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Twenty-five year results of the national cancer institute randomized breast conservation trial.

ABSTRACT: Breast conservation therapy (BCT) consisting of lumpectomy and postoperative radiation has become an accepted alternative to mastectomy (MRM) for the treatment of early stage breast cancer. We currently report the 25 year outcomes of a single institution, prospective, randomized clinical trial at the National Cancer Institute. 237 women with pathologically confirmed invasive breast tumors 5 cm or less were accrued between 1979 and 1987 and randomized to receive either BCT or MRM. Overall survival was the primary endpoint. Patients with node positive disease were included and treated with doxorubicin and cyclophosphamide. Both arms received axillary dissection. BCT patients had radiation to the whole breast followed by a boost. At a median follow-up of 25.7 years, overall survival was 43.8% for the MRM group and 37.9% for BCT (P = 0.38). Although the cumulative incidence of a disease-free survival event was higher in BCT patients (29.0% MRM vs. 56.4% BCT, P = 0.0017), the additional treatment failures were primarily isolated ipsilateral breast tumor recurrences (IBTR's) requiring salvage mastectomy. 22.3% of BCT patients experienced an IBTR. Distant disease and second cancers were similar in both arms. After 25 years, long term survival between BCT and MRM continues to be similar in patients treated for early stage breast cancer. Patients receiving BCT may be at risk for additional treatment-related morbidity, which may occur as a late event. Further studies are required to delineate patients at higher risk for these events, and prolonged follow up should be encouraged after treatment for all women.

SUBMITTER: Simone NL

PROVIDER: S-EPMC8369835 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe long-term effects of mobile health (mHealth) interventions have not been documented, especially in resource-constrained settings.ObjectiveThis study aimed to assess the effects of a 1-year mHealth intervention on blood pressure levels and body weight in low-resource urban settings in Peru, 4 years after the completion of the original study.MethodsFour years after the original Grupo de Investigación en Salud Móvil en America Latina (GISMAL) study, we attempted to contact the 212 individuals originally enrolled in the study in Peru. The primary outcomes were systolic and diastolic blood pressure levels and hypertension incidence. Secondary outcome measures were body weight, BMI, and self-reported target behaviors. The study personnel collecting the data were masked to the group assignment. Linear mixed models were used to evaluate the effects of the intervention on primary and secondary outcomes in an intention-to-treat analysis.ResultsData from 164 (77.4%) of the 212 originally enrolled participants were available and analyzed (80 in the intervention group and 84 in the control group). The intervention did not result in changes in systolic (-2.54 mm Hg, 95% CI -8.23 to 3.15) or diastolic (3.41 mm Hg, 95% CI -0.75 to 7.57) blood pressure compared with the control group. The intervention reduced the risk of developing hypertension, but the result was not significant (risk ratio (RR) 0.76, 95% CI 0.45-1.28). However, those who received the intervention had lower body weight (-5.42 kg, 95% CI -10.4 to -0.48) and BMI (-2.56 kg/m2, 95% CI -4.46 to -0.66). In addition, compared to the control participants, those who received ≥50% of the scheduled calls during the intervention had greater reductions in body weight (-6.23 kg, 95% CI -11.47 to -0.99) and BMI (-2.81 kg/m2, 95% CI -4.77 to -0.85).ConclusionsAn mHealth intervention comprising motivational interview calls and SMS text messaging appears to have effects on health 4 years after intervention completion. Although there were no effects on blood pressure levels, important reductions in body weight and BMI were seen 5 years after randomization. Thus, mHealth appears to be a promising preventive strategy for noncommunicable diseases in resource-constrained settings.Trial registrationClinicaltrials.gov NCT01295216; https://clinicaltrials.gov/ct2/show/NCT01295216.

Project description:ImportanceNeoadjuvant systemic therapy (NST) is often administered to enable breast-conserving therapy (BCT) in stages II to III breast cancer.ObjectivesTo prospectively evaluate the role of NST in conversion from BCT ineligibility to BCT eligibility and to assess the association of response to NST, germline BRCA (gBRCA) status, and region of treatment with surgical choice in women with triple-negative breast cancer (TNBC).Design, setting, and participantsThis prespecified secondary analysis of a multicentered, phase 3, double-blind, randomized clinical trial (BrighTNess) enrolled 634 eligible women across 145 centers in 15 countries in North America, Europe, and Asia. Women with operable, clinical stages II to III TNBC who underwent gBRCA mutation testing before initiating NST were eligible to participate. Data were collected from April 1, 2014, to December 8, 2016. This preplanned analysis was performed from January 5, 2018, to October 28, 2019.InterventionsStudy participants were randomized to receive 12 weeks of weekly paclitaxel alone or with the addition of carboplatin and/or veliparib, followed by 4 cycles of doxorubicin hydrochloride and cyclophosphamide.Main outcomes and measuresSurgeons assessed BCT candidacy by clinical and radiographic criteria before and after NST. Surgical choices and whether BCT eligibility was associated with the likelihood of pathologic complete response were then analyzed.ResultsAmong the 634 randomized patients (median age, 51 [range, 22-78] years), pre- and post-NST assessments were available for 604 patients. Of 141 patients deemed BCT ineligible at baseline, 75 (53.2%) converted to BCT eligible. Overall, 342 (68.1%) of 502 patients deemed BCT eligible after NST underwent BCT, including 42 (56.0%) of the 75 who converted to BCT eligible. Patients treated in Europe and Asia were more likely to undergo BCT (odds ratio, 2.66; 95% CI, 1.84-3.84) compared with those treated in North America. Among patients without gBRCA mutation undergoing mastectomy, those treated in North America were more likely to undergo contralateral prophylactic mastectomy (57 of 81 [70.4%] vs 6 of 30 [20.0%]; P < .001). Rates of pathologic complete response were similar between patients deemed BCT eligible at baseline and those who were BCT ineligible but converted to BCT eligibility after NST (55.3 [235 of 425] vs 49.3% [37 of 75]; P = .38).Conclusions and relevanceThis prospective analysis of NST and BCT eligibility in TNBC demonstrates a conversion from BCT ineligibility to BCT eligibility of 53.2%. Lower BCT rates among eligible patients and higher bilateral mastectomy rates among patients without gBRCA mutation in North America merit investigation.Trial registrationClinicalTrials.gov identifier: NCT02032277.

Project description:PurposePrevious studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented.MethodsWomen ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens.ResultsA total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/β estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred.ConclusionAt 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

Project description:CD44 is a transmembrane glycoprotein involved in numerous cellular functions, including cell adhesion and extracellular matrix interactions. It is known to be functionally diverse, with alternative splice variants increasingly implicated as a marker for tumor-initiating stem cells associated with poor prognosis. Here, we evaluate CD44 as a potential marker of long-term breast cancer outcomes. Tissue specimens from patients treated on the National Cancer Institute 79-C-0111 randomized trial of breast conservation versus mastectomy between 1979 and 1987 were collected, and immunohistochemistry was performed using the standard isoform of CD44. Specimens were correlated with patient characteristics and outcomes. Survival analysis was performed using the log rank test. Fifty-one patients had evaluable tumor sections and available long-term clinical follow up data at a median follow up of 25.7 years. Significant predictors of OS were tumor size (median OFS 25.4 years for ≤2 cm vs. 7.5 years for >2 cm, p = 0.001), nodal status (median OS 17.2 years for node-negative patients vs. 6.7 years for node positive patients, p = 0.017), and CD44 expression (median OS 18.9 years for CD44 positive patients vs. 8.6 years for CD44 negative patients, p = 0.049). There was a trend toward increased PFS for patients with CD44 positive tumors (median PFS 17.9 vs. 4.3 years, p = 0.17), but this did not reach statistical significance. These findings illustrate the potential utility of CD44 as a prognostic marker for early stage breast cancer. Subgroup analysis in patients with lymph node involvement revealed CD44 positivity to be most strongly associated with increased survival, suggesting a potential role of CD44 in decision making for axillary management. As there is increasing interest in CD44 as a therapeutic target in ongoing clinical trials, the results of this study suggest additional investigation regarding the role CD44 in breast cancer is warranted.

Project description:ObjectiveTo evaluate the safety and efficacy of golimumab through 5 years in adults with active rheumatoid arthritis (RA) who had not previously received methotrexate (MTX).MethodsIn the GO-BEFORE study, 637 MTX-naive adult patients with active RA were randomized (1:1:1:1) to placebo?+?MTX (group 1), golimumab 100 mg?+?placebo (group 2), golimumab 50 mg?+?MTX (group 3), or golimumab 100 mg?+?MTX (group 4). Inadequate responders in groups 1, 2, and 3 entered early escape at week 28 to golimumab 50 mg?+?MTX, golimumab 100 mg?+?MTX, or golimumab 100 mg?+?MTX, respectively; remaining patients in group 1 could cross over to golimumab 50 mg?+?MTX at week 52. Assessments included the American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) response, the Disease Activity Score in 28 joints (DAS28) using C-reactive protein (CRP) level, and the modified Sharp/van der Heijde score (SHS). Efficacy was analyzed using an intent-to-treat (ITT) analysis. Pharmacokinetics and immunogenicity were evaluated at selected visits.ResultsA total of 422 patients completed golimumab treatment through week 256. At week 256, 72.8%, 54.6%, and 38.0% of all patients in the full ITT population (n?=?637) had an ACR20/50/70 response, respectively; 84.1% had a good or moderate DAS28-CRP response; and 72.7% had a clinically meaningful improvement in physical function. Radiographic progression was minimal in all treatment groups through week 256, and the overall mean change from baseline in SHS was 1.36. Serum trough golimumab concentrations were approximately dose proportional and maintained through week 256. Antibodies to golimumab occurred in 9.6% of patients through week 256. Infections were the most common type of adverse event (AE); 204 of 616 patients (33.1%) had ?1 serious AE.ConclusionClinical efficacy with golimumab treatment was maintained through week 256 of the GO-BEFORE trial of MTX-naive RA patients. No unexpected AEs occurred; safety results through 5 years are consistent with earlier reports.

Project description:PURPOSE:The adoption of hypofractionated whole-breast irradiation (HF-WBI) remains low, in part because of concerns regarding its safety when used with a tumor bed boost or in patients who have received chemotherapy or have large breast size. To address this, we conducted a randomized, multicenter trial to compare conventionally fractionated whole-breast irradiation (CF-WBI; 50 Gy/25 fx + 10 to 14 Gy/5 to 7 fx) with HF-WBI (42.56 Gy/16 fx + 10 to 12.5 Gy/4 to 5 fx). PATIENTS AND METHODS:From 2011 to 2014, 287 women with stage 0 to II breast cancer were randomly assigned to CF-WBI or HF-WBI, stratified by chemotherapy, margin status, cosmesis, and breast size. The trial was designed to test the hypothesis that HF-WBI is not inferior to CF-WBI with regard to the proportion of patients with adverse cosmetic outcome 3 years after radiation, assessed using the Breast Cancer Treatment Outcomes Scale. Secondary outcomes included photographically assessed cosmesis scored by a three-physician panel and local recurrence-free survival. Analyses were intention to treat. RESULTS:A total of 286 patients received the protocol-specified radiation dose, 30% received chemotherapy, and 36.9% had large breast size. Baseline characteristics were well balanced. Median follow-up was 4.1 years. Three-year adverse cosmetic outcome was 5.4% lower with HF-WBI ( Pnoninferiority = .002; absolute risks were 8.2% [n = 8] with HF-WBI v 13.6% [n = 15] with CF-WBI). For those treated with chemotherapy, adverse cosmetic outcome was higher by 4.1% (90% upper confidence limit, 15.0%) with HF-WBI than with CF-WBI; for large breast size, adverse cosmetic outcome was 18.6% lower (90% upper confidence limit, -8.0%) with HF-WBI. Poor or fair photographically assessed cosmesis was noted in 28.8% of CF-WBI patients and 35.4% of HF-WBI patients ( P = .31). Three-year local recurrence-free survival was 99% with both HF-WBI and CF-WBI ( P = .37). CONCLUSION:Three years after WBI followed by a tumor bed boost, outcomes with hypofractionation and conventional fractionation are similar. Tumor bed boost, chemotherapy, and larger breast size do not seem to be strong contraindications to HF-WBI.

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Twenty-five year results of the national cancer institute randomized breast conservation trial.

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