Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450(CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of ...Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450(CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning(null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, par-ticularly in terms of response to tamoxifen therapy and breast cancer outcome.展开更多
Vacuum-assisted breast biopsy (VABB) plays a fundamental role in the preoperative assessment of breast lesions pro- viding large histology samples that are useful to define diagnoses and biological parameters to guide...Vacuum-assisted breast biopsy (VABB) plays a fundamental role in the preoperative assessment of breast lesions pro- viding large histology samples that are useful to define diagnoses and biological parameters to guide treatment planning. This technique has been used in our institute since 2000 and two new wireless handheld ultrasound-guided VABB de- vices have been introduced since May 2012. In this report we analyze our experience with these revolutionary devices which are able to provide the option of single-insertion contiguous tissue samples respectively with a 13/14-gauge aperture. Our initial experience on 75 lesions shows that these devices are safe, fast, procedurally advantageous for operators and well accepted by patients. Finally VABB procedures can markedly reduce the need for surgical biopsy.展开更多
<strong>Objective:</strong> To evaluate the role of invasive imaging in the identification and pre-surgical localization of endoductal breast lesions. <strong>Methods:</strong> We retrospective...<strong>Objective:</strong> To evaluate the role of invasive imaging in the identification and pre-surgical localization of endoductal breast lesions. <strong>Methods:</strong> We retrospectively evaluated cytological outcomes, non-invasive/invasive breast imaging obtained between January 2016 and December 2019 in women with pathological nipple discharge (PND). We analysed sensitivity, specificity, positive predictive value and negative predictive value. We also evaluated the advantages of a pre-surgical radiological study using an endoductal contrast medium (with 3D-technique, in young women with dense breasts). <strong>Results:</strong> A total of 286 women with PND underwent cytological examination, mammography and/or breast ultrasound. When the cytological outcome was reported as “negative” (66.78%) in agreement with negative noninvasive imaging, patients were sent to follow up. Patients with cytological outcomes defined as “bloody with papillary clusters” (29.37%) “bloody not associated to cytological modifications” (2.44%), or “atypical/suspected” for malignant (1.39%) underwent an invasive procedure. Sensitivity, specificity, positive predictive value and negative predictive value were, respectively: 92.63%, 100%, 100% and 96.46% for cytological examination;64.28%, 96.95%, 60% and 97.44% for mammography;41.11%, 97.44%, 88.09% and 78.27% for ultrasound;93.68%, 100%, 100% and 96.95% for invasive procedures. Post-surgical histological outcomes confirmed the diagnosis. <strong>Conclusion:</strong> In absence of a standard diagnostic algorithm, we recommend invasive procedures to identify intraductal breast lesions and for preoperative planning. Digital imaging and new technologies such as 3D-tomosynthesis lead to a renaissance of breast invasive imaging;they are confirmed to be an essential diagnostic modality for preoperative planning, to define localization and extension of multiple coexisting endoductal lesions.展开更多
Objective: Major international guidelines have not standardized the sequence of diagnostic examinations during the follow-up of a patient with a diagnosed breast cancer. The aim of this study is to investigate the acc...Objective: Major international guidelines have not standardized the sequence of diagnostic examinations during the follow-up of a patient with a diagnosed breast cancer. The aim of this study is to investigate the accuracy of sonography in the diagnosis of loco-regional lymphatic recurrences in comparison to the core needle biopsy results. Materials and Methods: Among 6455 patients who were followed up with clinical examination, mammography and ultrasound between January 2004 and November 2011, 125 (1.93%) patients had to be investigated with a core needle biopsy of a sonographically suspicious loco-regional lymph node. Results: Among the whole series, a total of 142 ultrasound-guided core needle biopsies were performed. Follow-up for the primary tumor lasted for a median time of 6.1 years (range 1 - 27 years). Ultrasound of suspicious loco-regional lymph nodes showed a sensitivity of 89.5%, a specificity of 87.1% and a positive predictive value of 89.5%. Conclusions: In our experience, ultrasound of suspicious loco-regional lymph nodes showed good accuracy and it should be a part of the standard examinations performed during follow-up for breast cancer.展开更多
Follow-up data of a series of 75 breast cancer patients with sentinel node (SN) micrometastases only (between 0.2 and 2 mm) and favorable histopathological features of the primary tumor (well-differentiated, T1 tumors...Follow-up data of a series of 75 breast cancer patients with sentinel node (SN) micrometastases only (between 0.2 and 2 mm) and favorable histopathological features of the primary tumor (well-differentiated, T1 tumors without lymphovascular invasion) who refused completion axillary lymph node dissection (ALND) or who were unsuitable for surgery were assessed in order to detect the rate of axillary recurrence after an adjuvant chemoand/or hormonal adjuvant treatment was given. The great majority of patients (81.3%) did not undergo ALND due to the existence of favorable histopathologic factors while the rest were equally distributed among over 75-year-old women (10.6%) and patients at a high surgical risk due to comorbid conditions (9.3%). Sixty-six patients (88%) underwent conservative treatment (lumpectomy followed by adjuvant breast radiotherapy) while the remaining nine patients (12%) had total mastectomy;72 out of 75 patients (96%) received some forms of adjuvant chemoand/or hormone-therapy. After a median follow-up of 38 months (range 12 - 84 months), nine out of 75 patients (12%) had a disease relapse, only one of them (1.3%) being affected by an axillary recurrence in the untreated axilla three years after primary surgery. On these grounds, completion ALND could be safely omitted in patients with SN micrometastasis and favorable histopathological characteristics of the primary neoplasm due to the very low rate of axillary recurrence with no detrimental effect on survival.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(a novel coronavirus),which was first identified amid an outbreak of respiratory illness cases in Wuha...BACKGROUND The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(a novel coronavirus),which was first identified amid an outbreak of respiratory illness cases in Wuhan,China and declared a global health emergency,is currently considered an additional challenge in the management of patients with breast cancer(BC).Cancer patients are more vulnerable to becoming infected with severe acute respiratory syndrome coronavirus 2 and are more likely to suffer additional complications that can increase mortality.Identifying those BC patients who require more urgent therapy than others in the current situation is essential.These recommendations are based on and have been adapted from those similarly published by international scientific societies for BC management.They are divided mainly by clinical stage(early,advanced),subtype[luminal,human epidermal growth factor receptor 2(HER2),triple-negative],or type of medical treatment and setting(neoadjuvant,adjuvant,metastatic).Recommendations for HER2 and triplenegative subtypes are similar,whereas in luminal subtype there are various options of management.The objective is to adapt guidelines to local context through relevant decision-makers,avoiding duplication of efforts and optimizing use or resources.We hope that these recommendations will help medical oncologists provide the best quality care to BC patients during the COVID-19 pandemic with information tailored to our healthcare system.AIM To establish and adapt recommendations from those published by international scientific societies for BC management.METHODS The Peruvian Society of Medical Oncology developed a consensus and propose here a manuscript with recommendations for oncological medical treatment of BC during the COVID-19 pandemic.The Peruvian Society of Medical Oncology invited a panel of experts and opinion leaders on BC working in major health care systems around Peru.Panel experts selected three international clinical practice guidelines(National Comprehensive Cancer Network,European Society for Medical Oncology,Spanish Foundation Research Group in Breast Cancer),considering that these are more representative in COVID-19 management.Also,the panel agreed to include at least one European and American clinical practice guideline.RESULTS Recommendations about BC management during the COVID-19 pandemic were divided mainly by clinical stage(early,advanced),subtype(luminal,HER2,triplenegative),or type of medical treatment and setting(neoadjuvant,adjuvant,metastatic).Recommendations for HER2 and triple-negative subtypes were similar between clinical practice guidelines,whereas in luminal subtype there were various options of management.One hundred twelve recommendations were reviewed,adapted,and voted.A consensus was made in order to provide best decisions of management,avoid duplication of efforts,and optimize medical resources,considering health care system reality.These recommendations are not intended to replace clinical judgment.CONCLUSION Most of recommendations are similar,mainly in high-risk subtypes(HER2,triplenegative).Certain societies adapt them to deal with different situations involving the best decision in the management of BC patients.展开更多
BACKGROUND Pathological complete response(pCR) is rare in hormone receptor-positive(HR+)HER2-negative breast cancer(BC) treated with either endocrine therapy(ET) or chemotherapy. Radical resection of locoregional rela...BACKGROUND Pathological complete response(pCR) is rare in hormone receptor-positive(HR+)HER2-negative breast cancer(BC) treated with either endocrine therapy(ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures.The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced p CR after treatment with palbociclib.CASE SUMMARY We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a p CR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified asendocrine-sensitive, a condition associated with high sensitivity to palbociclib.CONCLUSION This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional relapse of BC, enabling surgical resection of a lesion initially considered inoperable.展开更多
Objective: To test the feasibility of a fully paperless system, termed “paperlite” in a UK breast screening service. To demonstrate in NHS practice, how workload and workflow could be improved by moving to a paperle...Objective: To test the feasibility of a fully paperless system, termed “paperlite” in a UK breast screening service. To demonstrate in NHS practice, how workload and workflow could be improved by moving to a paperless system and discovering what impact this has upon the complexity within the service. Setting: Warwickshire, Solihull and Coventry Breast Screening Service in the West Midlands of England. Methods: Quality improvement methodologies were employed, including value stream mapping, task analysis and a time-and-motion study. Results: The screening centred screened approximately 50,000 women per year. If they were to implement a paperless system, the administrative workload would decrease. The time saving per batch of screens, which could be achieved by moving to the paperless system ranged from 19 to 56 minutes (mean = 36 minutes). When calculated by batch the mean time saving per woman screened by moving to the paperless system was 42 seconds. This equates to 583 hours of administrative work per year in a centre screening 50,000 women. Conclusions: The paperless system has many benefits compared to the original system in terms of reductions in waste, time and cost. The simplification and standardisation of the process resulted in fewer tasks and interfaces where errors could occur, hence inadvertently improving patient safety. The limitation of the work is the heavy reliance on technology, live interfacing with computer databases and software stability is necessary for a paperless system to be used in NHS practice.展开更多
目的（a）通过英国进行的≥50岁的女性乳腺筛查计划（每3年进行1次筛查）,比较用硬拷贝图像阅读的全数字乳腺成像（FFDM）与荧光胶片乳腺成像（SFM）的表现；（b）对发表的资料与英国的数据行Meta分析。方法该研究符合英国国家健康服务...目的（a）通过英国进行的≥50岁的女性乳腺筛查计划（每3年进行1次筛查）,比较用硬拷贝图像阅读的全数字乳腺成像（FFDM）与荧光胶片乳腺成像（SFM）的表现；（b）对发表的资料与英国的数据行Meta分析。方法该研究符合英国国家健康服务中心办公室研究伦理委员会（UK National Health Service Central Office for Research Ethics Committee）的指导方针：因为是匿名资料的回顾性分析．无需告知病人。自2006年1月-2007年6月,筛查中心对8478名伦敦人进行了FFDM筛查,对31720人进行了SFM筛查。展开更多
Adiponectin(APN), an adipokine produced by adipocytes, has been shown to have a critical role in the pathogenesis of obesityassociated malignancies. Through its receptor interactions, APN may exert its anti-carcinogen...Adiponectin(APN), an adipokine produced by adipocytes, has been shown to have a critical role in the pathogenesis of obesityassociated malignancies. Through its receptor interactions, APN may exert its anti-carcinogenic effects including regulating cell survival, apoptosis and metastasis via a plethora of signalling pathways. Despite the strong evidence supporting this notion, some work may indicate otherwise. Our review addresses all controversies critically. On the whole, hypoadiponectinaemia is associated with increased risk of several malignancies and poor prognosis. In addition, various genetic polymorphisms may predispose individuals to increased risk of obesity-associated malignancies. We also provide an updated summary on therapeutic interventions to increase APN levels that are of key interest in this field. To date efforts to manipulate APN levels have been promising, but much work remains to be done.展开更多
AIM:To evaluate the impact of incidental gallbladder cancer on surgical experience.METHODS:Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery,one university based and one at a publi...AIM:To evaluate the impact of incidental gallbladder cancer on surgical experience.METHODS:Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery,one university based and one at a public hospital,were retrospectively reviewed.Gallbladder pathology was diagnosed by history,physical examination,and laboratory and imaging studies [ultrasonography and computed tomography(CT)].Patients with gallbladder cancer(GBC) were further analyzed for demographic data,and type of operation,surgical morbidity and mortality,histopathological classification,and survival.Incidental GBC was compared with suspected or preoperatively diagnosed GBC.The primary endpoint was diseasefree survival(DFS).The secondary endpoint was the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention.RESULTS:Nineteen patients(11 women and eight men) were found to have GBC.The male to female ratio was 1:1.4 and the mean age was 68 years(range:45-82 years).Preoperative diagnosis was made in 10 cases,and eight were diagnosed postoperatively.One was suspected intraoperatively and confirmed by frozen sections.The ratio between incidental and nonincidental cases was 9/19.The tumor node metastasis stage was:pTis(1),pT1a(2),pT1b(4),pT2(6),pT3(4),pT4(2);five cases with stageⅠa(T1 a-b);two with stageⅠb(T2 N0);one with stage Ⅱa(T3 N0);six with stage Ⅱb(T1-T3 N1);two with stage Ⅲ(T4 Nx Nx);and one with stage Ⅳ(Tx Nx Mx).Eighty-eight percent of the incidental cases were discovered at an early stage(≤Ⅱ).Preoperative diagnosis of the 19 patients with GBC was:GBC with liver invasion diagnosed by preoperative CT(nine cases),gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum(one case),porcelain gallbladder(one case),gallbladder adenoma(one case),and chronic cholelithiasis(eight cases).Every case,except one,with a T1b or more advanced invasion underwent Ⅳb + Ⅴ wedge liver resection and pericholedochic/hepatoduodenal lymphadenectomy.One patient with stage T1b GBC refused further surgery.Cases with Tis and T1a involvement were treated with cholecystectomy alone.One incidental case was diagnosed by intraoperative frozen section and treated with cholecystectomy alone.Six of the nine patients with incidental diagnosis reached 5-year DFS.One patient reached 38 mo survival despite a port-site recurrence 2 years after original surgery.Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5-year DFS.CONCLUSION:Laparoscopic cholecystectomy does not affect survival if implemented properly.Reoperation should have two objectives:R0 resection and clearance of the lymph nodes.展开更多
AIM: To investigate cell type specific distribution of β-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters.
Whole breast external beam radiotherapy is an effective adjuvant treatment for early breast cancer, and was a key factor in the move from mastectomy to breast-conserving surgery for women with low-risk disease. The lo...Whole breast external beam radiotherapy is an effective adjuvant treatment for early breast cancer, and was a key factor in the move from mastectomy to breast-conserving surgery for women with low-risk disease. The logical development from partial surgical removal of the breast is partial breast radiotherapy. Several methods of delivery have been investigated, but as yet none has been widely accepted.展开更多
It has always been disappointing to receive a histology report after an axillary dissection (ALND) saying that the only positive lymph node was the sentinel lymph node (SLN). It is for this reason that there have been...It has always been disappointing to receive a histology report after an axillary dissection (ALND) saying that the only positive lymph node was the sentinel lymph node (SLN). It is for this reason that there have been many efforts to create the best predictive model in order to avoid non sentinel node dissection and in fact there are in use many of them with a reasonable success rate. The publication of the multicenter study by Giuliano et al. showed a disease free survival and overall survival rate equal between patients with positive SLN with or without axillary dissection in a large group of patients. Breast surgeons around the world have long before been interested in reducing even more the need for axillary lymph node dissection, so they easily grasped the chance of those results and applied them in their practice. Objections have been expressed regarding the integrity of the study methods and the results which make the need for a second study to confirm those results absolutely necessary.展开更多
Activating PIK3CA mutations,present in up to 40%of hormone receptor-positive(HR^(+)),human epidermal growth factor receptor 2-negative(Her2^(-))breast cancer(BC)patients,can be effectively targeted with the alpha isof...Activating PIK3CA mutations,present in up to 40%of hormone receptor-positive(HR^(+)),human epidermal growth factor receptor 2-negative(Her2^(-))breast cancer(BC)patients,can be effectively targeted with the alpha isoform-specific Pl3K inhibitor Alpelisib.This treatment significantly improves outcomes for HR^(+),Her2^(-),and PIK3CA-mutated metastatic BC patients.However,acquired resistance,often due to aberrant activation of the mTOR complex 1(mTORC1)pathway,remains a significant clinical challenge.Our study,using in vitro and orthotopic xenograft mouse models,demonstrates that constitutively active mTORC1 signaling renders PI3K inhibitor-resistant BC exquisitely sensitive to various drugs targeting cancer metabolism.Mechanistically,mTORC1 suppresses the induction of autophagy during metabolic perturbation,leading to energy stress,a critical depletion of aspartate,and ultimately cell death.Supporting this mechanism,BC cells with CRISPR/Cas9-engineered knockouts of canonical autophagy genes showed similar vulnerability to metaboliclly active drugs InBC patients,high mTORC1 activity,indicated by 4E-BP1^(T37/46) phosphorylation correlated with p62 accumulation,a sign of impaired autophagy.Together,these markers predicted poor overall survival in multiple BC subgroups.Our findings reveal that aberrant mTORC1 signaling,a common cause of PI3K inhibitor resistance in BC,creates a druggable metabolic vulnerability by suppressing autophagy.Additionall,the combination of 4E-BP1^(T37/46) phosphorylation and p62 accumulation serves as a biomarker for poor overall survival,suggesting their potential utility in identifying BC patients who may benefit from metabolic therapies.展开更多
文摘Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450(CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning(null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, par-ticularly in terms of response to tamoxifen therapy and breast cancer outcome.
文摘Vacuum-assisted breast biopsy (VABB) plays a fundamental role in the preoperative assessment of breast lesions pro- viding large histology samples that are useful to define diagnoses and biological parameters to guide treatment planning. This technique has been used in our institute since 2000 and two new wireless handheld ultrasound-guided VABB de- vices have been introduced since May 2012. In this report we analyze our experience with these revolutionary devices which are able to provide the option of single-insertion contiguous tissue samples respectively with a 13/14-gauge aperture. Our initial experience on 75 lesions shows that these devices are safe, fast, procedurally advantageous for operators and well accepted by patients. Finally VABB procedures can markedly reduce the need for surgical biopsy.
文摘<strong>Objective:</strong> To evaluate the role of invasive imaging in the identification and pre-surgical localization of endoductal breast lesions. <strong>Methods:</strong> We retrospectively evaluated cytological outcomes, non-invasive/invasive breast imaging obtained between January 2016 and December 2019 in women with pathological nipple discharge (PND). We analysed sensitivity, specificity, positive predictive value and negative predictive value. We also evaluated the advantages of a pre-surgical radiological study using an endoductal contrast medium (with 3D-technique, in young women with dense breasts). <strong>Results:</strong> A total of 286 women with PND underwent cytological examination, mammography and/or breast ultrasound. When the cytological outcome was reported as “negative” (66.78%) in agreement with negative noninvasive imaging, patients were sent to follow up. Patients with cytological outcomes defined as “bloody with papillary clusters” (29.37%) “bloody not associated to cytological modifications” (2.44%), or “atypical/suspected” for malignant (1.39%) underwent an invasive procedure. Sensitivity, specificity, positive predictive value and negative predictive value were, respectively: 92.63%, 100%, 100% and 96.46% for cytological examination;64.28%, 96.95%, 60% and 97.44% for mammography;41.11%, 97.44%, 88.09% and 78.27% for ultrasound;93.68%, 100%, 100% and 96.95% for invasive procedures. Post-surgical histological outcomes confirmed the diagnosis. <strong>Conclusion:</strong> In absence of a standard diagnostic algorithm, we recommend invasive procedures to identify intraductal breast lesions and for preoperative planning. Digital imaging and new technologies such as 3D-tomosynthesis lead to a renaissance of breast invasive imaging;they are confirmed to be an essential diagnostic modality for preoperative planning, to define localization and extension of multiple coexisting endoductal lesions.
文摘Objective: Major international guidelines have not standardized the sequence of diagnostic examinations during the follow-up of a patient with a diagnosed breast cancer. The aim of this study is to investigate the accuracy of sonography in the diagnosis of loco-regional lymphatic recurrences in comparison to the core needle biopsy results. Materials and Methods: Among 6455 patients who were followed up with clinical examination, mammography and ultrasound between January 2004 and November 2011, 125 (1.93%) patients had to be investigated with a core needle biopsy of a sonographically suspicious loco-regional lymph node. Results: Among the whole series, a total of 142 ultrasound-guided core needle biopsies were performed. Follow-up for the primary tumor lasted for a median time of 6.1 years (range 1 - 27 years). Ultrasound of suspicious loco-regional lymph nodes showed a sensitivity of 89.5%, a specificity of 87.1% and a positive predictive value of 89.5%. Conclusions: In our experience, ultrasound of suspicious loco-regional lymph nodes showed good accuracy and it should be a part of the standard examinations performed during follow-up for breast cancer.
文摘Follow-up data of a series of 75 breast cancer patients with sentinel node (SN) micrometastases only (between 0.2 and 2 mm) and favorable histopathological features of the primary tumor (well-differentiated, T1 tumors without lymphovascular invasion) who refused completion axillary lymph node dissection (ALND) or who were unsuitable for surgery were assessed in order to detect the rate of axillary recurrence after an adjuvant chemoand/or hormonal adjuvant treatment was given. The great majority of patients (81.3%) did not undergo ALND due to the existence of favorable histopathologic factors while the rest were equally distributed among over 75-year-old women (10.6%) and patients at a high surgical risk due to comorbid conditions (9.3%). Sixty-six patients (88%) underwent conservative treatment (lumpectomy followed by adjuvant breast radiotherapy) while the remaining nine patients (12%) had total mastectomy;72 out of 75 patients (96%) received some forms of adjuvant chemoand/or hormone-therapy. After a median follow-up of 38 months (range 12 - 84 months), nine out of 75 patients (12%) had a disease relapse, only one of them (1.3%) being affected by an axillary recurrence in the untreated axilla three years after primary surgery. On these grounds, completion ALND could be safely omitted in patients with SN micrometastasis and favorable histopathological characteristics of the primary neoplasm due to the very low rate of axillary recurrence with no detrimental effect on survival.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(a novel coronavirus),which was first identified amid an outbreak of respiratory illness cases in Wuhan,China and declared a global health emergency,is currently considered an additional challenge in the management of patients with breast cancer(BC).Cancer patients are more vulnerable to becoming infected with severe acute respiratory syndrome coronavirus 2 and are more likely to suffer additional complications that can increase mortality.Identifying those BC patients who require more urgent therapy than others in the current situation is essential.These recommendations are based on and have been adapted from those similarly published by international scientific societies for BC management.They are divided mainly by clinical stage(early,advanced),subtype[luminal,human epidermal growth factor receptor 2(HER2),triple-negative],or type of medical treatment and setting(neoadjuvant,adjuvant,metastatic).Recommendations for HER2 and triplenegative subtypes are similar,whereas in luminal subtype there are various options of management.The objective is to adapt guidelines to local context through relevant decision-makers,avoiding duplication of efforts and optimizing use or resources.We hope that these recommendations will help medical oncologists provide the best quality care to BC patients during the COVID-19 pandemic with information tailored to our healthcare system.AIM To establish and adapt recommendations from those published by international scientific societies for BC management.METHODS The Peruvian Society of Medical Oncology developed a consensus and propose here a manuscript with recommendations for oncological medical treatment of BC during the COVID-19 pandemic.The Peruvian Society of Medical Oncology invited a panel of experts and opinion leaders on BC working in major health care systems around Peru.Panel experts selected three international clinical practice guidelines(National Comprehensive Cancer Network,European Society for Medical Oncology,Spanish Foundation Research Group in Breast Cancer),considering that these are more representative in COVID-19 management.Also,the panel agreed to include at least one European and American clinical practice guideline.RESULTS Recommendations about BC management during the COVID-19 pandemic were divided mainly by clinical stage(early,advanced),subtype(luminal,HER2,triplenegative),or type of medical treatment and setting(neoadjuvant,adjuvant,metastatic).Recommendations for HER2 and triple-negative subtypes were similar between clinical practice guidelines,whereas in luminal subtype there were various options of management.One hundred twelve recommendations were reviewed,adapted,and voted.A consensus was made in order to provide best decisions of management,avoid duplication of efforts,and optimize medical resources,considering health care system reality.These recommendations are not intended to replace clinical judgment.CONCLUSION Most of recommendations are similar,mainly in high-risk subtypes(HER2,triplenegative).Certain societies adapt them to deal with different situations involving the best decision in the management of BC patients.
文摘BACKGROUND Pathological complete response(pCR) is rare in hormone receptor-positive(HR+)HER2-negative breast cancer(BC) treated with either endocrine therapy(ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures.The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced p CR after treatment with palbociclib.CASE SUMMARY We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a p CR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified asendocrine-sensitive, a condition associated with high sensitivity to palbociclib.CONCLUSION This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional relapse of BC, enabling surgical resection of a lesion initially considered inoperable.
文摘Objective: To test the feasibility of a fully paperless system, termed “paperlite” in a UK breast screening service. To demonstrate in NHS practice, how workload and workflow could be improved by moving to a paperless system and discovering what impact this has upon the complexity within the service. Setting: Warwickshire, Solihull and Coventry Breast Screening Service in the West Midlands of England. Methods: Quality improvement methodologies were employed, including value stream mapping, task analysis and a time-and-motion study. Results: The screening centred screened approximately 50,000 women per year. If they were to implement a paperless system, the administrative workload would decrease. The time saving per batch of screens, which could be achieved by moving to the paperless system ranged from 19 to 56 minutes (mean = 36 minutes). When calculated by batch the mean time saving per woman screened by moving to the paperless system was 42 seconds. This equates to 583 hours of administrative work per year in a centre screening 50,000 women. Conclusions: The paperless system has many benefits compared to the original system in terms of reductions in waste, time and cost. The simplification and standardisation of the process resulted in fewer tasks and interfaces where errors could occur, hence inadvertently improving patient safety. The limitation of the work is the heavy reliance on technology, live interfacing with computer databases and software stability is necessary for a paperless system to be used in NHS practice.
文摘目的（a）通过英国进行的≥50岁的女性乳腺筛查计划（每3年进行1次筛查）,比较用硬拷贝图像阅读的全数字乳腺成像（FFDM）与荧光胶片乳腺成像（SFM）的表现；（b）对发表的资料与英国的数据行Meta分析。方法该研究符合英国国家健康服务中心办公室研究伦理委员会（UK National Health Service Central Office for Research Ethics Committee）的指导方针：因为是匿名资料的回顾性分析．无需告知病人。自2006年1月-2007年6月,筛查中心对8478名伦敦人进行了FFDM筛查,对31720人进行了SFM筛查。
文摘Adiponectin(APN), an adipokine produced by adipocytes, has been shown to have a critical role in the pathogenesis of obesityassociated malignancies. Through its receptor interactions, APN may exert its anti-carcinogenic effects including regulating cell survival, apoptosis and metastasis via a plethora of signalling pathways. Despite the strong evidence supporting this notion, some work may indicate otherwise. Our review addresses all controversies critically. On the whole, hypoadiponectinaemia is associated with increased risk of several malignancies and poor prognosis. In addition, various genetic polymorphisms may predispose individuals to increased risk of obesity-associated malignancies. We also provide an updated summary on therapeutic interventions to increase APN levels that are of key interest in this field. To date efforts to manipulate APN levels have been promising, but much work remains to be done.
文摘AIM:To evaluate the impact of incidental gallbladder cancer on surgical experience.METHODS:Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery,one university based and one at a public hospital,were retrospectively reviewed.Gallbladder pathology was diagnosed by history,physical examination,and laboratory and imaging studies [ultrasonography and computed tomography(CT)].Patients with gallbladder cancer(GBC) were further analyzed for demographic data,and type of operation,surgical morbidity and mortality,histopathological classification,and survival.Incidental GBC was compared with suspected or preoperatively diagnosed GBC.The primary endpoint was diseasefree survival(DFS).The secondary endpoint was the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention.RESULTS:Nineteen patients(11 women and eight men) were found to have GBC.The male to female ratio was 1:1.4 and the mean age was 68 years(range:45-82 years).Preoperative diagnosis was made in 10 cases,and eight were diagnosed postoperatively.One was suspected intraoperatively and confirmed by frozen sections.The ratio between incidental and nonincidental cases was 9/19.The tumor node metastasis stage was:pTis(1),pT1a(2),pT1b(4),pT2(6),pT3(4),pT4(2);five cases with stageⅠa(T1 a-b);two with stageⅠb(T2 N0);one with stage Ⅱa(T3 N0);six with stage Ⅱb(T1-T3 N1);two with stage Ⅲ(T4 Nx Nx);and one with stage Ⅳ(Tx Nx Mx).Eighty-eight percent of the incidental cases were discovered at an early stage(≤Ⅱ).Preoperative diagnosis of the 19 patients with GBC was:GBC with liver invasion diagnosed by preoperative CT(nine cases),gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum(one case),porcelain gallbladder(one case),gallbladder adenoma(one case),and chronic cholelithiasis(eight cases).Every case,except one,with a T1b or more advanced invasion underwent Ⅳb + Ⅴ wedge liver resection and pericholedochic/hepatoduodenal lymphadenectomy.One patient with stage T1b GBC refused further surgery.Cases with Tis and T1a involvement were treated with cholecystectomy alone.One incidental case was diagnosed by intraoperative frozen section and treated with cholecystectomy alone.Six of the nine patients with incidental diagnosis reached 5-year DFS.One patient reached 38 mo survival despite a port-site recurrence 2 years after original surgery.Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5-year DFS.CONCLUSION:Laparoscopic cholecystectomy does not affect survival if implemented properly.Reoperation should have two objectives:R0 resection and clearance of the lymph nodes.
基金Supported by TMH-IRG for project funding(account number-466),Advanced Center for Treatment Research and Education in Cancer,India for funding to Gupta lab
文摘AIM: To investigate cell type specific distribution of β-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters.
文摘Whole breast external beam radiotherapy is an effective adjuvant treatment for early breast cancer, and was a key factor in the move from mastectomy to breast-conserving surgery for women with low-risk disease. The logical development from partial surgical removal of the breast is partial breast radiotherapy. Several methods of delivery have been investigated, but as yet none has been widely accepted.
文摘It has always been disappointing to receive a histology report after an axillary dissection (ALND) saying that the only positive lymph node was the sentinel lymph node (SLN). It is for this reason that there have been many efforts to create the best predictive model in order to avoid non sentinel node dissection and in fact there are in use many of them with a reasonable success rate. The publication of the multicenter study by Giuliano et al. showed a disease free survival and overall survival rate equal between patients with positive SLN with or without axillary dissection in a large group of patients. Breast surgeons around the world have long before been interested in reducing even more the need for axillary lymph node dissection, so they easily grasped the chance of those results and applied them in their practice. Objections have been expressed regarding the integrity of the study methods and the results which make the need for a second study to confirm those results absolutely necessary.
基金support provided by the Core Facilities for Metabolomics,Flow Cytometry,Cellular Imaging,Preclinical Imagingthe animal facility at Philipps-University of Marburg.N.G.was supported by the Clinician Scientist program(SUCCESS-program)of the Philipps-University of Marburg,the University Cancer Center(UCT)Frankfurt-Marburg+6 种基金the University Hospital of Giessen and Marburg(UKGM)research grants of the Deutsche Forschungsgemeinschaft(GRK 2573/2-2024)University Medical Center Giessen and Marburg(UKGM)(3/2022 MR to N.G.)von Behring-Rontgen-Stiftung(70_0027 to N.G.)Stiftung P.E.Kempkes(01/2021 to N.G.)Medizinstiftung(04/2021 to N.G.)M.F.F.reports funding from the Deutsche Forschungsgemeinschaft(INST 90/1048-1 FUGG).
文摘Activating PIK3CA mutations,present in up to 40%of hormone receptor-positive(HR^(+)),human epidermal growth factor receptor 2-negative(Her2^(-))breast cancer(BC)patients,can be effectively targeted with the alpha isoform-specific Pl3K inhibitor Alpelisib.This treatment significantly improves outcomes for HR^(+),Her2^(-),and PIK3CA-mutated metastatic BC patients.However,acquired resistance,often due to aberrant activation of the mTOR complex 1(mTORC1)pathway,remains a significant clinical challenge.Our study,using in vitro and orthotopic xenograft mouse models,demonstrates that constitutively active mTORC1 signaling renders PI3K inhibitor-resistant BC exquisitely sensitive to various drugs targeting cancer metabolism.Mechanistically,mTORC1 suppresses the induction of autophagy during metabolic perturbation,leading to energy stress,a critical depletion of aspartate,and ultimately cell death.Supporting this mechanism,BC cells with CRISPR/Cas9-engineered knockouts of canonical autophagy genes showed similar vulnerability to metaboliclly active drugs InBC patients,high mTORC1 activity,indicated by 4E-BP1^(T37/46) phosphorylation correlated with p62 accumulation,a sign of impaired autophagy.Together,these markers predicted poor overall survival in multiple BC subgroups.Our findings reveal that aberrant mTORC1 signaling,a common cause of PI3K inhibitor resistance in BC,creates a druggable metabolic vulnerability by suppressing autophagy.Additionall,the combination of 4E-BP1^(T37/46) phosphorylation and p62 accumulation serves as a biomarker for poor overall survival,suggesting their potential utility in identifying BC patients who may benefit from metabolic therapies.
