Tumor biology correlates with rates of breastconserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer findings from the ACOSOG Z1071 (alliance) prospective multicenter clinical trial
Boughey J.C.,Mayo Medical School |
McCall L.M.,Duke University |
Ballman K.V.,Alliance Statistics and Data Center |
Mittendorf E.A.,The Surgical Center |
And 6 more authors.
Annals of Surgery | Year: 2014
Objective: To determine the impact of tumor biology on rates of breastconserving surgery and pathologic complete response (pCR) after neoadjuvant chemotherapy. CopyrightBackground: The impact of tumor biology on the rate of breastconserving surgery after neoadjuvant chemotherapy has not been well studied.Methods: We used data from ACOSOG Z1071, a prospective, multicenter study assessing sentinel lymph node surgery after neoadjuvant chemotherapy in patients presenting with nodepositive breast cancer from 2009 through 2011, to determine rates of breastconserving surgery and pCR after chemotherapy by approximated biologic subtype.Results: Of the 756 patients enrolled on Z1071, 694 had findings available from pathologic review of breast and axillary specimens from surgery after chemotherapy. Approximated subtype was triplenegative in 170 (24.5%), human epidermal growth factor receptor 2 (HER2)positive in 207 (29.8%), and hormonereceptorpositive, HER2negative in 317 (45.7%) patients. Patient age, clinical tumor and nodal stage at presentation did not differ across subtypes. Rates of breastconserving surgery were significantly higher in patients with triplenegative (46.8%) and HER2positive tumors (43.0%) than in those with hormonereceptorpositive, HER2negative tumors (34.5%) (P = 0.019). Rates of pCR in both the breast and axilla were 38.2% in triplenegative, 45.4% in HER2positive, and 11.4% in hormonereceptorpositive, HER2negative disease (P 0.0001). Rates of pCR in the breast only and the axilla only exhibited similar differences across tumor subtypes.Conclusions: Patients with triplenegative and HER2positive breast cancers have the highest rates of breastconserving surgery and pCR after neoadjuvant chemotherapy. Patients with these subtypes are most likely to be candidates for less invasive surgical approaches after chemotherapy. © 2014 by Lippincott Williams & Wilkins.
DeMatteo R.P.,Sloan Kettering Cancer Center |
Ballman K.V.,Alliance Statistics and Data Center |
Antonescu C.R.,Sloan Kettering Cancer Center |
Corless C.,Oregon Health And Science University |
And 9 more authors.
Annals of Surgery | Year: 2013
Objective: To conduct the first adjuvant trial of imatinib mesylate for treatment of gastrointestinal stromal tumor (GIST). Background: GIST is the most common sarcoma. Although surgical resection has been the mainstay of therapy for localized, primary GIST, postoperative tumor recurrence is common. The KIT protooncogene or, less frequently, platelet-derived growth factor receptor alpha is mutated in GIST; the gene products of both are inhibited by imatinib mesylate. Methods: This was a phase II, intergroup trial led by the American College of Surgeons Oncology Group, registered at ClinicalTrials.gov as NCT00025246. From September 2001 to September 2003, we accrued 106 patients who had undergone complete gross tumor removal but were deemed at high risk for recurrence. Patients were prescribed imatinib 400 mg per day for 1 year and followed with serial radiologic evaluation. The primary endpoint was overall survival (OS). Results: After a median follow-up of 7.7 years, the 1-, 3-, and 5-year OS rates were 99%, 97%, and 83%, which compared favorably with a historical 5-year OS rate of 35%. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 96%, 60%, and 40%. On univariable analysis, age and mitotic rate were associated with OS. On multivariable analysis, the RFS rate was lower with increasing tumor size, small bowel site, KIT exon 9 mutation, high mitotic rate, and older age. Conclusions: Adjuvant imatinib in patients with primary GIST who are at high risk of recurrence prolongs OS compared with that of historical controls. Optimal duration of adjuvant therapy remains undefined. © 2013 Lippincott Williams & Wilkins.
Boughey J.C.,Mayo Medical School |
Suman V.J.,Alliance Statistics and Data Center |
Mittendorf E.A.,University of Texas M. D. Anderson Cancer Center |
Ahrendt G.M.,University of Pittsburgh |
And 7 more authors.
Annals of Surgery | Year: 2015
Objective: To evaluate factors affecting sentinel lymph node (SLN) identification after neoadjuvant chemotherapy (NAC) in patients with initial nodepositive breast cancer. Background: SLN surgery is increasingly used for nodal staging after NAC and optimal technique for SLN identification is important. Methods: The American College of Surgeons Oncology Group Z1071 prospective trial enrolled clinical T0-4, N1-2, M0 breast cancer patients. After NAC, SLN surgery and axillary lymph node dissection (ALND) were planned. Multivariate logistic regression modeling assessing factors influencing SLN identification was performed. Results: Of 756 patients enrolled, 34 women withdrew, 21 were ineligible, 12 underwent ALND only, and 689 had SLN surgery attempted. At least 1 SLN was identified in 639 patients (92.7%: 95% CI: 90.5%-94.6%). Among factors evaluated, mapping technique was the only factor found to impact SLN identification; with use of blue dye alone increasing the likelihood of failure to identify the SLN relative to using radiolabeled colloid +/- blue dye (P = 0.006; OR = 3.82; 95% CI: 1.47-9.92). The SLN identification rate was 78.6% with blue dye alone; 91.4% with radiolabeled colloid and 93.8% with dual mapping agents. Patient factors (age, body mass index), tumor factors (clinical T or N stage), pathologic nodal response to chemotherapy, site of tracer injection, and length of chemotherapy treatment did not significantly affect the SLN identification rate. Conclusions: The SLN identification rate after NAC was higher when mapping was performed using radiolabeled colloid alone or with blue dye com- pared with blue dye alone. Optimal tracer use is important to ensure successful identification of SLN(s) after NAC. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Sha D.,Molecular Therapeutics |
Sha D.,Shandong University |
Lee A.M.,Molecular Therapeutics |
Shi Q.,Alliance Statistics and Data Center |
And 3 more authors.
Clinical Cancer Research | Year: 2014
Purpose: A let-7 microRNA-complementary site (LCS6) polymorphism in the 3′ untranslated region of the KRAS gene has been shown to disrupt let-7 binding and upregulate KRAS expression. We evaluated the LCS6 genotype and its association with KRAS mutation status, clinicopathologic features, and disease-free survival (DFS) in patients with stage III colon cancer who enrolled in a phase III clinical trial (NCCTG N0147). Experimental Design: The LCS6 genotype was assayed by real-time PCR in DNA extracted from whole blood (n = 2,834) and compared with paired tumor tissue (n = 977). χ2 and two-sample t tests were used to compare baseline factors and KRAS mutation status between patients defined by LCS6 variant status. Log-rank tests and multivariate Cox models assessed associations between LCS6 status and DFS, respectively. Results: We identified 432 (15.2%) blood samples and 143 (14.6%) tumor samples heterozygous or homozygous for the LCS6 G-allele, and 2,402 of 2,834 (84.8%) blood samples and 834 of 977 (85.4%) tumor samples homozygous for the LCS6 T-allele. Genotype results were highly concordant (99.8%) in cases with paired blood and tumor tissue (n = 977). G-allele carriers were significantly more frequent in Caucasians versus other races (χ2 test, P < 0.0001). The LCS6 genotype was not associated with KRAS mutation status, clinicopathologic features (all P > 0.2), or DFS (log-rank P = 0.49; HR, 0.929; 95% confidence interval, 0.76-1.14), even after combining LCS6 genotype with KRAS mutation status. Conclusions: In the largest association study investigating the LCS6 polymorphism in colon cancers, the germline LCS6 genotype was not associated with KRAS mutation status or with clinical outcome in patients with stage III tumors. ©2014 AACR.
Navari R.M.,Indiana University |
Qin R.,Alliance Statistics and Data Center |
Ruddy K.J.,Mayo Medical School |
Liu H.,Alliance Statistics and Data Center |
And 6 more authors.
New England Journal of Medicine | Year: 2016
Background We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (=70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapyinduced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. © 2016 Massachusetts Medical Society.