsilateral breast tumor recurrence (IBTR) rate, distant metastasis rate, breast-related death, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. After a median follow-up of 60 months, no significant differences in local recurrence, distant metastasis rate, breast-related death, and DFS were noted. The OS was similar (P = 0.56) between the BCSNR group (91.7%) and other operations group (93.0%). The IBTR rate was considered low in both groups, however resulted greater (P = 0.005) in the BCSNR group (5.3%) than in other operations group (1.6%). BCSNR did not affect the survival of elderly patients with breast cancer with clinically negative axillary lymph nodes. IBTR was infrequent in both groups; however, there was a significant difference between the two groups. BCSNR is a feasible treatment modality for patients with breast cancer ≥ 70 years old with clinically negative axillary lymph nodes.

Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial.

BACKGROUND: HER2 dual-blockade combined with aromatase inhibitors (AI) is a promising strategy to improve progression-free survival (PFS) in hormone receptor (HR) positive, metastatic breast cancer (MBC). Pyrotinib is a novel irreversible epidermal growth factor receptor/HER2 dual tyrosine kinase inhibitor. However, there is scarcity of data on the effectiveness and safety of pyrotinib combined with trastuzumab and AI as first-line treatment in a metastatic setting. METHODS/DESIGN: The present study is a prospective, randomized, open-label trial. 198 patients with HER2+/HR+ MBC will be recruited. Eligible patients will be allocated (2:1) to either an experimental group (pyrotinib + trastuzumab + AI) or a control group (trastuzumab + AI). Allocation will be stratified by 1) time since adjuvant hormone therapy (≤ 12 months/> 12 months/no prior hormone therapy); 2) lesion sites (visceral / non-visceral). The primary endpoint is PFS. DISCUSSION: To our knowledge, this is the first prospective randomized controlled trial to assess dual HER2-blockade with pyrotinib in the metastatic setting. This study will provide valuable evidence regarding the efficacy and safety of pyrotinib when combined with trastuzumab and an AI as first-line treatment for MBC. Moreover, it will also evaluate the feasibility of endocrine therapy as an alternative to chemotherapy in providing de-escalation therapy with less toxicity for advanced HR+/HER2+ patients. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03910712 . Registered on 10 Apr. 2019.

Breast-conserving surgery without axillary lymph node surgery or radiotherapy is safe for HER2-positive and triple negative breast cancer patients over 70 years of age.

PURPOSE: The prognosis of elderly patients with hormone receptor-positive breast cancer is very good, and their survival is unaffected by performing breast-conserving surgery (BCS) without radiotherapy. Therefore, we aimed to verify that BCS without axillary lymph node dissection, sentinel lymph node biopsy, or radiotherapy (BCSNR) is safe for patients over 70 years of age with luminal-type breast cancer, as well as for those with HER2-positive and triple negative breast cancer (TNBC). METHODS: This study retrospectively included 450 patients > 70-year-old with breast cancer from 2010 to 2016. The patients were divided into two groups, one treated with BCSNR and the other treated with mastectomy and axillary lymph node dissection (MALND), with a median follow-up period of 5 years. Disease-free survival (DFS), overall survival, local recurrence, distant metastasis, and ipsilateral breast tumor recurrence (IBTR) were compared between the two groups. RESULTS: The 5-year DFS for patients who underwent BCSNR and MALND was 90.1 and 91.3% (p = 0.903), respectively. In the BCSNR and MALND groups, respectively, the 5-year DFS for patients with luminal A type breast cancer was 99.2 and 100% (p = 0.167), that for patients with luminal B type breast cancer was 89.2 and 95.5% (p = 0.138), that for patients with HER2-positive breast cancer was 86.7 and 75.9% (p = 0.455), and that for TNBC patients was 71.7 and 89.7% (p = 0.195). IBTR significantly differed between the BCSNR and MALND groups for patients with TNBC (18.9% vs 0.0%, p = 0.040) and luminal B type patients (5.6% vs 0.0%, p = 0.043). CONCLUSION: BCSNR is not only suitable for elderly patients with luminal-type breast cancer but also for those with HER2-positive breast cancer and TNBC.

Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 1 (PREX1) is a Novel Predictor of Prognosis for Breast Cancer Patients: A Retrospective Case Series.

BACKGROUND In previous studies, higher expression of PREX1 (PtdIns (3,4,5)P3-dependent Rac exchanger 1) has been detected in some subsets of breast cancer, and activation of PREX1 has been associated with tumor progression in vivo. However, an association between PREX1 and breast cancer prognosis has not been examined. MATERIAL AND METHODS In this study, we investigated the expression and correlation of PREX1 with important clinical factors and prognosis of patients with breast cancer. Immunohistochemical staining was performed for 121 tumor tissue specimens obtained from primary breast cancer lesions. RESULTS We found that 55 tissues exhibited positive staining for PREX1. Moreover, tumors positive for PREX1 were found to have significant association with recurrence rate (P=0.000) and metastasis rate (P=0.001). Univariate and multivariate regression analyses also identified PREX1 expression as an independent variable of disease-free survival. Our analyses indicate that high levels of PREX1 expression were related to longer disease-free survival in patients with breast cancer (P=0.013). CONCLUSIONS PREX1 is a favorable variable of prognosis for breast cancer patients, these study results need to be confirmed in larger research studies.

GnRHa for Ovarian Protection and the Association between AMH and Ovarian Function during Adjuvant Chemotherapy for Breast Cancer.

Background: Chemotherapy impairs ovarian function in premenopausal breast cancer patients. Many breast cancer patients experience menopause earlier and therefore lose their reproductive abilities. The protective effect of gonadotropin-releasing hormone agonist (GnRha) upon the ovary is clearly apparent for hormone receptor (HR) negative patients, although the available data is not consistent for the patient body as a whole when considered regardless of HR status. It is also unknown whether levels of Anti-Mullerian Hormone (AMH) can reflect the influence of chemotherapy upon the ovary. Methods: We randomly assigned 98 premenopausal breast cancer patients regardless HR-positive or -negative to receive either standard chemotherapy with GnRHa (GnRHa group) or standard chemotherapy without GnRHa (control group). Our primary end point was ovarian failure rate (OVF) at 1 year. In addition, we observed the change of AMH level during chemotherapy and the association between AMH and OVF. Results: OVF was significantly lower (44.7%) in the GnRHa group than in the control group (80.6%; P=0.002). Median AMH levels were significantly higher before chemotherapy when compared to after 1/2cycles of chemotherapy, both in the GnRHa group (1.86ng/ml vs 0.12ng/ml; P=0.000) and in the control group (1.57ng/ml vs 0.10ng/ml; P=0.000). OVF was 91.3% in the AMH baseline level <1.1ng/ml group and 63.5% in the AMH baseline level >1.1ng/ml group (P=0.013). Conclusion: Data showed that GnRHa may have a protective effect on young breast cancer patients regardless of HR during chemotherapy. AMH could reflect changes of OVF during chemotherapy and predict OVF after chemotherapy.

The influence on survival of delay in the treatment initiation of screening detected non-symptomatic breast cancer.

We aimed to determine whether the detection-to-treatment interval of non-symptomatic breast cancer is associated with factors that can predict survival outcomes. A retrospective review of the Breast Surgery Department Database at Peking Union Medical College Hospital (PUMCH) was performed, and a total of 1084 non-symptomatic invasive breast cancer patients were included. The findings revealed that detection-to-treatment interval was significantly longer for women who were older (p = 0.001), lived in rural areas (p = 0.024), had lower education (p = 0.024), and had detection in other institutions (p = 0.006). Other sociodemographic and clinicopathological characteristics were not associated to longer interval. A median follow-up of 35 months (range: 6-60 months) was carried out and a long delay at more than 90 days did not significantly decrease the DFS (univariate, P = 0.232; multivariate, P = 0.088). For triple negative breast cancer, there was a worse DFS if the interval was longer than 90 days both in multivariate analysis (hazard ratio [HR] = 3.40; 95% CI, 1.12-10.35; P = 0.031) and univariate analysis (HR = 2.86; 95% CI, 1.03-7.91; P = 0.042). Further studies on care before initial treatment of non-symptomatic breast cancers are warranted.

Efficacy and safety of taxane plus anthracycline with or without cyclophosphamide in Chinese node-positive breast cancer patients: an open-label, randomized controlled trial.

PURPOSE: To evaluate and compare the efficacy and safety of the taxane plus anthracycline (TA) regimen vs. the taxane plus anthracycline plus cyclophosphamide (TAC) regimen as adjuvant chemotherapy in Chinese patients with node-positive breast cancer (BCa). METHODS: Patients with BCa (n = 640) were recruited between January 2010 and June 2012. All patients were randomized to receive six cycles of adjuvant therapy with the TA or TAC regimen. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS), quality of life (QoL), and chemotherapy-related toxicity. Finally, 630 patients were evaluable, with a median follow-up of 70 months. RESULTS: There were no differences in the 70-month median DFS and OS between the two groups (DFS: TA 79.7% vs. TAC 75.6%, P = 0.371; OS: TA vs. TAC, 85.1% vs. 87.6%, P = 0.271). The TA group had lower frequencies grade III/IV vomiting (TA vs. TAC, 11.7% vs. 18.1%, P = 0.025) and nausea (13.0% vs. 19.4%, P = 0.031). The health-related QoL score was higher in the TA group (74.1 ± 5.3 vs. 67.9 ± 4.4, P = 0.001 vs. TAC). CONCLUSIONS: In the adjuvant setting, compared with the TAC regimen, the TA regimen exhibits no significant difference with respect to DFS and OS in Chinese patients with node-positive BCa. On the other hand, TA is associated with less severe adverse events, lower economic burden, and better QoL.

Predictors of nonsentinel lymph node metastasis in patients with breast cancer with metastasis in the sentinel node.

To predict the factors related to axillary nonsentinel lymph node (NSLN) metastasis in patients with positive sentinel lymph node (SLN) of early breast cancer.The retrospective data are collected from the patients with positive SLN who received further completion axillary lymph node dissection (cALND) in Peking Union Medical Hospital between March 2016 and December 2017. Univariate analysis was conducted on data with various clinicopathologic factors at first. Those factors with statistic significance (P < .05) in univariate analysis were then used to implement multivariate analysis and logistic regression.There were total of 734 patients who received SLN biopsy , among whom 153 cases were included in our study. About 39.22% (60/153) of 153 paitents with positive SLN had no NSLN metastasisted to SLN. Univariate analysis showed that 3 variables were significantly correlated with NSLN involvement: tumor size (X = 10.384, P = .001), SLN metastasis ratio (number of positive SLNs/number of SLNs removed × 100%) (X = 10.365, P = .001) and the number of negative sentinel nodes (X = 10.384, P = .006). In multivariate analysis and logistic regression, tumor size (odds ratio [OR] = 3.392, 95% confidence interval [CI]: 1.409-8.166, P = .006) and SLN metastasis ratio (OR = 3.514, 95% CI: 1.416-8.72, P = .007) were the independent risk factors. While the number of negative sentinel nodes (OR = 0.211, 95% CI: 0.063-0.709, P = .014) was the independent protective factor. The calculated risk resulted in an area under the curve of 0.746 (95% CI: 0.644-0.848), suggesting stable discriminative capability in Chinese population.For those patients with positive SLN, larger tumor burden and SLN metastasis ratio are independent risk factors for NSLN metastasis. However, the more of the detected negative SLN, the less possibility with NSLN involvement.

MicroRNA­320a suppresses tumor cell growth and invasion of human breast cancer by targeting insulin­like growth factor 1 receptor.

The present study was performed to investigate the biological functions of microRNA­320a in human breast cancer and the underlying mechanisms. MicroRNA­320a expression was downregulated in human breast cancer, compared with the normal control. Overexpression of microRNA­320a induced apoptosis, and inhibited cell viability and invasion in MDA­MB­231cells while downregulation of microRNA­320a reduced apoptosis, and increased cell viability and invasion in MDA­MB­231 cells. Then, overexpression of microRNA­320a suppressed insulin­like growth factor 1 receptor (IGF­1R), p­AKt and cyclin D1 protein expression in MDA­MB­231cells. In addition, the downregulation of microRNA­320a induced IGF­1R, p­Akt and cyclin D1 protein expression in MDA­MB­231cells. Furthermore, the IGF­1R inhibitor increased the effects of microRNA­320a on the apoptosis of MDA­MB­231 cells. The p­Akt inhibitor (MK 2206 dihydrochloride, 2.5 nM) increased the effects of microRNA­320a on the apoptosis of MDA­MB­231 cells. These results revealed that microRNA­320a suppresses tumor cell growth and invasion of human breast cancer by targeting IGF­1R.

Clinical characteristics, classification and surgical treatment of periductal mastitis.

BACKGROUND: This study aimed to describe the clinical characteristics of periductal mastitis (PDM), propose the practical clinical classification system and evaluate the results of different surgical treatments in different type of PDM patients. METHODS: A retrospective study was carried out at department of breast surgery, Peking Union Medical College Hospital, Beijing, China. A total of 152 patients with the diagnosis of PDM were reviewed from March 2012 to December 2016. All of the patients underwent surgery. Data were collected regarding clinical manifestation, treatment, and outcomes. RESULTS: The median age was 36 years. A subareolar breast mass was the most frequent symptom. The most common clinical manifestations were mass (98.0%), rubefaction (41.1%), nipple retraction (36.8%), abscess (36.8%), skin ulceration (25.7%), and mammary duct fistula (19.1%). Fourteen (9.2%) patients were recurrent PDM at first hospitalization. Eight (5.3%) patients had prolactinoma. Five (3.3%) patients were taking antipsychotic medications. Only four (2.6%) patients were smokers. Eight patients were highly suspected to be breast cancer before surgery. A four-type classification system was first proposed according to clinical manifestations. The different surgeries in each category were evaluated. After 3 years median follow-up, 11 (7.2%) patients got recurrence including two initial recurrent PDM. CONCLUSIONS: Periductal mastitis is a distinct benign breast condition of unknown etiology. Mass, abscess and fistula are most common manifestations of the disease. Wide surgical excision, fistulectomy and extended excision with transfer of a random breast dermo-glandular flap (BDGF) are effective surgical modalities for different type of PDM.

Comparison of sentinel lymph node biopsy guided by blue dye with or without indocyanine green in early breast cancer.

BACKGROUND: There were limited data available for a head-to-head comparison of the identification rate and survival between the combined method of indocyanine green fluorescence and blue dye versus the traditional blue dye alone method for sentinel lymph node (SLN) biopsy. METHODS: From January 2013 to December 2015, 523 eligible breast cancer patients were included in this nonrandomized prospective analysis. The identification rates, the number of SLNs identified, and the disease-free survival (DFS) between the two mapping methods were compared. RESULTS: The identification rate of SLNs was significantly higher with the combined method than that with the blue dye alone method (99.2% vs 93.3%, respectively; P < 0.001). The average number of SLNs identified per patient in the combined method group was 3.7 ± 2.4, which was more than that in the blue dye alone group (3.2 ± 1.6; P = 0.004). With a median follow-up of 29 months, 0.5% patients in the combined group, and 1.3% patients in the blue dye group had axillary recurrences. The DFS between the two groups showed no significant difference (P = 0.161). CONCLUSION: The combined method achieved a higher identification rate and lower rate of axillary recurrence compared to the blue dye alone method.

Concurrent administration of trastuzumab and anthracyclines as adjuvant regimen for HER2-positive breast cancer: a randomised controlled trial.

BACKGROUND: The regimen of concurrent administration of trastuzumab and anthracyclines in the adjuvant treatment of breast cancer has never been evaluated prospectively for fear of cardiac toxicity. METHODS: Patients with HER2-positive operable breast cancer were randomised to receive adjuvant treatment with concurrent or sequential administration of trastuzumab and anthracyclines. Cardiac monitoring was scheduled at baseline and every 3 months after the first dose of trastuzumab. The primary study endpoint was cardiac safety. Secondary endpoints were disease-free and overall survival. RESULTS: From 2011 to 2014, 201 participants were enrolled and randomised. The median follow-up time was 42 months. Nineteen patients (19.4%) in the concurrent group and 22 patients (22.4%) in the sequential group met the criteria for cardiac events with non-significant difference (P=0.598). There was no difference in the mean LVEF between the two groups at the baseline and at 3, 6, 9, 12, and 24 months after the first dose of trastuzumab. No case of congestive heart failure or cardiac death occurred. The differences between the efficacies of the two regimens, defined by disease-free or overall survival, were not significant. CONCLUSIONS: Concurrent administration of trastuzumab and anthracyclines is a safe adjuvant regimen and it provides evidence for further clinical trials.

A rare mixed breast cancer of intraductal and solid papillary with tubular carcinoma histotypes in a young woman.

Mixed breast cancer, especially of uncommon breast cancer histotypes, is rare, limiting our understanding of the disease and influencing diagnostic and management outcomes. We report a case of mixed breast cancer, with features of intraductal and solid papillary and tubular carcinomas, which appeared in a young patient. Physical examination, ultrasonography, molybdenum target mammography, and histopathology were performed for a definitive diagnosis. Tumor resection followed by radiotherapy and adjuvant chemotherapy was selected as the therapeutic strategy, and the patient was followed up thrice post treatment. We discuss the detailed diagnosis, treatment, and follow-up, together with a literature review of mixed breast cancer, to help optimize clinical management of mixed breast cancer.

Association of striking life events with primary breast cancer in 265 Chinese women: a case-control study.

The current case-control study investigated the relationship between striking life events and breast cancer in Chinese women. A total of 265 primary breast cancer patients and 265 controls were enrolled with matching for age and completed questionnaires. Logistic regression analysis was used. Thirty-nine breast cancer patients reported striking life events and twenty-four of the controls reported striking life events. The number of striking life events was significantly greater in patients (p = 0.04). It indicated a striking life event led to a 1.726-fold increased HR (95% CI 1.005-2.965, p < 0.05) for breast cancer with adjustment for age, and a 1.811-fold increased HR (95% CI 1.021 - 3.212, P < 0.05) with adjustment for age, BMI, and late age at menopause. High BMI (OR: 1.680, 95% CI: 1.258-2.196, p < 0.05) and a family history of breast cancer (OR: 2.244, 95% CI: 1.065-4.729, p < 0.05, respectively) increased the risk of breast cancer, and late age at menopause decreased the risk for breast cancer (OR: 0.513, 95% CI: 0.303-0.868, p < 0.05). Our findings indicate a significant association between striking life events and breast cancer in Chinese women, especially in the subpopulation with high BMI or family history of breast cancer.

Expression and function of MutT homolog 1 in distinct subtypes of breast cancer.

Human MutT homolog 1 (MTH1) detoxifies the oxidized DNA precursor 8-oxo-2'-deoxyguanosine-5'-triphosphate and serves a tumor suppressive role in distinct types of cancer. In the present study, the expression of MTH1 was examined in various subtypes of breast cancer, and the effect of its suppression on breast cancer growth was characterized in vitro and in vivo. MTH1 mRNA and protein levels were assessed using the reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. The effect of MTH1 expression on the proliferation of breast cancer cells was investigated in vitro using Cell Counting Kit-8 and colony formation assays, and in vivo using breast cancer cell line xenografts in mice. The toxicity of the MTH1 inhibitor TH588 was investigated in nude mice. A marked increase in MTH1 protein and mRNA levels was demonstrated in breast cancer tissues compared with the non-cancerous control. However, no apparent differences in MTH1 expression were observed between distinct molecular subtypes of breast cancer. MTH1 overexpression was demonstrated to be independent of patient age, tumor size and lymph node metastasis. Inhibition of MTH1 decreased cancer cell viability and the clonogenic potential of cancer cells in a dose-dependent manner. These results were confirmed by decreased in vivo proliferation of MCF7, MDA-MB-231 and MDA-MB-453 cancer cell lines, representing distinct subtypes of breast cancer. Although inhibition of MTH1 activity decreased xenograft growth in mice, no major adverse effects of TH588 were detected on the basis of blood biochemistry, and liver and kidney function. The results of the present study suggested that MTH1 is overexpressed in the majority of breast cancers, independent of the molecular identity and clinicopathological features of the tumor, including patient age, tumor size and lymph node metastasis. Inhibition of MTH1 activity suppressed the growth of three subtypes of breast cancer, including luminal, basal-like and human epidermal growth factor receptor 2-positive, in vitro and in vivo. Treatment with the MTH1 inhibitor appears to be safe; however, further studies are required prior to the clinical use of MTH1 inhibitors.

NOTCH1 is a poor prognostic factor for breast cancer and is associated with breast cancer stem cells.

Recently, the human gene NOTCH1 has been found to be implicated in cancer cell metastasis and the maintenance of cancer stem cells. However, for breast cancer in particular, an association between NOTCH1 levels and metastasis has not been determined. In this study, we investigated the expression status and correlation of NOTCH1 with clinically important factors related to metastasis and the cancer stem cell marker ALDH1. NOTCH1 and ALDH1 levels in 115 tumor tissues from primary lesions were determined by immunohistochemical staining. Most tissues were stained positive for both NOTCH1 and ALDH1, and NOTCH1 positivity was significantly associated with ALDH1 levels. NOTCH1 levels were significantly associated with TNM stage, metastasis, and triple-negative breast cancer. Moreover, both univariate and multivariate regression analyses revealed that basal-like features and NOTCH1 positivity were associated with disease-free survival as independent predictors. These analyses indicated that breast cancer patients testing positive for NOTCH1 had shorter disease-free survival. Our findings suggest that NOTCH1 may be involved in metastasis and is closely correlated with breast cancer stem cells.