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1.
Guo-Chun Zhang Xue-Ke Qian Zi-Bai Guo Chong-Yang Ren Meng Yao Xue-Rui Li Kun Wang Jian Zu Ning Liao 《Medical oncology (Northwood, London, England)》2012,29(5):3222-3231
Trastuzumab-containing neoadjuvant chemotherapy achieves a pathologic complete response (pCR) rate of about 40?% in HER2-positive breast cancers, and pCR predicts better survival. A cohort of 102 consecutive Chinese HER2-positive stage II/III patients with neoadjuvant trastuzumab/taxanes were retrospectively analyzed, to evaluate the role of hormonal receptor (HR) status and Ki67 index, along with other parameters, in pCR and survival prediction. pCR rate of the cohort was 44.1?% (45/102). Fifty-three patients were HR-positive and 49 were HR-negative. Median Ki67 index was 40?%, and 49 patients had a high Ki67 index (>40?%) whereas 53 had a low Ki67 index (??40?%). HR status and Ki67 index were confirmed as the only two parameters associated with pCR in multivariate analysis (hazard ratio?=?2.952; 95?% CI, 1.227?C7.105; P?=?0.016 for HR status and hazard ratio?=?2.583, 95?% CI 1.107?C6.026, P?=?0.028 for Ki67 index). Patients with coexisting HR-negative and high Ki67 index had higher pCR rate (69.2?%), compared to those with either HR-negative alone or high Ki67 alone (hazard ratio?=?3.038; 95?% CI, 1.102?C8.372; P?=?0.029), and to those with coexisting HR-positive and low Ki67 index as well (hazard ratio?=?7.071; 95?% CI, 2.150?C23.253; P?=?0.001). In a median follow-up duration of 25.9?months, 11 disease-free survival events (DFS) were recorded. pCR predicted better DFS (log rank P?=?0.018) and was the only significant factor in Cox regression analysis (hazard ratio?=?0.184; 95?% CI, 0.038?C0.893; P?=?0.036). Our study indicates that HR status and Ki67 index are predictors for pCR but not for DFS in HER2-positive patients with neoadjuvant trastuzumab/taxanes, which deserves further investigations. 相似文献
2.
von Minckwitz G Untch M Nüesch E Loibl S Kaufmann M Kümmel S Fasching PA Eiermann W Blohmer JU Costa SD Mehta K Hilfrich J Jackisch C Gerber B du Bois A Huober J Hanusch C Konecny G Fett W Stickeler E Harbeck N Müller V Jüni P 《Breast cancer research and treatment》2011,125(1):145-156
Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors. 相似文献
3.
Anne-Sophie Hamy-Petit Lisa Belin Hélène Bonsang-Kitzis Caroline Paquet Jean-Yves Pierga Florence Lerebours Paul Cottu Roman Rouzier Alexia Savignoni Marick Lae Fabien Reyal 《British journal of cancer》2016,114(1):44-52
Background:
Trastuzumab was introduced a decade ago and has improved outcomes for HER2-positive breast cancer. We investigated the factors predictive of pathological complete response (pCR), prognostic factors for disease-free survival (DFS), and interactions between pCR and DFS after neoadjuvant treatment.Methods:
We identified 287 patients with primary HER2-positive breast cancers given neoadjuvant chemotherapy (NAC) between 2002 and 2011. Univariate and multivariate analyses of clinical and pathological factors associated with pCR and DFS were performed.Results:
pCR rates differed between patients receiving neoadjuvant trastuzumab treatment or not (47.7% versus 19.3%, P<0.0001). DFS also differed significantly between patients receiving adjuvant trastuzumab or not (hazard ratio=4.84, 95% CI (2.52; 9.31), P<0.001). We analysed 199 patients given neoadjuvant and adjuvant trastuzumab. Multivariate analysis identified older age and hormone receptor-negative tumours as independent predictors of pCR. T stage (hazard ratio=2.55, 95% CI (1.01; 6.48), P=0.05) and strict pCR (hazard ratio=9.15, 95% CI (1.22; 68.83), P=0.03) were independent predictors of DFS. The latter association was significant in the HR-negative subgroup (P=0.02) but not in the HR-positive subgroup (P=0.12).Conclusions:
Major pCR and DFS gains in HER2-positive BC were observed since ‘trastuzumab'' era. Further improvements rely on the enrollment of accurately selected patients into clinical trials. 相似文献4.
《Annals of oncology》2014,25(2):384-391
BackgroundSubtypes defined by hormonal receptor (HR) and HER2 status have not been well studied in inflammatory breast cancer (IBC). We characterized clinical parameters and long-term outcomes, and compared pathological complete response (pCR) rates by HR/HER2 subtype in a large IBC patient population. We also compared disease-free survival (DFS) and overall survival (OS) between IBC patients who received targeted therapies (anti-hormonal, anti-HER2) and those who did not.Patients and methodsWe retrospectively reviewed the records of patients diagnosed with IBC and treated at MD Anderson Cancer Center from January 1989 to January 2011. Of those, 527 patients had received neoadjuvant chemotherapy and had available information on estrogen receptor (ER), progesterone receptor (PR), and HER2 status. HR status was considered positive if either ER or PR status was positive. Using the Kaplan–Meier method, we estimated median DFS and OS durations from the time of definitive surgery. Using the Cox proportional hazards regression model, we determined the effect of prognostic factors on DFS and OS. Results were compared by subtype.ResultsThe overall pCR rate in stage III IBC was 15.2%, with the HR-positive/HER2-negative subtype showing the lowest rate (7.5%) and the HR-negative/HER2-positive subtype, the highest (30.6%). The HR-negative, HER2-negative subtype (triple-negative breast cancer, TNBC) had the worst survival rate. HR-positive disease, irrespective of HER2 status, had poor prognosis that did not differ from that of the HR-negative/HER2-positive subtype with regard to OS or DFS. Achieving pCR, no evidence of vascular invasion, non-TNBC, adjuvant hormonal therapy, and radiotherapy were associated with longer DFS and OS.ConclusionsHormone receptor and HER2 molecular subtypes had limited predictive and prognostic power in our IBC population. All molecular subtypes of IBC had a poor prognosis. HR-positive status did not necessarily confer a good prognosis. For all IBC subtypes, novel, specific treatment strategies are needed in the neoadjuvant and adjuvant settings. 相似文献
5.
《Annals of oncology》2013,24(8):1999-2004
BackgroundWe sought to determine the prognostic value of pathologic response to neoadjuvant chemotherapy with concurrent trastuzumab.Patients and methodsTwo hundred and twenty-nine women with HER2/neu (HER2)-overexpressing breast cancer were treated with neoadjuvant chemotherapy plus trastuzumab between 2001 and 2008. Patients were grouped based on pathologic complete response (pCR, n = 114) or less than pCR (<pCR, n = 115); as well as by pathologic stage. Locoregional recurrence-free (LRFS), distant metastasis-free (DMFS), recurrence-free (RFS), and overall survival (OS) rates were compared.ResultsThe median follow-up was 63 (range 53–77) months. There was no difference in clinical stage between patients with pCR or <pCR. Compared with patients achieving <pCR, those with the pCR had higher 5-year rates of LRFS (100% versus 95%, P = 0.011), DMFS (96% versus 80%, P < 0.001), RFS (96% versus 79%, P < 0.001), and OS (95% versus 84%, P = 0.006). Improvements in RFS and OS were seen with decreasing post-treatment stage. Failure to achieve a pCR was the strongest independent predictor of recurrence (hazard ratio [HR] = 4.09, 95% confidence interval [CI]: 1.67–10.04, P = 0.002) and death (HR = 4.15, 95% CI: 1.39–12.38, P = 0.011).ConclusionspCR and lower pathologic stage after neoadjuvant chemotherapy with trastuzumab are the strongest predictors of recurrence and survival and are surrogates of the long-term outcome in patients with HER2-overexpressing disease. 相似文献
6.
Kaufmann M Graf E Jonat W Eiermann W Vescia S Geberth M Conrad B Gademann G Albert US Loibl S von Minckwitz G Schumacher M;German Adjuvant Breast Cancer Study Group 《European journal of cancer (Oxford, England : 1990)》2007,43(16):2351-2358
GABG-IV B-93 is a prospective, randomised study comparing goserelin (n=384) with no further treatment (n=392) in hormone receptor (HR)-negative breast cancer patients (n=465) after 3 cycles cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for patients with 0-3 positive lymph nodes (LN) or 4 cycles epirubicin, cyclophosphamide (EC) followed by 3 cycles CMF for patients with 4-9 positive LN. After completion of the ZEBRA trial the study was amended to enrol also HR-positive patients with 1-9+LN (n=311). After a median follow-up of 4.7 years neither HR-negative nor HR-positive patients showed a benefit for goserelin. The adjusted estimated hazard ratio for event-free survival in HR-negative patients was 1.01 (goserelin versus control, 95% confidence interval [CI] 0.72-1.42, P=0.97) and 0.77 in HR-positive patients (95% CI 0.47-1.24, P=0.27). These results do not support the general use of goserelin after adjuvant chemotherapy in this group of premenopausal patients. 相似文献
7.
《Annals of oncology》2008,19(7):1242-1248
BackgroundThe purpose of this retrospective study was to determine, in a cohort of patients with breast cancer and central nervous system (CNS) metastases, the effect of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive disease and to compare this with that of patients with HER2-negative disease.MethodsFive hundred and ninety-eight patients with invasive breast cancer, CNS metastases and known HER2 status were identified. Time to CNS metastases and survival after CNS metastases were estimated by the Kaplan–Meier method, and Cox models were fitted to determine the association between HER2 status, trastuzumab treatment and outcomes after adjustment for other patient characteristics.ResultsIn the multivariable model, patients with HER2-negative disease [Hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.15–1.95, P = 0.003] and patients with HER2-positive disease who did not receive trastuzumab (HR 2.13, 95% CI 1.51–3.00, P < 0.0001) had shorter times to CNS metastases compared with patients with HER2-positive disease who had received trastuzumab as first-line therapy for metastases. Furthermore, patients with HER2-negative disease (HR 1.66, 95% CI 1.31–2.12, P < 0.0001) and patients with HER2-positive disease who had never received trastuzumab (HR 1.34, 95% CI 0.78–2.30, P = 0.28) had an increased hazard of death compared with patients with HER2-positive disease who had received trastuzumab before or at the time of CNS metastases diagnosis.ConclusionIn our cohort of patients with breast cancer and CNS metastases, patients with HER2-positive disease treated with trastuzumab had longer times to development of and better survival from CNS metastases compared with patients with HER2-positive disease who had never received trastuzumab and patients with HER2-negative breast cancer. 相似文献
8.
《Clinical breast cancer》2022,22(6):611-618
BackgroundHormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status is critical for determining management of breast cancer. Previous reports of small cohorts with weak HR-positive (HR+)/HER2-negative (HER2-) disease showed similar rates of pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) as triple negative breast cancer (TNBC). This study aims to further characterize this group, focusing on pCR rates following NAC.Patients and MethodsPatients with stage I-III, HR+/HER2- breast cancer were identified using the University of Wisconsin Hospital Cancer Registry. Medical records were reviewed for demographics, tumor characteristics with quantification level of estrogen and progesterone receptor (≤33%), treatment, and follow-up data.ResultsData was reviewed from 2,900 patients and a total of 64 patients met inclusion criteria. Eighty percent received chemotherapy, about half with NAC (n = 30, 48%). Of 28 patients who received NAC followed by breast and axillary surgery, 12 (43%; 95% CI 25%-63%) had pCR (ypT0/Tis/ypN0). Of the 11 patients who had biopsyproven nodal disease at diagnosis and NAC followed by axillary surgery, 7 (64%, 95% CI 31%-89%) patients had pCR at the axilla. Only one patient with pCR developed recurrent disease. For those that recurred, median time to recurrence was 13.6 (5.6-48.7) months.ConclusionsBreast cancers that are HER2- and weakly HR+ treated with NAC demonstrated pCR rate more similar to TNBC than breast cancers that are strong HR+. Neoadjuvant approaches may improve pCR rates, which provides important prognostic information. Clinical trials should be developed to focus on this unique patient cohort. 相似文献
9.
Lu Yao Juan Zhang Yiqiang Liu Tao Ouyang Jinfeng Li Tianfeng Wang Zhaoqing Fan Tie Fan Benyao Lin Yuntao Xie 《中国癌症研究》2015,27(6):553-561
Background
We recently showed HER2-positive breast cancers are less likely to respond to neoadjuvant anthracycline chemotherapy. Here, we investigated whether HER2-positive breast cancers responded to sequential neoadjuvant anthracycline followed by paclitaxel plus carboplatin regimen in the absence of trastuzumab.Methods
Women (n=372) with operable primary breast cancer initially received two cycles of neoadjuvant anthracyclines, the clinical tumor response was assessed, then patients were received four cycles of paclitaxel plus carboplatin regimen. All the patients did not received trastuzumab treatment in the neoadjuvant setting. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core-biopsy breast cancer tissue obtained before the neoadjuvant chemotherapy.Results
Eighteen percent (67/372) of patients achieved a pathologic complete response (pCR) in their breast. HER2-positive tumors had a significant higher pCR rate than HER2-negative tumors (33.0% versus 13.5%, P<0.001) in this cohort of 372 patients, and positive HER2 status remained an independent favorable predictor of pCR in a multivariate analysis [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.18 to 4.36, P=0.015]. Furthermore, patients who responded to initial anthracycline regimens were more likely to respond to paclitaxel plus carboplatin than patients who did not (pCR, 27.2% versus 14.6%, P=0.005). Patients with HER2-positive tumors exhibited a significant higher pCR rate than did patients with HER2-negative tumors in both anthracycline response group (40.5% versus 20.0%, P=0.025) and anthracycline non-response group (28.3% versus 11.3%, P=0.002).Conclusions
Under the circumstance of no trastuzumab treatment, women with HER2-positive cancers derive a large benefit from paclitaxel-carboplatin-based neoadjuvant chemotherapy. 相似文献10.
Ines Vaz-Luis Rebecca A Ottesen Melissa E Hughes P Kelly Marcom Beverly Moy Hope S Rugo Richard L Theriault John Wilson Joyce C Niland Jane C Weeks Nancy U Lin 《Breast cancer research : BCR》2012,14(5):1-14
Introduction
In gene expression experiments, hormone receptor (HR)-positive/human epidermal growth factor-2 (HER2)-positive tumors generally cluster within the luminal B subset; whereas HR-negative/HER2-positive tumors reside in the HER2-enriched subset. We investigated whether the clinical behavior of HER2-positive tumors differs by HR status.Methods
We evaluated 3,394 patients who presented to National Comprehensive Cancer Network (NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007. Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive (HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression were used to compare groups.Results
Median follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total) to present with high histologic grade and higher stages (P <0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53, 95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to 2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002). As compared with patients with HR+/HER2+ disease, those with HR-/HER2+ disease had significantly increased hazard of early, but not late, death (hazard ratio of death zero to two years after diagnosis = 1.92, 95% CI: 1.28 to 2.86, P = 0.002, hazard ratio of death two to five years after diagnosis = 1.55, 95% CI: 1.19 to 2.00, P = 0.001; hazard ratio of death more than five years after diagnosis = 0.81, 95% CI: 0.55 to 1.19, P = 0.285, adjusting for age, race/ethnicity, stage at diagnosis, grade and year of diagnosis).Conclusions
Presenting features, patterns of recurrence and survival of HER2-positive breast cancer differed by HR status. These differences should be further explored and integrated in the design of clinical trials. 相似文献11.
Debu Tripathy Peter A. Kaufman Adam M. Brufsky Musa Mayer Marianne Ulcickas Yood Bongin Yoo Cheng Quah Denise Yardley Hope S. Rugo 《The oncologist》2013,18(5):501-510
Background.
Limited data are available describing the natural history of patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer (MBC). We examined first-line treatment patterns and clinical outcomes in patients with HER2-positive, HR-positive MBC in a real-world setting.Methods.
registHER is a prospective, observational cohort of 1,023 patients with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up time: 27 months). Demographics, first-line treatment patterns, and clinical outcomes were examined for 530 HER2-positive, HR-positive patients. Progression-free survival (PFS) and overall survival (OS) times were examined. Multivariate analyses adjusted for baseline demographic and prognostic factors.Results.
HER2-positive, HR-positive patients receiving first-line trastuzumab plus hormonal therapy had significantly longer PFS times than patients who received hormonal therapy only (13.8 vs. 4.8 months; adjusted hazard ratio [HR]: 0.37, 95% confidence interval [CI]: 0.22–0.60); a nonsignificant reduction in OS time was observed (adjusted HR: 0.55, 95% CI: 0.27–1.14). Compared with patients who received first-line trastuzumab plus chemotherapy, patients who received first-line trastuzumab plus chemotherapy and hormonal therapy had longer median PFS times (20.4 months vs. 9.5 months; adjusted HR: 0.53, 95% CI: 0.42–0.68); a statistically significant reduction in risk of death was observed (adjusted HR: 0.50, 95% CI: 0.36–0.70). Sequential use of chemotherapy and hormonal therapy was associated with improved OS times when compared with concurrent use (adjusted PFS HR: 0.81, 95% CI: 0.54–1.21; adjusted OS HR: 0.48, 95% CI: 0.26–0.89).Conclusions.
These real-world data in patients with HER2-positive/HR-positive MBC provide evidence that, with or without chemotherapy, dual targeting of HRs and HER2 receptors is associated with significantly prolonged PFS and OS times. 相似文献12.
Mette S. van Ramshorst Claudette E. Loo Emilie J. Groen Gonneke H. Winter-Warnars Jelle Wesseling Frederieke van Duijnhoven Marie-Jeanne T. Vrancken Peeters Gabe S. Sonke 《Breast cancer research and treatment》2017,164(1):99-106
Background
Neoadjuvant treatment of HER2-positive breast cancer frequently leads to a pathologic complete response (pCR), which is associated with favourable long-term outcome. Treatment regimens typically consist of 6–9 cycles of trastuzumab-based chemotherapy, although many patients achieve early radiologic complete response (rCR). If rCR accurately predicts pCR, the number of chemotherapy cycles can possibly be reduced.Methods
We performed a diagnostic accuracy study to determine the association between rCR and pCR in patients with stage II–III HER2-positive breast cancer treated with neoadjuvant trastuzumab-based chemotherapy at the Netherlands Cancer Institute. RCR was defined as the disappearance of pathologic contrast enhancement in the original tumour region on repeated magnetic resonance imaging (MRI). PCR was defined as the absence of invasive tumour cells in the resected breast specimen (ypT0/is). Diagnostic accuracy was estimated in the overall population and in subgroups based on hormone receptor (HR) status. The prognostic value of rCR for recurrence-free interval was evaluated as an exploratory analysis.Results
We identified 296 eligible patients with 297 HER2-positive tumours (154 HR-negative and 143 HR-positive) treated with neoadjuvant trastuzumab-based chemotherapy between 2004 and 2016. Overall, the rCR rate was 69% (206/297) and the pCR rate was 61% (181/297). Among 206 patients with rCR, 150 also had pCR (negative predictive value [NPV] = 150/206 = 73%). Among 91 patients without rCR, 60 had residual tumour at pathology (positive predictive value [PPV] = 60/91 = 66%). The NPV was better in HR-negative compared to HR-positive tumours (88 vs. 57%), while the PPV was better in HR-positive tumours (50 vs. 78%). Achieving rCR was associated with a 5-year recurrence-free interval of 88% compared to 68% without rCR (hazard ratio 0.34, 95% confidence interval 0.17–0.65, P = 0.001).Conclusion
Achieving rCR corresponds well with pCR in HER2-positive breast cancer, particularly in the HR-negative subgroup. RCR is also associated with improved long-term outcome.13.
Helena R. Chang MD PhD John Glaspy MD MPH Mary Ann Allison MD Frederic C. Kass MD Robert Elashoff PhD Debra U. Chung PharmD Jeffrey Gornbein DrPH 《Cancer》2010,116(18):4227-4237
BACKGROUND:
In this study, the authors evaluated whether a pathologic complete response (pCR) or a clinical complete response (cCR) to neoadjuvant treatment in patients with locally advanced breast cancer differed among the 3 subtypes of breast cancer: triple‐negative breast cancer (TNBC), human epidermal growth factor receptor 2 (HER2)‐positive breast cancer, and hormone receptor‐positive/HER2‐negative breast cancer. Whether a cCR or a pCR was correlated with fewer recurrences and better survival also was investigated.METHODS:
Patients with stage II/III breast cancer received 4 cycles of neoadjuvant docetaxel and carboplatin (TC) every 3 weeks. Patients with HER2‐positive tumors were randomized to receive either additional weekly trastuzumab preoperatively or TC alone. Postoperatively, all patients received 4 cycles of TC, and all HER2‐positive patients received a total of 52 weeks of trastuzumab. The recurrence‐free survival (RFS) and overall survival (OS) rates at 2 years were reported.RESULTS:
Seventy‐four patients were enrolled, including 11 patients with TNBC, 30 patients with HER2‐positive tumors, and 33 patients with hormone receptor‐positive/HER2‐negative tumor. The cCR rates were 45.4%, 50% and 40.6% in TNBC, HER2‐positive, and hormone receptor‐positive/HER2‐negative groups, respectively. The pCR rate for the entire group was 26.8%, and patients with TNBC had the best response (54.6%) followed by patients with HER2‐positive tumors (24.1%) and patients with hormone receptor‐positive/HER2‐negative tumors (19.4%; P = .0126). The pCR rate for patients with HER2‐positive tumors improved from 7% to 40% if trastuzumab was added (P = .08). Infiltrating ductal cancer, TNBC, negative estrogen receptor and/or progesterone receptor status, tumor classification predicted a pCR (P ≤ .05). Multivariate analysis using a logistic regression test indicated that tumor type was an independent predictor. The RFS rate for patients who did versus patients who did not achieve a pCR was 93.8% versus 78.4% at 2 years, respectively, and 83.3% versus 58% at 3 years, respectively (P = .1227); whereas, for patients who did versus patients who did not achieve a cCR, the RFS rate was 80.9% versus 83.9%, respectively, at 2 years and 65% versus 64.3%, respectively, at 3 years (P = .999).CONCLUSIONS:
The current results indicated that the TC combination is promising for the treatment of TNBC. The addition of trastuzumab to TC improved the pCR rate significantly in patients with HER2‐positive breast cancer. Cancer 2010. © 2010 American Cancer Society. 相似文献14.
S Pernas M Gil-Gil MO de Olza A Gumà F Climent A Petit MJ Pla A García-Tejedor A López-Ojeda C Falo A Fernandez-Otega C Mesia FJ Pérez-Martin A Urruticoechea JR Germà 《Breast cancer research and treatment》2012,134(3):1161-1168
One of the most efficacious primary therapies in HER2-positive breast cancer was published by the M.D. Anderson group in 2005. This randomized trial evaluated the addition of trastuzumab to a taxane-anthracycline based chemotherapy. Despite largely significant differences in pathological complete response (pCR) in the trastuzumab group (65 vs. 26?%) this regimen did not become a common standard due to toxicity concerns and its premature closure with a small sample size. In order to evaluate the efficacy and safety of this regimen in an off-trial setting we conducted a prospectively monitorized series of consecutive patients with early or locally advanced Her-2 positive breast cancer following the same treatment strategy. Stage II-IIIC HER2-positive breast cancer patients, including inflammatory disease, were treated with weekly-trastuzumab for 24?weeks administered concurrently with all primary chemotherapy containing paclitaxel (80?mg/m(2)) for 12?weeks and 4 cycles of FEC-75 (fluorouracil 500?mg/m(2), epirubicine 75?mg/m(2), and cyclophosphamide 500?mg/m(2)) followed by surgery. The objectives were efficacy, in terms of pCR in both the breast and lymph nodes, and safety, with close cardiac monitoring during and after treatment. From August 2004 to February 2009, 83 patients were included. Most patients (73.5?%) had node involvement and 13.2?% had inflammatory disease. Fifty-one patients (61.4?%) achieved a pCR in breast and axilla (95?% CI 50-72?%). HR-negative tumors were associated with higher pCR rate than HR-positive tumors (77 vs. 48?%, P?=?0.006). At a median follow-up of 50.2?months no patient developed symptomatic cardiac failure, and 9 patients (10.8?%) presented a transient asymptomatic decrease in left ventricular ejection fraction. Primary therapy with concurrent trastuzumab plus paclitaxel-FEC for HER2-positive breast cancer in everyday practice is highly effective and safe confirming the results observed in a randomized trial stopped prematurely. 相似文献
15.
A Sapino F Montemurro C Marchiò G Viale J Kulka M Donadio A Bottini G Botti A P dei Tos A Bersiga S Di Palma M Truini G Sanna M Aglietta G Bussolati 《Annals of oncology》2007,18(12):1963-1968
BACKGROUND: Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry. We previously showed that BiotHER immunoreactivity is highly correlated with HER2 amplification and indicated that it could be associated with better clinical outcome in advanced breast cancer patients receiving trastuzumab. PATIENTS AND METHODS: Tumor specimens and clinical information from 234 patients who received trastuzumab-based treatments were collected from 10 institutions. HER2 amplification and BiotHER immunoreactivity were assessed centrally. The effect of BiotHER positivity on response rate (RR), time to progression and survival were studied by univariate and multivariate analysis in patients presenting HER2-amplified breast cancer. The pathologic reviews of the assays were blinded to patient outcomes. RESULTS: BiotHER was positive in 109/194 (56%) HER2-amplified breast cancers and in one not amplified tumor. RRs were 74% [95% (confidence interval) CI 64%-81%] and 47% (95% CI 36%-58%) in BiotHER-positive and -negative tumors, respectively (P < 0.001). BiotHER immunoreactivity was independently associated with increased probability of tumor response (odds ratio 3.848; 95% CI 1.952-7.582), with reduced risk of disease progression [hazard ratio (HR) 0.438; 95% CI 0.303-0.633] and with reduced risk of death (HR 0.566; 95% CI 0.368-0.870) by multivariate analysis. CONCLUSION: The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers. 相似文献
16.
《Annals of oncology》2008,19(12):2020-2025
Background: The aim of this study was to compare the extent of pathologic response in patients with HER2-positive (HER2+) breast cancer treated with standard neoadjuvant chemotherapy, with or without trastuzumab (H), according to hormone receptor (HR) status.Patients and methods: We included 199 patients with HER2+ breast cancer from three successive cohorts of neo-adjuvant chemotherapy on the basis of paclitaxel (Taxol) (P) administered weekly (w) or three weekly (3-w), followed by 5-fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). Residual cancer burden (RCB) was determined from pathologic review of the primary tumor and lymph nodes and was classified as pathologic complete response (pCR) or minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) residual disease.Results: In HR-positive (HR+) cancers, a higher rate of pathologic response (pCR/RCB-I) was observed with concurrent H + 3-wP/FEC (73%) than with 3-wP/FEC (34%, P = 0.002) or wP/FAC (47%; P = 0.02) chemotherapy alone. In HR-negative (HR-) cancers, there were no significant differences in the rate of pathologic response (pCR/RCB-I) from 3-wP/FAC (50%), wP/FAC (68%), or concurrent H + 3-wP/FEC (72%).Conclusions: Patients with HR+/HER2+ breast cancer obtained significant benefit from addition of trastuzumab to P/FEC chemotherapy; pathologic response rate was similar to that seen in HR-/HER2+ breast cancers. 相似文献
17.
Bayraktar S Gonzalez-Angulo AM Lei X Buzdar AU Valero V Melhem-Bertrandt A Kuerer HM Hortobagyi GN Sahin AA Meric-Bernstam F 《Cancer》2012,118(9):2385-2393
BACKGROUND:
The aim of this study was to evaluate the pathologic complete response (pCR) rates and relapse‐free survival (RFS) and overall survival (OS) of patients receiving neoadjuvant systemic therapy (NST) with trastuzumab in combination with an anthracycline‐ or nonanthracycline‐based regimen.METHODS:
In this retrospective nonrandomized study, the authors reviewed records of 300 patients with HER2‐positive breast cancer treated with either sequential paclitaxel and trastuzumab and FEC75 in combination with trastuzumab (PH‐FECH) or docetaxel, carboplatin, and trastuzumab (TCH). The Kaplan‐Meier product‐limit method was used to estimate RFS and OS rates. Logistic regression models and Cox proportional hazards models were fit to determine the associations between NST, pCR, and survival.RESULTS:
There was no significant difference in the decline in cardiac ejection fraction; however, patients who received PH‐FECH had fewer cardiac comorbidities at baseline (P = .002). pCR rates were 60.6% and 43.3% for patients who received PH‐FECH (n = 235) and TCH (n = 65), respectively (P = .016). Patients who received PH‐FECH were 1.45 times more likely to have a pCR (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06‐1.98; P = .02). Three‐year RFS rates were 93% and 71% (P < .001), and 3‐year OS rates were 96% and 86% (P = .008) for patients who received PH‐FECH and TCH, respectively. Patients who received PH‐FECH had a lower risk of recurrence (hazard ratio [HR], 0.27; 95% CI, 0.12‐0.60; P = .001) and death (HR, 0.37; 95% CI, 0.12‐1.13; P = .08) than those treated with TCH.CONCLUSIONS:
The type of NST in HER2‐positive breast cancer is predictive of pCR rate independent of disease and patient characteristics. Although TCH is active, PH‐FECH shows a higher pCR rate and RFS advantage. Cancer 2012. © 2011 American Cancer Society. 相似文献18.
《Clinical breast cancer》2019,19(6):e690-e700
Over the past several years, targeted therapy has been increasingly used in the management of breast cancer. Reported results for targeted therapies are variable, as some randomized controlled trials (RCTs) reported a strong effect, whereas others reported no or minimal effect on the outcomes. Accordingly, the present study aimed to assess the effect of the addition of targeted therapies to neoadjuvant chemotherapy on tumor response rates, breast conserving surgeries, and survival outcomes. PubMed and the Cochrane register of clinical trials were searched on April 28, 2017 for RCTs comparing addition of targeted therapies to neoadjuvant chemotherapy. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the screening of records and data extraction were performed by 2 independent reviewers. Publication bias and risk of bias were assessed by the Egger test and the Cochrane tool for risk of bias assessment, respectively. The fixed effect method or random effect method were used to synthesize the results depending on the heterogeneity assessed by the I2 statistic. A total of 17 RCTs including trastuzumab (n = 5), bevacizumab (n = 7), and other targeted therapies (n = 5) were found eligible. Pathologic complete response was significantly higher with trastuzumab (relative risk [RR], 2.20; 95% confidence interval [CI], 1.62-2.99) and bevacizumab (RR, 1.23; 95% CI, 1.11-1.37), but not with other targeted therapies. Bevacizumab for human epidermal growth factor receptor 2 (HER2)-negative breast cancer was found to be associated with improved overall (hazard ratio, 0.69; 95% CI, 0.53-0.90) and disease-free survival (hazard ratio, 0.83; 95% CI, 0.67-1.03). The addition of targeted therapies may not significantly increase breast conserving surgery rates (RR, 1.04; 95% CI, 0.97-1.12). The addition of targeted therapies, especially trastuzumab for patients with HER2-positive breast cancer and bevacizumab for patients with HER2-negative breast cancer significantly increased pathologic complete response, overall response, and clinical complete response but not breast conserving surgery rates. 相似文献
19.
Rashmi K. Murthy Akshara S. Raghavendra Kenneth R. Hess Takeo Fujii Bora Lim Carlos H. Barcenas Hong Zhang Mariana Chavez-Mac-Gregor Elizabeth A. Mittendorf Jennifer K. Litton Sharon H. Giordano Alastair M. Thompson Vicente Valero Stacy L. Moulder Debu Tripathy Naoto T. Ueno 《Clinical breast cancer》2018,18(6):e1283-e1288
Introduction
Several human epidermal growth factor 2 (HER2)-targeted regimens are used to treat HER2-positive (HER2+) breast cancer (BC). The goal of this study was to retrospectively determine the pathologic complete response (pCR) rate for trastuzumab and pertuzumab (HP)-containing regimens compared with trastuzumab (H)-containing regimens for stage II to III HER2+ BC.Patients and Methods
Patients (n = 977) with stage II to III HER2+ BC who received neoadjuvant HER2-targeted therapy from 2005 to 2016 and underwent definitive breast and axillary lymph node surgery were identified. pCR was defined as ypT0/is, ypN0. Univariate/multivariate logistic regression and the χ2 test for comparing proportions was used for the statistical analysis.Results
The pCR rate was higher for the HP group (n = 170) compared with the H group (n = 807): 59% versus 46% (odds ratio, 1.7; 95% confidence interval, 1.21-2.37; P = .0021). After adjustment for clinically important factors (age, date of diagnosis, stage, tumor grade, nodal status, hormone receptor [HR] status, menopausal status, and chemotherapy backbone) the adjusted odds ratio was 2.25 (95% confidence interval, 1.08-4.73; P = .032). In multivariate analysis, a significant predictor of pCR in both groups included HR status (HR-negative > HR-positive).Conclusion
These results demonstrate that HP-containing regimens yield higher pCR rates compared with H-containing regimens in patients with stage II to III HER2+ BC in clinical practice regardless of chemotherapy backbone. 相似文献20.
Rachel L. Theriault Jennifer K. Litton Elizabeth A. Mittendorf Huiqin Chen Funda Meric-Bernstam Mariana Chavez-MacGregor Phuong K. Morrow Wendy A. Woodward Aysegul Sahin Gabriel N. Hortobagyi Ana M. Gonzalez-Angulo 《Clinical breast cancer》2011,11(5):325-331