AIM To determine influence of neoadjuvant-chemotherapy(NAC)over tumor-infiltrating-lymphocytes(TIL)intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de E...AIM To determine influence of neoadjuvant-chemotherapy(NAC)over tumor-infiltrating-lymphocytes(TIL)intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010.Immunohistochemistry staining for CD3,CD4,CD8 and FOXP3 was performed in tissue microarrays(TMA)sections.Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples.STATA software was used and P value<0.05 was considered statistically significant.RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response(pCR)(P=0.0251)and outcome(P=0.0334).TIL evaluated in TMA sections showed low level of agreement with full-face sections(ICC=0.017-0.20)and was not associated to pCR or outcome.TIL in post-NAC samples were not associated to response or outcome.PostNAC lesions with pC R had similar TIL levels than those without pCR(P=0.6331).NAC produced a TIL decrease in full-face sections(P<0.0001).Percentage of TIL subpopulations was correlated with their absolute counts.Higher counts of CD3,CD4,CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival(DFS).Higher counts of CD3 in pre-NAC samples had longer overallsurvival.Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR.Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS.Higher counts of CD4 in post-NAC samples were associated with pCR.CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival.TIL in full-face differ from TMA sections,absolute count and percentage analysis of TIL subpopulation closely related.展开更多
AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patien...AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001), PgR-positive(P < 0.001), Luminal A(P < 0.001), cN 0(P = 0.002) and p CR(P = 0.002) in the whole population. Overall survival was associated with clinical stage Ⅱ(P = 0.017) in Luminal A, older age(P = 0.042) in Luminal B, and pC R in TNBC(P = 0.005).CONCLUSION Predictive and prognostic values of clinicopathological features, like p CR and s TIL, differ depending on the evaluated molecular subtype.展开更多
Background: Cancer is a leading cause of death worldwide as well as in Peru. The national cancer plan includes decentralization, but one of the greatest barriers is our complicated geography. San Martin is a departmen...Background: Cancer is a leading cause of death worldwide as well as in Peru. The national cancer plan includes decentralization, but one of the greatest barriers is our complicated geography. San Martin is a department located in the Peruvian jungle where there are no public services for cancer care. Our aim was to implement a “distance telemedicine-enabled” outpatient chemotherapy module, monitored by oncologists. Methods: The implementation was conducted in 3 stages: 1) Planning and Organization: working teams were formed, a chemotherapy room was developed and people were trained. 2) Execution: patients from San Martín region, aged >18 years with pathological confirmation of cancer, requiring systemic chemotherapy, ECOG <3, and first course of chemotherapy received at INEN without adverse reaction were selected. 3) Evaluation: adverse events, cost-user evaluation and quality of life (QoL) were assessed. Results: By November 2015, a module with a chemotherapy room with 18 chairs, a pharmacy, a hospitalization room, 1 medical office, a training room, a nutrition area, and a nursing station was implemented. 3 physicians, 3 nurses and 1 pharmacist were trained. Through March 2018, 501 sessions of teleoncology were completed to deliver 232 cycles of chemotherapy for 56 patients aged 19 - 78 years with different solid tumors, with no serious adverse event, without negatively affecting their QoL, and with an average out-of-pocket expense saving of 500 PEN. Conclusions: Using information and communication technology, a telechemotherapy module was successfully implemented in the Peruvian jungle, without adversely affecting the QoL of patients. Neither patients nor family members needed to travel to Lima to receive chemotherapy. This first program can be replicated in other rural and remote regions through non-specialized personnel and facilities, providing chemotherapy services equivalent to a tertiary center through trained health care professionals, supported through telemedicine.展开更多
BACKGROUND Breast cancer(BC)frequency in males is extremely low and tumor features vary from its female counterpart.Breast cancer clinical and pathological features differ by race in women.Tumor infiltrating lymphocyt...BACKGROUND Breast cancer(BC)frequency in males is extremely low and tumor features vary from its female counterpart.Breast cancer clinical and pathological features differ by race in women.Tumor infiltrating lymphocyte(TIL)levels,mismatch repair(MMR)protein loss,androgen receptor(AR)expression,and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC.There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC.AIM To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population.METHODS This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018.Standard pathological features,TIL levels,MMR proteins,AR immunohistochemistry staining,and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material.Percentage of AR and estrogen receptor(ER)positive cells was additionally calculated by software after slide scanning.Statistical analyses included association tests,intraclass correlation test and Kaplan Meier overall survival curves.RESULTS The median age was 63 years and most cases were ER-positive(85.7%),HER2 negative(87.2%),Luminal-A phenotype(60%)and clinical stage II(41.5%)among our male breast tumors.Median TIL was 10%and higher levels tended to be associated with Luminal-B phenotype and higher grade.AR-positive was found in 85.3%and was correlated with ER(intraclass index of 0.835,P<0.001).Loss of MMR proteins was found in 15.4%and PIK3CA mutation(H1047R)in 14.3%(belonged to the Luminal-A phenotype).Loss of MMR proteins was associated with AR-negative(P=0.018)but not with ER(P=0.43)or TIL(P=0.84).Early stages(P<0.001)and lower grade(P=0.006)were associated with longer overall survival.ER status,phenotype,AR status,TIL level,MMR protein loss nor PIK3CA mutation was not associated with survival(P>0.05).CONCLUSION Male BC is usually ER and AR positive,and Luminal-A.MMR loss and PIK3CA mutations are infrequent.Stage and grade predicted overall survival in our South American country population.展开更多
文摘AIM To determine influence of neoadjuvant-chemotherapy(NAC)over tumor-infiltrating-lymphocytes(TIL)intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010.Immunohistochemistry staining for CD3,CD4,CD8 and FOXP3 was performed in tissue microarrays(TMA)sections.Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples.STATA software was used and P value<0.05 was considered statistically significant.RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response(pCR)(P=0.0251)and outcome(P=0.0334).TIL evaluated in TMA sections showed low level of agreement with full-face sections(ICC=0.017-0.20)and was not associated to pCR or outcome.TIL in post-NAC samples were not associated to response or outcome.PostNAC lesions with pC R had similar TIL levels than those without pCR(P=0.6331).NAC produced a TIL decrease in full-face sections(P<0.0001).Percentage of TIL subpopulations was correlated with their absolute counts.Higher counts of CD3,CD4,CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival(DFS).Higher counts of CD3 in pre-NAC samples had longer overallsurvival.Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR.Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS.Higher counts of CD4 in post-NAC samples were associated with pCR.CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival.TIL in full-face differ from TMA sections,absolute count and percentage analysis of TIL subpopulation closely related.
文摘AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001), PgR-positive(P < 0.001), Luminal A(P < 0.001), cN 0(P = 0.002) and p CR(P = 0.002) in the whole population. Overall survival was associated with clinical stage Ⅱ(P = 0.017) in Luminal A, older age(P = 0.042) in Luminal B, and pC R in TNBC(P = 0.005).CONCLUSION Predictive and prognostic values of clinicopathological features, like p CR and s TIL, differ depending on the evaluated molecular subtype.
文摘Background: Cancer is a leading cause of death worldwide as well as in Peru. The national cancer plan includes decentralization, but one of the greatest barriers is our complicated geography. San Martin is a department located in the Peruvian jungle where there are no public services for cancer care. Our aim was to implement a “distance telemedicine-enabled” outpatient chemotherapy module, monitored by oncologists. Methods: The implementation was conducted in 3 stages: 1) Planning and Organization: working teams were formed, a chemotherapy room was developed and people were trained. 2) Execution: patients from San Martín region, aged >18 years with pathological confirmation of cancer, requiring systemic chemotherapy, ECOG <3, and first course of chemotherapy received at INEN without adverse reaction were selected. 3) Evaluation: adverse events, cost-user evaluation and quality of life (QoL) were assessed. Results: By November 2015, a module with a chemotherapy room with 18 chairs, a pharmacy, a hospitalization room, 1 medical office, a training room, a nutrition area, and a nursing station was implemented. 3 physicians, 3 nurses and 1 pharmacist were trained. Through March 2018, 501 sessions of teleoncology were completed to deliver 232 cycles of chemotherapy for 56 patients aged 19 - 78 years with different solid tumors, with no serious adverse event, without negatively affecting their QoL, and with an average out-of-pocket expense saving of 500 PEN. Conclusions: Using information and communication technology, a telechemotherapy module was successfully implemented in the Peruvian jungle, without adversely affecting the QoL of patients. Neither patients nor family members needed to travel to Lima to receive chemotherapy. This first program can be replicated in other rural and remote regions through non-specialized personnel and facilities, providing chemotherapy services equivalent to a tertiary center through trained health care professionals, supported through telemedicine.
基金the Consejo Nacional de Ciencia,Tecnologia e Innovacion Tecnologica,No.198-2015-FONDECYT.
文摘BACKGROUND Breast cancer(BC)frequency in males is extremely low and tumor features vary from its female counterpart.Breast cancer clinical and pathological features differ by race in women.Tumor infiltrating lymphocyte(TIL)levels,mismatch repair(MMR)protein loss,androgen receptor(AR)expression,and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC.There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC.AIM To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population.METHODS This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018.Standard pathological features,TIL levels,MMR proteins,AR immunohistochemistry staining,and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material.Percentage of AR and estrogen receptor(ER)positive cells was additionally calculated by software after slide scanning.Statistical analyses included association tests,intraclass correlation test and Kaplan Meier overall survival curves.RESULTS The median age was 63 years and most cases were ER-positive(85.7%),HER2 negative(87.2%),Luminal-A phenotype(60%)and clinical stage II(41.5%)among our male breast tumors.Median TIL was 10%and higher levels tended to be associated with Luminal-B phenotype and higher grade.AR-positive was found in 85.3%and was correlated with ER(intraclass index of 0.835,P<0.001).Loss of MMR proteins was found in 15.4%and PIK3CA mutation(H1047R)in 14.3%(belonged to the Luminal-A phenotype).Loss of MMR proteins was associated with AR-negative(P=0.018)but not with ER(P=0.43)or TIL(P=0.84).Early stages(P<0.001)and lower grade(P=0.006)were associated with longer overall survival.ER status,phenotype,AR status,TIL level,MMR protein loss nor PIK3CA mutation was not associated with survival(P>0.05).CONCLUSION Male BC is usually ER and AR positive,and Luminal-A.MMR loss and PIK3CA mutations are infrequent.Stage and grade predicted overall survival in our South American country population.
