RESUMEN
The prognosis of HER2-positive breast cancer (BC) has improved with the development of anti-HER2 therapies; however, the problem remains that there are still cases where anti-HER2 therapies do not respond well. We found that the expression of SREBF2, a master transcriptional factor in the mevalonate pathway, was correlated with ERBB2 (HER2) expression and a poor prognosis in HER2-positive BC. The target gene expressions of SREBF2 were associated with higher expression of ERBB2 in HER2-positive BC cells. Statins, anti-hypercholesterolemia drugs that inhibit the mevalonate pathway, enhanced the efficacy of HER2-targeting agents with inducing apoptosis in a geranylgeranylation-dependent manner. Mechanistically, statins specifically inhibited membrane localization of Rac1, a target protein of geranylgeranylation, and suppressed the activation of HER2 downstreams AKT and ERK pathways. Consistently, retrospective analysis showed a longer recurrence-free survival in Rac1-high/HER2-positive BC patients treated with HER2-targeting agents with statins than without statins. Our findings thus suggest that Rac1 expression could be used as a biomarker to stratify HER2-positive BC patients that could benefit from dual blockade, i.e., targeting HER2 with inhibition of geranylgeranylation of Rac1 using statins, thereby opening avenues for precision medicine in a new subset of Rac1-high/HER2-positive BC.
RESUMEN
BACKGROUND: The mechanism of late recurrence (LR) of estrogen receptor (ER)-positive breast cancer remains unclear, as previous studies have separately investigated "gene expression profiles" and "clinicopathological factors." Thus, this study aimed to evaluate the predictive capability of LR by combining the two independent factors of gene expression profiles (42-gene classifier: 42GC) and clinicopathological factors (Clinical Treatment Score post-5 years: CTS5) in multiple large cohorts. METHODS: We analyzed microarray CEL file data downloaded from public databases of 28 global cohorts. A total of 2,454 patients with ER-positive breast cancer were analyzed for 42GC, and 1,263 of these, with complete clinicopathological data were analyzed for CTS5. RESULTS: In the analysis of recurrent patients, the 42GC LR and CTS5 low-risk group tended to have LR. Notably, in the analysis of patients with and without recurrence, the highest LR rate beyond 5 years was observed in the CTS5 high-risk group. The combination of the 42GC and CTS5 high-risk groups showed the highest LR rate (16.9%), significantly exceeding that of the 42GC non-LR (NLR) and CTS5 low-risk combination (5.41%) (p = 0.038, odds ratio = 3.53). Furthermore, incorporating a third factor, 95GC, potentially reduced the number of patients prioritized for extended hormonal therapy for approximately one-quarter of patients. CONCLUSIONS: Results confirmed that the two factors, gene expression profiles and clinicopathological factors, affect the time of recurrence. It also showed that the biological predisposition for LR (CTS5 low-risk) differed from the high LR rate (CTS5 high-risk). In clinical practice, patients with the 42GC LR and CTS5 high-risk combination should be prioritized for extended hormonal therapy. The addition of CTS5 and 95GC to 42GC allows for better risk classification of LR.
RESUMEN
Background This study was aimed at analyzing the impact of postoperative radiotherapy (PORT) after breast-conserving surgery (BCS) on Japanese patients with early-stage breast cancer and exploring the potential of PORT omission. Materials and methods Data from 794 patients with early-stage breast cancer (T1-2, N0-1), who underwent BCS with (n = 310) or without PORT (n = 484) were retrospectively analyzed. Local control (LC) rate and breast cancer-specific survival (BCSS) were compared between the groups that received and did not receive PORT in the whole cohort and low-risk cohort (i.e., the cohort with negative surgical margin, lymph node negativity, and estrogen receptor positivity, excluding young age of 49 or less), and in low-risk subgroup using propensity-score matching. Results PORT was associated with better LC but not BCSS in the total population. In the low-risk cohort, the incidence of local recurrence in patients without and with PORT was 5.3% and 4.8%, respectively, at 10 years (p = 0.591), and 7.8% and 4.8%, respectively, according to propensity-score matching (p = 0.485). Conclusion PORT improved LC in the total population, but not BCSS or overall survival (OS). In the low-risk group analysis (negative surgical margin, lymph node negativity, estrogen receptor positivity, and age 50 years or more), equivalent LC, BCSS, and OS were found including propensity-matched comparison. Therefore, this study showed that the omission of PORT could be a treatment option for low-risk Japanese patients. Further multi-center prospective studies are warranted to validate these findings and reduce the unnecessary burden of PORT for patients and institutions.
RESUMEN
BACKGROUND: EndoPredict® (EP) is a multigene assay to predict distant recurrence risk in luminal breast cancer. EP measures the expression of 12 genes in primary tumor by qRT-PCR from formalin-fixed paraffin-embedded (FFPE) tissues and calculates EP risk score that indicates the risk of distant recurrence. We evaluated the performance of EP in predicting distant recurrence risk using microarray data from fresh frozen (FF) tissues. We also examined the applicability of EP to microarray data from FFPE tissues. METHODS: We analyzed the publicly available data of 431 node-negative and 270 node-positive patients with luminal breast cancer who received endocrine therapy alone. We evaluated the prognostic value of EP using microarray data from FF tissues. Next, we created an algorithm to calculate EP risk score using microarray data from FFPE tissues. We examined the correlation coefficient of EP risk score and concordance rate of EP risk high/low using microarray data from FFPE/FF tissue pairs in a validation set of 39 patients. RESULTS: In 431 node-negative patients, the distant recurrence-free survival (DRFS) rate was significantly worse in those with high EP risk scores (P = 3.68 × 10-6, log-rank). The 5-year DRFS was 95.2% in those with low EP risk score. In the validation set, the correlation coefficient of EP risk score was 0.93 and the concordance rate of EP risk high/low was 91.7%. CONCLUSIONS: EP using microarray data from FF tissues was useful in predicting distant recurrence risk in luminal breast cancer, and EP might be utilized in microarray data from FFPE tissues.
Asunto(s)
Neoplasias de la Mama , Recurrencia Local de Neoplasia , Adhesión en Parafina , Receptor ErbB-2 , Receptores de Estrógenos , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Receptores de Estrógenos/metabolismo , Persona de Mediana Edad , Anciano , Pronóstico , Adulto , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Perfilación de la Expresión Génica , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35-69 years from the Japan Multi-Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and ≥7 hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure-time metabolic equivalents (METs), frequency of leisure-time physical activity, and daily walking time, were examined. During 315,189 person-years of follow-up, 554 incident cases of BC were identified. When compared to participants who spent <7 h/d sedentary, those who spent ≥7 h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07-1.71). The corresponding HRs among participants who spent ≥7 h/d sedentary with more physical activity, such as ≥1 h/d for leisure-time METs, ≥3 days/week of leisure-time physical activity, and ≥1 h/d of daily walking were 1.58 (95% CI, 1.11-2.25), 1.77 (95% CI, 1.20-2.61), and 1.42 (95% CI, 1.10-1.83), respectively, compared with those who spent <7 h/d sedentary. This study found that spending ≥7 h/d of sedentary time is associated with the risk of BC. Neither leisure-time physical activity nor walking had a BC-preventive effect in those with ≥7 h/d of sedentary time.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Conducta Sedentaria , Japón/epidemiología , Estudios de Cohortes , Actividad Motora , Factores de RiesgoRESUMEN
Background To analyze the feasibility of omitting postoperative radiotherapy (PORT) after breast-conserving surgery (BCS) in Japanese patients with ductal carcinoma in situ (DCIS). Materials and methods We retrospectively analyzed 88 patients with small pure DCIS (median diameter 1.1 cm, ≤ 4 cm) who underwent BCS with (n = 39) or without (n = 49) PORT. The primary and secondary endpoints were ipsilateral breast tumor recurrence (IBTR) and overall survival (OS), respectively, between the groups that received PORT and those that did not. Results The PORT group included a high number of margin-positive cases. The incidence of IBTR was 2.4% (95% confidence interval (CI), 0.3-15.7%) and 2.8% (95% CI, 0.4-18.2%) at five years and 5.5% (95% CI, 1.4-20.6%) and 2.8% (95% CI, 0.4-18.2%) at 10 years in patients without and with PORT, respectively (p = 0.686). In the margin-negative group, only one patient showed IBTR without RT (2.3%), whereas no patient with PORT experienced IBTR (0%). To date, there have been no regional or distant metastases; therefore, no patient has experienced breast cancer-related deaths. The OS rates were 97.7% (95% CI, 84.9-99.6%) and 100% at 10 years in patients without and with PORT, respectively (p = 0.372). Conclusion This study suggests that the omission of PORT after BCS could be a feasible option for selected Japanese patients but requires further investigation to identify the low-risk factor in patients who can omit PORT.
RESUMEN
BACKGROUND/AIM: Palbociclib was the first cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved worldwide. Currently, CDK4/6 inhibitors are strongly recommended for endocrine therapy in the first or second line with hormone receptor-positive advanced breast cancer. It is expected the use of CDK4/6 inhibitor will further increase. Therefore, the aim was to investigate and better understand the use of palbociclib. PATIENTS AND METHODS: We retrospectively analyzed the data of patients with advanced breast cancer who were treated with palbociclib in three hospitals between 2018 and 2022. Clinical data were obtained from the patients' medical electronic records. RESULTS: A total of 143 patients were enrolled. The median age was 66 years (range=33-89), and the majority (90.9%) were postmenopausal patients. In total, median time-to-treatment discontinuation (TTD) (95% confidence interval, CI) was 7 (6-10) months. Median TTD (95% CI) was 13 (7-20) months for the first or second line, and significantly prolonged compared to TTD for the third or later lines with palbociclib (p<0.0001). The importance of front-line use was indicated. Multivariate analyses showed that no visceral metastasis or first or second line therapy influenced the longer TTD. Between patients above or below 70 years of age, older age did not negatively affect TTD, though there were significantly more cases of dose reduction or withdrawal in patients over 70 years old. The variation of adverse events (AEs) among hospitals was very large (9.0%, 31.3%, 4.5%). We found that understanding of AE management was important. CONCLUSION: This study showed that dose reduction or withdrawal of palbociclib had no harmful effects in Japanese patients. Efficacy was also high in older patients. It is important to manage palbociclib administration more safely and appropriately. A combination of dose reduction and withdrawal is key to this therapeutic strategy.
Asunto(s)
Neoplasias de la Mama , Anciano , Femenino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Receptor ErbB-2 , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The prognosis of lymphnode positive breast cancer is worse than that of lymph node negative breast cancer but some cases may not require chemotherapy. We investigated the ability of the new multi-gene assays, 95GC and 155GC, to identify patients with lymphnode positive Luminal-type breast cancer whose chemotherapy can be omitted relatively safely. PATIENTS AND METHODS: We extracted 1721 cases of lymphnode positive Luminal-type breast cancer from 22 public database Caucasoid cohorts and 3 Asian cohorts, and performed recurrence prognosis analysis with 95GC and 155GC. RESULTS: Using 95GC, the cases were stratified as the high (n = 917) and low (n = 202) groups according to the prognosis of lymphnode positive Luminal-type endocrine only breast cancer. The 5 years DRFS in the low risk group was relatively good at 90%, and no additional effect of chemotherapy was observed, suggesting omission of chemotherapy. The recurrence prognosis was also significantly dichotomized into the high and low risks by 95GC in 21GC RS 0-25 cases. Here, we found a group with poor prognosis even in post-menopause RS 0-25 and requiring chemotherapy. Additionally, a group in which the prognosis was good in pre-menopause RS 0-25, and the omission of chemotherapy could be considered. Patients in the high-risk group at 155GC had poor prognosis after chemotherapy. 155GC also showed a group that chemotherapy alone was not sufficient. CONCLUSION: In this study, we demonstrated the possibility of accurately selecting patient groups for which chemotherapy can be omitted from lymphnode positive Luminal-type breast cancer.
Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Pronóstico , Quimioterapia Adyuvante , Factores de Riesgo , Receptores de EstrógenosRESUMEN
Curebest™ 95GC breast (95GC) is a multigene classifier we developed for the prognostic prediction of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and node-negative (ER+/HER2-/n0) invasive breast cancer treated with adjuvant endocrine therapy alone. The aim of the preset study was to evaluate the clinical utility of 95GC in a multiinstitutional registry study. Patients (n=215) with ER+/HER2-/n0 invasive breast cancer who had undergone the 95GC assay in seven hospitals were consecutively recruited in the registry study at various postoperative times. At recruitment, no patients had disease recurrences and were prospectively followed up for a median of 62 (range, 6-91) postoperative months. Of the 124 patients classified as 95GC low risk, 118 received adjuvant endocrine therapy alone and six received adjuvant chemo-endocrine therapy. Only two patients developed distant recurrences, and the 5-year distant recurrence-free survival (DRFS) was as high as 98.0%. Of the 91 patients classified as 95GC high risk, 81 received adjuvant chemo-endocrine therapy and 10 received adjuvant endocrine therapy alone. A total of four of these patients developed distant recurrences (5-year DRFS=95.5%). Among the 95GC high-risk patients, prognosis was significantly improved for the 81 treated with adjuvant chemo-endocrine therapy compared with for the 77 (historical controls) treated with adjuvant endocrine therapy alone (P=0.0002; hazard ratio, 0.24). Compared with the St. Gallen 2013 guideline, a significant de-escalation from 73.1% (155/212) to 40.6% (86/212) in adjuvant chemotherapy was achieved. The excellent prognosis of patients with ER+/HER2-/n0 invasive breast cancer classified as 95GC low risk could be validated in the present registry study, indicating that 95GC is useful for safe de-escalation of adjuvant chemotherapy in patients with ER+/HER2-/n0 invasive breast cancer.
RESUMEN
PURPOSE: We have shown that "Click-to-sense" (CTS) assay based on the visualization of cancer cells by fluorescence probe targeted for acrolein is useful for differentiating between the malignant and benign lesions of the breast. In the present study, we aimed to apply CTS assay to the examination of the simulated surgical margins, being compared with frozen section (FS) analysis. EXPERIMENTAL DESIGN: The simulated surgical margin samples (n = 300) were obtained from 1 to 2 cm distant sites from the tumor margin in the mastectomy specimens of breast cancer patients, and divided into the training (n = 150) and validation (n = 150) set. The samples were subjected to CTS assay, subsequently to FS analysis and finally to permanent section (PS) analysis. RESULTS: Diagnostic accuracy of the CTS assay and FS analysis was evaluated in the examination of the simulated surgical margin status finally determined by the PS analysis. In the training set, sensitivity, specificity, and accuracy was 89.3%, 98.4%, and 96.7% for the CTS assay and 89.3%, 98.4%, and 96.7% for the FS analysis. In the validation set, sensitivity, specificity, and accuracy was 93.3%, 98.3%, and 97.3% for the CTS assay, and 93.3%, 99.2%, and 98.0% for the FS analysis. CONCLUSIONS: The CTS assay is as accurate as the FS analysis in the examination of the simulated surgical margins in breast cancer patients, and it seems to have a potential to replace the FS analysis for the intra-operative examination of surgical margins in breast-conserving surgery since it is less labor-intensive and more time-saving than the FS analysis.
Asunto(s)
Neoplasias de la Mama , Secciones por Congelación , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Márgenes de Escisión , Mastectomía , Mastectomía Segmentaria , Estudios RetrospectivosRESUMEN
BACKGROUND: Everolimus is a mechanistic-target-of-rapamycin (mTOR) inhibitor bearing a potent antitumor effect against hormone receptor-positive breast cancer. Here, we report the case of a patient with recurrent breast cancer who developed osteomyelitis during the treatment with everolimus plus exemestane. CASE PRESENTATION: A 56-year-old woman with early-stage breast cancer underwent right mastectomy and axillary lymph node dissection at the age of 45. Four years after the surgery, she experienced relapse at the chest wall. Radiotherapy was performed on the chest wall, including the sternum, and denosumab was administered. After several regimens of hormonal therapies, everolimus in combination with exemestane was administered. Three months later, the patient visited our clinic because of continuous fever. A computed tomography scan showed an osteolytic change in the sternal bone with pneumomediastinum, which indicated sternal osteomyelitis. Extensive debridement followed by secondary reconstruction of the chest wall was successfully performed. CONCLUSIONS: Everolimus may cause osteomyelitis of the affected bone as a result of tumor necrosis. Everolimus-induced osteomyelitis may be manageable by extensive debridement performed without delay.
RESUMEN
The diagnostic accuracy of the multigene panel test (MPT) and OncoScan™ in the determination of HER2 amplification in breast tumors remains controversial. In the present study, HER2 copy number was analyzed using both MPT and OncoScan™ in 45 breast tumors and was compared with that in fluorescent in situ hybridization (FISH) analysis. Tumors with low cellularity were examined using tumor cell enrichment and fluorescenceactivated cell sorting. Both MPT and OncoScan™ exhibited significant correlations with FISH with respect to the determination of HER2 amplification in breast tumors. However, the correlation coefficient was significantly higher for the comparison of MPT and FISH (r=0.770) compared with that between OncoScan™ and FISH (r=0.564). The accuracy of MPT (93.3%) was slightly higher compared with that in OncoScan™ (84.4%) in determining the HER2 status, which was mostly explained by the higher sensitivity of MPT in tumors with low cellularity (83.3 vs. 33.3%), but not in those with high cellularity (81.8 vs. 72.7%). The specificity was 100% for both tests. The MPT exhibited higher sensitivity in the determination of the amplification of other genes, including MYC, fibroblast growth factor receptor 1 and GATA binding protein 3 in tumors with low cellularity compared with that in tumors with high cellularity. OncoScan™ exhibited low sensitivity without tumor cell enrichment. The results suggested that MPT could be a promising method to determine HER2 status in breast tumors and that it could exhibit improved accuracy compared with that in OncoScan™ in tumors with low cellularity.
Asunto(s)
Neoplasias de la Mama/genética , Análisis Mutacional de ADN/métodos , Amplificación de Genes/genética , Genes erbB-2/genética , Hibridación Fluorescente in Situ/métodos , Receptor ErbB-2/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Receptor ErbB-2/metabolismoRESUMEN
PURPOSE: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk. METHODS: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. RESULTS: 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows. CONCLUSIONS: The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.
Asunto(s)
Neoplasias de la Mama , Biomarcadores de Tumor/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Quimioterapia Adyuvante , Femenino , Perfilación de la Expresión Génica , Humanos , Recurrencia Local de Neoplasia/genética , Pronóstico , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Estudios RetrospectivosRESUMEN
We aimed to validate the cosmetic utility of addition of nipple-areola recentralization (NAR) to rotation flap according to nipple tumor distance (NTD) as a volume displacement technique after breast conserving surgery (BCS) for lower-outer and upper-inner breast cancers. Twenty breast cancer patients who had been treated with rotation flap with (Group 1; nâ¯=â¯6) or without (Group 2; nâ¯=â¯14) NAR after BCS for lower-outer or upper-inner located tumors, and those who had undergone BCS without oncoplastic surgical technique for tumors in the same area (Control group; nâ¯=â¯43), were retrospectively investigated. Cosmetic outcome was evaluated using Harvard scale and/or BCCT.core. As a result, the ratio of patients categorized as excellent/good was 83% in Group 1 and 93% in Group 2, respectively, and there was no significant difference between them (Pâ¯=â¯0.521). In addition, Group 1â¯+â¯2 showed a significantly higher ratio of patients classified as excellent/good than the control group (90% vs. 56%; Pâ¯=â¯0.009). After adjustment of clinical background parameters using propensity score matching analysis between Group 1â¯+â¯2 and the control group, 12 pairs with similar background factors were matched. Among them, Group 1â¯+â¯2 showed a higher ratio of patients categorized as excellent/good than the control group (92% vs. 42%; Pâ¯=â¯0.034). In conclusion, addition of NAR to rotation technique according to NTD may enable us to perform a volume displacement after BCS for lower-outer or upper-inner located tumors irrespective of NTD without sacrificing postoperative breast appearance.
Asunto(s)
Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Mastectomía Segmentaria , Pezones/cirugía , Colgajos Quirúrgicos/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estética , Femenino , Humanos , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Satisfacción del Paciente/estadística & datos numéricos , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
PURPOSE: To compare the diagnostic performance of ring-type dedicated breast PET (dbPET), whole-body PET (WBPET), and DCE-MRI for predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). METHODS: This prospective study included 29 women with histologically proven breast cancer on needle biopsy between July 2016 and July 2019 (age: mean 55 years; range 35-78). Patients underwent WBPET followed by ring-type dbPET and DCE-MRI pre- and post-NAC for preoperative evaluation. pCR was defined as an invasive tumor that disappeared in the breast. Standardized uptake values corrected for lean body mass (SULpeak) were calculated for dbPET and WBPET scans. Maximum tumor length was measured in DCE-MRI images. Reduction rates were calculated for quantitative evaluation. Two radiologists independently evaluated the qualitative findings. Reduction rates and qualitative findings were compared between the pCR (n = 7) and non-pCR (n = 22) groups for each modality. Differences in quantitative and qualitative data between the two groups were analyzed statistically. RESULTS: Significant differences were observed in the reduction rates of dbPET and DCE-MRI (P = 0.01 and 0.03, respectively) between the two groups. Univariate and multiple logistic regression analyses revealed that SULpeak reduction rates in WBPET and dbPET (P = 0.02 and P = 0.01, respectively) and in dbPET (odds ratio, 16.00; 95% CI 1.57-162.10; P = 0.01) were significant indicators associated with pCR, respectively. No between-group differences were observed in qualitative findings in the three modalities. CONCLUSION: SULpeak reduction rate of dbPET > 82% was an independent indicator associated with pCR after NAC in breast cancer.
Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Adulto , Anciano , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Estudios Prospectivos , Resultado del TratamientoRESUMEN
HER2 amplification is seen in 20-25% of primary breast cancer cases, and HER2 detection is performed routinely in primary operable, as well as metastatic breast cancer patients. Currently, HER2 is the only gene of which amplification is routinely assayed by fluorescent in situ hybridization (FISH) and/or immunohistochemistry (IHC). However, histochemical assay (FISH/IHC) of multiple target genes is laborious and time-consuming, and simultaneous amplification by microarray is preferred. OncoScan™ is a microarray-based assay capable of whole-genome copy number analysis using DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues. In the current study, we aimed to investigate the impact of tumor cellularity on the accuracy of OncoScan™ in the determination of HER2 amplification. Our results demonstrated that HER2 amplification by OncoScan™ is accurate, and has a high concordance rate of 93.3% with FISH. However, the concordance rate is poor (66.7%) in cases with a tumor cellularity < 20%. Nevertheless, the addition of FISH to breast tumors with a tumor cellularity < 20% and a HER2 copy number of 4 appears to be useful to minimize false-negative results by OncoScan™.
Asunto(s)
Neoplasias de la Mama/genética , Amplificación de Genes , Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Femenino , Humanos , Receptor ErbB-2 , Estudios Retrospectivos , Análisis de Matrices Tisulares/instrumentación , Análisis de Matrices Tisulares/normasRESUMEN
In clinical decision-making, to decide the indication for adjuvant chemotherapy for estrogen receptor-positive (ER+), human epidermal growth factor receptor-2-negative (HER2-), and node-negative (n0) breast cancer patients, the accurate estimation of recurrence risk is essential. Unfortunately, conventional prognostic factors, such as tumor size, histological grade and ER, progesterone receptor (PR), and HER2 status as well as Ki67 index, are not sufficiently accurate for such estimation. Therefore, several multigene assays (MGAs) based on the mRNA expression analysis of multiple genes in tumor tissue have been developed to better predict patient prognosis. These assays include Oncotype DX, MammaPrint, PAM50, GGI, EndoPredict, and BCI. We developed Curebest™ 95-Gene Classifier Breast (95GC) classifier, which is unique in that mRNA expression data of all 20 000 human genes are secondarily obtainable, as the 95GC assay is performed using Affymetrix microarray. This can capture mRNA expression of not only 95 genes but also every gene at once, and such gene expression data can be utilized by the other MGAs that we have developed, such as the 155GC, which is used for the prognostic prediction of ER+/HER2- breast cancer patients treated with neoadjuvant chemotherapy. We also developed the 42GC for predicting late recurrence in ER+/HER2- breast cancer patients. In this mini-review, our recent attempt at the development of various MGAs, which is expected to facilitate the implementation of precision medicine in ER+/HER2- breast cancer patients, is presented with a special emphasis on 95GC.
Asunto(s)
Neoplasias de la Mama/genética , Receptor ErbB-2/genética , Receptores de Estrógenos/genética , Neoplasias de la Mama/patología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Medicina de Precisión/métodos , Pronóstico , ARN Mensajero/genética , Receptores de Progesterona/genéticaRESUMEN
Ten stage I/II breast cancer patients with one or two suspicious lymph nodes (LNs) detected on ultrasonography underwent sentinel LN biopsy (SLNB) after the introduction of Twirl® breast markers into each suspicious LN revealed that each Twirl®-marked LN was SLN and was likely the first SLN. Three patients had less than three SLN metastases and were candidates for sparing completion axillary lymph node dissection (cALND). Indeed, of them, one underwent breast-conserving surgery without cALND and the other two underwent total mastectomy with cALND. These results suggest that, as all suspicious LNs are SLNs, patients can be treated with SLNB alone if they fulfill the ACOSOG Z-0011 criteria, despite suspicious LNs yielding positive results on preoperative fine-needle aspiration cytology.
Asunto(s)
Neoplasias de la Mama/patología , Metástasis Linfática/diagnóstico , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Femenino , HumanosRESUMEN
Humoral immunity plays a substantial role in the suppression of breast cancer. We have revealed that a high serum concentration of anti-HER2 autoantibody (HER2-AAb) is associated with favorable outcomes in patients with invasive breast cancer. Thus, we aimed to clarify the association between high serum concentration of HER2-AAb and humoral immune response in the tumor microenvironment. Out of 500 consecutive patients with invasive breast cancer, we selected those whose HER2-AAb values were high (n = 33) or low (n = 20) based on the distribution of HER2-AAb values of 100 healthy individuals. Tumor and regional lymph node formalin-fixed paraffin-embedded samples prepared from the surgical specimens were subjected to immunohistochemistry. We confirmed that the recurrence-free survival of the high HER2-AAb group was significantly longer than that of the low HER2-AAb group (p = 0.015). The numbers of tumor-infiltrating CD20+ immune cells (ICs) (p < 0.001), IGKC+ICs (p = 0.023), and CXCL13+ ICs (p = 0.044) were significantly higher in the high HER2-AAb group than in the low HER2-AAb group. The number of CD4+ ICs in the B-cell follicles of the regional lymph nodes was also significantly greater in the high HER2-AAb group than in the low HER2-AAb group (p = 0.026). Our findings indicate that a high level of HER2-AAb is associated with enhanced humoral immunity against breast cancer and thus may provide a rationale for the association of HER2-AAb with favorable prognosis.
Asunto(s)
Autoanticuerpos/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/inmunología , Carcinoma Ductal de Mama/inmunología , Carcinoma Lobular/inmunología , Receptor ErbB-2/inmunología , Adulto , Anciano , Autoanticuerpos/inmunología , Biomarcadores de Tumor/inmunología , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/sangre , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/sangre , Carcinoma Lobular/patología , Carcinoma Lobular/cirugía , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Inmunidad Humoral/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Microambiente Tumoral/inmunologíaRESUMEN
BACKGROUND: The aim of our study is to find microRNAs (miRNAs) associated with sentinel lymph node metastasis (SLNM) and to develop a prediction model for SLNM in ER-positive and HER2-negative (ER+/HER2-) breast cancer. PATIENTS AND METHODS: In the present study, only ER+/HER2- primary breast cancer was considered. The discovery set for SLNM-associated miRNAs included 10 tumors with and 10 tumors without SLNM. The training and validation sets both included 100 tumors. miRNA expression in tumors was examined comprehensively by miRNA microarray in the discovery set and by droplet digital PCR in the training and validation sets. RESULTS: In the discovery set, miR-98, miR-22, and miR-223 were found to be significantly (P < 0.001, fold-change > 2.5) associated with SLNM. In the training set, we constructed the prediction model for SLNM using miR-98, tumor size, and lymphovascular invasion (LVI) with high accuracy (AUC, 0.877). The accuracy of this prediction model was confirmed in the validation set (AUC, 0.883), and it outperformed the conventional Memorial Sloan Kettering Cancer Center nomogram. In situ hybridization revealed the localization of miR-98 expression in tumor cells. CONCLUSIONS: We developed a prediction model consisting of miR-98, tumor size, and LVI for SLNM with high accuracy in ER+/HER2- breast cancer. This model might help decide the indication for SLN biopsy in this subtype.