Outcomes after adjuvant radiotherapy in breast cancer patients with and without germline mutations: A large, single-institutional experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1502-1502
Author(s):  
Bhavana Sree Vangara Chapman ◽  
Diane D. Liu ◽  
Shane Richard Stecklein ◽  
Angelica Gutierrez Barrera ◽  
Wendy A. Woodward ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Chest Wall ◽  
Adjuvant Radiotherapy ◽  
De Novo ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Pathogenic Variant ◽  
Increased Risk

1502 Background: Women with germline mutations in DNA repair pathways are at an increased risk of developing breast cancer. We posit that tumors arising in these patients may be more sensitive to radiotherapy and, therefore, patients may experience improved locoregional control and survival outcomes following adjuvant radiotherapy as compared to patients without DNA repair pathway mutations. Methods: We evaluated the records of 2,221 women with stage 0-III de novo primary breast cancer treated with surgery and adjuvant radiotherapy who all underwent genetic testing at our institution from 1993 to 2018. Mutations were categorized as pathogenic variant, variant of unknown significance (VUS), or negative. The Kaplan-Meier method was used to estimate the locoregional recurrence rate (LRR), rate of distant metastasis (DM), disease-free survival (DSS), and overall survival (OS) from the time of surgery. Results: The median age at diagnosis was 45 years (range 19-84). Median follow-up time was 7 years (95% confidence interval 6.6-7.4). Among 1,960 patients with evaluable radiation records, 752 (38.4%) received breast only radiation, 12 (0.6%) received chest wall only radiation, and 1,196 (61.0%) received breast/chest wall and regional nodal radiation. A total of 255 (11.4%) and 162 (7.3%) patients had a pathogenic variant mutation and a VUS only, respectively. Pathogenic variant and VUS in BRCA1/2 mutations were detected in 216 (9.7%) and 82 (3.7%) patients, respectively. Perturbations in ATM, CHEK2, MLH, MSH2/6, MUTYH, PALB2, RAD50/51, and/or TP53 were detected in 71% (85/119) of patients who tested positive for a non- BRCA1/2 pathogenic variant or VUS. On univariate analysis, there was no significant association between BRCA1/2 mutation status or any genetic mutation and rate of LRR or DM, DSS, or OS ( p > 0.10 for all). Clinicopathological features including advanced stage and lymphovascular invasion were associated with higher cumulative incidence of LRR and DM as well as shorter DFS and OS ( p < 0.01 for all). Conclusions: Herein we report on the largest cohort of women with breast cancer treated with adjuvant radiotherapy at a single institution who have undergone germline testing. Our findings suggest that the overall prognosis of breast cancer treated with adjuvant radiotherapy in patients with germline BRCA1/2 or other genetic predisposition is similar to patients with sporadic breast cancer. Further investigation to evaluate acute or late toxicities and secondary cancers as a result of radiotherapy is warranted.

Breast cancer prognosis in BRCA1/2  mutation carriers: A case control study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1554-1554
Author(s):  
Grazia Arpino ◽  
Matilde Pensabene ◽  
Valeria Forestieri ◽  
Caterina Condello ◽  
Maria Anna Sarno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Germ Line ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Radical Mastectomy ◽  
Cancer Prognosis ◽  
Histologic Subtype ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of

1554 Background: We evaluated the clinical impact of germ-line BRCA1/2 mutations and variants of unknown clinical significance (VUS) for BRCA1/2 in patients (pts) with early breast cancer (BC). Methods: Twenty-eight BRCA-positive (BRCA+) BC pts with germ-line BRCA1 /2 mutations and 16 VUS BC pts were selected from our database and matched (1:3) with 154 nonhereditary BC controls (sporadic controls, SC, defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. Clinical characteristics, recurrence (rec) pattern, disease free survival (DFS) and overall survival (OS) were analyzed. Results: Compared with VUS and SC, BRCA+ pts were less likely to express estrogen receptor (64% vs. 89% vs. 54% respectively p<.005) and progesterone receptor (64% vs. 86% vs. 59% respectively p<.005) but more likely to be triple negative (0 vs. 3.4% vs 47.4% respectively p<.005). Compared with VUS and SC, BRCA+ pts were more likely treated by radical mastectomy (37.5% vs. 26.4% vs. 59.3% % respectively p<.005). Pattern of rec was also different. Compared with VUS and SC, BRAC+ pts developed more second tumors (11% vs. 6.3% vs. 1.9% respectively p<.0001) but less local or distant rec (31% vs. 2.6 vs. 0% for local rec and 12% vs. 16% vs. 11% for distant rec respectively p<.0001). Controlateral BC was more frequent in VUS compared to the BRAC+ and SC pts (12% vs. 7% vs. 1% respectively, p<.0001). At a median follow up of 88 months, at univariate analysis, BRAC+ but not VUS pts had worse OS compared to SC (p=.006). No difference in DFS was observed for VUS or BRAC+ when compared to SC pts. After adjustment for age, stage, grade, nodal status, hormone receptors, adjuvant therapy and year of diagnosis, BRCA+ pts continued to have and increased risk of death compared to SC (HR 5.9, 95% CI 1.9-18.1, p<.002). Most of the deaths observed in BRAC+ pts were not cancer related. Conclusions: Despite decrease incidence of local or distant recs, BRAC+ pts seems to be more likely to die compared to SC. Development of second cancers and unknown effects of BRCA1/2 mutations on nonneoplastic diseases that cause death may account for this findings.

Co-expression of ER-beta and HER2 associated with poorer prognosis in primary breast cancer

2009 ◽  
Vol 32 (3) ◽  
pp. 250 ◽  
Author(s):  
Wen-sheng Qui ◽  
Lu Yue ◽  
Ai-ping Ding ◽  
Jian Sun ◽  
Yang Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Differentiation ◽  
Primary Breast Cancer ◽  
Tumour Size ◽  
Univariate Analysis ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Er Alpha

Purpose: To assess the prognostic value of co-expression of estrogen receptor (ER)-beta and human epidermal growth factor receptor 2 (HER2) in primary breast cancer patients in China. Methods: Tumour specimens from 308 patients undergoing surgery for primary breast cancer were evaluated. Expression of ER-beta and HER-2 was investigated by the immunohistochemistry. Results: 123 patients (40%) were ER-beta positive and 58 (18.5 %) were HER2 positive. Among the 58 HER2 positive patients, 44 were ER-beta positive and 14 were ER-beta negative. ER-beta positive was associated with HER2 positive (75.9%, P=0.018) as well as ER-alpha positive (79.7%, P=0.023), poor cell differentiation (77.2% grade 2 or 3, P=0.010) and menopause age < 45 yr (55.3%, P=0.031). HER2 positive was associated with poor cell differentiation (93.1%, P=0.001), ?3cm tumour size (67.2%, P=0.011). Conclusion: Both ER-beta positive and HER2 positive status was associated with poorer overall survival (OS) by univariate analysis. In both HER2 positive and HER2 negative subgroups, ER-beta positive was associated with poorer distant disease free survival (DDFS) but not OS, which implied that ER-beta might relate to metastasis in breast cancer.

scholarly journals Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Solene De Talhouet ◽  
Julien Peron ◽  
Aurelie Vuilleumier ◽  
Alex Friedlaender ◽  
Valeria Viassolo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Brca1 And Brca2 ◽  
Free Survival ◽  
Entire Cohort ◽  
Dna Damaging Agents ◽  
Impact On Survival ◽  
Brca1 Brca2 ◽  
Brca1 And Brca2 Mutations

Abstract BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents. There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 mutation, and 659 were non-carriers. In the entire cohort, there was a prolonged disease-free survival (DFS) for BRCA carriers (hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.44–0.90 for BRCA1; HR = 0.72; 95%CI, 0.47–1.1 for BRCA2; p = 0.020) and a trend toward prolonged disease-specific survival (DSS; HR = 0.65; 95%CI, 0.40–1.1 for BRCA1; HR = 0.78; 95%CI, 0.44–1.38 for BRCA2; p = 0.19) though not statistically significant. In the TNBC group, BRCA carriers had prolonged DFS (adjusted HR = 0.50; 95%CI, 0.28–0.89 for BRCA1; adjusted HR = 0.37; 95%CI, 0.11–1.25, for BRCA2; p = 0.034) and DSS (adjusted HR = 0.42; 95%CI, 0.21–0.82 for BRCA1; adjusted HR = 0.45; 95%CI, 0.11–1.9 for BRCA2; p = 0.023). In the non-TNBC group, the BRCA1 or BRCA2 mutations did not have any impact on survival. These results suggest that BRCA1/BRCA2 germline mutations are associated with prolonged survival only if women were diagnosed with TNBC.

scholarly journals Comparison between male and female breast cancer survival using propensity score matching analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Serena Scomersi ◽  
Fabiola Giudici ◽  
Giuseppe Cacciatore ◽  
Pasquale Losurdo ◽  
Stefano Fracon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Cancer Survival ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Female Breast Cancer ◽  
Lymph Node Status ◽  
Propensity Score Matching Analysis

AbstractMale breast cancer (MBC) is a rare disease. The few studies on MBC reported conflicting data regarding survival outcomes compared to women. This study has two objectives: to describe the characteristics of a single-cohort of MBC and to compare overall survival (OS) and disease-free survival (DFS) between men and women using the propensity score matching (PSM) analysis. We considered MBC patients (n = 40) diagnosed between January 2004 and May 2019. Clinical, pathological, oncological and follow-up data were analyzed. Univariate analysis was performed to determine the prognostic factors on OS and DFS for MBC. We selected female patients with BC (n = 2678). To minimize the effect of the imbalance of the prognostic factors between the two cohorts, the PSM method (1:3 ratio) was applied and differences in survival between the two groups were assessed. The average age of MBC patients was 73 years. The 5-year OS and DFS rates were 76.7% and 72.2% respectively. The prognostic factors that significantly influenced OS and DFS were tumor size and lymph node status. After the PSM, 5 year-OS was similar between MBC and FBC (72.9% vs 72.3%, p = 0.70) while we found a worse DFS for MBC (72.2% vs 91.4%, p  = 0.03). Our data confirmed previous reported MBC characteristics: we found a higher risk of recurrence in MBC compared to FMC but similar OS. MBC and FMC are different entities and studies are needed to understand its epidemiology and guide its management.

scholarly journals Association of a Novel KIF26B Gene Polymorphism with Susceptibility to Schizophrenia and Breast Cancer: A Case-Control Study

2021 ◽  
Author(s):  
Saman SARGAZI ◽  
Milad HEIDARI NIA ◽  
Shekoufeh MIRINEJAD ◽  
Mahdiyeh MOUDI ◽  
Mahdiyeh JAFARI SHAHROUDI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Case Control Study ◽  
De Novo ◽  
Case Control ◽  
Amplification Refractory Mutation System ◽  
Salting Out ◽  
Current Case ◽  
Increased Risk ◽  
Mutation System ◽  
Control Study

Background: KIF26B gene is found to play essential roles in regulating different aspects of cell proliferation and development of the nervous system. We aimed to determine if rs12407427 T/C polymorphism could affect susceptibility to schizophrenia (SZN) and breast cancer (BC), the two genetically correlated diseases. Methods: The current case-control study was performed from Aug 2018 to Dec 2018. Briefly, 159 female pathologically confirmed BC cases referring to Alzahra Hospital, Isfahan, Iran, and 102 psychologically confirmed SZN patients (60 males and 42 females) admitted to Baharan Hospital, Zahedan, Iran, were enrolled. Using the salting-out method, genomic DNA was extracted, and variants were genotyped using allele-specific amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method. Results: The results revealed a significant association between the KIF26B rs12407427 codominant CT (P=0.001), CC (P=0.0001), dominant CT+CC, and recessive CC (P=0.001) genotypes with the risk of developing SZN. Significant correlations were also found regarding rs12407427 and BC susceptibility in different inheritance models, including over-dominant CT (P=0.026), dominant CT+CC (P=0.001), recessive CC (P=0.009), and codominant CT and CC (P=0.001) genotypes. The over-presence of the C allele was also correlated with an increased risk for SZN (P=0.0001) and BC (P=0.0001). Finally, computational analysis predicted that T/C variation in this polymorphism could change the binding sites in proteins involved in splicing. Conclusion: rs12407427 T/C as a de novo KIF26B variant might be a novel genetic biomarker for SZN and/or BC susceptibility in a sample of the Iranian population.

Is It The Time That We Can Depend on Bioscore as a New Staging System in Non-Metastatic Breast Cancer to Predict the Disease-Free Survival?

2021 ◽  
Author(s):  
Rehab Farouk Mohamed ◽  
Donia Hussein Abd El Hameed ◽  
Mohamed Alaa Eldeen Hassan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Free Survival ◽  
Disease Free

Abstract Purpose: Novel molecular characterization of breast cancer with cellular markers has allowed a new classification that offers prognostic value. This study investigates the prognostic value of the Bioscore among non-metastatic breast cancer patients with respect to disease free survival (DFS).Methods: This study included 317 patients with non-metastatic surgically treated breast cancer; they were identified in the period from January 2015 to December 2018 at Clinical Oncology Department of Assiut University Hospital. Many variables were used; pathologic stage (PS), T stage (T), nodal stage (N), grade (G), estrogen receptor (ER), progesterone receptors (PR), and human epidermal growth factor receptor (HER2) status. Univariate & two multivariate analyses were performed to identify which of these variables are associated with disease-free survival (DFS). Results: The only significant factors in the Univariate analysis were PS3, T2, T3, T4, N3, G2, G3, ER -ve, PR -ve, and HER2 –ve. The factors which were significant in the first multivariate analysis; PS3, G3, ER –ve, and in the second one were; T2, T4, N3, G3, and ER –ve. Two sets of models were built to determine the utility of combining variables. Models incorporating G and E status had the highest C-index (0.72) for T+N + G + ER in comparison with (0.69) for (PS+ G + ER) and the lowest AIC (953.01) for T + N + G + E and (966.9) for PS + G + E. Conclusions: This study confirms the prognostic significance of bioscore in non-metastatic breast cancer in concerning DFS.

Full-Thickness Chest Wall Resection for Recurrent Breast Carcinoma: An Institutional Review and Meta-analysis

2005 ◽  
Vol 71 (9) ◽  
pp. 711-715 ◽  
Author(s):  
Colette R.J. Pameijer ◽  
David Smith ◽  
Laurence E. Mccahill ◽  
David N. Bimston ◽  
Lawrence D. Wagman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chest Wall ◽  
English Literature ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Entire Group ◽  
Chest Wall Resection ◽  
Full Thickness ◽  
Recurrent Breast ◽  
Disease Free

Locoregional recurrence of breast cancer can occur in up to 30 per cent of patients and has often been considered to indicate a poor prognosis. We reviewed our experience with full-thickness chest wall resection for recurrent breast cancer and conducted a meta-analysis of the English literature to determine patient characteristics and outcomes. Twenty-two women with isolated chest wall recurrence of breast cancer were treated between 1970 and 2000 at our institution. We reviewed their preoperative demographics, operative management and outcome, and combined our results with seven other English language studies. A majority of women (90%) underwent a mastectomy as initial management of their breast cancer. Only 18 per cent of patients had meta-static disease at the time of chest wall resection, and 71 per cent of patients had an R0 resection. The 5-year disease-free survival at City of Hope National Medical Center (COH) was 67 per cent and was 45 per cent for the entire group of 400 patients. The 5-year overall survival was 71 per cent for the COH group and 45 per cent for the entire group. Several studies reported prognostic factors, the most common being a better prognosis in patients with a disease-free interval greater than 24 months. Full-thickness chest wall resection for patients with isolated local recurrence of breast cancer can provide long-term palliation and even cure in some patients.

Effectiveness of adjuvant chemotherapy in combination with tamoxifen for node-positive postmenopausal breast cancer patients.

1997 ◽  
Vol 15 (4) ◽  
pp. 1385-1394 ◽  
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancer Patients ◽  
Node Positive ◽  
Increased Risk ◽  
Node Positive Disease ◽  
Er Positive ◽  
Risk Of Relapse

PURPOSE Adjuvant tamoxifen has been shown to reduce relapse and mortality among node-positive post-menopausal breast cancer patients. The value of adding chemotherapy to tamoxifen is controversial. PATIENTS AND METHODS Between July 1986 and April 1993, 1,266 postmenopausal breast cancer patients with node-positive disease were randomly assigned to receive one of four adjuvant therapy regimens: (A) tamoxifen alone for 5 years; (B) tamoxifen plus three courses of early cyclophosphamide, methotrexate, and fluorouracil (CMF) on months 1, 2, and 3; (C) tamoxifen plus delayed single courses of CMF on months 9, 12, and 15; (D) tamoxifen plus early and delayed CMF on months 1, 2, 3, 9, 12, and 15. The two-by-two factorial design allowed two direct comparisons: early CMF (B and D) versus no early CMF (A and C), and delayed CMF (C and D) versus no delayed CMF (A and B). Estrogen receptor (ER) status was known for all patients and was used to stratify the randomization. A total of 1, 212 patients (96%) were eligible and assessable. The median follow-up duration was 60 months. RESULTS The results of the two-by-two factorial comparisons were as follows: (1) early CMF added to tamoxifen significantly improved 5-year disease-free survival (DFS; 64% v 57%; hazards ratio [HR], 0.79; 95% confidence interval [CI], 0.66 to 0.95; P = .01); and (2) delayed CMF added to tamoxifen did not improve DFS (5-year DFS, 61% v 60%; HR, 0.97; 95% CI, 0.81 to 1.17; P = .77). For patients with ER-positive tumors, the addition of CMF, either early or delayed or both, reduced the relative risk of relapse by 22% to 36%. In contrast, for patients with ER-negative tumors, tamoxifen with delayed CMF was associated with a nonsignificant increased risk of relapse (HR, 1.27; 95% CI, 0.92 to 1.76; P = .15). CONCLUSION Postmenopausal patients with node-positive breast cancer should be offered combination chemotherapy in addition to tamoxifen. Tamoxifen should not be initiated before CMF, as this might be detrimental, especially for patients with ER-negative tumors.

scholarly journals Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients

2020 ◽  
pp. 153537022095861
Author(s):  
Iman H Ibrahim ◽  
Heba G Abdel-Aziz ◽  
Fatema EM Hassan ◽  
Hesham SA El-Sameea
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Breast Cancer Progression ◽  
Protein Coding ◽  
Free Survival ◽  
Disease Free ◽  
Gata3 Protein

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

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