scholarly journals Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore

2021 ◽  
pp. jmedgenet-2020-107471
Author(s):  
Pei Sze Ng ◽  
Rick ACM Boonen ◽  
Eldarina Wijaya ◽  
Chan Eng Chong ◽  
Milan Sharma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rare Variants ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Population Based ◽  
Breast Cancer Patients ◽  
Dna Double Strand Breaks ◽  
Functional Impact ◽  
Missense Variants ◽  
Increased Risk

BackgroundRare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population.MethodsMutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.ResultsPTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.ConclusionDespite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

Chemotherapy and Cardiotoxicity in Older Breast Cancer Patients: A Population-Based Study

2005 ◽  
Vol 23 (34) ◽  
pp. 8597-8605 ◽  
Author(s):  
John J. Doyle ◽  
Alfred I. Neugut ◽  
Judith S. Jacobson ◽  
Victor R. Grann ◽  
Dawn L. Hershman
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Increased Risk

Purpose Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged ≥ 65 years with long-term follow-up. Patients and Methods In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women ≥ 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. Results Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. Conclusion When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.

scholarly journals Acute Care Use by Breast Cancer Patients on Adjuvant Chemotherapy in Alberta: Demonstrating the Importance of Measurement to Improving Quality

2021 ◽  
Vol 28 (6) ◽  
pp. 4420-4431
Author(s):  
Che Hsuan David Wu ◽  
May Lynn Quan ◽  
Shiying Kong ◽  
Yuan Xu ◽  
Jeffrey Q. Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Acute Care ◽  
Population Based ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Institutional Differences ◽  
Improvement Programs ◽  
Ed Visits

Breast cancer patients receiving adjuvant chemotherapy are at increased risk of acute care use. The incidence of emergency department (ED) visits and hospitalizations (H) have been characterized in other provinces but never in Alberta. We conducted a retrospective population-based cohort study using administrative data of women with stage I-III breast cancer receiving adjuvant chemotherapy. Rates of ED and H use in the 180 days following chemotherapy initiation were determined, and logistic regression was performed to identify risk factors. We found that 47% of women receiving adjuvant chemotherapy experienced ED or H, which compared favourably to other provinces. However, Alberta had the highest rate of febrile neutropenia-related ED visits, and among the highest chemotherapy-related ED visits. The incidence of acute care use increased over time, and there were significant institutional differences despite operating under a single provincial healthcare system. Our study demonstrates the need for systematic measurement and the importance of quality improvement programs to address this gap.

Pregnancy after breast cancer: A population-based study of survival and obstetric outcomes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18783-e18783
Author(s):  
Jose Alejandro Rauh-Hain ◽  
Roni Nitecki ◽  
Alexander Melamed ◽  
Jose Zubizarreta ◽  
Shuangshuang Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Health Planning ◽  
Population Based ◽  
Cox Proportional Hazards Model ◽  
Obstetric Outcomes ◽  
Breast Cancer Patients ◽  
Bipartite Matching ◽  
Increased Risk

e18783 Background: Studies have suggested that pregnancy after breast cancer is safe, but the women who are able to conceive after cancer may also have a better prognosis. We sought to evaluate survival and obstetric outcomes among breast cancer patients in a population-based cohort. Methods: We studied women aged 18-45 years with a history of stage I-III breast cancer reported to the California Cancer Registry (CCR, 2000-2012). CCR data were linked to the 2000-2012 California Office of Statewide Health Planning and Development (OSHPD) birth cohort to ascertain both oncologic characteristics and obstetric outcomes. We compared overall survival (OS) for breast cancer patients who did or did not conceive at least 1 year after diagnosis. Breast cancer patients who conceived were matched in a 1:5 ratio to breast cancer patients who did not conceive via optimal bipartite matching accounting for follow-up time such that controls were diagnosed within a 3-month window of the cases and were alive at the time the case delivered; the distributions of cases and controls were directly balanced on socioeconomic and clinical covariates including stage, hormone receptors, and receipt of chemotherapy and radiation. For the obstetric outcomes, propensity score matching in a 1:5 ratio was used to match the same breast cancer patients who conceived to population based controls without cancer who delivered during the study years. Wald statistics, conditional Cox proportional hazards model, and conditional logistic regressions were used to evaluate outcomes. Results: We matched 417 patients aged 18-45 years at time of breast cancer diagnosis who conceived at least one year following diagnosis with 2,085 breast cancer patients who did not conceive. All covariates were balanced within 0.1 mean standardized difference. The majority of the cohort was non-Hispanic White (51%), with stage II disease (53%). The 5-year overall survival for cases relative to controls was 97.6% and 95.7% respectively. There was no difference in overall survival between patients who conceived and those who did not conceive following treatment for breast cancer (HR 0.58, 95% CI 0.3-1.1). Breast cancer patients did not have higher risks of preterm birth before 37 weeks (odds ratio [OR] 0.91, 95% CI 0.39-2.14), small-for-gestational age birthweight ( < 10th percentile: OR 0.93, 95% CI 0.67-1.29; < 5th percentile: OR 0.67, 95% CI 0.39-1.14), cesarean delivery (OR 1.12, 95% CI 0.92-1.35), severe maternal morbidity (OR 1.14, 95% CI 0.61-2.12), or neonatal morbidity (OR 1.08, 95% CI 0.77-1.53) relative to controls. Conclusions: In a population-based cohort, breast cancer patients who conceived at least 1 year after diagnosis did not have worse OS than matched breast cancer patients who did not conceive. Breast cancer patients who conceived during the study period did not have an increased risk of adverse obstetric outcomes compared to population-based controls without cancer.

scholarly journals 523Use of beta blockers and death from breast cancer in New Zealand breast cancer patients

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Oliver Scott ◽  
Sandar TinTin ◽  
Alana Cavadino ◽  
Mark Elwood
Keyword(s):  
Breast Cancer ◽  
New Zealand ◽  
Beta Blockers ◽  
Cancer Registries ◽  
Population Based ◽  
Breast Cancer Patients ◽  
Short Term ◽  
Breast Cancer Death ◽  
Increased Risk

Abstract Background Beta blockers (BB), used for a range of cardiovascular indications, have been associated with improved, worsened, and unchanged breast cancer outcomes in previous studies. This study examines the association between the use of BBs and death from breast cancer in a large, representative sample of New Zealand women. Methods Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to pharmaceutical data, hospital discharges, and death records. The median follow up time was 4.51 years. Cox proportional hazard models were used to assess the hazard of breast cancer specific death (BCD) associated with post-diagnostic BB use. Results Of the 14,976 women included in analysis, 21% used a BB after diagnosis. Although not significant, beta blocker use increased the risk of BCD (adjusted hazard ratio: 1.08; 95% CI: 0.93-1.26). The increased risk was seen only in those with at least one cardiac condition, and was also reduced by lagging the exposure, suggesting effects of BB use close to the end of life. The increased risk was also confined to short term use (0-3 months). BB use for more than 1 year was associated with a decreased risk of BCD, and the risk steadily decreased to HR 0.53 (95% CI: 0.33-0.85) for use for 3+ years. Conclusions Any increased risk associated with BB use is likely to be due to a combination of confounding by indication and short-term use. Long-term BB use may confer some protection for BCD. Key messages The effect of beta blockers is difficult to separate from the indications for the drug. While there was no significant overall effect, there was a suggestion that beta blockers may be protective for breast cancer death with long-term exposure.

ER, PR & HER2 Receptor status in recurrent breast cancer: Its relation to age & time of recurrence

2020 ◽  
Vol 22 (1) ◽  
pp. 16-20
Author(s):  
Abu Khaled Muhammad Iqbal ◽  
Nasima Akhter ◽  
Hasan Shahrear Ahmed ◽  
Md Rassell ◽  
AMM Yahia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Approach ◽  
Recurrent Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Receptor ◽  
Younger Patients ◽  
Receptor Status ◽  
Increased Risk ◽  
Neoplastic Lesions ◽  
Recurrent Breast

Background: Malignant neoplastic lesions of the breast are one of the main causes of cancer death among women. In tumor cells the expression status of Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers affecting the treatment approach, management and prognosis of breast carcinoma. Objective: To explore the relation of receptor status in recurrent breast cancer to age and time of recurrence. Methods: This study was conducted in National Institute of Cancer Research and Hospital (NICRH) and included 81 female patients between 20 to 75 years with recurrent breast cancer. Detection of receptor status of ER +ve/-ve, PR +ve/-ve, Her-2+ve/-ve was based on the immunohistochemistry staining of tissue samples of malignant neoplastic lesions prepared from tissue biopsies of patients with recurrent breast cancer. All the information were recorded through the pre-structured data collection sheet and analyzed. Results: This study showed that most of the recurrent breast cancer patients were Triple negative breast cancer (TNBC) (39.5%) and among them most of them were younger patients. Younger patients with TNBC had increased risk of recurrence. Most of the recurrence occurred within 1-2 years. Conclusion: It can be concluded that the assessment of the expression of these biornarkers in recurrent tumors provides reliable information for the treatment approach of locoregional tumors. Journal of Surgical Sciences (2018) Vol. 22 (1): 16-20

Antiestrogen use in breast cancer patients reduces the risk of subsequent lung cancer: A population-based study

2017 ◽  
Vol 48 ◽  
pp. 22-28 ◽  
Author(s):  
Sung-Chao Chu ◽  
Chia-Jung Hsieh ◽  
Tso-Fu Wang ◽  
Mun-Kun Hong ◽  
Tang-Yuan Chu
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Cancer Patients ◽  
Population Based ◽  
Breast Cancer Patients ◽  
Population Based Study
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