Omitting radiotherapy in women >= 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe

Purpose: The aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET). Patients and Methods: Eligibility criteria were: consecutive patients with age >= 65 years, BCS + sentinel node biopsy, clear margins, unifocal T1N0M0 breast cancer tumor, Elston-Ellis histological grade 1 or 2 and estrogen receptor-positive tumor. After informed consent, adjuvant ET for 5 years was prescribed. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer and overall survival. Results: Between 2006 and 2012, 603 women were included from 14 Swedish centers. Median age was 71.1 years (range 65-90). After a median follow-up of 68 months 16 IBTR (cumulative incidence at five-year follow-up; 1.2%, 95% CI, 0.6% to 2.5%), 6 regional recurrences (one combined with IBTR), 2 distant recurrences (both without IBTR or regional recurrence) and 13 contralateral breast cancers were observed. There were 48 deaths. One death (2.1%) was due to breast cancer and 13 (27.1%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.0% (95% CI, 90.5% to 94.9%). Conclusion: BCS and ET without RT seem to be a safe treatment option in women >= 65 years with early breast cancer and favorable histopathology. The risk of IBTR is comparable to the risk of contralateral breast cancer. Moreover, concurrent morbidity dominates over breast cancer as leading cause of death in this cohort with low-risk breast tumors. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.Peer reviewe

NQO1 expression correlates inversely with NFκB activation in human breast cancer

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Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial

IMPORTANCE Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear. OBJECTIVE To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized (1: 1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m(2)) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries. INTERVENTION Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year. MAIN OUTCOMES AND MEASURES The primary objectivewas DFS; secondary objectives included distant disease-free survival, overall survival, cardiac DFS, and safety. RESULTS In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease-free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m(2) had inferior and those treated with 100 mg/m(2) had similar DFS as patients in the 1-year group. CONCLUSIONS AND RELEVANCE Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study.Peer reviewe

Adjuvant Capecitabine for Early Breast Cancer: 15-Year Overall Survival Results From a Randomized Trial

PURPOSEFew data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer.METHODSThe Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients.RESULTSThe data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5-16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8-16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group. In exploratory subgroup analyses, patients with estrogen receptor–negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF.CONCLUSIONAddition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.</p

Chemosensitivity in Breast Cancer

Breast cancer mortality in Sweden is now in decline, thanks to early detection and the wide use of adjuvant endocrine therapy and chemotherapy. While hormone receptor status is predictive of response to endocrine treatment, there is no clinically useful predictive marker of a patient’s response to chemotherapy. Consequently, patients receive chemotherapy with considerable toxicity but minimal benefit. The aim of this thesis was to investigate a number of methods with the potential to predict response to chemotherapy and thus enhance treatment efficacy in breast cancer patients. We found that topo IIα, the key target enzyme of topo II inhibitors, is significantly expressed in nonproliferating breast cancer cells. This finding may explain why topo II inhibitors are effective in patients with slow growing tumors and a low proliferation rate. Topo IIα gene amplification was suggestive of increased response to anthracyclines in advanced breast cancer, whereas the oncogene HER2 had no predictive value by itself. These findings are in accordance with current knowledge. Cyclin A, a marker of cell proliferation, showed good prognostic value but did not predict response to chemotherapy in advanced breast cancer. In vitro chemosensitivity testing with FMCA predicted tumor response in patients with advanced breast cancer with a sensitivity of 89% and a specificity of 53%. Our results are consistent with the results from similar assays, which predict drug resistance with good accuracy while clinical drug sensitivity is less reliably predicted. The use of FMCA and similar assays is not yet recommended outside clinical trials; their main utility is in preclinical testing of new anti-cancer drugs, including targeted therapies. The combination of epirubicin, capecitabine, and cisplatin (EXC) demonstrated high clinical response rate (74%) and pathological complete response rate (22%) in locally advanced breast cancer, but with cumbersome toxicity. The fluoropyrimidine biomarkers TS, TP, and DPD did not predict response to the EXC regimen

Sector Resection With or Without Postoperative Radiotherapy for Stage I Breast Cancer:20-Year Results of a Randomized Trial

Purpose To investigate how radiotherapy (XRT) adds to tumor control using a standardized surgical technique with meticulous control of surgical margins in a randomized trial with 20 years of follow-up. Patients and Methods Three hundred eighty-one women with pT1N0 breast cancer were randomly assigned to sector resection with (XRT group) or without (non-XRT group) postoperative radiotherapy to the breast. With follow-up through 2010, we estimated cumulative proportion of recurrence, breast cancer death, and all-cause mortality. Results The cumulative probability of a first breast cancer event of any type after 20 years was 30.9% in the XRT group and 45.1% in the non-XRT group (hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.82). The benefit of radiotherapy was achieved within the first 5 years. After 20 years, 50.4% of the women in the XRT group died compared with 54.0% in the non-XRT group (HR, 0.92; 95% CI, 0.71 to 1.19). The cumulative probability of contralateral cancer or death as a result of cancer other than breast cancer was 27.1% in the XRT group and 24.9% in the non-XRT group (HR, 1.17; 95% CI, 0.77 to 1.77). In an anticipated low-risk group, the cumulative incidence of first breast cancer of any type was 24.8% in the XRT group and 36.1% in the non-XRT group (HR, 0.61; 95% CI, 0.35 to 1.07). Conclusion Radiotherapy protects against recurrences during the first 5 years of follow-up, indicating that XRT mainly eradicates undetected cancer foci present at primary treatment. The similar rate of recurrences beyond 5 years in the two groups indicates that late recurrences are new tumors. There are subgroups with clinically relevant differences in risk. </jats:sec

TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer

The purpose of this study was to evaluate amplification of topoisomerase IIalpha (TOP2A) and HER2 genes as predictors of response to chemotherapy in advanced breast cancer. Gene copy number of TOP2A and HER2 were analysed with chromogenic in situ hybridization (CISH) on paraffin-embedded tissue sections from the primary tumour of 85 patients treated with anthracycline containing chemotherapy. TOP2A gene amplification was present in 14 (16%) and HER2 gene amplification in 38 (45%) of the primary tumours. Two of the 14 cases with TOP2A amplification were amplified without concurrent HER2 amplification. Neither TOP2A nor HER2 gene amplification were significantly associated with response to chemotherapy (p = 0.35 and p = 0.49, respectively)

Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer

Although adjuvant polychemotherapy improves outcomes for early breast cancer, the significant variability in terms of pharmacokinetics results in differences in efficacy and both short and long-term toxicities. Retrospective studies support the use of dose tailoring according to the hematologic nadirs. The SBG 2004-1 trial was a randomized feasibility phase II study which assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC regimen (group C). Women aged 18-65 years, ECOG PS 0-1 with at least one positive axillary lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term toxicity have been previously published. Here, we report safety and efficacy data after 10 years of follow-up. A total of 124 patients were included in the study. After a median follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and 63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C, respectively. There were no cases of clinically diagnosed cardiotoxicity or hematologic malignancies. No patient was lost to follow-up. In this randomized phase II trial, tailored dose adjuvant chemotherapy was feasible, without an increased risk for long-term adverse events after a median follow-up of 10 years