Fluorouracil, Doxorubicin, and Cyclophosphamide (FAC) Versus FAC Followed by Weekly Paclitaxel As Adjuvant Therapy for High-Risk, Node-Negative Breast Cancer: Results From the GEICAM/2003-02 Study

2013 ◽  
Vol 31 (20) ◽  
pp. 2593-2599 ◽  
Author(s):  
Miguel Martín ◽  
Amparo Ruiz ◽  
Manuel Ruiz Borrego ◽  
Agustí Barnadas ◽  
Sonia González ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Sensory Neuropathy ◽  
Weekly Paclitaxel ◽  
Node Negative ◽  
Primary Surgery ◽  
Disease Free

Purpose Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established. Patients and Methods Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival. Results After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio [HR], 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%). Conclusion For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.

scholarly journals Adding pertuzumab to adjuvant therapy for high-risk HER2-positive early breast cancer in APHINITY: a GRADE analysis

2020 ◽  
Vol 9 (6) ◽  
pp. 423-430 ◽  
Author(s):  
Alberto Zambelli ◽  
Giovanni Pappagallo ◽  
Paolo Marchetti
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Distant Relapse ◽  
Disease Free

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population.

Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer Patients With Tumors not Expressing Estrogen Receptors

2000 ◽  
Vol 18 (3) ◽  
pp. 584-584 ◽  
Author(s):  
Marco Colleoni ◽  
Marco Bonetti ◽  
Alan S. Coates ◽  
Monica Castiglione-Gertsch ◽  
Richard D. Gelber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Early Initiation ◽  
Study Group ◽  
Free Survival ◽  
Primary Surgery ◽  
Premenopausal Patients ◽  
Disease Free

PURPOSE: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose tumors did not express any estrogen receptor (ER). PATIENTS AND METHODS: We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years. RESULTS: Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.33 to 0.72; P = .0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P = .019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER (1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P = .40). CONCLUSION: In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant.

Overview of randomized perioperative polychemotherapy trials in women with early-stage breast cancer.

1997 ◽  
Vol 15 (7) ◽  
pp. 2526-2535 ◽  
Author(s):  
P C Clahsen ◽  
C J van de Velde ◽  
A Goldhirsch ◽  
J Rossbach ◽  
M R Sertoli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Node Negative ◽  
Disease Free

PURPOSE To determine whether perioperative polychemotherapy (PeCT) can significantly prolong the overall survival of women with early-stage breast cancer. METHODS A meta-analysis that used updated individual patient data from all available randomized trials of PeCT, both published and unpublished, was conducted. Data on 6,093 patients (1,124 deaths and 1,912 recurrences) from five clinical trials were available (median follow-up duration, 5.3 years; maximum, 11.3 years). RESULTS No significant effect of PeCT on overall survival was observed. However, patients who received PeCT had a significantly longer disease-free survival (hazards ratio [HR], 0.89; 95% confidence interval [CI], 0.82 to 0.98; P = .02). Time to local recurrence was significantly prolonged in the PeCT arm (HR, 0.68; 95% CI, 0.58 to 0.80; P < .0001). Likewise, there was a borderline significant difference in favor of PeCT in terms of time to distant metastases (HR, 0.90; 95% CI, 0.81 to 1.00; P = .05). Subgroup analyses suggest that node-negative women benefited the most from treatment. CONCLUSION At present, there is no evidence that PeCT is able to prolong overall survival in patients with early-stage breast cancer; however, further follow-up evaluation is required. PeCT significantly prolongs disease-free survival, especially in node-negative women, which emphasizes once more the need for clinical trials in this subgroup.

Phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of adagloxad simolenin (OBI-822) and OBI-821 treatment in patients with early-stage triple-negative breast cancer (TNBC) at high risk for recurrence.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS599-TPS599
Author(s):  
Hope S. Rugo ◽  
Louis W. C. Chow ◽  
Javier Cortes ◽  
Peter A. Fasching ◽  
Pei Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
High Risk ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Invasive Disease ◽  
Free Survival ◽  
Disease Free

TPS599 Background: Adagloxad simolenin (AS) is a therapeutic vaccine comprising the tumor-associated antigen Globo H linked to the carrier protein keyhole limpet hemocyanin (KLH). The KLH provides antigenic immune recognition and T-cell responses. AS is co-administered with a saponin-based adjuvant OBI-821 to induce a humoral response. A phase 2 trial showed that AS/OBI-821 exhibited a trend for superior progression-free survival vs placebo in patients whose breast cancers have higher Globo H expression. Methods: Patients with TNBC (ER/PR < 5%, and HER2-negative) with nonmetastatic disease and either 1) residual invasive disease of ≥1 cm in the breast or ≥1 positive axillary node following neoadjuvant chemotherapy or 2) ≥4 axillary lymph nodes with invasive carcinoma treated with adjuvant chemotherapy are included. Patients are prescreened for Globo H expression using a validated IHC assay (H-score of ≥15). Patients will receive either AS (30 μg) with OBI-821 (100 μg) or volume-matched placebo (1:1), administered as SC injections. Up to 21 SC injections of study treatment (or placebo), will be administered over 100 weeks, given on the following schedule: weekly for 4 doses; every 2 weeks for 4 doses; every 4 weeks for 4 doses; and then every 8 weeks for 9 doses. Patients may terminate treatment due to disease recurrence or unacceptable toxicity, withdrawal of consent, protocol violation, loss to follow-up or death. The primary objective is to determine the effect of AS/OBI-821 treatment on invasive disease-free survival in patients with TNBC at high risk for recurrence. Secondary objectives are to determine the impact of AS/OBI-821 treatment on overall survival, quality of life (QoL), breast cancer-free interval, distant disease-free survival, safety, and tolerability. Imaging and clinical examination will be performed regularly for 5 years. QoL will be assessed using the EORTC Core Quality of Life Questionnaire (QLQ)-C30 plus the EORTC Breast Cancer-specific QLQ-BR23 questionnaire and the European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire. Adverse events will be graded/recorded as per National Cancer Institute CTCAE v5.0. An estimated 668 subjects will be enrolled, treated for up to 2 years and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last subject randomized. Survival follow-up is for 5 years from randomization of last subject. Clinical trial information: NTC03562637 .

Long-Term Survival Outcomes of Patients with Small (≤ 1 Centimetre) Node-Negative HER2-Positive Breast Cancer Not Treated with Adjuvant Anti-HER2-Targeted Therapy: A 10-Year Follow-Up Study

Breast Care ◽  
2021 ◽  
Author(s):  
Jenni S. Liikanen ◽  
Marjut Leidenius ◽  
Heikki Joensuu ◽  
Tuomo J. Meretoja
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Disease Free Survival ◽  
Survival Outcomes ◽  
Her2 Expression ◽  
Term Survival ◽  
Node Negative ◽  
Her2 Breast Cancer

Introduction Human epidermal growth factor receptor 2 (HER2) expression is considered an unfavourable prognostic factor in early breast cancer when the patients are not treated with HER2-targeted therapy. However, the long-term prognostic importance of HER2-expression in small (≤1 cm, stage pT1a-b), node-negative HER2+ breast cancer is still incompletely known. Methods A retrospective analysis was performed based on a prospectively collected database including patients with pT1 breast cancer operated at the Helsinki University Hospital, Finland, between March 2000 and April 2006. In this database, 44 patients with pT1a-bN0M0, HER2+ cancer, not treated with adjuvant anti-HER2-targeted therapy (the HER2+ group) and 291 pT1a-bN0M0, hormone receptor positive, HER2- negative cancers (the ER+/HER2- group) were identified and included in the study. Survival outcomes were analysed using the Kaplan-Meier method. Results The median follow-up time was 9.7 years after primary breast surgery. Ten-year distant disease-free survival (DDFS) was 84.0% in the HER2+ group and 98.2% in the ER+/HER2- group (p < 0.001). Ten-year overall survival was only 78.5% in the HER2+ group, but 91.7% in the ER+/HER2- group (p = 0.09). Conclusions Cancer HER2-status is strongly associated with unfavourable DDFS during the first decade of follow-up in patients with small (pT1a-bN0M0) breast cancer when adjuvant anti-HER2-targeted treatment is not administered.

scholarly journals Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

2019 ◽  
Vol 37 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Thomas Ruhstaller ◽  
Anita Giobbie-Hurder ◽  
Marco Colleoni ◽  
Maj-Britt Jensen ◽  
Bent Ejlertsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Luminal Breast Cancer ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Disease Free

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

Use of tamoxifen for breast cancer: twenty-eight years later.

1995 ◽  
Vol 13 (2) ◽  
pp. 513-529 ◽  
Author(s):  
I A Jaiyesimi ◽  
A U Buzdar ◽  
D A Decker ◽  
G N Hortobagyi
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Postmenopausal Women ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Hormonal Treatment ◽  
Er Positive ◽  
Disease Free ◽  
Prevention Of Breast Cancer

PURPOSE The mechanisms of antitumor activity, clinical pharmacology, toxicity, and efficacy of tamoxifen in women with early and advanced breast cancer and the drug's potential role in prevention of breast cancer were reviewed. DESIGN A comprehensive review of the literature from 1966 to 1994 was conducted; reports were identified using the Cancerline and Medline data bases. RESULTS The cellular actions of tamoxifen are not completely understood, but it appears that the drug's antiproliferative effects are mediated primarily by inhibition of the activities of estrogen through binding to estrogen receptors (ERs). Disease-free and overall survival rates have been increased in postmenopausal women with ER-positive tumors when tamoxifen has been used as adjuvant therapy (irrespective of nodal status). In premenopausal women, adjuvant therapy with tamoxifen has been associated with prolongation of disease-free survival, but its impact on survival remains to be defined. Tamoxifen is the initial hormonal treatment of choice in both premenopausal and postmenopausal women with ER-positive metastatic disease. Retrospective review of adjuvant therapy studies showed an approximately 39% reduction in the incidence of contralateral primary breast carcinoma in tamoxifen-treated women, which indicates that tamoxifen could have a role in breast cancer prevention. CONCLUSION The use of tamoxifen has resulted in a substantial modification of breast cancer's natural history, particularly in postmenopausal women. Ongoing clinical trials will examine the effects of tamoxifen therapy on lipids, coagulation proteins, bone, and endometrium, and its effectiveness as an agent in the prevention of breast cancer.

Time Trends in Systemic Adjuvant Treatment for Node-Negative Breast Cancer

1999 ◽  
Vol 17 (5) ◽  
pp. 1458-1458 ◽  
Author(s):  
Nicole Hébert-Croteau ◽  
Jacques Brisson ◽  
Jean Latreille ◽  
Gilles Gariépy ◽  
Caty Blanchette ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Adjuvant Treatment ◽  
Minimal Risk ◽  
Node Negative ◽  
Risk Of Recurrence ◽  
Consensus Recommendations ◽  
Node Negative Breast Cancer ◽  
Systemic Adjuvant Therapy

PURPOSE: We conducted a population-based study in Quebec, Canada, to assess longitudinal changes in systemic adjuvant therapy for node-negative breast cancer. MATERIALS AND METHODS: A stratified random sample was selected among women with newly diagnosed node-negative breast cancer in 1988, 1991, and 1993. Information on the patient, her tumor, source of care, and treatment was abstracted from medical charts. Patients were classified as being at minimal, moderate, or high risk of recurrence on the basis of criteria proposed at the 4th International Conference on Adjuvant Therapy of Primary Breast Cancer (St. Gallen, Switzerland, 1992), and systemic adjuvant treatment received was dichotomized as being consistent or not consistent with consensus recommendations. RESULTS: Overall, 1,578 cases of invasive breast carcinoma were reviewed. The proportion of patients who were given hormonal or cytotoxic treatment increased from 51.7% to 73.1% from 1988 to 1993. Virtually all women at minimal risk were treated in 1991 and 1993 according to the consensus statement. The proportions of women so treated were 75.0% and 65.4% in the moderate- and high-risk categories, respectively, in 1991. In 1993, these proportions were 71.4% and 67.0%, respectively. Omission of chemotherapy, especially in high-risk women with estrogen receptor–negative tumors who were 50 to 69 years of age, was the most frequent inconsistency with guidelines. CONCLUSION: Systemic adjuvant therapy for node-negative breast cancer has gained acceptance. Better understanding of the decision-making process, of the perception of the risks and benefits involved, and of the impact of alternative strategies for the dissemination of consensus recommendations are needed to promote the use of chemotherapy in specific categories of women who are at high risk of recurrence.

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