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This trial demonstrated that the addition of radiation therapy to tomoxifen significantly decreased the rate of local relapse in women 50 years of age or older who had T1 or T2 node-negative breast cancer. 769 women with early breast cancer were randomly assigned to receive breast irradiation plus tamoxifen or tamoxifen alone. As compared with tamoxifen alone, radiotherapy plus tamoxifen significantly reduces the risk of breast and auxiliary recurrence after lumpectomy in women with small, node-negative, hormone-receptor-positive breast cancers.

Background: We used two models to simulate a proposed noninferiority trial of radiotherapy (RT) omission in low-risk invasive breast cancer to illustrate how modeling could be used to predict the trial's outcomes, inform trial design, and contribute to practice debates.Methods: The proposed trial was a prospective randomized trial of no-RT vs RT in women age 40 to 74 years undergoing lumpectomy and endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, stage I breast cancer with an Oncotype DX score of 18 or lower. The primary endpoint was recurrence-free interval (RFI), including locoregional recurrence, distant recurrence, and breast cancer death. Noninferiority required the two-sided 90% confidence interval of the RFI hazard ratio (HR) for no-RT vs RT to be entirely below 1.7. Model inputs included published data. The trial was simulated 1000 times, and results were summarized as percent concluding noninferiority and mean (standard deviation) of hazard ratios for Model GE and Model M, respectively.Results: Noninferiority was demonstrated in 18.0% and 3.7% for the two models. The respective means (SD) of the RFI hazard ratios were 1.8 (0.7) and 2.4 (0.9); most were locoregional recurrences. The mean five-year RFI rates for no-RT vs RT (SD) were 92.7% (2.9%) vs 95.5% (2.2%) and 88.4% (2.0%) vs 94.5% (1.6%). Both models showed little or no difference in breast cancer-specific or overall survival. Alternative definitions of low risk based on combinations of age and grade produced similar results.Conclusions: The proposed trial was unlikely to show noninferiority of omitting radiotherapy even using alternative definitions of low-risk, as the endpoint included local recurrence. Future trials regarding radiotherapy should address absolute reduction in recurrence and impact of type of recurrence on the patient. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy after breast conservation has become the standard of care. Prior meta-analyses on effects of radiotherapy predated availability of gene expression profiling (GEP) to assess recurrence risk and/or did not include all relevant outcomes. This analysis used GEP information with pooled individual-level data to evaluate the impact of omitting radiotherapy on recurrence and mortality.Methods: We considered trials that evaluated or administered radiotherapy after lumpectomy in women with low-risk breast cancer. Women included had undergone lumpectomy and were treated with hormonal therapy for stage I, ER+ and/or PR+, HER2- breast cancer with Oncotype scores no greater than 18. Recurrence-free interval (RFI), type of RFI (locoregional or distant), and breast cancer-specific and overall survival were compared between no radiotherapy and radiotherapy using adjusted Cox models. All statistical tests were two-sided.Results: The final sample included 1778 women from seven trials. Omission of radiotherapy was associated with an overall adjusted hazard ratio of 2.59 (95% confidence interval [CI] = 1.38 to 4.89, P = .003) for RFI. There was a statistically significant increase in any first locoregional recurrence (P = .001), but not distant recurrence events (P = .90), or breast cancer-specific (P = .85) or overall survival (P = .61). Five-year RFI rate was high (93.5% for no radiotherapy vs 97.9% for radiotherapy; absolute reduction = 4.4%, 95% CI = 0.7% to 8.1%, P = .03). The effects of radiotherapy varied across subgroups, with lower RFI rates for those with Oncotype scores of less than 11 (vs 11-18), older (vs younger), and ER+/PR+ status (vs other).Conclusions: Omission of radiotherapy in hormone-sensitive patients with low recurrence risk may lead to a modest increase in locoregional recurrence event rates, but does not appear to increase the rate of distant recurrence or death. [ABSTRACT FROM AUTHOR]

Background: To examine the association between metformin use and mortality in patients with diabetes and cervical cancer. Methods: Using Ontario health databases, a retrospective, population-based cohort study was conducted in women with diabetes ≥age 66 years diagnosed with cervical cancer between 1997 and 2010. The association between metformin exposure and cervical cancer-specific mortality was examined using Fine- Gray regression models, with noncancer death as a competing risk and cumulative metformin use as a time-varying exposure. The association with overall mortality was examined using Cox regression models. Results: Among the 181 women with diabetes and cervical cancer, there were 129 deaths, including 61 cervical cancer-specific deaths. The median follow-up was 5.8 years (interquartile range 4.2-9.6 years) for surviving patients. Cumulative dose of metformin after cervical cancer diagnosis was independently associated with a decreased risk of cervical cancer-specific mortality and overall mortality in a dose-dependent fashion [HR 0.79; 95% confidence interval (CI), 0.63-0.98; and HR 0.95; 95% CI, 0.90-0.996 per each additional 365 g of metformin use, respectively]. There was no significant association between cumulative use of other antidiabetic drugs and cervical cancer-specific mortality. Conclusion: This study suggests an association between cumulative metformin use after cervical cancer diagnosis and lower cervical cancer-specific and overall mortality among older women with diabetes. Impact: Cumulative dose of metformin use after cervical cancer diagnosis among older women with diabetes may be associated with a significant decrease in mortality. This finding has important implications if validated prospectively, as metformin is inexpensive and can be easily combined with standard treatment for cervical cancer. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the optimal recommended program for the follow-up of patients who are disease free after completed primary therapy for cervical cancer. Methods: Systematic search of MEDLINE, EMBASE and the Cochrane Library databases (1980–November 2007). Results: Seventeen retrospective trials were identified. Most studies reported similar intervals for follow-up and ranged from a low of 9 visits to a high of 28 visits over 5 years. Follow-up visits typically occurred once every 3–4 months for the first 2 years, every 6 months for the next 3 years and then annually until year 10. All 17 trials reported that a physical exam was performed at each visit. Vaginal vault cytology was analyzed in 13 trials. Other routine surveillance tests included chest x-ray, ultrasound, CT scans, MRI, intravenous pyelography and tumour markers. Median time to recurrence ranged from 7–36 months after primary treatment. Rates of recurrence ranged from 8–26% with 14–57% of patients recurring in the pelvis, and 15–61% of patients recurring at distant or multiple sites. Of the 8–26% of patients who experienced disease recurrence, the vast majority, 89–99%, had recurred by year 5. Upon recurrence, median survival was 7–17 months. Asymptomatic recurrent disease was detected using physical exam in 29–71%, chest x-ray in 20–47%, CT in 0–34% and vaginal vault cytology in 0–17% of patients, respectively. Conclusion: There is modest low quality evidence to inform the most appropriate follow-up strategy for patients with cervical cancer who are clinically disease free after receiving primary treatment. Follow-up visits should include a complete physical examination whereas, frequent vaginal vault cytology does not add significantly to the detection of early disease recurrence. Patients should return to annual population-based screening after 5 years of recurrence-free follow-up. [Copyright &y& Elsevier]