Long-term risk of subsequent ipsilateral lesions after surgery with or without radiotherapy for ductal carcinoma in situ of the breast.
18 Aug 2021-British Journal of Cancer (Springer Science and Business Media LLC)-Vol. 125, Iss: 10, pp 1443-1449
TL;DR: In this paper, the impact of Radiotherapy (RT) following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces ipsilateral breast event rates in clinical trials was assessed.
Abstract: BACKGROUND Radiotherapy (RT) following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces ipsilateral breast event rates in clinical trials. This study assessed the impact of DCIS treatment on a 20-year risk of ipsilateral DCIS (iDCIS) and ipsilateral invasive breast cancer (iIBC) in a population-based cohort. METHODS The cohort comprised all women diagnosed with DCIS in the Netherlands during 1989-2004 with follow-up until 2017. Cumulative incidence of iDCIS and iIBC following BCS and BCS + RT were assessed. Associations of DCIS treatment with iDCIS and iIBC risk were estimated in multivariable Cox models. RESULTS The 20-year cumulative incidence of any ipsilateral breast event was 30.6% (95% confidence interval (CI): 28.9-32.6) after BCS compared to 18.2% (95% CI 16.3-20.3) following BCS + RT. Women treated with BCS compared to BCS + RT had higher risk of developing iDCIS and iIBC within 5 years after DCIS diagnosis (for iDCIS: hazard ratio (HR)age < 50 3.2 (95% CI 1.6-6.6); HRage ≥ 50 3.6 (95% CI 2.6-4.8) and for iIBC: HRage<50 2.1 (95% CI 1.4-3.2); HRage ≥ 50 4.3 (95% CI 3.0-6.0)). After 10 years, the risk of iDCIS and iIBC no longer differed for BCS versus BCS + RT (for iDCIS: HRage < 50 0.7 (95% CI 0.3-1.5); HRage ≥ 50 0.7 (95% CI 0.4-1.3) and for iIBC: HRage < 50 0.6 (95% CI 0.4-0.9); HRage ≥ 50 1.2 (95% CI 0.9-1.6)). CONCLUSION RT is associated with lower iDCIS and iIBC risk up to 10 years after BCS, but this effect wanes thereafter.
Citations
More filters
TL;DR: In this paper , X-ray diffraction, scanning electron microscopy and Raman and Fourier transform infrared spectroscopy were used to determine physicochemical and crystallographic properties of type II breast calcifications located in formalin fixed paraffin embedded DCIS breast tissue samples.
Abstract: Ductal carcinoma in situ (DCIS) is frequently associated with breast calcification. This study combines multiple analytical techniques to investigate the heterogeneity of these calcifications at the micrometre scale. X-ray diffraction, scanning electron microscopy and Raman and Fourier-transform infrared spectroscopy were used to determine the physicochemical and crystallographic properties of type II breast calcifications located in formalin fixed paraffin embedded DCIS breast tissue samples. Multiple calcium phosphate phases were identified across the calcifications, distributed in different patterns. Hydroxyapatite was the dominant mineral, with magnesium whitlockite found at the calcification edge. Amorphous calcium phosphate and octacalcium phosphate were also identified close to the calcification edge at the apparent mineral/matrix barrier. Crystallographic features of hydroxyapatite also varied across the calcifications, with higher crystallinity centrally, and highest carbonate substitution at the calcification edge. Protein was also differentially distributed across the calcification and the surrounding soft tissue, with collagen and β-pleated protein features present to differing extents. Combination of analytical techniques in this study was essential to understand the heterogeneity of breast calcifications and how this may link crystallographic and physicochemical properties of calcifications to the surrounding tissue microenvironment.
5 citations
TL;DR: In this article , the authors compared treatment outcomes among breast conserving surgery (BCS), BCS with adjuvant radiotherapy, and total mastectomy (MT) for young ductal carcinoma in situ (DCIS) women.
2 citations
TL;DR: In this paper , a systematic review was conducted to estimate the risk of second primary non-breast cancer among breast cancer patients older than 15 years, and the results showed that women diagnosed with breast cancer before menopause were at higher risk of developing second primary cancer.
Abstract: Objectives The aim of this study was to estimate the extra risk of second primary cancer among breast cancer patients. Methods and materials This is a systematic review. A comprehensive search of literature was performed in PubMed, Web of Science, Cochrane library, and Scopus. The search included all published studies up to October 2022. This systematic review included studies published in the English language that reported the risk of second primary non-breast cancer [i.e., standardized incidence ratio (SIR)] among breast cancer patients older than 15 years. After evaluating the methodological quality of the selected studies, SIRs were pooled with consideration of heterogeneity among studies. The estimates were pooled by age and time since the diagnosis of primary breast cancer for both sexes (male and female). Age was categorized based on before 50 years and after 50 years, and time was categorized as duration of less than and more than 10 years, respectively. Results From 2,484 articles, 30 articles were eligible for inclusion in the systematic review and meta-analysis. The studies varied in terms of population, number of cases, study design, setting, and year of implementation of the research. The estimated SIR for men and women was 1.28 (95% CI: 1.18, 1.38) and 1.27 (95% CI: 1.15, 1.39), respectively. Women diagnosed with breast cancer before menopause [SIR: 1.52 (95% CI: 1.34, 1.71) vs. 1.21 (95% CI: 1.08, 1.34)] as well as women after 10 years since their breast cancer diagnosis [1.33 (95% CI: 1.22, 1.431) vs. 1.24 (95% CI: 1.10, 1.37)] were at a higher risk of developing second primary cancer. Among men, while there were no differences in risk based on age, with the increase of time, the risk of second primary cancer was reduced [SIR: 1.22 (95% CI: 1.12, 1.33) vs. 1.00 (95% CI: 0.79, 1.22)]. Conclusion There is an extra risk of second primary cancer among breast cancer patients. The extra risk should be considered for further screening and preventive measures among this population. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336062, identifier (CRD42022336062).
1 citations
TL;DR: In this paper , the authors explored crystallographic and chemical features of Ductal Carcinoma in-situ (DCIS) microcalcifications to identify unique prognostic biomarkers of invasive progression.
Abstract: Abstract Ductal carcinoma in-situ (DCIS) accounts for 20–25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation.
References
More filters
TL;DR: In this paper, a class of tests developed for comparing the cumulative incidence of a particular type of failure among different groups is presented. The tests are based on comparing weighted averages of the hazards of the subdistribution for the failure type of interest.
Abstract: In this paper, for right censored competing risks data, a class of tests developed for comparing the cumulative incidence of a particular type of failure among different groups. The tests are based on comparing weighted averages of the hazards of the subdistribution for the failure type of interest. Asymptotic results are derived by expressing the statistics in terms of counting processes and using martingale central limit theory. It is proposed that weight functions very similar to those for the $G^p$ tests from ordinary survival analysis be used. Simulation results indicate that the asymptotic distributions provide adequate approximations in moderate sized samples.
4,469 citations
TL;DR: The data show that aneuploid rearrangements occurred early in tumour evolution and remained highly stable as the tumour masses clonally expanded, which has important implications for the diagnosis, therapeutic treatment and evolution of chemoresistance in breast cancer.
Abstract: SUMMARY Sequencing studies of breast tumor cohorts have identified many prevalent mutations, but provide limited insight into the genomic diversity within tumors. Here, we developed a whole-genome and exome single cell sequencing approach called Nuc-Seq that utilizes G2/M nuclei to achieve 91% mean coverage breadth. We applied this method to sequence single normal and tumor nuclei from an estrogen-receptor positive breast cancer and a triple-negative ductal carcinoma. In parallel, we performed single nuclei copy number profiling. Our data show that aneuploid rearrangements occurred early in tumor evolution and remained highly stable as the tumor masses clonally expanded. In contrast, point mutations evolved gradually, generating extensive clonal diversity. Many of the diverse mutations were shown to occur at low frequencies (<10%) in the tumor mass by targeted single-molecule sequencing. Using mathematical modeling we found that the triplenegative tumor cells had an increased mutation rate (13.3X) while the ER+ tumor cells did not. These findings have important implications for the diagnosis, therapeutic treatment and evolution of chemoresistance in breast cancer.
954 citations
TL;DR: Through 8 years of follow-up, findings continue to indicate that lumpectomy plus radiation is more beneficial than Lumpectomy alone for women with localized, mammographically detected DCIS.
Abstract: PURPOSEIn 1993, findings from a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial to evaluate the worth of radiation therapy after lumpectomy concluded that the combination was more beneficial than lumpectomy alone for localized intraductal carcinoma-in-situ (DCIS). This report extends those findings.PATIENTS AND METHODSWomen (N = 818) with localized DCIS were randomly assigned to lumpectomy or lumpectomy plus radiation (50 Gy). Tissue was removed so that resected specimen margins were histologically tumor-free. Mean follow-up time was 90 months (range, 67 to 130). Size and method of tumor detection were determined by central clinical, mammographic, and pathologic assessment. Life-table estimates of event-free survival and survival, average annual rates of occurrence for specific events, relative risks for event-specific end points, and cumulative probability of specific events comprising event-free survival are presented.RESULTSThe benefit of lumpectomy plus radiation was virtually unchan...
802 citations
TL;DR: With long-term follow-up, RT after LE for DCIS continued to reduce the risk of LR, with a 47% reduction at 10 years, and all patient subgroups benefited from RT.
Abstract: Purpose The European Organisation for Research and Treatment of Cancer conducted a randomized trial investigating the role of radiotherapy (RT) after local excision (LE) of ductal carcinoma-in-situ (DCIS) of the breast. We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence (LR) and related to clinical, histologic, and treatment factors.
603 citations
TL;DR: Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% and was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size.
Abstract: Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2 P <.00001), and it was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size. The proportional reduction in ipsilateral breast events was greater in older than in younger women (2P < .0004 for difference between proportional reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years, 10.8% vs 27.8% at ages ≥ 50 years) but did not differ significantly according to any other available factor. Even for women with negative margins and small low-grade tumors, the absolute reduction in the 10-year risk of ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002). After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality.
574 citations