Adjuvant tamoxifen switched to exemestane treatment in postmenopausal women with estrogen receptor-positive early breast cancer:A pragmatic,multicenter,and prospective clinical trial in China

Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.

A double constrained robust capon beamforming based imaging method for early breast cancer detection

Ultra-wideband （UWB） microwave images are proposed for detecting small malignant breast tumors based on the large contrast of electric parameters between a malignant tumor and normal breast tissue. In this study, an antenna array composed of 9 antennas is applied to the detection. The double constrained robust capon beamforming （DCRCB） algorithm is used for reconstructing the breast image due to its better stability and high signal-to-interference-plus-noise ratio （SINR）. The successful detection of a tumor of 2 mm in diameter shown in the reconstruction demonstrates the robustness of the DCRCB beamforming algorithm. This study verifies the feasibility of detecting small breast tumors by using the DCRCB imaging algorithm.

The 10-Year Local Recurrence and Partial Breast Radiotherapy for Early Breast Cancer Treated by Conservative Surgery

To study the local recurrence and the role of whole breast radiotherapy for early breast cancer treated by conservative surgery. METHODS From April 1990 to December 2000, 49 patients with early primary breast cancer were treated by conservative surgery in our hospital. The cases were comprised of Stage 0, 1; Stage Ⅰ, 31; and Stage Ⅱa, 17. Forty cases underwent quadrantectomy plus axillary lymph node dissection, and the other 9 cases had lumpectomy alone. Irradiation, which was received by 39 patients, was administered by using low tangential half fields with 6 MV X-ray to decrease the pulmonary irradiative volume. The dose to the whole breast was 45 Gy/22 ～23f/4.5W, then a 15 Gy boost dose was delivered to the tumor bed by an electron beam. The other patients underwent an irradiated regional field according to postoperative pathology. RESULTS All patients were followed-up for 10 years or more. The 10- year local recurrence rates, distant metastasis rates and survival rates were 6.1%, 4.1% and 98.0% respectively. All of the 3 patients who had a local recurrence had infiltrative carcinomas and negative lymph nodes. The 10-year local recurrence rate was higher （2.6% vs. 20.0%） with nonpostoperative whole breast radootherapy, but the statistical difference was not marked because of the low number of cases. All of the recurrent lesions localized within 3 cm of the primary lesion. CONCLUSION Original recurrence of the tumor was the main type of local recurrence. Radiotherapy after conservative surgery is very essential. After conservative surgery it is feasible that irradiation can be delivered alone to the neighboring region of the tumor bed. Partial breast radiotherapy can substitute for whole breast radiotherapy.

Clinical Observation of Breast Conserving Surgery and Modified Radical Mastectomy in the Treatment of Early Breast Cancer

The purpose of the study was to compare the clinical efficacy of breast conserving surgery and modified radical mastectomy in the treatment of early breast cancer.Firstly,the clinical data of 74 patients with early breast cancer treated in our hospital from June 2015 to June 2016 were retrospectively analyzed.Among them,37 patients treated with breast-conserving surgery were set as the study group,and 37 patients treated with modified radical surgery were set as the control group,and the therapeutic effects of the two groups were compared.The results showed that compared with the control group,the incision length,intraoperative blood loss,operation time and hospital stay time were better in the study group,and the excellent and good rate of postoperative breast beauty was higher,with statistically significant differences(P<0.05).There were no statistically significant differences in distant metastasis rate,local recurrence rate,axillary lymph node recurrence rate and fatality rate between the two groups(P>0.05).Therefore,breast-conserving surgery and modified radical surgery have better efficacy in the treatment of early breast cancer,but breast-conserving surgery has more advantages,such as smaller incision,less intraoperative blood loss,shorter operative time and hospital stay,and better postoperative aesthetic effect,which can be used as the first choice for early breast cancer.

Effect of Breast Conserving Sentinel Lymph Node Biopsy(SLNB)and Modified Radical Mastectomy on Patients with Early Breast Cancer

Objective:To study the clinical effect of breast conserving combined with sentinel lymph node biopsy and modified radical mastectomy in patients with early breast cancer.Methods:Female patients with early breast cancer in clinical stage I and II were selected as the main objects of this study,the study period started from July 2017 to July 2020.In the breast conserving and sentinel lymph node biopsy patients,50 cases were randomly selected as the experimental group;50 cases in the modified radical mastectomy patients were randomly selected as the control group.The clinical intervention effect of the two groups was analyzed.Results:the perioperative indexes of the experimental group were shorter than those of the control group,the patients recovered faster,the incidence of complications in the experimental group was lower,and the quality of life scores of the experimental group were significantly higher than those of the control group,and the difference was statistically significant,the intervention effect of the experimental group was also better.Conclusion:The application of breast conserving and sentinel lymph node biopsy in the treatment of early breast cancer can promote the recovery of patients,shorten the operation time and reduce the rate of complications,which has significant clinical significance.

Assessing the Clinical Efficacy and Effectiveness of Sentinel Lymph Node Biopsy Combined with Breast-Conserving Surgery for Early-Stage Breast Cancer

Objective:To analyze the impact of sentinel lymph node biopsy(SLNB)combined with breast-conserving surgery in the clinical treatment of early-stage breast cancer.Methods:80 patients with early-stage breast cancer admitted to the Second Department of Breast Surgery at Dezhou Second People’s Hospital from September 2020 to September 2022 were selected and randomly divided into a control group and an observation group using the random number table method,with 40 cases in each group.The control group underwent a modified radical mastectomy,while the observation group underwent SLNB combined with breast-conserving surgery.The surgical efficacy and prognosis between the two groups were compared.Results:The observation group exhibited shorter operation,hospitalization,and extubation times,as well as less intraoperative blood loss and drainage volume,all of which were significantly better than those in the control group(P<0.05).Additionally,the observation group demonstrated a higher rate of excellent breast cosmetology and quality of life,with lower complication incidence,significantly outperforming the control group(P<0.05).There was no statistical difference in the metastasis rate and recurrence rate between the two groups(P>0.05).Conclusion:The combination of SLNB and breast-conserving surgery proves highly effective for patients with early-stage breast cancer,presenting fewer complications and enhancing both breast cosmetic outcomes and quality of life.

Two Modified Surgical Procedures for Treating Early Stage Breast Cancer in China

Conventional pedicled-flap based surgeries in treating breast cancer have their limitations. New surgical regimens are yet to be explored, which will follow the oncological principle of being “to- tal tumor free”, whilst fit into the unique characteristics of China＇s own medical system as well as pa- tients＇ demand. From 2007 to 2013, 143 patients with early stage breast cancer were included in the study, with the average age of 46.1 years. Fifty-three patients were subjected to modified breast con- serving surgery （MBCS）＋latissimus dorsi （LD） flap reconstruction, 41 to skin sparing mastectomy （SSM）＋implant＋LD flap reconstruction, 29 to MBCS＋distal transverse rectus abdominis myocutaneous （DTRAM） flap reconstruction, and 20 to SSM＋DTRAM flap reconstruction. The results showed that out of the 143 patients, there was no graft loss. Minor complications included 4 cases of fat liquefaction, and 6 cases of seratoma, which all resolved after conservative treatment. Five patients had visible protu- berance in the abdomen, but not leading to any gastrointestinal symptoms. The reconstructed breasts all presented good shape. 96.7% of the patients were satisfied with the outcome. The follow-up period var- ied from 6 months to 60 months, and only one patient died from tumor metastasis in the brain. No local recurrence occurred. It was concluded that these two modified pedicled-flap surgeries are readily practi- cal, and aesthetically satisfactory, with high applicability in China. They do not compromise the on- cological outcomes, but also are well-accepted by Chinese patients.

The use of liquid biopsy in early breast cancer:clinical evidence and future perspectives

Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is gaining momentum as a diagnostic modality adopted in the clinical management of breast cancer.Prospective studies testing several technologies demonstrated clinical validity and,in some cases,achieved the United States Food and Drug Administration approval.The initial testing and clinical application of liquid biopsy focused primarily on the diagnosis,while molecular characterization and monitoring of metastatic disease,with larger data from prospective studies,came in the last two decades.Although its role in metastatic setting is thus widely recognized,the current evidence does not provide support for the routine clinical use of liquid biopsy methods for the earlier stage of this disease.Considering the relevance of early detection,characterization,and management of breast cancer in the early-stage,this clinical setting is the most suitable to increase the chances for effective treatment selection and improved prognosis,and a better understanding of the main application of liquid biopsy tools in the earlier stage of breast cancer is therefore crucial.The aim of this review is to provide an overview of the clinical evidence and subsequent potential applications of liquid biopsy in early breast cancer,identifying the main existing caveats and the possible future scenarios.

MICROW AVE-INDUCED THERMOA COUSTIC IMAGING FOR EARLY BREAST CA NCER DETECTION

Microwave induced thermoacoustic tomography(TAT)is a noninvasive,nonionizing modality based on the inherent differences in microwave absorpt ion of malignant breast tissues and normal adipose dominated breast tissues.In this paper,a TAT system based on multielement acquisition system was built to receive signals.Slices from different layers in the sample were composed into a three-dimensional(3D)volume.Based on the 3D volume,inherent differences in microw ave absorption bet ween different biological tisues can be converted into structure information.Our experimental results of some minicked and human tumors indicate that TAT may potentially be used to detect early-stage breast cancers with high contrast.

Adjuvant Taxanes in Breast Cancer: A Critical Re-appraisal

Purpose: Several studies have reported a positive impact for taxanes in adjuvant breast cancer (BC) treatment in terms of reduced recurrence and mortality. However the impact of the magnitude on overall survival (OS) remains partially controversial. Methods: We examined the impact of taxane-containing adjuvant therapy for patients with early BC on OS, based on the number of deaths and on the calculated number of patients who need to be treated with taxanes to avoid one death (NNT). We classified patients in three different groups according to whether taxanes were administered concurrently or sequentially, and whether all treatment arms had the same or different duration. Results: 1) Taxanes in combination therapy: 8258 patients (4373 with taxanes and 3885 without taxanes), with 723 OS events. Overall survival for taxane-treated patients was 92.7% versus 89.6% for patients not receiving taxanes. NNT was 33. 2) Sequential treatment of unequal duration in the treatment arms: 14,228 patients (7970 with taxanes and 6256 without). Overall survival in taxane-treated patients was 86% compared with 83.2% for patients not receiving taxanes. NNT was 44. 3) Sequential treatment and similar duration in treatment arms: 9511 women (5093 with taxanes and 4418 without). Overall survival in patients treated with taxanes was 87% versus 85% in patients not receiving taxanes. NNT was 50. When the results of all these trials were considered together, the NNT stands at 43 patients. Conclusion: Taxanes afford a modest increase in overall survival in BC patients regardless of how they are given. Translational trials may well help to improve patient selection in the future.

Impact of adjuvant chemotherapy delay on survival in cancer breast patients

Objective： The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. It is usually prescribed within 2-3 months after definitive surgery. The aim of this retrospective study was to assess the impact of adjuvant chemotherapy （CT） delay beyond 3 weeks （ 21 days） in premenopausal patients with ER-absent tumors being treated for early stages breast cancer on overall survival （OS） and disease-free survival （DFS）. Methods： This retrospective study was conducted through revision of medical records of premenopausal patients diagnosed with early stage ｜-｜IIA breast cancer and ER-absent tumors who received adjuvant CT after definitive surgery at the Department of Clinical Oncology, Ain-Shams University Hospitals. Results： Between 2005 and 2008, 105 patients were retrospectively analyzed and included. Patients were divided into 2 groups： Group A including 48 patients who started adjuvant CT 〈 21 days of surgery and group B which included 57 patients who had CT delay 〉 21 days. Both groups were matched demographically. Comparisons of overall survival, and disease-free survival between group A and group B patients all favored group A. At 5-year the OS rates were 87% and 73% for groups A and B respectively （P = 0.001）, while DFS rates were 85% and 64% in groups A and B respectively （P = 0.001）. Analysis of other prognostic factors （age, T, N, grade, HER2 status, surgery type, CT type, local radiotherapy received） were analyzed. Only nodal status predicted for worse DFS （P = 0.05） and OS （P = 0.006）. Conclusion： Delay in initiating adjuvant chemotherapy for early stage breast cancer patients with ER-absent tumors was associated with a decrease in both OS and DFS rates.

Relationship between serum HER2 extracellular domain levels, tissue HER2 expression, and clinico-pathological parameters in early stage breast cancer

Background Measurement of human epidermal growth factor receptor 2 （HER2） protein in the serum of metastatic breast cancer patients has previously been reported, but there are no consistent data to support the clinical utility of serum HER2 extracellular domain for patients with early stage breast cancer. We aimed to evaluate the correlation between serum extracellular domain levels and tissue HER2 expression, and analyzed their relationship with clinico-pathological parameters in patients with early stage disease. Methods A prospective study was conducted on 232 breast cancer patients with stage I-III prior to treatment. Preoperative serum samples were measured by enzyme-linked immunosorbent assay. Tissue HER2 status was analyzed by immunohistochemistry and fluorescence in situ hybridization assays. Results The median serum extracellular domain concentration was 6.8 ng/ml. The best diagnostic cut-off value was 7.4 ng/ml, with 62.9% sensitivity and 85.3% specificity. High serum extracellular domain levels were reported in 89 patients （38.3%）, and HER2-positive expression was observed in 77 patients （33.2%）. Multivariate analysis showed that elevated serum extracellular domain correlated with postmenopausal status （P 〈0.001）, high histological grade （P 〈0.001）, negativity of both estrogen （P=0.012） and progesterone receptors （P 〈0.001）, and high levels of carcinoembryonic antigen 153 （P=-0.048）. Conclusions We recommend that 7.4 ng/ml should be used as the cut-off value when evaluating serum extracellular domain levels in early stage of breast cancer. Patients with high serum extracellular domain levels have a certain clinico- pathological characteristics, may provide a basis for clinical practice.

CACA Guidelines for Holistic Integrative Management of Breast Cancer

Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caused by breast cancer.In terms of absolute numbers of cases and deaths,China ranks frst in the world.The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China.Methods:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and consensus.Results:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer patients.Conclusion:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

Prognostic value of the 21-gene recurrence score in ER-positive,HER2-negative,node-positive breast cancer was similar in nodenegative diseases:a single-center study of 800 patients

Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer.This study aimed to evaluate the prognostic significance of the 21-gene recurrence score(RS)in Chinese patients with pN0-l,estrogen receptor-positive(ER+),human epidermal growth factor receptor 2-negative(HER2)breast cancer.Among 800 patients recruited between 2009 and 2016,the median RS was 24(0-69),with 27.4%,46.8%,and 25.9%patients classified into low-,intermediate-,and high-risk groups.Cox regression analysis demonstrated that the high-risk category was associated with significantly higher odds of invasive disease-free survival(IDFS)and distant disease-free survival(DDFS)events compared with the low-risk category(IDFS:HR=2.450,95%Cl 1.017-5.902,P=0.046;DDFS:HR=2.829,95%Cl 1.013-7.901,P=0.047).No significant association between RS category and overall survival(OS)was found(intermediate vs.low:HR=1.244,95%Cl 0.292-5.297,P=0.768;high vs.low:HR=2.933,95%Cl 0.759-11.327,P=0.119).RS,as a continuous variable,was a highly significant predictor for IDFS(HR=1.028,95%Cl 1.010-1.047,P=0.002),DDFS(HR=1.030,95%Cl 1.010-1.051,P=0.003),and OS(HR=1.034,95%Cl 1.007-1.063,P=0.014).Our findings suggested that RS may predict IDFS in Chinese patients with ER+/HER2 breast cancer with NO or N1 disease.

Circulating tumor cells and drug history in primary breast cancer patients

Aim:Different types of chronic medication may affect breast cancer prognosis.Circulating tumor cells(CTCs)play an important role in cancer metastasis formation.There is no evidence of how chronic medication affects CTCs and breast cancer prognosis.The aim of this study was to evaluate association between chronic medication and CTCs in patients with primary breast cancer.Methods:This study involved 414 patients with stage I-III primary breast cancer.Chronic drug history was collected from patients’medical records and included all drugs that were prescribed for patients over at least the last 6 months prior to CTCs evaluation.CTCs were detected using a quantitative real-time polymerase chain reaction(qRT-PCR)-based method at the time of breast surgery.Results:There was no association between CTCs,including their different subpopulations and chronic medication.Chronic medication using angiotensin-converting-enzyme inhibitors(ACEi),metformin,and insulin were associated with inferior disease-free survival(HR=0.49,95%CI 0.26-0.94,P=0.007 for ACEi;HR=0.27,95%CI 0.08-0.91,P<0.001 for metformin;and HR=0.12,95%CI 0.01-2.91,P<0.001 for insulin)and this was most pronounced in patients with epithelial to mesenchymal transition(CTC_EMT)phenotype.In multivariate analysis,chronic administration of metformin and/or insulin was an independent predictor of inferior outcome.Conclusion:Our findings show that there was no association between chronically used medication and CTCs in primary breast cancer patients.However,administration of ACEi,metformin,and/or insulin could negatively affect prognosis of patients with CTC_EMT.

Genetic counseling in post-genomic era: Don't pretend to know the meaning of a gene mutation if you don't know

In this post-genomic era, more and more susceptibility loci of many possible genetic diseases are published. As our knowledge about these susceptibility loci is limited and partial, we should be very careful and responsible when patients seek genetic counseling about these possible genetic diseases. We should apply Confucius' s principle about knowledge and information to genetic conseling, and tell the truth to our patients about what we know and what we do not know. Like many other cancers, breast cancer is a very complicated, multifactorial disease; genetic factors, lifestyles and eating habits, environmental factors, and viral infections might be involved in breast cancer; hence, it is difficult to figure out the real etiology of breast cancer. It is not crystal clear that a person who carries mutations of the breast cancer 1, early onset and/or breast cancer 2, early onset genes would eventually get breast cancer in her/his lifetime. No person should undergo a preventive double mastectomy, unless we know the etiology of breast cancer someday.