Anthracycline exposure and breast cancer risk in female Hodgkin lymphoma survivors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12074-12074
Author(s):  
Suzanne I.M. Neppelenbroek ◽  
Yvonne M. Geurts ◽  
Berthe M.P. Aleman ◽  
Cecile P.M. Janus ◽  
Saskia E Rademakers ◽  
...  

12074 Background: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Recently concern has been raised that anthracyclines may also increase BC risk, based on studies in childhood cancer survivors with/without a history of chest RT. So far, the association between anthracyclines and BC risk has not been examined in cancer survivors treated at adolescent/adult ages. Now that RT dose and volumes are decreasing, the potential contribution of anthracyclines to BC risk is an important issue. Methods: We assessed BC risk in a cohort of 2314 female 5-year HL survivors, treated at ages 15-50 years and diagnosed between 1965 and 2008 in 20 Dutch hospitals. Treatment factors were time-dependently included in the analysis, focusing on the effect of anthracycline exposure on BC risk. Results: After a median follow-up of 18.8 years, 258 women developed invasive BC or ductal carcinoma in situ as a subsequent malignancy. The 30-year cumulative incidence was 15.0% (95% Confidence Interval (CI) 12.8-17.4%). Mantle field RT (or other RT involving both axillae) was associated with increased risk of BC (Hazard ratio (HR) 1.9; 95% CI 1.2-2.8) compared to no supradiaphragmatic RT or RT to the neck only (Table 1). Gonadotoxic treatment (>4.2 g/m2 procarbazine or pelvic RT) significantly decreased this risk. In a multivariable analysis, anthracycline exposure was associated with increased BC risk (HR 1.8; 95% CI 1.3-2.5) in patients who received a cumulative dose of >200 mg/m2. Among patients exposed to gonadotoxic treatment, the HR of BC associated with >200mg/m2 anthracyclines was 3.8 (95% CI 2.0-7.2), with a trend for higher risk with higher anthracycline dose (HR 1.58 per 100mg/m2 anthracycline, p<0.001). Conclusions: Our results suggest an association of anthracyclines with BC risk in HL survivors. Also when accounting for the protective effect of gonadotoxic treatment on RT-associated BC risk, anthracyclines significantly contributed to a higher BC risk.[Table: see text]

2018 ◽  
Vol 2 (2) ◽  
Author(s):  
Meghan R Flanagan ◽  
Mei-Tzu C Tang ◽  
Michelle L Baglia ◽  
Peggy L Porter ◽  
Kathleen E Malone ◽  
...  

AbstractBackgroundWomen with ductal carcinoma in situ (DCIS) have an elevated risk of a second breast cancer, but few data are available regarding the impact of modifiable lifestyle factors on this risk.MethodsIn a population-based case–control patient study of women with a history of DCIS in western Washington diagnosed between 1996 and 2013, 497 patients diagnosed with DCIS and a second ipsilateral or contralateral invasive or in situ breast cancer were enrolled. There were 965 matched control patients with one DCIS diagnosis. Associations between anthropometric factors and risk of an invasive or in situ second breast cancer event were evaluated using conditional logistic regression. Statistical tests were two-sided.ResultsObesity (body mass index [BMI] ≥ 30 kg/m2) at initial DCIS diagnosis was associated with a 1.6-fold (95% confidence interval [CI] = 1.2 to 2.2) increased risk of any second breast cancer and a 2.2-fold increased risk of a contralateral second breast cancer (95% CI = 1.4 to 3.3) compared with normal weight women (BMI < 25 kg/m2). BMI and weight, both at initial DCIS diagnosis and at the time of the second breast cancer diagnosis, were positively associated with risk of any second and second invasive breast cancers (odds ratio = 1.01–1.04, all P ≤ .03).ConclusionsAlthough additional confirmatory studies are needed, obesity appears to be an important contributor to the risk of second breast cancers within the growing population of women with DCIS. This has potential clinical relevance with respect to identifying which women with a history of DCIS may require more careful monitoring and who may benefit from lifestyle modifications.


2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 177-177
Author(s):  
Marina De Brot ◽  
Shirin Muhsen ◽  
Victor P. Andrade ◽  
Starr Koslow Mautner ◽  
Melissa Murray ◽  
...  

177 Background: Pleomorphic lobular carcinoma in situ (PLCIS) is an increasingly diagnosed variant of lobular carcinoma in situ. Histologically, it resembles ductal carcinoma in situ (DCIS), leading to controversy over proper management. Yet, the natural history of PLCIS is unknown. Here we describe our experience with PLCIS. Methods: Review of pathology reports (1995–2012) identified 233 cases of LCIS variants. Patients with synchronous ipsilateral DCIS or invasive cancer (IC) were excluded leaving 25 cases for review. Consensus review by 3 pathologists further excluded 7; leaving 18 cases, 12 of which were classified as PLCIS and 6 as LCIS with pleomorphic features (LCIS-PF). (Table) PLCIS was defined by cellular dyshesion, nuclear pleomorphism with a 2-3 fold size variation, conspicuous nucleoli, mitoses and abundant cytoplasm; lesions not meeting all parameters were classified as LCIS-PF. Loss of e-cadherin was confirmed; clinical data were obtained from medical records. Results: Mean patient age at diagnosis of PLCIS/LCIS-PF was 57 yrs (42-67 yrs). All cases presented with imaging abnormalities. A previous history of breast cancer was present in 7/18 (39%) pts (3/7, ipsilateral; 4/7, contralateral). Following PLCIS/LCIS-PF diagnosis, 6/18 (33%) pts underwent mastectomy and 12/18 had excision alone, with (n=3) or without chemoprevention (n=9). Margin status was negative in 4/12 pts; close in 3/12 pts and positive in 5/12 pts undergoing excision. At a median follow-up of 27 mos (2-148 mos), 2/12 pts treated with excision developed ipsilateral breast cancer (1 DCIS; 1 IC). Both had close margins at initial excision; median time to cancer, 54 mos. Conclusions: Pure PLCIS is an uncommon lesion. Synchronous malignancy or prior history of breast cancer are often present in patients with PLCIS, contributing to the difficulty in determining the actual risk conferred by this lesion and appropriate management. Efforts to systematically characterize LCIS variants and prospective documentation of outcomes are needed to clarify the significance of these lesions. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 519-519
Author(s):  
Marc D Ryser ◽  
Laura Hendrix ◽  
Samantha M. Thomas ◽  
Thomas Lynch ◽  
Anne McCarthy ◽  
...  

519 Background: Most women diagnosed with ductal carcinoma in situ (DCIS) undergo surgical resection, potentially leading to overtreatment of patients who would not develop clinically significant breast cancer in the absence of locoregional treatment. We compared the risk of ipsilateral invasive breast cancer (iIBC) between DCIS patients who received breast conserving surgery (BCS) for their index diagnosis of DCIS (BCS group) and patients who did not receive any locoregional treatment within 6 months of diagnosis (surveillance [SV] group). Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-14 was selected from 1,330 Commission on Cancer-accredited facilities (20/site). Excluding patients who received a mastectomy ≤6 months, the final analytic cohort contained 14,245 (88.2%) BCS and 1,914 (11.8%) SV patients. Subsequent breast events were abstracted up to 10 years after diagnosis. Primary outcome was the 8-year absolute difference in iIBC risk between BCS and SV; a subgroup analysis was performed for grade I/II patients. A propensity score (PS) model for treatment was fitted with sampling design (SD) weighting and random effects for patients within facilities. Absolute risk differences were estimated using PS-SD-weighted Kaplan Meier estimators. Results: Overall, median age at diagnosis was 61 years (IQR: 52-69) and median follow-up was 5.8 years (95% CI 5.7-6.1). The majority of patients were Caucasian (81.9%), with estrogen receptor-positive (80.6%), and nuclear grade I/II (54.5%) DCIS. The fraction of patients with a Charlson comorbidity score of ≥2 was higher in SV (14.2%) compared to BCS (6.4%, p < 0.001). The 8-year risk of iIBC was 3.0% (95% CI: 2.4%-3.6%) for BCS and 7.7% (95% CI: 4.9%-10.5%) for SV, with an absolute risk difference of 4.7% (95% CI: 4.5%-4.9%; log-rank p < 0.001). Among patients with grade I/II tumors, the 8-year risk of iIBC was 3.1% (95% CI: 2.3%-4.0%) for BCS and 6.1% (95% CI: 2.5%-9.8%) for SV; difference: 3.0% (95% CI: 2.7%-3.2%; p = 0.005). Conclusions: Despite an increased risk of iIBC in SV patients compared to BCS patients, the 8-year risk did not exceed 10% in either group. The risk of recurrence in BCS patients was comparable to previously reported estimates. These data demonstrate a considerable degree of overtreatment among patients with non-high grade DCIS. Prospective clinical trials will help determine the tradeoffs between universally directed as opposed to selectively applied surgery for low risk DCIS.


2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 57-57
Author(s):  
Melissa Louise Pilewskie ◽  
Cristina Olcese ◽  
Anne Eaton ◽  
Sujata Patil ◽  
Elizabeth Ann Morris ◽  
...  

57 Background: Perioperative MRI is frequently obtained in women with breast cancer; however, studies have not shown decreased rates of re-excision, and some report unnecessary increases in mastectomy rates. We examined LRR rates among women with DCIS who underwent perioperative MRI as compared to those who did not. Methods: All women who underwent breast-conserving surgery for DCIS in 1997-2010 were included from a prospectively maintained database. Patient characteristics and rates of LRR were compared in women with and without an MRI. Univariate and multivariate analyses were performed. Analysis was repeated in the subset of women who did not receive RT. Results: 2,321 cases were identified; 596 had MRI and 1,725 did not. Women who had MRI were younger, more likely to be premenopausal, have a family history of breast cancer, have a clinical presentation, receive RT and endocrine therapy, be treated in later years, and had fewer close/positive margins. At median follow-up of 57 months there were 184 IBTRs; 5-year LRR rates were 8.5% (MRI) and 7.2% (no MRI) (p = 0.52), and 8-year rates were 14.6% and 10.2%, respectively. MRI was not associated with lower LRR rates after adjustment for age, menopausal status, family history, presentation, adjuvant therapy, margin status, number of excisions, and year of surgery in both the entire cohort and in the subgroup who did not receive RT. Select factors from multivariate analysis for patients with all covariates available are shown in the Table. Conclusions: We observed no association between perioperative MRI and LRR rates for patients with DCIS, even when RT was not given. The benefit of perioperative MRI for DCIS remains uncertain. [Table: see text]


2016 ◽  
Vol 34 (9) ◽  
pp. 910-918 ◽  
Author(s):  
Tara O. Henderson ◽  
Chaya S. Moskowitz ◽  
Joanne F. Chou ◽  
Angela R. Bradbury ◽  
Joseph Phillip Neglia ◽  
...  

Purpose Little is known about the breast cancer risk among childhood cancer survivors who did not receive chest radiotherapy. We sought to determine the magnitude of risk and associated risk factors for breast cancer among these women. Patients and Methods We evaluated cumulative breast cancer risk in 3,768 female childhood cancer survivors without a history of chest radiotherapy who were participants in the Childhood Cancer Survivor Study. Results With median follow up of 25.5 years (range, 8 to 39 years), 47 women developed breast cancer at a median age of 38.0 years (range, 22 to 47 years) and median of 24.0 years (range, 10 to 34 years) from primary cancer to breast cancer. A four-fold increased breast cancer risk (standardized incidence ratio [SIR] = 4.0; 95% CI, 3.0 to 5.3) was observed when compared with the general population. Risk was highest among sarcoma and leukemia survivors (SIR = 5.3; 95% CI, 3.6 to 7.8 and SIR = 4.1; 95% CI, 2.4 to 6.9, respectively). By the age of 45 years, the cumulative incidence of breast cancer in sarcoma and leukemia survivors was 5.8% (95% CI, 3.7 to 8.4) and 6.3% (95% CI, 3.0 to 11.3), respectively. No other primary cancer diagnosis was associated with an elevated risk. Alkylators and anthracyclines were associated with an increased breast cancer risk in a dose-dependent manner (P values from test for trend were both < .01). Conclusions Women not exposed to chest radiotherapy who survive childhood sarcoma or leukemia have an increased risk of breast cancer at a young age. The data suggest high-dose alkylator and anthracycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.


2018 ◽  
Vol 2 (1) ◽  
Author(s):  
Polly A Newcomb ◽  
Scott V Adams ◽  
Sophie Mayer ◽  
Michael N Passarelli ◽  
Lesley Tinker ◽  
...  

Abstract Background Postmenopausal bone fracture's have been proposed as a marker of lifetime estrogen exposure and have been associated with decreased risk of breast and endometrial cancer. It is plausible that prediagnostic fractures may be related to survival of estrogen-sensitive cancers. Methods We evaluated a cohort of breast (n = 6411), endometrial (n = 1127), and ovarian (n = 658) cancer cases diagnosed between 1992 and 2010 while participating in the Women’s Health Initiative. Postmenopausal fracture history was assessed from baseline reports of fractures after age 55 years and incident fractures that occurred at least one year prior to cancer diagnosis during study follow-up. Using Cox regression, we compared women with and without a history of fractures with respect to overall and cancer-specific survival. Estimates were adjusted for participant factors, including hormone therapy use; hormone receptor status was not included in our analysis. Results Among women with breast cancer, a history of prediagnostic fractures at any site was associated with poorer overall survival (hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.05 to 1.43). A history of hip, forearm, or spine fractures, or hip fracture alone, was associated with increased risk of mortality (HR = 1.26, 95% CI = 1.01 to 1.58, and HR = 2.05, 95% CI = 1.27 to 3.32, respectively). Fracture history was associated neither with cancer-specific survival among breast cancer survivors, nor with overall or disease-specific mortality among endometrial and ovarian cancer survivors. Conclusions Postmenopausal breast cancer patients with a history of fractures, especially of the hip, are more likely to die of any cause than breast cancer survivors without a fracture history. Identifying and intervening in fracture risk factors should be standard of care for all women diagnosed with breast cancer.


Author(s):  
Samantha L Heller ◽  
Anastasia Plaunova ◽  
Yiming Gao

Abstract Ductal carcinoma in situ (DCIS), breast cancer confined to the milk ducts, is a heterogeneous entity. The question of how and when a case of DCIS will extend beyond the ducts to become invasive breast cancer has implications for both patient prognosis and optimal treatment approaches. The natural history of DCIS has been explored through a variety of methods, from mouse models to biopsy specimen reviews to population-based screening data to modeling studies. This article will review the available evidence regarding progression pathways and will also summarize current trials designed to assess DCIS progression.


2021 ◽  
Author(s):  
Esther H. Lips ◽  
Tapsi Kumar ◽  
Anargyros Megalios ◽  
Lindy L. Visser ◽  
Michael Sheinman ◽  
...  

Pure ductal carcinoma in situ (DCIS) is being diagnosed more frequently through breast screening programmes and is associated with an increased risk of developing invasive breast cancer. We assessed the clonal relatedness of 143 cases of pure DCIS and their subsequent events using a combination of whole exome, targeted and copy number sequencing, supplemented by single cell analysis. Unexpectedly, 18% of all invasive events after DCIS were clonally unrelated to the primary DCIS. Single cell sequencing of selected pairs confirmed our findings. In contrast, synchronous DCIS and invasive disease (n=44) were almost always (93%) clonally related. This challenges the dogma that most invasive events after DCIS represent invasive transformation of the initial DCIS and suggests that DCIS could be an independent risk factor for developing invasive disease as well as a precursor lesion.


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