First Diagnosis Of Breast Cancer Research Articles

Timing of genetic testing in BRCA1/2 and PALB2-Associated breast cancer: Preoperative result disclosure increases uptake of risk-reducing mastectomy and reduces unnecessary exposure to radiotherapy

IntroductionThe impact of timing of genetic testing on uptake of risk reducing mastectomy (RRM) in affected female BRCA1/2 or PALB2 carriers remains an area of evolving interest, particularly with the introduction of mainstream genetic testing initiatives. MethodsWomen with stage I-III breast cancer and a confirmed germline pathogenic variant in BRCA1/2 or PALB2 between 2000 and 2023 were identified from an institutional genetics database. Uptake of RRM was evaluated according to disclosure of genetic testing results before or after index surgery for a first diagnosis of breast cancer. ResultsThe cohort included 287 female BRCA1/2 or PALB2 carriers with a median age of 44 years (IQR, 36–52). Overall, 155 (54 %) carriers received genetic testing results before and 132 (46 %) after index breast surgery. Receipt of genetic testing results before surgery was associated with a higher rate of index bilateral mastectomy (58.7 % vs. 7.6 %, p < 0.001) and a commensurate decrease in adjuvant radiation (41.9 % vs. 74.2 %, p < 0.001). At a median follow up of 4.4 years after genetic testing, 219 (76.3 %) affected carriers had undergone bilateral RRM, including 83.9 % with preoperative knowledge and 67.4 % of patients with postoperative knowledge of their germline pathogenic variant (log rank, p < 0.001). On multivariate regression, disclosure of genetic testing results before index breast surgery was independently associated with long-term uptake of bilateral mastectomy (HR 1.69, 95 % CI 1.21–2.38). ConclusionGenetic testing results delivered prior to index breast surgery increase uptake of bilateral RRM in affected BRCA1/2 and PALB2 carriers. Efforts to mainstream genetic testing would help optimize surgical decision-making.

Impact of promoter region mutations of Pim-1 on c-Myc expression as well as survival in patients with breast cancer

Purpose: Breast cancer accounts for most cancer-related deaths in women with over 2.3 million new breast cancer cases diagnosed every year worldwide. Pim kinases are oncogenic proteins that play important role in various cancers. Pim-1 contains 1.7 kb promoter region without any transcriptional regulation, which is a characteristic feature of a housekeeping or constitutive promoter. This study was carried out to ascertain potential mutations in the promoter region of Pim-1 in breast cancer and also to comprehend the effect of mutations on c-Myc expression as well as on patients’ survival. Methods: Ninety-six Indian subjects with a first diagnosis of breast cancer who underwent surgery at our hospital were recruited in this study. Genomic DNA was isolated from whole blood, amplified and sequenced to identify potential mutations at the promoter region of Pim-1. FFPE sections were used to determine the c-Mycexpression in all the studied groups. Results: We observed a transversion (C&gt;A at –502) and a deletion (–754Cdel) mutation in the promoter region with negligible association with tumor biology and c-Myc expression. Positive c-Myc expression was noted in almost 50% of the studied population with absolute nuclear staining or both cytoplasmic/nuclear staining. As per survival analysis, promoter region mutations did not modulate the patients’ survival, but patients with negative c-Myc expression had better disease-free survival compared with positive c-Myc expression. Conclusion: Our findings identified the presence of mutation in the promoter region of Pim-1 with negligible impact on c-Myc expression in patients with breast cancer.

First diagnosed invasive lobular carcinoma of the breast combined with gastric metastasis and bone metastasis: a case report and review of the literature

RationaleChinese women topped the list of new breast cancers, the first diagnosed gastric metastasis and bone metastasis is extremely infrequent. The clinical and pathological diagnosis of metastatic breast cancer is difficult. To our knowledge, this is the first reported case of the first diagnosis of breast cancer with both gastric metastasis and bone metastasis.Case reportThe female patient was found to have abdominal distension for 15 days with nausea and vomiting. The patient underwent a gastroscopy at an outside hospital 4 days ago, showing: duodenal bulb changes, gastric retention and chronic non-atrophic gastritis. Gastroscopic biopsy showed chronic inflammation and edema of the duodenal mucosa with glandular hyperplasia. Conservative treatment was given with no relief of symptoms. She was seen in our hepatobiliary and pancreatic surgery department. After admission, palliative surgery was performed, and the swelling and surrounding involved tissues were taken for examination during surgery. The rapid pathological return could not exclude tumor lesions, and the postoperative pathology confirmed the diagnosis of invasive lobular carcinoma of the breast with gastric metastases, and the systemic examination revealed combined bone metastases.DiagnosisPathology and immunohistochemistry(IHC), a whole-body bone scan confirmed the first diagnosis of breast cancer with both gastric and bone metastases.InterventionsPalliative treatment with bisphosphonates and CDK4/6i (Palbociclib) in combination with AI (Exemestane) was administered.OutcomesThe patient is currently under regular evaluation and is being followed up.

Abstract P5-12-06: Comprehensive analysis of DNA damage repair gene germline mutations in Chinese breast cancer patients

Abstract Background: Germline DNA damage repair (DDR) mutations has been associated with increased cancer risk, PARP inhibitor therapeutic opportunity for breast cancer (BC) patients. However, the profile of germline mutations in BC covering comprehensive DDR genes remains unclear. Methods: A total of 341 women with breast cancer who tested 102 germline related genes (including 50 DDR genes) between April 2021 to May 2022 in Guangdong Provincial People’s Hospital were identified. Variants were classified into pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign and benign groups according to the ACMG/AMP Standards and Guidelines. We defined pathogenic and likely pathogenic variants as deleterious mutations. Results: The median age of 341 breast cancer patients was 48 (range, 20-89) at the first diagnosis of BC. A total of 47 patients (13.78%) carried 53 deleterious germline variants in 21 cancer predisposition genes, 16 of which were DDR genes. DDR deleterious mutations were detected in genes including BRCA2 (n=18), BRCA1(n=7), FANCA (n=4), PMS2 (n=4), PALB2(n=2), RECQL4(n=2), PALB2 (n=2), etc. The younger age at diagnosis (less than 40-year-old) were significantly associated with deleterious mutations in DDR pathway(P=0.02). At least one VUS was identified in 238 (69.79%) patients. The top 5 DDR VUS genes were FANCM (n=21), ATM (n=20), RAD54L (n=17), FANCD2 (n=15) and ATR (n=14). Breast or ovarian cancer family history were significantly correlated with VUS germline mutations in DDR pathway(P=0.039). Interesting, we found that patients with pCR efficacy of neoadjuvant therapy were more likely to have VUS mutations in DDR pathway (table 1). Conclusion: We provided a comprehensive view of germline DDR gene mutations in BC patients and also analyzed the association between clinical characteristics and germline DDR mutation status. DDR mutations are prevalent in Chinese BC patients. Patients with younger and breast or ovarian cancer family history were more likely to carry DDR alterations. Moreover, patients with higher frequency of DDR VUS mutations may benefit from neoadjuvant therapy. Table 1. Clinicopathological characteristics between germline mutation carriers and non-carriers Citation Format: Ning Liao, Li Cao, Guochun Zhang, Junyun Wang, Airong Yang, Yulei Wang, Kai Li, Lingzhu Wen, Chongyang Ren, Minghan Jia, Cheukfai Li, Hsiaopei Mok, Bo Chen, Jianguo Lai, Weikai Xiao. Comprehensive analysis of DNA damage repair gene germline mutations in Chinese breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-12-06.

Cardiac Tamponade in Patients With Breast Cancer: A Systematic Review.

Cardiac tamponade is a rare presentation in breast cancer and may be associated with poor prognosis. In this article, we reviewed the characteristics and survival outcomes of patients with breast cancer who developed cardiac tamponade. Three databases (PubMed, EMBASE and SCOPUS) were searched for relevant articles published from 1978 to 2022 and 16 articles were identified comprising 64 cases. The median age of the cases was 52 years. Cardiac tamponade was diagnosed with echocardiogram or computerized tomography of the chest or both in 91.9%, 1.6% and 6.5% of the cases, respectively. Cytology of the pericardial fluid was done in 90.5% of the cases while biopsy in addition to cytology was done in 9.5% of cases. Tamponade was proven to be malignant in 97.4% of the cases. The initial treatment for tamponade was pericardiocentesis. Adjunct therapies ranged from the insertion of a pericardial window, pericardiectomy, radiotherapy and chemotherapy. The median time from the first treatment of breast cancer to the onset of tamponade was 24 months while the median survival following diagnosis of tamponade was 13 months. There was no significant correlation (spearman rank-sum correlation coefficient= 0.35, p = 0.165) between time to tamponade (interval time from the first diagnosis of breast cancer and the onset of cardiac tamponade) and survival. Cardiac tamponade may adversely affect survival in patients with breast cancer. Early diagnosis with echocardiogram and cytology may guide management and expectations. Further observational studies are needed to determine the predictors of cardiac tamponade and optimal treatment in patients with breast cancer.

Association between Breast Cancer and Second Primary Lung Cancer among the Female Population in Taiwan: A Nationwide Population-Based Cohort Study.

Simple SummaryThere is an increasing number of patients with breast cancer and second primary lung cancer clinically. The aim of our population-based cohort study was to investigate this correlation in Taiwanese women using the National Health Insurance Research Database from Taiwan National Health Insurance. We confirmed that patients with breast cancer had a significantly higher risk of developing second primary lung cancer compared with patients without breast cancer, particularly in younger groups and in those without any comorbidities. The special association is meant to raise awareness and provoke interest in routine lung cancer screening for female patients who were diagnosed with breast cancer at a relatively young age.Purpose: A special association between breast cancer and second primary lung cancer in Taiwanese women has been discovered not only in clinical practice, but also in a large population-based study. We hereby investigate the association between breast cancer and second primary lung cancer in Taiwanese women. Methods: This study was conducted from the National Health Insurance Research Database (NHIRD) from Taiwan National Health Insurance (NHI). Patients older than 18 years old and hospitalized with a first diagnosis of breast cancer during 2000 to 2012 were enrolled in the breast cancer group. Patients who were cancer free were frequency-matched with the breast cancer group by age (every five-year span) and index year. The ratio of breast cancer group to non-breast cancer group was 1:4. The event as the outcome in this study was lung cancer. The comorbidities viewed as important confounding factors included coronary artery disease, stroke, hypertension, diabetes, chronic obstructive pulmonary disease, hyperlipidemia, tuberculosis, chronic kidney disease, and chronic liver disease and cirrhosis. We estimated the hazard ratios (HRs), adjusted hazard ratios (aHRs), and 95% confidence intervals (CIs) for risk of lung cancer in the breast cancer group and non-breast cancer group using Cox proportional hazard models. Sensitivity analysis was also done using propensity score matching. All of the statistical analyses were performed using SAS statistical software, version 9.4 (SAS Institute Inc., Cary, NC). Results: There were 94,451 breast cancer patients in the breast cancer group and 377,804 patients in the non-breast cancer group in this study. After being stratified by age, urbanization level, and comorbidities, the patients with breast cancer had a significantly higher risk of lung cancer compared with the patients without breast cancer, particularly for those who aged between 20 and 49 years (aHR = 2.10, 95% CI = 1.71–2.58), 50 and 64 years (aHR = 1.35, 95% CI = 1.15–1.58), and those without any comorbidities (aHR = 1.92, 95% CI = 1.64–2.23). Conclusion: Patients with breast cancer had a significantly higher risk of developing second primary lung cancer compared with patients without breast cancer, particularly in younger groups and in those without any comorbidities. The special association may be attributed to some potential risk factors such as genetic susceptibility and long-term exposure to PM2.5, and is supposed to increase public awareness. Further studies are necessary given the fact that inherited genotypes, different subtypes of breast cancer and lung cancer, and other unrecognized etiologies may play vital roles in both cancers’ development.

Contralateral Breast Screening with Preoperative MRI: Long-Term Outcomes for Newly Diagnosed Breast Cancer.

Background The diagnostic value of screening the contralateral breast with MRI in patients with newly diagnosed breast cancer is poorly understood. Purpose To assess the impact of MRI for screening the contralateral breast on long-term outcomes in patients with newly diagnosed breast cancer and to determine whether subgroups with unfavorable prognoses would benefit from MRI in terms of survival. Materials and Methods Data on consecutive patients with newly diagnosed breast cancer seen from January 2008 to December 2010 were reviewed retrospectively. Patients with neoadjuvant chemotherapy, previous breast cancer, distant metastasis, absence of contralateral mammography at diagnosis, and no planned surgical treatment were excluded. Groups that did and did not undergo preoperative MRI were compared. Survival analysis was performed using the Kaplan-Meier method for propensity score-matched groups to estimate cause-specific survival (CSS) and overall survival (OS). A marginal Cox proportional hazards model was used to evaluate association of MRI and clinicopathologic variables with OS. Results Of 1846 patients, 1199 fulfilled the inclusion criteria. Median follow-up time was 10 years (range, 0-14 years). The 2:1 matched sample comprised 705 patients (470 in the MRI group and 235 in the no-MRI group); median ages at surgery were 59 years (range, 31-87 years) and 64 years (range, 37-92 years), respectively. MRI depicted contralateral synchronous disease more frequently (27 of 470 patients [5.7%] vs five of 235 patients [2.1%]; P = .047) and was associated with a higher OS (hazard ratio [HR], 2.51; 95% CI: 1.25, 5.06; P = .01). No differences were observed between groups in metachronous disease rate (MRI group: 21 of 470 patients [4.5%]; no-MRI group: 10 of 235 patients [4.3%]; P > .99) or CSS (HR, 1.34; 95% CI: 0.56, 3.21; P = .51). MRI benefit was greater in patients with larger tumor sizes (>2 cm) (HR, 2.58; 95% CI: 1.11, 5.99; P = .03) and histologic grade III tumors (HR, 2.94; 95% CI: 1.18, 7.32; P = .02). Conclusion Routine MRI screening of the contralateral breast after first diagnosis of breast cancer improved overall survival; the most pronounced benefit was found in patients with larger primary tumor size and primary tumors of histologic grade III. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Taourel in this issue.

Germline Mutational Landscape in Chinese Patients With Advanced Breast Cancer

BackgroundGenetic testing for breast cancer (BC) patients may shift the paradigm towards more personalized management and treatment strategies. While gene alterations may be ethnic-specific in breast cancer, our understanding of genetic epidemiology of BC remains mainly driven by data from Caucasian populations and further limited to selected handful of genes.MethodsWe collected whole blood samples from 356 BC patients at metastatic first line BC and primary stage IV disease at Beijing Cancer Hospital between Jan. 2013 to Dec. 2019. A comprehensive 600-gene cancer panel was used to detect germline variants in the covered genes with a median 300x sequencing depth. Variants were classified into pathogenic, likely pathogenic, variant of uncertain significance, likely benign and benign groups according to the ACMG/AMP Standards and Guidelines. Pathogenic and likely pathogenic variants were considered as deleterious mutations.ResultsThe median age of 356 BC patients was 49 years (range, 21-87 years) at the first diagnosis of BC. Deleterious germline mutations across 48 cancer-related genes were identified in 21.6% (77/356) of the patients. The most prevalent mutations were BRCA1/2 mutations (7.0%), followed by ATM and RAD50 mutations (1.4% each). In addition, patients with family history were more likely to carry BRCA1 mutations (P=0.04). Moreover, patients with triple-negative breast cancer (TNBC) were more likely to harbor BRCA1 mutations than those with HR+ or HER2+ breast cancer (P=0.006). While there was no significant survival difference observed in BRCA1/2 carriers relative to non-carriers, patients with DNA damage repair (DDR) gene mutations (mostly frequently BRCA, ATM, RAD50) had worse disease-free survival (P=0.02).ConclusionsThe most prevalent germline mutations in a large cohort of Chinese patients with advanced BC were BRCA1/2 mutations, followed by ATM and RAD50 mutations. In total, approximately 16.0% (57/356) of patients carry deleterious mutations in DDR pathway. Patients with breast or ovarian cancer family history were more likely to carry BRCA1/2 mutations, and ones with DDR mutations had worse survival. These findings suggest that DDR mutations are prevalent in Chinese BC patients who may potentially benefit from treatment with Poly (ADP-ribose) polymerase inhibitors.

High clinical value of bone scintigraphy as a staging method for breast cancer

Bone scintigraphy is a sensitive method for imaging bone metastases in patients with breast cancer. Despite its firm establishment in clinical routine, there are hardly any reliable data from larger homogeneous collectives on the value of bone scintigraphy in the context of staging of first diagnosed breast cancer patients. The aim of our work was to evaluate the real-life performance of bone scintigraphy as a staging examination in female patients with the initial diagnosis of breast cancer. We retrospectively evaluated the data of the patients examined in the year 2015 with the first diagnosis of breast cancer at the University Hospital Marburg by bone scintigraphy. In addition a follow-up over a period of 30 months after the first bone scintigraphy was performed. For this purpose we evaluated whether the results of this initial diagnostic could be confirmed in following diagnostic. 207/258 patients showed no suspicious findings in the initial bone scintigraphy, 48 had an unclear finding, which is why 42 patients received further diagnostics. In follow-up, new bone metastases were found in 4 patients, all of these had scintigraphic findings in the primary diagnosis, which were considered "unclear". Depending on the evaluation of the event (suspicious for metastasis/suspicious for metastasis and unclear), the sensitivity was 37.5%/100%, the specificity 100%/80%, the positive predictive value 100%/15.7% and the negative predictive value 98%/100%. By using bone scintigraphy and, if necessary, subsequent further imaging or histological clarification, a clinically significant diagnosis was obtained in 99,2% of the examined patients and confirmed in the follow-up. This result shows the good real-life performance of bone scintigraphy as a staging examination in patients with first diagnosed breast carcinomas.

Structured reporting of x-ray mammography in the first diagnosis of breast cancer: a Delphi consensus proposal

BackgroundRadiology is an essential tool in the management of a patient. The aim of this manuscript was to build structured report (SR) Mammography based in Breast Cancer.MethodsA working team of 16 experts (group A) was composed to create a SR for Mammography Breast Cancer. A further working group of 4 experts (group B), blinded to the activities of the group A, was composed to assess the quality and clinical usefulness of the SR final draft. Modified Delphi process was used to assess level of agreement for all report sections. Cronbach’s alpha (Cα) correlation coefficient was used to assess internal consistency and to measure quality analysis according to the average inter-item correlation.ResultsThe final SR version was built by including n = 2 items in Personal Data, n = 4 items in Setting, n = 2 items in Comparison with previous breast examination, n = 19 items in Anamnesis and clinical context; n = 10 items in Technique; n = 1 item in Radiation dose; n = 5 items Parenchymal pattern; n = 28 items in Description of the finding; n = 12 items in Diagnostic categories and Report and n = 1 item in Conclusions. The overall mean score of the experts and the sum of score for structured report were 4.9 and 807 in the second round. The Cronbach’s alpha (Cα) correlation coefficient was 0.82 in the second round. About the quality evaluation, the overall mean score of the experts was 3.3. The Cronbach’s alpha (Cα) correlation coefficient was 0.90.ConclusionsStructured reporting improves the quality, clarity and reproducibility of reports across departments, cities, countries and internationally and will assist patient management and improve breast health care and facilitate research.

Abstract P2-09-03: Pathogenic variants among female breast cancer patients with a subsequent cancer demonstrate preventable cancer burden

Abstract Background: Among females with breast cancer, multiple primary cancers (MPCs) are a hallmark of cancer predisposition syndromes. Herein we report the frequency of germline pathogenic/likely pathogenic variants (PVs) among females with breast cancer (BC) and primary cancer of &amp;gt;1 other site who underwent multi-gene panel testing (MGPT) through a single lab. Among females first diagnosed with BC who had a PV in an actionable gene, we quantified the frequency of subsequent breast and non-breast cancers. Among those who later developed a second BC, ovarian, endometrial or colon cancer, we determined the percentage of patients with MPCs who would have been identified as high-risk if all women had had MGPT after a first diagnosis of breast cancer. Methods: Females with breast cancer and MPCs who underwent germline genetic testing with Ambry Genetics from 3/2012 to 12/2016 were included in our cohort. Eligible individuals had multigene panel testing, which included 21 genes at minimum (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53). Clinical factors including age at diagnosis, age at testing and cancer type were obtained from test requisition forms and clinical notes. Patients with &amp;gt;1 PV were excluded from the analysis. Results: Of the 6617 patients with MPCs including BC tested for the 21 genes in the analytic cohort, most were white (70.8%), with median age at testing 63 years (IQR: 16). The median ages of first and second cancer diagnosis were 49 (IQR: 18) and 59 (IQR: 16) years, respectively. Considering the diagnostic order of BC, PV prevalence was 16.5% (444/2687) with BC as the 1st cancer diagnosis, 11.2% (296/2641) with BC as the 2nd cancer diagnosis, 15.2% (49/323) as 3rd or later diagnosis (p&amp;lt;0.001). Based on the PV identified through genetic testing, 411 of 2687 (15.3%) females with BC as a first diagnosis would have been identified as high-risk and 227 (8.4%) as eligible for altered surveillance or risk-reducing interventions for a cancer that they subsequently developed. Specifically, of the 318 (11.8%) females with a PV in ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PTEN, STK11, or TP53, 73 (23%) developed a subsequent BC. Of the 241 (9.0%) females with PVs in genes including ovarian cancer susceptibility (BRCA1, BRCA2, BRIP1, PALB2, RAD51C, or RAD51D), 143 (59.3%) developed ovarian cancer, 21 of whom also developed a second breast cancer. Among the 41 (1.5%) females with Lynch syndrome, 25 (61.0%) were later diagnosed with endometrial cancer and 10 (24.4%) were diagnosed with colorectal cancers (3 had both). Conclusions: Our data show a significant prevalence of germline PV in cancer susceptibility genes in women with MPC including BC. Further, the data suggest that a strategy testing all BC patients at diagnosis to identify actionable PV could permit the appropriate use of risk-reducing and surveillance strategies to reduce the occurrence of MPC among BC survivors. Citation Format: Brittany L. Bychkovsky, Min-Tzu Lo, Amal Yussuf, Carrie Horton, Parichehr Hemyari, Holly LaDuca, Judy E. Garber, Huma Q. Rana. Pathogenic variants among female breast cancer patients with a subsequent cancer demonstrate preventable cancer burden [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-03.

166P Breast cancer at the age of 90 and above

The elderly population in Germany is increasing, which results in more frequent first diagnosis of breast cancer in patients at age 90 and above. Evidence about tumor characteristics is very limited and often filled in as established.

Clinicopathologic Profile of Breast Cancer in Germline ATM and CHEK2 Mutation Carriers.

The most common breast cancer (BC) susceptibility genes beyond BRCA1/2 are ATM and CHEK2. For the purpose of exploring the clinicopathologic characteristics of BC developed by ATM or CHEK2 mutation carriers, we reviewed the archive of our Family Cancer Clinic. Since 2018, 1185 multi-gene panel tests have been performed. Nineteen ATM and 17 CHEK2 mutation carriers affected by 46 different BCs were identified. A high rate of bilateral tumors was observed in ATM (26.3%) and CHEK2 mutation carriers (41.2%). While 64.3% of CHEK2 tumors were luminal A-like, 56.2% of ATM tumors were luminal B-like/HER2-negative. Moreover, 21.4% of CHEK2-related invasive tumors showed a lobular histotype. About a quarter of all ATM-related BCs and a third of CHEK2 BCs were in situ carcinomas and more than half of ATM and CHEK2-related BCs were diagnosed at stage I-II. Finally, 63.2% of ATM mutation carriers and 64.7% of CHEK2 mutation carriers presented a positive BC family history. The biological and clinical characteristics of ATM and CHEK2-related tumors may help improve diagnosis, prognostication and targeted therapeutic approaches. Contralateral mastectomy should be considered and discussed with ATM and CHEK2 mutation carriers at the first diagnosis of BC.

The study of genetic and clinicopathological characterisation of Turkish bilateral breast cancer patients

Introduction. Although bilateral breast cancers are a rare condition in the general population, the incidence has increased significantly in BRCA1 and BRCA2 gene carrier breast cancer patients. Besides the genetic susceptibility, many risk factors such as age, first breast cancer diagnosis age, lifestyle, and environmental factors may be effective in the development of this type of cancer. This study aimed to determine BRCA1/2 gene carriage in patients with bilateral breast cancer and to find out the risk factors that may lead to contralateral cancer formation. Material and methods . From 2016 to 2018, in Turkey, we grouped 31 women diagnosed with bilateral breast cancer synchronously and metasynchronously. Analysis of BRCA1 and BRCA2 genes of these women evaluated for clinical and pathological tumour characteristics was performed using the NGS technique. Results. No significant difference was found between the metachronous (MBBC) and synchronous (SBBC) groups in terms of clinical and pathological tumour characteristics. MBBC patients’ age at first diagnosis of breast cancer was lower than SBBC. Also, there was a statistically significant relationship between chronic diseases and MBBC cancers (c2 = 11.519; p = 0.001). In our study, disease-related variants were found only in three patients, and two of these variants were identified the first time in the literature. Conclusion. The risk of bilateral breast cancer of BRCA1/2 carriers increases when the first breast cancer is diagnosed at a young age and there is a significant family history of cancer. MBBC is associated with chronic diseases, and large-scale research will contribute to clarifying this relationship.

Development and Validation of a Risk Model for Breast Cancer–Related Lymphedema

Approximately 1 in 5 patients with breast cancer who undergo axillary lymph node dissection will develop lymphedema. To appropriately triage and monitor these patients for timely diagnosis and treatment, robust risk models are required. To evaluate the prognostic value of mammographic breast density in estimating lymphedema severity. This prognostic study collected data from July 16, 2018, to March 3, 2020, from the electronic health records of patients of the Cancer Rehabilitation and Survivorship Program at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada. Participants included women who had completed curative treatment for a first diagnosis of breast cancer and who were referred to the program. Also included were a sample of patients in the general breast oncology population who were receiving follow-up care at the center during the same period but who were not referred to the program. All patients attended follow-up appointments at the Princess Margaret Cancer Centre from January 1, 2016, to May 1, 2018. The cohort was randomly split 2:1 to group patients into a training cohort and a validation cohort. Participant demographic and clinical characteristics included age, sex, body mass index (BMI), medical history, cancer characteristics, and cancer treatment. Spearman correlation coefficient between measured and predicted volume of lymphedema was calculated. Area under the curve (AUC) values were generated for predicting the occurrence of at least mild lymphedema (volume, >200 mL) and severe lymphedema (volume, >500 mL) at the time of initial lymphedema diagnosis. A total of 373 female patients (median [interquartile range] age, 52.3 [45.9-60.1] years) were eligible for this analysis. Multivariate linear regression identified 3 patient factors (age, BMI, and mammographic breast density), 1 cancer factor (number of pathological lymph nodes), and 1 treatment factor (axillary lymph node dissection) as independent prognostic variables. In validation testing, Spearman correlation revealed a statistically significant moderate correlation (coefficient, 0.42; 95% CI, 0.26-0.56; P < .001) between measured volume and predicted volume of lymphedema. The AUC values were 0.72 (95% CI, 0.60-0.83) for predicting the occurrence of mild lymphedema and 0.83 (95% CI, 0.74-0.93) for severe lymphedema. This prognostic study found that patients with low breast density appeared to be at a higher risk of developing severe lymphedema. The finding suggests that by combining breast density with established risk factors a multivariate linear regression model could be used to predict the development of lymphedema and provide volumetric estimates of lymphedema severity in patients with breast cancer.

Prevalence of Germline Pathogenic and Likely Pathogenic Variants in Patients With Second Breast Cancers.

BackgroundFew studies have examined gene-specific associations with contralateral and/or second breast cancer (SBC).MethodsThe frequency of pathogenic and likely pathogenic (P/LP) variants in clinically actionable genes (BRCA1, BRCA2, PTEN, TP53, CHEK2, CDH1, ATM, PALB2, NBN, and NF1) was compared between women with a primary breast cancer (PBC) and SBC who underwent multigene panel testing at a single diagnostic testing laboratory. Race- and ethnicity-specific logistic regression burden tests adjusted for age at diagnosis of first breast cancer, histology, presence of first- or second-degree relatives with breast cancer, and prior testing for BRCA1/2 genes were used to test for associations with SBC. All statistical tests were 2-sided.ResultsThe study was comprised of 75 550 women with PBC and 7728 with SBC. Median time between breast cancers for SBC was 11 (interquartile range = 6–17) years. Restricting to women tested for all actionable genes (n = 60 310), there were 4231 (7.8%) carriers of P/LP variants in actionable genes among the controls (PBC) compared with 652 (11.1%) women with SBC (P< .001). Among Caucasians, exclusive of Ashkenazi Jewish women, those carrying a P/LP variant in a clinically actionable gene were 1.44 (95% confidence interval [CI] = 1.30 to 1.60) times as likely to have SBC than noncarriers, after accounting for potential confounders. Among African American and Hispanic women, a P/LP variant in a clinically actionable gene was 1.88 (95% CI = 1.36 to 2.56) and 1.66 (9% CI = 1.02 to 2.58) times as likely to be associated with SBC, respectively (P < .001 and P = .03).ConclusionWomen with P/LP variants in breast cancer predisposition genes are more likely to have SBC than noncarriers. Prospective studies are needed confirm these findings.

Impact of Primary Subtype on Pattern of Metastases and Survival in Young Women with Metastatic Breast Cancer

Metastatic breast cancer is a heterogeneous disease that varies in biology and organ involvement, and can have a more aggressive course in young patients. This study aimed to describe the pattern of distant metastases of young women with stage 4, or metastatic, breast cancer (MBC). A retrospective study was performed examining women diagnosed with MBC at age 50 years or younger and managed at our institution between 2001 and 2018. Data including primary breast cancer receptor status (ER, PR, and HER2) and distant metastases at MBC diagnosis were recorded. Patients were classified into groups based on receptor status. Metastatic pattern of various MBC groups was assessed using Chi-Square test. Kaplan-Meier method was used to analyze overall survival. 485 patients were eligible for this study. Median age at MBC diagnosis was 42 years (range 25 to 50). Median follow-up time for all patients was 7.1 years. Median survival for all patients is shown in table 1. Primary breast cancer in 230 patients (47%) was ER+ &/or PR+ & HER2- (HR+HER2-), in 78 patients (16%) was ER- & PR- & HER2- (triple-negative), in 59 patients (12%) was ER+ & /or PR+ & HER2+ (HR+HER2+), in 51 patients (11%) was HER2+ & ER- & PR- (HER2+HR-), and in 67 patients (14%) was unclassified. Almost all unclassified patients had unknown HER2 status (65 patients) and received their breast cancer diagnosis prior to 2001 when HER2 testing was not universal, but the majority (45 patients) were known to be hormone receptor positive. 102 patients (21%) had MBC at first diagnosis of breast cancer. The incidence of bone metastasis, brain metastasis, and single metastasis are shown in the table 1. HR+HER2-, HR+HER2+, and unclassified patients had a significantly higher incidence of bone metastasis at MBC diagnosis compared with triple negative and HER2+HR- patients (p<0.05). Conversely, triple negative and HER2+HR- patients had a significantly higher incidence of brain metastasis at MBC diagnosis compared with HR+HER2-, HR+HER2+, and unclassified patients (p<0.05). Incidence of single metastasis at MBC diagnosis was similar across all groups (p = 0.861). Of the 75 patients with single metastasis, 50 had a bone metastasis, 9 had a brain metastasis, and 16 had a metastasis to another site. At MBC diagnosis in young women, the incidence of bone and brain metastasis in HR+HER2+ patients may be closer to that of HR+HER2- patients rather than HER2+HR- patients. In our cohort, the incidence of single metastasis did not appear to vary across primary subtypes.Abstract 2095; TableAll Patients (n = 485)HR+HER2- (n = 230)Triple-negative (n = 78)HR+HER2+ (n = 59)HER2+HR- (n = 51)Unclassified (n = 67)P-valueBone metastasis at MBC diagnosis322 (66%)175 (76%)37 (47%)44 (75%)19 (37%)47 (70%)p<0.05Brain metastasis at MBC diagnosis53 (11%)15 (7%)16 (21%)7 (12%)10 (20%)5 (7%)p<0.05Single metastasis at MBC diagnosis75 (15%)35 (15%)15 (19%)9 (15%)6 (12%)10 (15%)P = 0.861Median Survival (years)3.43.51.45.33.93.1p<0.05 Open table in a new tab

Changes in Perceived Social Support after Starting Treatment in Egyptian Patients with Operable Breast Cancer: A Longitudinal Observational Study

Background: Social support (SS) has been proven to be associated with improved outcome of early breast cancer. Little is known about the magnitude of social support available for Egyptian breast cancer patient and much less is known about the changes that occur in such support after the diagnosis of breast cancer and starting treatment. Methods: We designed a longitudinal questionnaire based prospective cohort study using the six item form of the Medical Outcomes Study- Social Support Survey (MOS-SSS) questionnaire and included patients with pathologically proven non-metastatic breast cancer 18-70 years of age. Patients completed the self administered questionnaire at 2 time points: at first diagnosis of breast cancer and after 3-6 months of starting treatment. Comparison of the pre and post treatment questionnaires was done using paired sample T test. Results: A total of 48 patients completed the 2 questionnaires. Median age was 48 years (range: 24-65 years). Seventy percent of our patients were married, 67% had more than 2 children and 77.8% were housewives. Around half of the patients (45.2%) had monthly income below 1200 EGP. Patients who had higher education level (p=0.002) and those who were living in Cairo (p=0.033) reported higher SS at baseline. Mean MOS-SSS score at baseline was 64.4 (±24.8) while after treatment was 76.4 (±22.3); p&lt;0.001. The increase in SS was consistent in most of the patient subgroups but was more prominent in illiterate patients compared to educated (p=0.033), those who work a handy job compared to housewife (p=0.04), and those who lived in Upper Egypt compared to Cairo residents (p=0.029). Conclusion: The majority of Egyptian breast cancer patients had a supportive environment after the diagnosis of breast cancer. A special attention should be paid to the at-risk groups with no sufficient SS during that period.

Behavior of metastatic breast cancer according to subtype.

To explore the impact of breast cancer subtype on metastatic behavior and long-term outcome defined as breast cancer specific survival (BCSS). Retrospective single centre cross-sectional study of 5972 patients with newly diagnosed, unilateral first diagnosis of breast cancer, diagnosed 2000-2010. Patients had either early breast cancer (EBC) treated primarily by surgery (SURG n = 5072), neoadjuvant systemic therapy (NEO n = 592), or upfront metastatic disease (META n = 308). Surrogate breast cancer subtypes were defined according to classical pathological criteria. Analysis was performed using Kaplan-Meier method and logistic/Cox regression. After median follow-up time of 103.6 months (IQR 73.4-139.2 months), 817 patients with EBC at diagnosis (14.4%) developed distant metastases of which 621 (12.2%) SURG and 196 (33.1%) NEO. Metastasis rate after EBC was: LuminalA 8.1%, LuminalB1(HER2-) 20.4%, LuminalB2(HER2+) without (neo)adjuvant trastuzumab 21.7%, LuminalB2(HER2+) with trastuzumab 9.0%, HER2Positive(ER-) without trastuzumab 30.0%, HER2Positive(ER-) with trastuzumab 19.9% and TripleNegative 25.3%. There were major differences in site of first metastases according to subtype. For single site first metastases, median BCSS assessed from time of metastases was worst for brain localization (13.9 months) and best for bone (48.4 months). Multiple sites of first metastases had worse BCSS from date of metastases than single site first metastases (median BCSS for 1 site 40.0, 2 sites 27.1, ≥ 3 sites 20.5 months). Median BCSS from date of metastases is longer in upfront metastases compared to secondary metastases after EBC (43.4 vs. 27.9 months). Tumor subtype influences the metastatic behavior and survival after development of distant metastases.

Quality of Life of Women After a First Diagnosis of Breast Cancer Using a Self-Management Support mHealth App in Taiwan: Randomized Controlled Trial.

BackgroundThere are over 2 million newly diagnosed patients with breast cancer worldwide with more than 10,000 cases in Taiwan each year. During 2017-2018, the National Yang-Ming University, the Taiwan University of Science and Technology, and the Taiwan Breast Cancer Prevention Foundation collaborated to develop a breast cancer self-management support (BCSMS) mHealth app for Taiwanese women with breast cancer.ObjectiveThe aim of this study was to investigate the quality of life (QoL) of women with breast cancer in Taiwan after using the BCSMS app.MethodsAfter receiving a first diagnosis of breast cancer, women with stage 0 to III breast cancer, who were recruited from social networking sites or referred by their oncologists or oncology case managers, were randomized 1:1 into intervention and control groups. Intervention group subjects used the BCSMS app and the control group subjects received usual care. Two questionnaires—the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) and the EORTC Breast Cancer-Specific Quality-of-Life Questionnaire (QLQ-BR23)—were distributed to subjects in both arms. Paper-based questionnaires were used at baseline; paper-based or Web-based questionnaires were used at 1.5-month and 3-month follow-up evaluations. All evaluations were self-assessed and anonymous, and participants were blinded to their allocation groups. Descriptive analysis, the Pearson chi-square test, analysis of variance, and the generalized estimating equation were used to analyze the data. Missing values, with and without multi-imputation techniques, were used for sensitivity analysis.ResultsA total of 112 women were enrolled and randomly allocated to either the experimental group (n=53) or control group (n=59). The follow-up completion rate was 89.3% (100/112). The demographic data showed homogeneity between the two groups in age (range 50-64 years), breast cancer stage (stage II), marital status (married), working status (employed), and treatment status (receiving treatments). The mean total QoL summary scores from the QLQ-C30 (83.45 vs 82.23, P=.03) and the QLQ-BR23 (65.53 vs 63.13, P=.04) were significantly higher among the experimental group versus the control group, respectively, at 3 months.ConclusionsThis research provides support for using a mobile health care app to promote the QoL among women in Taiwan after a first diagnosis of breast cancer. The BCSMS app could be used to support disease self-management, and further evaluation of whether QoL is sustained is warranted.Trial RegistrationClinicalTrials.gov NCT004174248; https://clinicaltrials.gov/ct2/show/NCT04174248