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 Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report.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.

5-Year Results of Dose-Intensive Sequential Adjuvant Chemotherapy for Women With High-Risk Node-Positive Breast Cancer: A Phase II Study

1999 ◽  
Vol 17 (4) ◽  
pp. 1118-1118 ◽  
Author(s):  
C. Hudis ◽  
M. Fornier ◽  
L. Riccio ◽  
D. Lebwohl ◽  
J. Crown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Pilot Study ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Free Survival ◽  
Dose Dense ◽  
Disease Free

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m2 as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m2 every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.

Long-Term Benefits of 5 Years of Tamoxifen: 10-Year Follow-Up of a Large Randomized Trial in Women at Least 50 Years of Age With Early Breast Cancer

2011 ◽  
Vol 29 (13) ◽  
pp. 1657-1663 ◽  
Author(s):  
Allan Hackshaw ◽  
Michael Roughton ◽  
Sharon Forsyth ◽  
Kathryn Monson ◽  
Krystyna Reczko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Contralateral Breast ◽  
Free Survival ◽  
Free Data ◽  
Cv Disease

Purpose The Cancer Research UK “Over 50s” trial compared 5 and 2 years of tamoxifen in women with early breast cancer. Results are reported after median follow-up of 10 years. Patients and Methods Between 1987 and 1997, 3,449 patients age 50 to 81 years with operable breast cancer who had been taking 20 mg of tamoxifen for 2 years were randomly assigned to either stop or continue for an additional 3 years, if they were alive and recurrence free. Data on recurrences, new tumors, deaths, and cardiovascular events were obtained (April 2010). Results There were 1,103 recurrences, 755 deaths as a result of breast cancer, 621 cardiovascular (CV) events, and 236 deaths as a result of CV events. Fifteen years after starting treatment, for every 100 women who received tamoxifen for 5 years, 5.8 fewer experienced recurrence, compared with those who received tamoxifen for 2 years. The risk of contralateral breast cancer was significantly reduced (hazard ratio, 0.70; 95% CI, 0.48 to 1.00). Among women age 50 to 59 years, there was a 35% reduction in CV events (P = .005) and 59% reduction in death as a result of a CV event (P = .02); in older women, the effect was much smaller and not statistically significant. Conclusion Taking tamoxifen for the recommended 5 years reduces the risk of recurrence or contralateral breast cancer 15 years after starting treatment. It also lowers the risk of CV disease and death as a result of a CV event, particularly among those age 50 to 59 years. Women should therefore be encouraged to complete the full course. Although aromatase inhibitors improve disease-free survival, tamoxifen remains a cheap and highly effective alternative, particularly in developing countries.

Subsequent pregnancy and long-term safety from breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13575-e13575
Author(s):  
Yunyeong Kim ◽  
Minsun Kang ◽  
Jaehun Jung ◽  
Eun Kyung Cho ◽  
Heung Kyu Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Tumor Subtypes ◽  
Study Population ◽  
Disease Free

e13575 Background: Long-term safety of pregnancy after breast cancer still remained controversial, especially according to tumor subtypes. Prior results of other studies have limitations of short follow-up periods or small groups. Methods: We analyzed a population-based retrospective cohort data extracted from a random sample of 50% of women aged between 20 and 60 years who were diagnosed with breast cancer from 2002 to 2017 in the Korean National Health Insurance Service database. Propensity score matching analysis for age and Charlson Comorbidity Index (CCI) variables was performed for pregnant groups and non-pregnant groups with the same type of hormone therapy, chemotherapy and surgery. Study population was categorized to 4 biologic subgroups by the combination of hormone therapy, chemotherapy and target therapy. In this observational study, 1,566 patients with pregnancy after breast cancer were matched (1:2) to 2,462 non-pregnant patients of similar characteristics, adjusting for guaranteed bias. The matched patients were followed up to 7 years, or disease and mortality occurrence after the diagnosis of breast cancer. Survival estimates were calculated using the Kaplan-Meier analysis, groups were compared with the log-rank test. Results: Mean time from diagnosis to pregnancy was 3.4 years in study population. At a follow-up of 7 years after pregnancy, no inferiority in disease-free survival and overall survival was observed in pregnant patients factoring in treatment bias. In sub-analysis according to tumor subtypes, no difference in disease-free survival was observed between pregnant and non-pregnant patients in HR-positive and triple negative subgroup ( p= 0.088, p= 0.048, respectively). Likewise, no overall survival difference was observed in ER-positive patients and triple negative patients ( p= 0.05∼0.73, p= 0.03∼0.09, respectively). Conclusions: Our observational data provides reassuring evidence on long-term safety of pregnancy in young breast cancer patients, regardless of tumor subtypes.

NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer: GBG 69–GeparSepto

2019 ◽  
Vol 37 (25) ◽  
pp. 2226-2234 ◽  
Author(s):  
Michael Untch ◽  
Christian Jackisch ◽  
Andreas Schneeweiss ◽  
Sabine Schmatloch ◽  
Bahriye Aktas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Loading Dose ◽  
Antibody Treatment ◽  
Free Survival ◽  
Disease Free

PURPOSE The GeparSepto trial demonstrated that weekly nanoparticle albumin-bound (NAB)–paclitaxel significantly improves the pathologic complete remission rate compared with weekly solvent-based (sb) paclitaxel followed by epirubicin plus cyclophosphamide as neoadjuvant treatment in patients with primary breast cancer (BC). Here, we report data on long-term outcomes. METHODS Patients with histologically confirmed primary BC were randomly assigned in a 1:1 ratio to 12 times weekly NAB-paclitaxel 150 mg/m2 (after study amendment, 125 mg/m2) or weekly sb-paclitaxel 80 mg/m2 followed in both arms by four times epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks. Patients with human epidermal growth factor receptor 2 (HER2)-positive BC received dual antibody treatment with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) concurrently to chemotherapy and continued for 1 year. RESULTS A total of 1,206 patients started treatment, 606 with NAB-paclitaxel and 600 with sb-paclitaxel. After a median follow-up of 49.6 months (range, 0.5 to 64.0 months), 243 invasive disease–free survival (iDFS) events were reported (143 in the sb-paclitaxel and 100 in the NAB-paclitaxel arm). At 4 years, overall patients treated with NAB-paclitaxel had a significantly better iDFS compared with sb-paclitaxel (84.0% v 76.3%; hazard ratio, 0.66; 95% CI, 0.51 to 0.86; P = .002), whereas overall survival did not significantly differ between the two treatment arms (89.7% v 87.2%, respectively; hazard ratio, 0.82; 95% CI, 0.59 to 1.16; P = .260). Long-term follow-up of the treatment-related peripheral sensory neuropathy (PSN) showed a significant decrease of the median time to resolve PSN after NAB-paclitaxel 125 mg/m2 compared with NAB-paclitaxel 150 mg/m2. CONCLUSION The significantly higher pathologic complete response rate with NAB-paclitaxel translated into a significantly improved iDFS in patients with early BC as compared with sb-paclitaxel. PSN improved much faster under NAB-paclitaxel 125 mg/m2 compared with NAB-paclitaxel 150 mg/m2.

Factors Predicting Long Term Survival after Reduced Intensity Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 326-326
Author(s):  
Charles F. Craddock ◽  
Sudhir Tauro ◽  
Joanne E. Gregory ◽  
Laura Buckley ◽  
Janice Ward ◽  
...  
Keyword(s):  
Older Patients ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Disease Free ◽  
Reduced Intensity

Abstract Allogeneic stem cell transplantation (SCT) performed using a reduced intensity conditioning (RIC) regimen represents an important new treatment modality in older patients with high risk acute myeloid leukaemia (AML) whose outlook with conventional chemotherapy would be poor. However assessment of its role has been hampered by the absence of long term follow-up data. Furthermore factors determining survival after RIC SCT have not been rigorously defined. In order to examine the anti-leukemic activity of RIC allografts in more detail we have examined the outcome of 170 patients with AML transplanted using a uniform conditioning regimen over a ten year period. Long term follow-up data (maximum 119 months) was collected on patients transplanted using a conditioning regimen consisting of fludarabine (30 mg/m2 x 5 days), melphalan 140 mg/m2 x 1 day and alemtuzemab (10 mg x 5 days). The median age of transplanted patients was 54 years (range 18–71). 88 patients were in CR1 at the time of transplant, 63 CR2/3 and 19 had relapsed or refractory disease. Cytogenetic information was available on 149 patients and of these 33 patients had adverse risk and 116 intermediate risk cytogenetics by MRC criteria. 83 transplants were performed using an HLA identical sibling donor and 87 using a volunteer unrelated donor. The 100 day transplant related mortality was 9%. 29% of patients developed Grade II-IV acute GVHD and 22% chronic GVHD. The 3 year overall survival (OS) for the whole group was 48% and 3 year disease free survival (DFS) 45%. 20 patients remain in remission more than five years post-transplant. Survival was significantly influenced by status at transplant (p=0.01), patient age (p= 0.01) and presentation cytogenetics (p=0.05) as determined by multivariate Cox proportional hazards regression. The 3 yr OS for patients transplanted in CR1 or CR2 was 51% and 52% respectively compared to 13% for patients with relapsed/refractory disease. Three year OS for patients with intermediate risk cytogenetics was 52% compared with 34% for adverse risk patients. Three year OS for patients under 60 years was 51% compared with 36% for older patients. This study demonstrates the ability of RIC allografts to deliver encouraging long term disease free survival rates in high risk AML. Pre-transplant characteristics can be used to predict outcome after a RIC allograft and older patients with active disease at the time of transplant or adverse cytogenetics require novel strategies in order to improve long term survival.

The role of C-reactive protein (CRP) as a prognostic biomarker in patients with early breast cancer (EBC) treated with neoadjuvant chemotherapy (NACT).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12545-e12545
Author(s):  
Hans-Christian Kolberg ◽  
Alexandra Edimiris ◽  
Oliver Hoffmann ◽  
Sarah Wetzig ◽  
Mohamed Shaheen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Reactive Protein ◽  
Strong Trend ◽  
Long Term Prognosis ◽  
Disease Free

e12545 Background: C-reactive protein (CRP) is an acute phase reactant influenced by inflammation and tissue damage. It has been demonstrated that elevated CRP levels are associated with poor outcome of cancer including metastatic breast cancer. However, evidence regarding an impact of CRP levels on outcome in early breast cancer (EBC) are missing. Methods: Patients after neoadjuvant chemotherapy (NACT) for EBC and with available data regarding CRP levels before therapy, pathologic complete remission (pCR) and follow-up were included. The association between CRP at baseline and outcome parameters was analyzed. Results: 156 women were included in this analysis, median follow up was 5.8 years. No association between CRP at baseline and pCR rates could be detected. 6.4% of the patients developed a local recurrence, 10.3% developed a distant recurrence and 5.1% died from breast cancer. A negative correlation (Spearman-Rho) between CRP at baseline and overall survival (OS) (Correlation coefficient (CC) -0.255; p = 0.45), disease free survival (DFS)(CC -0.348; p = 0.075), local recurrence free survival (LRFS)(CC -0.245; p = 0.327) and distant disease free survival (DDFS)(CC -0.422; p = 0.057) was not statistically significant, although especially in DFS and DDFS a strong trend was detected. The probability of death from breast cancer was 2% if the CRP was < 0.08 mg/dl and 40% if the CRP was > 2.08 m/dl, this association was highly statistically significant (Chi Square; p < 0.001). These results were independent from age, estrogen and progesterone receptor status, HER2 status and grading. Conclusions: CRP at baseline is not predictive for pCR in EBC after NACT in our patient dataset. However, an association of parameters of long-term prognosis with CRP could be demonstrated. Although the correlations of higher CRP at baseline and shorter OS, DFS, LRFS and DDFS were not significant, a strong trend could be detected that was reproduced in the analysis of different cut-offs for CRP and the probability of breast cancer mortality. Higher CRP-levels are indicating a worse prognosis in early breast cancer after NACT in this retrospective analysis. These results justify further investigation of CRP as a biomarker of long-term prognosis in early breast cancer in prospective trials.

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