Adjuvant randomized trials of doxorubicin/cyclophosphamide versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer.

1993 ◽  
Vol 11 (3) ◽  
pp. 454-460 ◽  
Author(s):  
M Kaufmann ◽  
W Jonat ◽  
U Abel ◽  
J Hilfrich ◽  
H Caffier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Trials ◽  
Disease Free Survival ◽  
Good Prognosis ◽  
Low Risk ◽  
Lower Probability ◽  
Node Positive ◽  
Risk Patients ◽  
To Receive ◽  
Positive Breast Cancer

PURPOSE We report two randomized trials of adjuvant systemic therapy in 747 patients < or = 65 years of age with histologically proven node-positive breast cancer. PATIENTS AND METHODS Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] i.v., eight cycles every 3 weeks) and the same chemotherapy plus Tam was made. RESULTS Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women < or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients > or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (< or = 49, > or = 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients < or = 49 years as well. However, the addition of Tam to AC in women age > or 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone. CONCLUSION Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk-adapted subsets of node-negative and node-positive patients.

Does Locoregional Radiation Therapy Improve Survival in Breast Cancer? A Meta-Analysis

2000 ◽  
Vol 18 (6) ◽  
pp. 1220-1229 ◽  
Author(s):  
Timothy J. Whelan ◽  
Jim Julian ◽  
Jim Wright ◽  
Alejandro R. Jadad ◽  
Mark L. Levine
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Systemic Therapy ◽  
Odds Ratio ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Radical Mastectomy ◽  
Node Positive ◽  
Meta Analyses ◽  
Positive Breast Cancer

PURPOSE: Recent randomized trials in women with node-positive breast cancer who received systemic treatment report that locoregional radiation therapy improves survival. Previous trials failed to detect a difference in survival that results from its use. A systematic review of randomized trials that examine the effectiveness of locoregional radiation therapy in patients treated by definitive surgery and adjuvant systemic therapy was conducted. METHODS: Randomized trials published between 1967 and 1999 were identified through MEDLINE database, CancerLit database, and reference lists of relevant articles. Relevant data was abstracted. The results of randomized trials were pooled using meta-analyses to estimate the effect of treatment on any recurrence, locoregional recurrence, and mortality. RESULTS: Eighteen trials that involved a total of 6,367 patients were identified. Most trials included both pre- and postmenopausal women with node-positive breast cancer treated with modified radical mastectomy. The type of systemic therapy received, sites irradiated, techniques used, and doses of radiation delivered varied between trials. Data on toxicity were infrequently reported. Radiation was shown to reduce the risk of any recurrence (odds ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.83), local recurrence (odds ratio, 0.25; 95% CI, 0.19 to 0.34), and mortality (odds ratio, 0.83; 95% CI, 0.74 to 0.94). CONCLUSION: Locoregional radiation after surgery in patients treated with systemic therapy reduced mortality. Several questions remain on how these results should be translated into current-day clinical practice.

Adjuvant CAF versus AC followed by paclitaxel for operable breast cancer with 4 or more involved axillary lymph nodes: Retrospective analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10610-10610
Author(s):  
J. Ahn ◽  
S. Kim ◽  
B. Son ◽  
S. Ahn ◽  
W. Kim
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Node Positive ◽  
Axillary Nodes ◽  
Significant Difference ◽  
Positive Breast Cancer

10610 Background: Recently, adjuvant AC followed by paclitaxel has improved disease-free survival (DFS) or overall survival (OS) of node-positive breast cancer. Although adjuvant TAC, as compared with FAC, significantly improves DFS and OS rate in node-positive breast cancer, AC→T has not been yet compared with FAC. Since 2001, we discussed the options of adjuvant CAF versus AC→T with patients who had 4 or more positive axillary nodes. We evaluated the efficacies of adjuvant CAF and AC→T, retrospectively. Methods: Between September 2001 and July 2004, a total of 1,394 patients underwent surgery and received adjuvant chemotherapy. Among them, 253 (18.1%) patients had 4 or more than axillary nodes and received either six cycles of CAF (n = 116) or 4 cycles of AC→T) (n = 137). The medical records and pathologic data of these patients were reviewed, retrospectively. Results: Median age of all patients was 46 years (range, 22∼76 years). The two groups were well balanced in terms of demographic and tumor characteristics. With a median follow-up period of 24 months (range, 6∼90 months), 49 (19.4%) patients had disease recurrence including 27 (23.3%) in CAF group and 22 (16.1%) in AC→T group (p = 0.155). The 3 year-DFS rate was 68.3% in CAF group and 71.1% in AC→T group (p = 0.9366), and the estimated 3-year OS rate was 90.3% and 92.3%, respectively (p = 0.8237). There was no significant difference in 3-year DFS rate according to hormone-receptor status. Febrile neutropenia occurred in 11 (9.6%) patients in CAF group and 7 (5.1%) patients in AC→T group (p = 0.222). Conclusion: Our data suggest that there is no significant difference in DFS or OS rates between six cycles of CAF and 4 cycles of AC followed by 4 cycles of paclitaxel as adjuvant chemotherapy in patients with 4 or more than involved axillary nodes. However, long-term follow-up period and prospective studies are needed to define better regimen. No significant financial relationships to disclose.

The prognostic value of nodal ratios in node-positive breast cancer: AUBMC experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21072-21072
Author(s):  
A. Shamseddine ◽  
H. Hatoum ◽  
Z. Salem ◽  
Z. Abdel Khalek ◽  
N. El Saghir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Axillary Lymph Node ◽  
Disease Free Survival ◽  
Axillary Lymph ◽  
Node Positive ◽  
The Impact ◽  
Positive Breast Cancer

21072 Background: Axillary lymph node metastasis has proven to be the most important factor affecting overall survival (OS) and disease free survival (DFS) in patients with breast cancer. Recent evidence suggests that axillary lymph node ratio (LNR) may be at least as important as absolute number of involved lymph nodes in predicting OS and DFS. The aim of this retrospective study is to evaluate the impact of axillary nodal ratios in node-positive breast cancer as a prognostic factor for survival. Methods: Data from 1181 patients with stage I, II and III breast cancer diagnosed at AUBMC between 1990 and 2001 were studied. The median age at diagnosis was 50 years (23 - 88); the median number of lymph nodes dissected was 17 (0 - 49). Survival was compared in 737 patients with node-positive disease according to a LNR below or more than 0.25 (defined as number of involved lymph nodes divided by total dissected axillary lymph nodes). Results: Patients with LNR = 0.25 had a median follow-up of 30 months (1.2–156) and a median DFS of 26 months (1–156). The 5-year survival was 26.2% (94/358) and the 5-year DFS was 22.9% (82/358). Patients with LNR <0.25 had a median follow-up of 36 months (1.2–157) and a median DFS of 36 months (1–157). The 5-year survival of 33.2% (245/737) and the 5-year DFS was 29.8 % (220/737). LNR showed significance as a continuous variable and a categorical variable (0, < 0.25, and = 0.25) with a p < 0.001 Conclusions: LNR significantly predicts OS and DFS in node-positive primary breast cancer. No significant financial relationships to disclose.

Oncotype DX DCIS use and clinical utility: A SEER population-based study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12046-e12046 ◽  
Author(s):  
Yao Yuan ◽  
Alison Len Van Dyke ◽  
Allison W. Kurian ◽  
Serban Negoita ◽  
Valentina I. Petkov
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Risk Group ◽  
Low Risk ◽  
Cancer Data ◽  
Gene Assay ◽  
Risk Patients ◽  
To Receive ◽  
In Situ Breast Cancer

e12046 Background: OncotypeDX DCIS is a 12-gene assay designed to predict the 10-year risk of local recurrence and to guide treatment decisions, specifically the benefit of radiation therapy in breast ductal carcinoma in situ (DCIS). The test became available in December 2011 and is not currently recommended by guidelines. The Surveillance, Epidemiology and End Results (SEER) program captures cancer data at the population-level and has been conducting annual linkages with Genomic Health Clinical Laboratory, the only lab performing the test, to identify patients receiving the test. Methods: SEER cases diagnosed with in situ breast cancer (DCIS or papillary in situ) between 2011-2015 were included in the analysis. SEER data on patient demographics, tumor characteristics, and treatments were combined with linkage variables for OncotypeDX DCIS tests reported by Genomic Health. Logistic regression was used to identify which patient related factors were associated with having received the test and to evaluate the relationship between test generated risk categories and treatments. Results: Of the 68,826 in situ breast cancer cases, 2,155 were linked to DCIS test data. Test utilization increased from < 1% to 5.3% for patients diagnosed in 2011 vs. 2015. Patients were less likely to receive the test if they had larger and higher-grade tumors, were divorced, had Medicaid insurance, and were in the lowest socioeconomic status tertile. The majority of patients (68%) were at low risk, 17% intermediate, and 15% in the high risk group. Patients at intermediate or high risk were more likely to receive radiation (OR = 2.4, 95% CI: 1.8-3.2 and OR = 3, 95% CI: 2.3,4.1, respectively) than the low risk group. High risk patients were more likely than low risk patients to receive chemotherapy (OR = 4.3, 95% CI: 1.2, 14.4) and to undergo mastectomy than lumpectomy (OR = 1.47, 95% CI: 1.12-1.93). Conclusions: Clinical adoption of the OncotypeDX DCIS test has been slow. The association between multiple demographic factors and receiving the test indicated disparities in the US population. Clinical factors also influenced whether patients received the test. OncotypeDX DCIS results appeared to guide clinical decisions.

scholarly journals Internal Mammary Node Irradiation in Node-Positive Breast Cancer Treated with Mastectomy and Taxane-Based Chemotherapy

2021 ◽  
Author(s):  
Won Kyung Cho ◽  
Jee Suk Chang ◽  
Seung Gyu Park ◽  
Nalee Kim ◽  
Doo Ho Choi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Locoregional Recurrence ◽  
Disease Free Survival ◽  
Internal Mammary Node ◽  
Free Survival ◽  
Node Positive ◽  
Internal Mammary ◽  
Positive Breast Cancer

Abstract Purpose: It is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy.Methods and Materials: We analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received adjuvant radiotherapy with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups.Results: After a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220-0.962). In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; p = 0.021) and OS (HR 0.233, p = 0.018).Conclusions: IMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy radiation therapy, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.

Adjuvant Clodronate Treatment Does Not Reduce the Frequency of Skeletal Metastases in Node-Positive Breast Cancer Patients: 5-Year Results of a Randomized Controlled Trial

2001 ◽  
Vol 19 (1) ◽  
pp. 10-17 ◽  
Author(s):  
Tiina Saarto ◽  
Carl Blomqvist ◽  
Pekka Virkkunen ◽  
Inkeri Elomaa
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Skeletal Metastases ◽  
Breast Cancer Patients ◽  
Control Groups ◽  
Node Positive ◽  
Final Population ◽  
Positive Breast Cancer

PURPOSE: Bisphosphonates have effectively reduced the development and progression of bone metastases in advanced breast cancer. The aim of this study was to determine whether bone metastases could be prevented by adjuvant clodronate treatment in patients with primary breast cancer. PATIENTS AND METHODS: Between 1990 and 1993, 299 women with primary node-positive breast cancer were randomized to clodronate (n = 149) or control groups (n = 150). Clodronate 1,600 mg daily was given orally for 3 years. All patients received adjuvant therapy: premenopausal six cycles of CMF chemotherapy and postmenopausal antiestrogens (randomized to tamoxifen 20 mg or toremifene 60 mg/d for 3 years). Seventeen patients were excluded from the analyses because of major protocol violations. The final population was 282 patients. Intent-to-treat analyses were also performed for all major end points. The follow-up time was 5 years for all patients. RESULTS: Bone metastases were detected equally often in the clodronate and control groups: 29 patients (21%) versus 24 patients (17%) (P = .27). The development of nonskeletal recurrence was significantly higher in the clodronate group compared with controls: 60 patients (43%) versus 36 patients (25%) (P = .0007). The overall survival (OS) and disease-free survival (DFS) rates were also significantly lower in the clodronate group than in the controls (OS, 70% v 83%, P = .009; DFS, 56% v 71%, P = .007, respectively). In multivariate analyses, clodronate remained significantly associated with DFS (P = .009). CONCLUSION: Adjuvant clodronate treatment does not prevent the development of bone metastases in node-positive breast cancer patients. However, clodronate seems to have a negative effect on DFS by increasing the development of nonskeletal metastases.

scholarly journals Real-world adjuvant TAC or FEC-D for HER2-negative node-positive breast cancer in women less than 50 years of age

2016 ◽  
Vol 23 (3) ◽  
pp. 164 ◽  
Author(s):  
S. Lupichuk ◽  
D. Tilley ◽  
X. Kostaras ◽  
A.A. Joy
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Granulocyte Colony Stimulating Factor ◽  
Free Survival ◽  
Node Positive ◽  
Patient Groups ◽  
Stimulating Factor ◽  
Disease Free ◽  
Positive Breast Cancer

Purpose We compared the efficacy, toxicity, and use of granulocyte colony–stimulating factor (G-CSF) with TAC (docetaxel–doxorubicin–cyclophosphamide) and FEC-D (5-fluorouracil–epirubicin–cyclophosphamide followed by docetaxel) in women less than 50 years of age.Methods The study included all women more than 18 years but less than 50 years of age with her2-negative, node-positive, stage II or III breast cancer diagnosed in Alberta between 2008 and 2012 who received TAC (n = 198) or FEC-D (n = 274).Results The patient groups were well-balanced, except that radiotherapy use was higher in the TAC group (91.9% vs. 79.9%, p < 0.001). At a median follow-up of 49.6 months, disease-free survival was 91.4% for TAC and 92.0% for FEC-D (p = 0.76). Overall survival (OS) was 96% with TAC and 95.3% with FEC-D (p = 0.86).The incidences of grades 3 and 4 toxicities were similar in the two groups (all p > 0.05). Overall, febrile neutropenia (FN) was reported in 11.6% of TAC patients and 15.7% of FEC-D patients (p = 0.26). However, use of G-CSF was higher in the TAC group than in the FEC-D group (96.4% vs. 71.5%, p < 0.001). Hospitalization for FN was required in 10.5% of TAC patients and 13.0% of FEC-D patients (p = 0.41). In G-CSF–supported and –unsupported patients receiving tac, FN occurred at rates of 11.1% and 33.3% respectively (p = 0.08); in patients receiving the FEC portion of FEC-D, those proportions were 2.9% and 8.1% respectively (p = 0.24); and in patients receiving docetaxel after FEC, the proportions were 4.1% and 17.6% respectively (p < 0.001).Conclusions In women less than 50 years of age receiving adjuvant TAC or FEC-D, we observed no differences in efficacy or other nonhematologic toxicities. Based on the timing and rates of FN, use of prophylactic G-CSF should be routine for the docetaxel-containing portion of treatment; however, prophylactic G-CSF could potentially be avoided during the FEC portion of FEC-D treatment.

Prognostic and predictive value of topoisomerase II alpha in a randomized trial comparing CMF to CEF in premenopausal women with node positive breast cancer (NCIC CTG MA.5)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 533-533 ◽  
Author(s):  
F. P. O’Malley ◽  
S. Chia ◽  
D. Tu ◽  
L. E. Shepherd ◽  
M. N. Levine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Topoisomerase Ii ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Topoisomerase Ii Alpha ◽  
Cancer Society ◽  
Global Test ◽  
Node Positive ◽  
Her 2 ◽  
Positive Breast Cancer

533 Background: It has been suggested that Topoisomerase II alpha (TOP2A) status rather than Her-2/neu status may predict response to anthracycline chemotherapy in breast cancer. Methods: In MA.5, 710 premenopausal women with node positive breast cancer were randomized to receive adjuvant CEF (epirubicin 60 mg/m2 & 5-FU 500 mg/m2 both IV, days 1 & 8, and cyclophosphamide 75 mg/m2 p.o. days 1 through 14); vs CMF (methotrexate 40 mg/m2 & 5-FU 600 mg/m2 both IV days 1 & 8 and cyclophosphamide 100 mg/m2 p.o. days 1 through 14), all for six 28-day cycles. Tissue microarrays (TMAs) were constructed from paraffin embedded specimens from 447 (63%) of these patients. TOP2A was measured by fluorescence-in-situ hybridization (FISH), classifying tumors into 3 groups by TOP2A/CEP 17 ratios: amplified (Amp) if ratio ≥2; deleted (Del) if ratio < 0.8; normal (N) if ratio 0.8 to 2. Cox models assessed interaction between treatment and TOP2A, adjusting for age, nodal status, ER, HER-2/neu status, grade, surgery and tumor size. Results: Thirty-one patients (6.9%) had tumours with Del TOP2A; 53 (11.9%) with Amp TOP2A; and 353 (81.2%) with N TOP2A. 5-year disease-free survival (DFS) was 48%, 51%, and 61% for patients with Del, Amp and N TOP2A respectively (p=0.22 adjusted global test). 5-year overall survival (OS) was 55%, 61% & 75% for patients with Del, Amp, and N TOP2A (p=0.67 adjusted global test). HRs for DFS and OS by treatment and TOP2A are presented in the table . Conclusions: TOP2A status was a significant predictive factor for benefit from CEF treatment for OS. Although there was a trend for TOP2A status predicting improved DFS with CEF, the test for interaction was not significant. In adjusted analysis TOP2A did not reach significance as a prognostic factor for DFS or OS. (This study was supported by the Canadian Breast Cancer Research Alliance (CBCRA), the National Cancer Institute of Canada (NCIC) and the Canadian Cancer Society.) [Table: see text] [Table: see text]

APHINITY trial (BIG 4-11): A randomized comparison of chemotherapy (C) plus trastuzumab (T) plus placebo (Pla) versus chemotherapy plus trastuzumab (T) plus pertuzumab (P) as adjuvant therapy in patients (pts) with HER2-positive early breast cancer (EBC).

2017 ◽  
Vol 35 (18_suppl) ◽  
pp. LBA500-LBA500 ◽  
Author(s):  
Gunter Von Minckwitz ◽  
Marion Jennifer Procter ◽  
Evandro De Azambuja ◽  
Dimitrios Zardavas ◽  
Adam Knott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Node Positive ◽  
Big 4 ◽  
Node Positive Disease ◽  
Grade 3 ◽  
One Year ◽  
To Receive

LBA500 Background: In previous trials P significantly prolonged progression free and overall survival and increased pCR rates when added to T+C in pts with HER2-positive breast cancer (BC). The APHINITY trial was designed to test whether the addition of P to adjuvant T+C improves pt outcomes. Methods: Pts with adequately excised HER2-positive, pT1-3 EBC were randomly assigned to receive standard adjuvant C plus one year of either T + P or T + Pla. Eligible pts had either node-positive disease, or node-negative disease (pN0) and a tumor size of > 1.0 cm. Pts with pN0, T1b tumors with high risk features were initially eligible. The primary efficacy endpoint was invasive disease-free survival (IDFS); we assumed a 3-year IDFS of 91.8% with P and 89,.2% with Pla. Results: 4805 pts were randomized to C and T plus either P (n = 2400) or Pla (n = 2405). Baseline demographics and tumor characteristics between the arms were well balanced, with 63% and 36% of pts having node-positive and hormone receptor negative EBC respectively. P and Pla treatments were completed in 84.5% and 87.4% of patients, respectively. IDFS events occurred in 171 (7.1%) P pts and 210 (8.7%) Pla pts (hazard ratio (HR) 0.81 (95% CI 0.68-1.00), P = 0.045). Estimates of IDFS at 3 years were 94.1% and 93.2% in the P and Pla arms, respectively. The node-positive cohort had a 3-year IDFS rate of 92.0% for P compared with 90.2% for Pla (HR 0.77 (95% CI 0.62-0.96), P = 0.019). The pN0 cohort had a 3-year IDFS rate of 97.5% for P and 98.4% for Pla; HR = 1.13 (95% CI 0.68-1.86). The safety profile of P was consistent with previous trials. For the primary cardiac endpoint (heart failure or cardiac death) and secondary cardiac endpoint (asymptomatic or mildly symptomatic LVEF decline) rates were low, 0.7% vs 0.3% and 2.7% vs 2.8%, in the P and Pla arms, respectively. Diarrhea grade ≥3 was more frequent with P (9.9% vs 3.7%). Conclusions: The APHINITY trial met its primary endpoint: P significantly improved IDFS in patients with HER2-positive EBC when added to T+C. No new safety signals were identified. Clinical trial information: NCT01358877.

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