ABSTRACT
BACKGROUND: HER2-low breast cancer (BC) is a newly defined subset of HER2-negative BC. However, it is still uncertain whether HER2-low BC can be categorized as a distinct biological/clinical subgroup with any prognostic significance. METHODS: Invasive BC cases (n = 10,215) with Stage I-III were retrospectively analyzed to determine the HER2 status. The HER2 status was then divided into 3 groups: HER2-0, HER2-low, and HER2-positive. RESULTS: The HER2 status was classified as HER2-0 in 1,227 cases (12.0%), HER2-low in 7,209 cases (70.6%), and HER2-positive in 1779 cases (17.4%). HER2-low cases had more positive nodes and were significantly associated with positive ER/PgR, lower nuclear grade, and lower Ki-67 index. HER2-0 had the lowest OS rate in the primary cases and after recurrence. HER2-0 in the node positive group had the lowest OS and was significantly different from HER2-low in the same group. The pathological complete response (pCR) rate for NAC was lowest in the HER2-low group. The DFS after NAC was significantly better in all the pCR cases, regardless of the HER2 status. However, the DFS was significantly lower in the HER2-low non-pCR cases. CONCLUSION: HER2-low accounted for 70% of the cases and correlated with favorable biological markers. The HER2-low group had a significantly better OS than the HER2-0 group. However, the response to NAC was low in the HER2-low group, and this group had the poorest prognosis among all the non-pCR cases. These findings indicate that HER2-low may have a different biology and prognosis and therefore should be classified as a new entity.
Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Humans , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Female , Receptor, ErbB-2/metabolism , Prognosis , Retrospective Studies , Middle Aged , Adult , Aged , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Receptors, Estrogen/metabolism , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , Aged, 80 and over , Survival RateABSTRACT
BACKGROUND: The role of endocrine therapy in the treatment of patients in a postmenopausal hormonal state and with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer (AMBC) is unclear. METHODS: We analyzed the data from 94 patients with ER-positive HER2-positive AMBC enrolled in the Safari study (UMIN000015168), a retrospective cohort study of 1072 ER-positive AMBC patients in a postmenopausal hormonal state who received fulvestrant 500 mg (F500): (1) to compare time to treatment failure (TTF) and overall survival (OS) by treatment group, and TTF by treatment line; (2) in patients who received endocrine therapy (including F500) or anti-HER2 therapy as initial systemic therapy before chemotherapy, to investigate relations between TTF for the first-line therapy or time to chemotherapy (TTC) and OS; (3) to investigate factors associated with OS. RESULTS: The TTF was longer in the patients treated with F500 as first- or second-line therapy (n = 20) than in those who received later-line F500 therapy (n = 74) (6.6 vs. 3.7 months; HR, 1.98; p = 0.014). In the 59 patients who received endocrine therapy or anti-HER2 therapy as initial systemic therapy before chemotherapy, those with TTC ≥3 years had longer median OS than those with TTC <3 years (10.5 vs. 5.9 years; HR, 0.32; p = 0.001). Longer TTC was associated with prolonged OS. CONCLUSIONS: In patients with ER-positive HER2-positive AMBC enrolled in the Safari study, TTF was longer in patients who received F500 as first- or second-line therapy. In patients who received chemotherapy-free initial systemic therapy, the prolonged OS in those with TTC ≥3 years suggests that this value may be a helpful cut-off for indicating clinical outcomes.
Subject(s)
Breast Neoplasms , Humans , Female , Fulvestrant/therapeutic use , Breast Neoplasms/pathology , Postmenopause , Retrospective Studies , Receptor, ErbB-2/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
BACKGROUND: Only old evidence exists to back up the use of medroxyprogesterone acetate. Therefore, this study aimed to explore the factors that influence the time to treatment failure of medroxyprogesterone acetate in real-world settings as late-line treatment. METHODS: This was a cohort study that used the database of the Safari study on oestrogen receptor-positive post-menopausal advanced breast cancer (UMIN000015168). We created Kaplan-Meier curves for time to treatment failure with medroxyprogesterone acetate. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the time to treatment failure of medroxyprogesterone acetate. RESULTS: From the 1031 patients in the Safari study, 279 patients were selected as the population for the analysis of effectiveness of medroxyprogesterone acetate monotherapy. In the analysis of medroxyprogesterone acetate by treatment line, the median time to treatment failure was 3.0 months for third-line treatment and 4.1 months for fourth and subsequent treatment lines. In cases where medroxyprogesterone acetate was used as a third-line or later endocrine treatment, multivariate analysis showed that the length of the disease-free interval was correlated with the length of time to treatment failure of medroxyprogesterone acetate (P = 0.004). With medroxyprogesterone acetate monotherapy as the fourth-line or later treatment, 20% of the patients achieved a time to treatment failure of 12 months or longer. CONCLUSION: In actual clinical practice, patients treated with medroxyprogesterone acetate alone as the fourth or subsequent treatment lines showed a time to treatment failure of 4 months, suggesting that there is merit in using medroxyprogesterone acetate even in late treatment lines, especially in patients with long disease-free interval and those who are difficult to treat using other antineoplastic agents.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Medroxyprogesterone Acetate/therapeutic use , Retrospective Studies , Medroxyprogesterone/therapeutic use , Postmenopause , Cohort StudiesABSTRACT
BACKGROUND: The Safari study (UMIN000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive advanced breast cancer treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure in patients with estrogen receptor-positive advanced breast cancer. The current study is an ad hoc analysis that focused on the relationship between the patient factors and overall survival after recurrence by adding factors generally associated with overall survival after recurrence. METHODS: The overall survival after recurrence in patients with estrogen receptor-positive human epidermal growth factor receptor 2 negative recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model. RESULTS: A total of 598 cases were used for the analysis of overall survival after recurrence. Multivariate analysis revealed that favorable overall survival (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥3 years), low nuclear or histological grade (G3 vs. G1), long time to treatment failure of initial palliative endocrine therapy (≥12 months) and long time to initial palliative chemotherapy (≥2 years). CONCLUSION: The results of this study indicate that sequential endocrine monotherapy may be a useful treatment option for patients with estrogen receptor-positive/human epidermal growth factor receptor 2 negative recurrent breast cancer who have been successfully treated with initial long-term palliative endocrine therapy.
Subject(s)
Breast Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Female , Fulvestrant/therapeutic use , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Postmenopause , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective StudiesABSTRACT
BACKGROUND: The one-step nucleic acid amplification (OSNA) assay can quantify the cytokeratin 19 messenger RNA copy number as a proxy for sentinel lymph node (SN) metastasis in breast cancer. A large-scale, multicenter cohort study was performed to determine the prognostic value of the SN tumor burden based on a molecular readout and to establish a model for the prediction of early systemic recurrence in patients using the OSNA assay. METHODS: SN biopsies from 4757 patients with breast cancer were analyzed with the OSNA assay. The patients were randomly assigned to the training or validation cohort at a ratio of 2:1. On the basis of the training cohort, the threshold SN tumor burden value for stratifying distant recurrence was determined with Youden's index; predictors of distant recurrence were investigated via multivariable analyses. Based on the selected predictors, a model for estimating 5-year distant recurrence-free survival was constructed, and predictive performance was measured with the validation cohort. RESULTS: The prognostic cutoff value for the SN tumor burden was 1100 copies/µL. The following variables were significantly associated with distant recurrence and were used to construct the prediction model: SN tumor burden, age, pT classification, grade, progesterone receptor, adjuvant cytotoxic chemotherapy, and adjuvant anti-human epidermal growth factor receptor 2 therapy. The values for the area under the curve, sensitivity, specificity, and accuracy of the prediction model were 0.83, 63.4%, 81.7%, and 81.1%, respectively. CONCLUSIONS: Using the OSNA assay, the molecular readout-based SN tumor burden is an independent prognostic factor for early breast cancer. This model accurately predicts early systemic recurrence and may facilitate decision-making related to treatment.
Subject(s)
Breast Neoplasms , Sentinel Lymph Node , Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cohort Studies , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoplasm Recurrence, Local/pathology , Pathology, Molecular , Sentinel Lymph Node/pathologyABSTRACT
PURPOSE: Radiotherapy (RT) and endocrine therapy (ET) are standard treatment options after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We investigated the national patterns of adjuvant therapy use after BCS for DCIS in Japan. METHODS: We obtained relevant data of patients diagnosed with DCIS undergoing surgery and treated with BCS between 2014 and 2016 from the Japanese Breast Cancer Registry database. The relationship between the clinicopathologic, institutional, and regional factors, and adjuvant treatment was examined using multivariable analyses. RESULTS: We identified 9516 patients who underwent BCS for DCIS. Overall, 23% received no adjuvant treatment, 71% received RT, 32% received ET, and 26% received combination therapy. The percentages of patients who received ET and combination therapy in 2016 were significantly lower [odds ratio (OR): 0.71, 0.77, respectively] than in 2014. The proportion of RT was low among young or elderly patients (OR: 0.75, 0.44, respectively) and in non-certified facilities (OR: 0.56). The proportion of ET was high in non-certified facilities (OR: 1.58) and among patients with positive margins (OR: 1.62). Combination therapy was higher among patients with positive margins (OR: 1.53). CONCLUSIONS: Our study found a distinct adjuvant treatment pattern after BCS for DCIS depending on clinicopathologic factors, year, age, which indicate that physicians provide individualized treatment according to the background of the patients and the biology of DCIS. The facilities and regions remain significant factors of influencing adjuvant treatment pattern.
Subject(s)
Breast Neoplasms/therapy , Carcinoma, Intraductal, Noninfiltrating/therapy , Mastectomy, Segmental , Radiotherapy, Adjuvant/trends , Adult , Age Factors , Breast Neoplasms/epidemiology , Carcinoma, Intraductal, Noninfiltrating/epidemiology , Cohort Studies , Humans , Japan/epidemiology , Margins of Excision , Middle Aged , Retrospective StudiesABSTRACT
PURPOSE: The sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC. METHODS: In this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative. RESULTS: A preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade ≥ 3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%). CONCLUSION: Sequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.
Subject(s)
Anthracyclines , Breast Neoplasms , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms/drug therapy , Bridged-Ring Compounds , Female , Furans , Humans , Ketones , Neoadjuvant Therapy , Prospective Studies , Receptor, ErbB-2/genetics , Taxoids , Treatment OutcomeABSTRACT
INTRODUCTION: The previous randomized phase 3 trial (SELECT BC) showed that S-1 as a first-line chemotherapy for metastatic breast cancer (MBC) is non-inferior to taxane with respect to overall survival. This study aimed to identify the usefulness of metabolism-related genes as predictive biomarkers for the response to S-1 compared with taxane using tumor tissue samples from the previous trial.â¯â¯ PATIENTS AND METHODS: In this SELECT BC-EURECA study, 147 patients with human epidermal growth factor 2 (HER2)-negative MBC who received either S-1 or taxane were evaluated. Formalin-fixed paraffin-embedded specimens were collected, and 14 genes involved in the pyrimidine metabolic pathway, estrogen receptor, progesterone receptor, HER2, Ki67, and beta-tubulin were measured using reverse transcription polymerase chain reaction in microdissected tumor specimens. The expression of each gene was categorized as low, intermediate, and high by tertile values.â¯â¯ RESULTS: Interaction tests to identify biomarkers for the response to S-1 compared with taxane, revealed the following as the top 3 biomarkers: RRM1 (P value = 0.24), GGH (P value = 0.25), and MTHFR (P value = 0.28). In the S-1 group, lower GGH and higher MTHFR expression were significantly correlated with better time to treatment failure. In the taxane group, there was no gene that was identified as a significant indicator of treatment failure. CONCLUSION: This biomarker analysis from SELECT BC did not identify any predictive biomarkers for the response to S-1 compared with taxane. Future studies with larger sample size and information on not only mRNA, but also protein and DNA for broad functional analyses are needed.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Breast Neoplasms/drug therapy , Oxonic Acid/therapeutic use , Tegafur/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Drug Combinations , Female , Health Status , Humans , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolismABSTRACT
BACKGROUND: To compare the breast cancer detection performance in digital mammograms of a panel of three unaided human readers (HR) versus a stand-alone artificial intelligence (AI)-based Transpara system in a population of Japanese women. METHODS: The subjects were 310 Japanese female outpatients who underwent digital mammographic examinations between January 2018 and October 2018. A panel of three HR provided a Breast Imaging Reporting and Data System (BI-RADS) score, and Transpara system provided an interactive decision support score and an examination-based cancer likelihood score. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared under each of reading conditions. RESULTS: The AUC was higher for human readers than with stand-alone Transpara system (human readers 0.816; Transpara system 0.706; difference 0.11; P < 0.001). The sensitivity of the unaided HR for diagnosis was 89% and specificity was 86%. The sensitivity of stand-alone Transpara system for cutoff scores of 4 and 7 were 93% and 85%, and specificities were 45% and 67%, respectively. CONCLUSIONS: Although the diagnostic performance of Transpara system was statistically lower than that of HR, the recent advances in AI algorithms are expected to reduce the difference between computers and human experts in detecting breast cancer.
Subject(s)
Artificial Intelligence , Breast Neoplasms/diagnosis , Early Detection of Cancer/methods , Mammography/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Adult , Aged , Aged, 80 and over , Breast/diagnostic imaging , Decision Support Systems, Clinical , Early Detection of Cancer/standards , Female , Humans , Japan , Mammography/standards , Middle Aged , ROC Curve , Radiologists/standards , Reference Standards , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Assessing survival risk is important for discussing treatment options with estrogen receptor-positive (ER+) advanced breast cancer (ABC) patients. However, there are few reports from large-scale databases on the survival risk factors in ER+ ABC. The Safari study (UMIN000015168) was a retrospective, multicenter cohort study involving 1072 Japanese patients receiving fulvestrant 500 mg mostly as a second- or later-line endocrine therapy for ER+ ABC. The follow-up data after the Safari study were examined, focusing on any relationship between clinicopathological factors and overall survival (OS) in ER+ ABC patients. METHODS: OS in patients with ER+ ABC was analyzed by univariate and multivariate analyses with a Cox proportional hazards model in this study. RESULTS: A total of 1031 cases were evaluable for OS analysis. Multivariate analysis showed that younger age (< 60 years), longer time from ABC diagnosis to fulvestrant use (≥ 3 years), no prior palliative chemotherapy before fulvestrant use, and progesterone receptor (PgR) negativity (PgR-) were significantly correlated with prolonged OS (median 7.0 years). For cases with histological or nuclear grade data, lower histological or nuclear grades were also correlated with longer OS. In recurrent metastatic cases, long disease-free interval (DFI) was not correlated with longer OS. CONCLUSIONS: In ER+ ABC patients whose treatment history included fulvestrant, younger age, longer time from ABC diagnosis to fulvestrant use, no prior palliative chemotherapy use, PgR-, and lower histological or nuclear grade correlated positively with prolonged OS.
Subject(s)
Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/mortality , Carcinoma, Lobular/mortality , Fulvestrant/therapeutic use , Neoplasm Recurrence, Local/mortality , Postmenopause , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Survival RateABSTRACT
PURPOSE: To evaluate the feasibility of proposed integrated slice-by-slice shimming (iShim) for whole-body diffusion weighted imaging (WB-DWI) in comparison to conventional 3D shim in patients with breast cancer. MATERIALS AND METHODS: Retrospective analysis of 116 consecutive patients (116 lesions) who underwent whole-body PET/MR using iShim (iShim group) were performed and compared with historical control of 103 patients (105 lesions) using 3D Shim (3D Shim group). RESULTS: As compared with dynamic contrast-enhanced (DCE) breast MRI, the apparent diffusion coefficient (ADC) value could not be determined for 15 (14%) of the 105 lesions of the 3D shim group and for 10 (9%) of the 116 lesions on iShim group. The intergroup difference failed to reach statistical significance (P = 0.1843). On the other hand, there was a significant difference in the frequencies of PET-positive and DWI-negative lesions between the 3D shim and iShim group (8.6% vs. 1.7%, respectively, P = 0.01942). CONCLUSION: In regard to detectability of breast cancers by DWI, iShim may allow improved detectability as compared to conventional 3D shim.
Subject(s)
Breast Neoplasms/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Image Processing, Computer-Assisted/methods , Whole Body Imaging/methods , Adult , Aged , Aged, 80 and over , Breast/diagnostic imaging , Breast/pathology , Breast Neoplasms/pathology , Contrast Media , Feasibility Studies , Female , Humans , Image Enhancement/methods , Imaging, Three-Dimensional/methods , Middle Aged , Multimodal Imaging/methods , Positron-Emission Tomography/methods , Retrospective StudiesABSTRACT
BACKGROUND: One-step nucleic acid amplification (OSNA) for cytokeratin 19 messenger RNA is an intraoperative diagnostic procedure for the detection of lymph node metastasis. OBJECTIVE: This study aimed to construct intraoperative nomograms using OSNA for the prediction of non-sentinel lymph node (NSLN) metastasis and four or more axillary lymph node (ALN) metastases. METHODS: Of the 4736 breast cancer patients (T1-3, N0) who underwent sentinel lymph node (SLN) biopsy and had SLNs examined intraoperatively with OSNA, 623 with SLN metastasis treated with completion ALN dissection (cALND) were retrospectively analyzed, and were randomly divided into training (n = 312) and validation (n = 311) sets. RESULTS: Of the clinicopathological parameters available preoperatively and intraoperatively, the multivariate analysis of the training set revealed that clinical tumor size and total tumor load (TTL) determined by OSNA were significantly associated with NSLN metastasis, and that clinical tumor size, number of macrometastatic SLNs, and TTL were significantly associated with four or more ALN metastases. Nomograms for NSLN metastasis and four or more ALN metastases were constructed using these parameters, and their area under the receiver operating characteristic curve (AUC) of the validation set were both 0.70, with a diagnostic accuracy similar to that of previously reported postoperative nomograms. CONCLUSIONS: We constructed intraoperative nomograms using OSNA for the prediction of NSLN metastasis and four or more ALN metastases. These nomograms are as accurate as the conventional postoperative nomograms and might be helpful for decision making regarding the indication for cALND or the choice of adjuvant chemotherapeutic regimens and radiation field.
Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/pathology , Lymphadenopathy/diagnosis , Nomograms , RNA, Messenger/analysis , Adult , Aged , Aged, 80 and over , Area Under Curve , Axilla , Breast Neoplasms/genetics , Female , Humans , Intraoperative Period , Keratin-19/genetics , Lymphatic Metastasis , Middle Aged , Nucleic Acid Amplification Techniques , Predictive Value of Tests , ROC Curve , Retrospective Studies , Risk Assessment/methods , Sentinel Lymph Node/pathology , Sentinel Lymph Node Biopsy , Tumor BurdenABSTRACT
AIMS: Maspin is known to be a tumour suppressor protein, but its prognostic significance in breast cancer patients is controversial. There is no report focusing on maspin expression in metastatic carcinoma of sentinel lymph nodes (SLNs); we thus investigated maspin mRNA expression in SLNs using the remaining specimens after the one-step nucleic acid amplification (OSNA) assay. METHODS AND RESULTS: Ninety-three breast cancer patients with SLNs metastasis detected by the OSNA assay were enrolled. All patients experienced additional axillary lymph nodes (LNs) dissection and all dissected LNs were examined histopathologically. Maspin mRNA expression in SLNs was detected in 49.5% (46 of 93) and was correlated significantly with the presence of non-SLN metastasis (P < 0.0001) and ≥4 LN metastases (P = 0.029). In a multivariate logistic analysis, maspin mRNA expression in SLNs (P = 0.0015) had the most significant effect on predicting non-SLN metastasis, followed by pathological tumour size (P = 0.0039) and lymphovascular invasion (P = 0.009). The status of maspin mRNA expression in SLNs was correlated significantly with that of maspin protein expression in the primary carcinoma (P < 0.0001). CONCLUSIONS: This is the first study, to our knowledge, demonstrating that maspin mRNA expression in SLNs is an independent predictor of non-SLN metastasis and the presence of ≥4 LN metastases in breast cancer patients with SLN metastasis. The investigation of maspin mRNA expression in SLNs using the remaining specimens after the OSNA assay may be useful for predicting the further progression of metastatic carcinoma in breast cancer patients with SLNs metastasis.
Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Lymphatic Metastasis/pathology , Sentinel Lymph Node/metabolism , Serpins/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Female , Humans , Middle Aged , Prognosis , Sentinel Lymph Node/pathology , Sentinel Lymph Node BiopsyABSTRACT
PURPOSE: To compare standardized uptake value (SUV) and apparent diffusion coefficient (ADC) values acquired using a PET/MRI scanner in breast cancer patients. MATERIALS AND METHODS: Whole-body PET/MRI and breast PET/MRI were performed in 108 consecutive patients. Ninety-four patients who had a total of 100 breast cancers were analyzed. SUVmax and ADCmean acquired using breast PET/MRI were compared with pathologic prognostic factors. RESULTS: All the lesions were visually detectable using PET and diffusion-weighted imaging (DWI) on breast PET/MRI; however, lesions were visually undetectable on whole-body DWI in 13 patients (13%) or on whole-body PET in 7 patients (7%). An analysis of ADCmean and SUVmax demonstrated a statistically significant correlation between whole-body imaging and breast imaging (rho = 0.613, p < 0.001 and rho = 0.928, p < 0.001, respectively). In a univariate analysis, SUVmax was significantly correlated with HER2 status (p < 0.001), Ki-67 (p = 0.014), tumor size (p = 0.0177), and nuclear grade (p = 0.0448). In multiple regression analysis, only tumor size (p = 0.00701) was shown to independently influence SUVmax. CONCLUSION: Prone breast imaging was more sensitive than whole-body PET/MRI for detection of breast cancers. Both SUVmax and ADCmean showed limited correlation with pathologic prognostic factors.
Subject(s)
Breast Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Radiopharmaceuticals , Whole Body Imaging/methods , Adult , Aged , Aged, 80 and over , Breast/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Middle Aged , Multimodal Imaging/methods , Reproducibility of Results , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2-) cases. METHODS: The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p < .001), no prior chemotherapy (p < .001), and F500 treatment line (p < .001) were correlated with prolonged TTF (median = 5.39 months). CONCLUSIONS: In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Estradiol/analogs & derivatives , Receptors, Estrogen/analysis , Adult , Aged , Aged, 80 and over , Breast Neoplasms/chemistry , Estradiol/therapeutic use , Female , Fulvestrant , Humans , Middle Aged , Postmenopause , Retrospective Studies , Time-to-Treatment , Treatment FailureABSTRACT
BACKGROUND: Sentinel lymph node biopsy (SLNB) alone has been compared with SLNB followed by axillary lymph node dissection (ALND) in sentinel lymph node (SLN)-positive breast cancer patients in randomized phase III trials: the addition of ALND did not further improve the patient's outcome. However, there is still some controversy, regarding the clinical application of SLNB alone. To identify the optimal axillary treatment in the era of SLNB, the Japanese Breast Cancer Society conducted a group study of SLNB in 2014. METHODS: A questionnaire on axillary surgery and radiation therapy was sent to 432 Japanese institutes in December 2014, and 309 (72 %) completed the questionnaire. RESULTS: SLNB was performed at 98 % of the institutes, and 77 % offered irradiation for cancer treatment. Regarding breast-conserving surgery (BCS), SLNB alone was indicated at 41 % of the institutes in the cases of SLN with micrometastases. However, in the cases of SLN with macrometastases, ALND was performed at 64 %. The proportion of ALND seemed to be higher in total mastectomy than in BCS regardless of the SLN-positive status. In the cases of SLN with micrometastases, the radiation field was localized in the conserved breast at about half of the institutes. On the other hand, in the cases of SLN with macrometastases, it was extended to axillary and/or supraclavicular lesions beyond the conserved breast at about 70 % of the institutes. CONCLUSIONS: Japanese breast physicians were conservative with respect to the omission of ALND in SLN-positive breast cancer, especially in the cases of SLN with macrometastases.
Subject(s)
Axilla/surgery , Breast Neoplasms/pathology , Sentinel Lymph Node Biopsy/methods , Axilla/pathology , Axilla/radiation effects , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Female , Humans , Japan , Lymph Node Excision , Lymphatic Metastasis/pathology , Mastectomy, Segmental/statistics & numerical data , Neoplasm Micrometastasis/pathology , Sentinel Lymph Node Biopsy/statistics & numerical data , Surveys and QuestionnairesABSTRACT
Tumor-infiltrating lymphocytes (TILs) have potential value for stratifying the treatment of breast cancer (BC), though their precise use remains unclear. We aimed to investigate the utility of TILs using an alternative approach in different settings. We reviewed patients with triple-negative (TN) or human epithelial growth factor receptor 2 (HER2)-positive invasive ductal carcinomas from a single institutional cohort and classified archived hematoxylin-eosin-stained samples in terms of TIL score as low (<10 %), intermediate, and high (>50 %). The prognostic and predictive values of TILs were analyzed retrospectively in both adjuvant and neo-adjuvant settings. In the adjuvant setting, the presence of TILs at primary surgery was a significant favorable prognostic factor among 154 TNBCs [relapse-free survival (RFS): p = 0.015], but not among 183 HER2+ BCs (RFS: p = 0.097). The TNBC low-TIL group tended to relapse earlier. In the neo-adjuvant setting, detection of TILs on biopsy before primary systemic therapy was associated with the ratio of patients achieving pathological complete response among 48 TNBCs (p = 0.024), but not among 58 HER2+ BCs (p = 0.30). The presence of TILs in surgical specimens after systemic therapy had prognostic value in HER2+ BC (RFS: p = 0.007). The impact of TILs differs between patients with TN and HER2+ BC treated with standard therapies. Our three-grade scale for TILs may contribute to our understanding of the importance of the tumor microenvironment in routine practice. TILs after primary systemic therapy may be useful for the further stratification of treatment of HER2+ BC.
Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Lymphocytes, Tumor-Infiltrating/pathology , Receptor, ErbB-2/metabolism , Triple Negative Breast Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/pathology , Female , Humans , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Young AdultABSTRACT
PURPOSE: Cancer-related fatigue (CRF) is one of the most common symptoms reported by cancer patients. This randomized trial investigated the efficacy of the amino acid jelly Inner Power(®) (IP), a semi-solid, orally administrable dietary supplement containing coenzyme Q10 and L-carnitine, in controlling CRF in breast cancer patients in Japan. METHODS: Breast cancer patients with CRF undergoing chemotherapy were randomly assigned to receive IP once daily or regular care for 21 days. The primary endpoint was the change in the worst level of fatigue during the past 24 h (Brief Fatigue Inventory [BFI] item 3 score) from day 1 (baseline) to day 22. Secondary endpoints were change in global fatigue score (GFS; the average of all BFI items), anxiety and depression assessed by the Hospital Anxiety and Depression Scale (HADS), quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Breast Cancer-Specific QLQ (EORTC QLQ-BR23), and adverse events. RESULTS: Fifty-nine patients were enrolled in the study, of whom 57 were included in the efficacy analysis. Median patient age was 50 years. Changes in the worst level of fatigue, GFS, and current feeling of fatigue were significantly different between the intervention and control groups, whereas the change in the average feeling of fatigue was not significantly different between groups. HADS, EORTC QLQ-C30, and EORTC QLQ-BR23 scores were not significantly different between the two groups. No severe adverse events were observed. CONCLUSION: IP may control moderate-severe CRF in breast cancer patients. TRIAL REGISTRATION: The registration number of this study in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) is UMIN000008646.
Subject(s)
Breast Neoplasms/physiopathology , Carnitine/administration & dosage , Fatigue/drug therapy , Ubiquinone/analogs & derivatives , Adult , Aged , Breast Neoplasms/drug therapy , Fatigue/etiology , Female , Humans , Middle Aged , Quality of Life , Ubiquinone/administration & dosageABSTRACT
BACKGROUND: The one-step nucleic acid amplification (OSNA) method can assess the expression level of cytokeratin 19 mRNA in sentinel lymph nodes in breast cancer. We compared the time required for diagnosis and concordance of results between the OSNA method and conventional intraoperative pathological examination. We then examined the relationship between the frequency of non-sentinel lymph node metastasis and (1) the expression level of CK19 mRNA in the sentinel lymph nodes and (2) clinico-pathological features of the primary tumor. METHODS: In the comparison study, pairs of sentinel lymph node sections from 53 consecutive patients were examined: one section by hematoxylin-eosin staining and the other by OSNA assay. The latter involved reverse-transcription loop-mediated isothermal amplification of cytokeratin 19 mRNA, assessed quantitatively. In the second phase, 306 sentinel lymph nodes were removed from 248 consecutive patients, and whole sentinel lymph nodes were examined by OSNA assay alone. RESULTS: OSNA assay was a little more time-consuming than conventional pathological diagnosis (34-45 vs. 22-25 min, p < 0.0001). Concordance between the two methods was 93%. The frequency of non-sentinel lymph node metastasis (p < 0.0001) and the total number of lymph node metastases (p < 0.0001) increased with the amount of cytokeratin 19 mRNA on OSNA assay. We found no significant relationship between the amount of cytokeratin 19 mRNA in sentinel lymph nodes and breast cancer immunohistochemical subtype. CONCLUSIONS: The OSNA method is suitable to detect sentinel lymph node metastasis and to predict the possibility of non-sentinel metastasis. This semi-automated quantitative analysis system reduces the burden on pathologists.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Keratin-19/genetics , Lymph Nodes/pathology , Nucleic Acid Amplification Techniques , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Female , Humans , Immunoenzyme Techniques , Intraoperative Period , Lymph Nodes/metabolism , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sentinel Lymph Node BiopsyABSTRACT
We experienced a case of endocrine therapy-resistant recurrent breast cancer with liver and bone metastases, treated with S-1 as first-line chemotherapy and maintaining a good quality of life. The patient was a 31-year-old premenopausal woman. She was diagnosed with cancer of the left breast(T1(18mm), N0, M(-))and underwent breast-conserving surgery, sentinel lymph node biopsy, and radiation therapy in August 2002. As there was hormone sensitivity, she was treated with LHRH analog for 3 years and tamoxifen for 5 years as adjuvant therapy. After her first childbirth, she had a recurrence of liver and bone metastases. After treatment with endocrine therapy failed, an oral administration of S-1 was initiated as first-line chemotherapy considering her QOL. She received 8 months of S-1 therapy with no severe adverse reactions and maintained a high quality of life. Treatment with S-1 is thought to be useful for first-line chemotherapy if the treatment demonstrates a therapeutic equivalence with taxane on patients' overall survival.