Konstantinos Papazisis - Academia.edu (original) (raw)

Papers by Konstantinos Papazisis

Cancers

Background: Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of... more Background: Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The purpose of this study was to investigate the clinical use and implementation of cascade family testing (CFT) in families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs) in cancer-related predisposition genes. Methods: Germline sequencing was carried out with NGS technology using a 52-gene panel, and cascade testing was performed by Sanger sequencing or MLPA. Results: In a cohort of 1785 breast cancer patients (families), 20.3% were found to have PVs/LPVs. Specifically, 52.2%, 25.1%, and 22.7% of patients had positive findings in high-, intermediate-, and low-penetrance breast cancer susceptibility genes, resp...

Anticancer Research, Jan 29, 2022

Background/Aim: This study aimed to provide real-world safety and effectiveness data of everolimu... more Background/Aim: This study aimed to provide real-world safety and effectiveness data of everolimus (EVE) plus exemestane (EXE) in estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2–) advanced breast cancer (aBC). Patients and Methods: This prospective observational study was conducted by 19 hospital-based oncologists in Greece. Eligible patients were treated with EVE+EXE in the first-line setting; EVE was initiated according to the approved label. Results: Overall, 75 eligible patients (mean age: 66.9 years; visceral metastases: 49.3%; bone-only metastases: 37.3%) were included in the effectiveness analyses. Over a median (interquartile range) of 12.1 months (range=4.2-20.5 months) of EVE treatment, the median progression-free survival was 18.0 months and the overall response rate was 22.7%. Among patients that received ≥1 EVE dose (n=80), the incidence of EVE-related adverse events was 72.5% (serious: 55.0%); stomatitis (22.5%), fatigue (22.5%), pneumonitis (18.8%); and cough (18.8%) were the most common. Conclusion: In the routine care in Greece, EVE demonstrates clinical benefit and a predictable safety profile.

Annals of Oncology, Sep 1, 2020

PubMed, Jul 17, 2021

Purpose: Early-stage, HER2-positive breast cancer is increasingly treated with neoadjuvant chemot... more Purpose: Early-stage, HER2-positive breast cancer is increasingly treated with neoadjuvant chemotherapy (NAC). After the positive results of the Neosphere trial, the standard of care has been the combination of chemotherapy with two anti-HER2 agents, trastuzumab and pertuzumab. Many oncologists use the sequence of four cycles of anthracycline-containing regimen followed by four cycles of taxane with the two monoclonals. We report here the cardiac safety of four cycles of epirubicin with cyclophosphamide followed by four cycles of docetaxel with trastuzumab and pertuzumab, given at the neoadjuvant setting in early, HER2-positive breast cancer. Methods: We retrospectively collected data from the medical records of patients treated at our clinic between 2014 and 2020. Results: It total, 55 patients treated with the same regimen were identified. There were 20 estrogen receptor (ER)-negative and 35 ER-positive patients. Complete pathologic response was observed in 64.8% of the patients. After a median cardiac follow-up of 2.61 years, and a total of 283 echocardiograms, there was only one recorded asymptomatic Left Ventricular Ejection Fraction (LVEF) fall > 25% and no symptomatic left ventricular systolic dysfunction. LVEF consistently dropped during treatment, but the drop was not significant enough to necessitate treatment interruption, and improved during follow-up. Conclusion: Our data confirm the effectiveness and cardiac safety of the aforementioned neoadjuvant regimen.

European Journal of Gynaecological Oncology, Feb 10, 2019

Annals of Oncology, Oct 1, 2019

Background The application of the Next Generation Sequencing (NGS) technology has facilitated mul... more Background The application of the Next Generation Sequencing (NGS) technology has facilitated multigene panel testing for hereditary breast cancer (BC) in clinical practice. We performed a retrospective analysis of individuals referred for testing in our lab aiming to investigate the contribution of included genes and evaluate current genetic testing guidelines in BC. Methods In total, 1141 BC patients and 184 unaffected individuals with family history (FH) of BC were referred from physicians for testing using a multigene panel. Genomic DNA was enriched for targeted regions of 33 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated computationally and by Multiplex Ligation-dependent Probe Amplification (MLPA). Results A pathogenic variant (PV) was identified in 22% (291/1325) of analyzed individuals and in specific in 23.2% of BC patients and 14.1% of unaffected individuals (P = 0.006). Among individuals with PVs, 49.1% were located in the BRCA1/2 genes whereas 8.6%, 22.7% and 19.6% occurred in other high, moderate and low-risk genes respectively. Notably, 21 of the 291 positive individuals (7.2%) carried clinically significant variants in two different genes and 6.5% had a LGR. A retrospective analysis of positive individuals showed that 88.3% of BC patients met the NCCN criteria for further genetic risk evaluation compared to 80.8% of unaffected individuals with FH of BC (P = 0.269). In BRCA-positive cases, NCCN criteria were met in 92.3% of the referrals compared to 81.8% in individuals positive for other genes (P = 0.008). Conclusions Extended multigene panel testing in hereditary BC facilitates the detection of nearly twice as many individuals that could benefit from personalized management. In our cohort, the currently used selection criteria for HBOC failed to identify only 12.7% of individuals positive for pathogenic variants, suggesting strong selection strategies from physicians. However, our results indicate that selection criteria perform better for the identification of BRCA-positive BC patients and should be revised to facilitate towards the inclusion of BC patients with PVs in other genes. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Cancer Research, May 1, 2008

235 Introduction: Sunitinib is a protein tyrosine kinase-inhibitor targeting VEGFR, c-kit and PDG... more 235 Introduction: Sunitinib is a protein tyrosine kinase-inhibitor targeting VEGFR, c-kit and PDGFR. It has been approved for the treatment of metastatic renal-cell carcinoma and gastrointestinal stromal tumors (GISTs). Although it has been shown to prolong disease-free and overall survival in renal-cell carcinoma patients, only 70% of the treated population receive a clinical benefit (CB) form the treatment. Currently there are no clear data to correlate response to sunitinib with any changes in angiogenetic factors in those patients. Surrogate markers that could predict clinical benefit to sunitinib would be an important aid in monitoring and following their treatment. Patients and methods: We have examined 32 patients with metastatic clear-cell renal carcinoma that received sunitinib, 50 mg daily for 30 out of 45 days per cycle. Blood samples were collected after informed consent in several time-points during their treatment and angiogenesis factors were estimated in the plasma with ELISA. Results: From the 27 evaluable for response patients (that received at least three months of therapy), twenty patients (74%) had a clinical benefit (CB), with 14 patients (52%) having a partial response and 6 (22%) disease stabilization. Seven patients (26%) experienced a disease progression (PD) and the treatment was discontinued. Side-effects included fatigue, mucositis, hypertension, skin discoloration, peripheral oedema and hypothyroidism (two patients). In three patients the dose was reduced to 37.5 mg per day due to adverse events; however there was no treatment discontinuation due to intolerance. Two patients experienced disease flare-up in the off-treatment periods and continued treatment with no-stop, 37.5 mg sunitinib daily. Soluble VEGF receptors (sVEGFR) were decreased during sunitinib treatment both in CB and in PD patients. During the off-treatment periods sVEGFR plasma levels were increased (buy a factor of 2) only in CB patients, having no difference in the non-responders9 group. Plasma PDGF levels were significantly lower in the CB group throughout the treatment period. Treatment with sunitinib resulted in lower PDGF levels in all patient group. On the contrary VEGF was increased, especially in patients that did not responded as well as in responders just before the subsequent disease progression. Conclusions: Sunitinib treatment offers a significant clinical benefit in the majority of patients with an acceptable and manageable toxicity profile. Monitoring plasma levels of angiogenetic factors may prove to be an important tool in predicting response to treatment or disease progression. The study is ongoing.

Background – aim: In carriers of BRCA1/2 pathogenic mutations (mut), it is expected that the germ... more Background – aim: In carriers of BRCA1/2 pathogenic mutations (mut), it is expected that the germline mut is present in all tissues, particularly in normal; the somatic mut status in normal tissues from these patients is usually not addressed. We investigated the mut status in normal and tumor tissues in a real-life cohort of BRCA1/2 carriers who underwent prophylactic surgery. Methods: All 53 women had known BRCA1/2 germline mut that had been assessed independently; 42 had previous cancer manifestation (PCM); all had prophylactic mastectomy; 22 had prophylactic hystero-salpingo-oophorectomy. By using a 60-gene NGS panel, we examined the mut status of 231 samples, 39 peripheral blood and 192 paraffin tissues (FFPE: 46 tumors, out of which 43 breast; 97 normal breast [NB]; 49 normal ovary and salpinx [NGYN]). Germline mut status was interrogated in tissues with the above panel, Sanger sequencing and a multiplex PCR protocol for large exonic deletions, along with extensive FFPE DNA quality control (QC) to exclude false negatives. Results: Eight patients carried germline BRCA2 and 45 BRCA1 mut (29 in the BRCT-domain; 31 substitutions/indels). We identified somatic mut in 85% of the tumors and in 64% of the normal samples; mut were found significantly more often (p=0.003) and in higher numbers (p<0.001) in NGYN than in NB. In NB and NGYN, top 3 genes with somatic mut were BRCA2 (28%), BRCA1 (17%), TP53 (7%). In tumors, somatic mut were most frequent in TP53 (49%; p<0.001) and BRCA1 (38%; p=0.039). Among all tissue types, the 5 tumors post-neoadjuvant treatment had the highest and NB the lowest mut load (p=0.001). In NB and NGYN, mut load was not affected by PCM or BRCA1 mut domain but it was higher in BRCA1 vs. BRCA2 carriers (p=0.027) and in those with BRCA1 substitutions/indels vs. exon deleting and skipping mut (p<0.001). In tumors, germline BRCA1 substitutions/indels were associated with higher mut load (p=0.014). We validated germline mut status in all blood samples and in 111 tissue samples that passed FFPE DNA QC from 40 patients. The germline mut was not found in 14 samples (4 breast tumors; 3 NB; 7 NGYN) from 10 (25%) patients, all BRCA1 carriers, 9 with germline mut in the BRCT-domain. The only non-BRCT domain germline mut that was lost in one breast tumor, p.V1234fs, was replaced by the R1751* (validated), again in the BRCT domain. In normal tissues, those with lost germline mut had significantly less somatic mut compared to those with preserved germline mut (p<0.001). Conclusions: In BRCA1/2 carriers, somatic mut in BRCA genes and TP53 are present in normal breast and GYN tissues, more frequently in the latter, and seem associated with the mutated gene and with the type of mut in the germline. The mut status of normal breast tissue does not seem to be affected by neoadjuvant chemotherapy for breast cancer. The observed BRCA1 germline mut loss, particularly in normal tissues, may be approached as a negative selection for the inherited mut; similarly to the described germline mut reversion after chemotherapy, tissues may react to deleterious effects of haploinsufficiency, which needs functional validation. Citation Format: Kotoula V, Demiri E, Fostira F, Vrettou E, Papadopoulou K, Tikas I, Papazisis K, Zaramboukas T, Asimaki-Vlachopoulou A, Miliaras S, Fountzilas E, Ananiadis A, Chrisafi S, Poulios C, Natsiopoulos I, Tsiftsoglou A, Fountzilas G. Germline and somatic mutation status in tissues from BRCA1/2 carriers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-04-04.

Oxford Medical Case Reports, Nov 1, 2022

Cyclin-dependent kinase 4/6 inhibitors (CKIs), ribociclib, palbocilb and abemaciclib, have been a... more Cyclin-dependent kinase 4/6 inhibitors (CKIs), ribociclib, palbocilb and abemaciclib, have been approved in combination with endocrine therapy for the treatment of hormone receptor-positive and human epidermal growth factor 2-negative advanced or metastatic breast cancer. Severe dermatological adverse events are rare with these agents; however, they require direct recognition and management in order not to become life-threatening. Erythema multiforme (EM) belongs to a dermatopathic spectrum that includes immune-mediated, widespread hypersensitivity reaction, which occurs with varying degrees of severity and affects the skin and/or the mucosa. We hereby present a case of ribociclib-and palbociclib-related EM. We sought to report this case given the implication of two agents from the same drug class in EM onset. We also aim to emphasize the breadth of mechanisms of actions of CKIs, with an impingement in the immune system as well, and the importance of promptly identifying and handling such skin toxicities.

Bioinorganic Chemistry and Applications, 2010

As part of our interest into the bioinorganic chemistry of gallium, gallium(III) complexes of the... more As part of our interest into the bioinorganic chemistry of gallium, gallium(III) complexes of the azole ligands 2,1,3benzothiadiazole (btd), 1,2,3-benzotriazole (btaH), and 1-methyl-4,5-diphenylimidazole (L) have been isolated. Reaction of btaH or btd with GaBr 3 or GaCl 3 resulted in the mononuclear complexes [GaBr 3 (btaH) 2 ] (1) and [GaCl 3 (btd) 2 ] (2), respectively, while treatment of GaCl 3 with L resulted in the anionic complex (LH) 2 [GaCl 4 ] (3). All three complexes were characterized by singlecrystal X-ray crystallography and IR spectroscopy, while their antiproliferative activities were investigated against a series of human and mouse cancer cell lines.

Radiology and Oncology, May 17, 2022

Background. The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly ... more Background. The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2− advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2− ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1.

Cancer Research, Mar 1, 2023

Background: DESTINY-Breast04 demonstrated that the HER2 targeting antibody–drug conjugate trastuz... more Background: DESTINY-Breast04 demonstrated that the HER2 targeting antibody–drug conjugate trastuzumab deruxtecan (T-DXd) significantly prolonged progression-free survival (PFS) and overall survival (OS) vs treatment of physician’s choice (TPC) in patients (pts) with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization negative) metastatic breast cancer (mBC) in pts in the hormone receptor−positive (HR+) cohort and all pts (HR+ and HR-; median PFS, 9.9 vs 5.1 months [mo], hazard ratio: 0.50; median OS, 23.4 vs 16.8 mo, hazard ratio: 0.64; both P < 0.0001; Modi et al. N Engl J Med 2022). Objective response rate (ORR) with T-DXd was ≥50% across cohorts. These subgroup analyses examine pt history and disease characteristics that may correlate with response to therapy. Methods: N = 557 pts with centrally confirmed HER2-low mBC were randomized 2:1 to T-DXd or TPC. Randomization was stratified by HER2 status (IHC 1+ vs 2+), 1 vs 2 prior lines of chemotherapy, and HR+ (with vs without prior treatment with cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) vs HR−. With the exception of the PFS and OS analyses by prior CDK4/6i use, all other described efficacy analyses were assessed post-hoc. Results: Benefit of T-DXd vs TPC was consistent in pts with or without prior CDK4/6i use (Table 1). Pts with high disease burden (ie, ≥3 metastatic sites) also benefited from T-DXd vs TPC (Table 2). There was a small subgroup (n = 22) among all pts (HR+ [n = 18] and HR− disease [n = 4]) with rapid progression prior to enrollment (disease progression within 6 mo of concluding a prior course of chemotherapy in early breast cancer). T-DXd showed responses in 7/14 (50%) pts in this subgroup vs 0/8 with TPC; this subgroup also had prolonged median PFS with T-DXd vs TPC (Table 3). Efficacy data for HER2 IHC 1+ vs 2+ and prior chemotherapy subgroups will be presented. Median OS was not reached for many subgroups (insufficient events in each group [data not shown]); however, subgroups in general showed OS benefit consistent with the primary analysis. With T-DXd, rates of interstitial lung disease/pneumonitis were similar in pts with/without prior CDK4/6i use. Conclusions: T-DXd treatment for HER2-low mBC in the phase 3 study DESTINY-Breast04 showed consistent efficacy independent of disease burden, prior CDK4/6i treatment, or rapid progression status. ILD is an important identified risk and requires proactive monitoring and management. These data continue to support the use of T-DXd as the new standard of care across subgroups of pts with HER2-low mBC. Editorial Acknowledgment Under guidance of the authors, assistance in medical writing and editorial support was provided by Eileen McIver, PhD, and Soniya Patel, PhD, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table 1. Efficacy by Prior CDK4/6i Treatment in Pts With HER2-Low Breast Cancer, HR+ Cohort. Table 2. Efficacy by Disease Burdena in Pts With HER2-Low Breast Cancer, ITT. Table 3. Efficacy by Rapid Progressor Statusa in Pts With HER2-Low Breast Cancer, ITT. Citation Format: Nadia Harbeck, Shanu Modi, William Jacot, Toshinari Yamashita, Joo Hyuk Sohn, Maria Vidal, Junji Tsurutani, Naoto T. Ueno, Aleix Prat, Naoki Niikura, Binghe Xu, Hope Rugo, Konstantinos Papazisis, Javier Cortés, Ian Krop, Dhiraj Gambhire, Lotus Yung, Yibin Wang, Jasmeet Singh, David Cameron. Trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: Subgroup analyses from DESTINY-Breast04 [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 P1-11-01.

Cancer Letters, May 1, 2005

The aim of this study was to explore a possible association between p53 codon 72, Her 2 codon 655... more The aim of this study was to explore a possible association between p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms and breast cancer in Northern Greece. We examined 42 women with breast cancer and 51 controls. A total of 42 women with breast cancer as well as healthy controls were investigated and results showed that p53 codon 72 polymorphism is statistically significantly associated with breast cancer (OR for Arg/Arg to non-Arg/Arg was 6.66, PZ0.0001 at 95% CI 2.63-16.9), but not Her 2 and MTHFR polymorphisms are associated with breast cancer (OR for Ile/Ile to non-Ile/Ile was 1.33, PZ 0.54 at 95% CI 0.52-3.38 and OR for T/T versus non-T/T was 1.07, PZ0.89 at 95% CI 0.35-3.25). All subjects were examined for p53 exons 5-8 mutations. Three novel sequence variations in exons 7 and 8 of TP53 gene were found in three patients. One of them induces an amino acid change at Ser 241Gly, the second is a silent mutation Gly244Gly, and the third one results in a premature stop codon 294 (Glu294stop) and a truncated p53 protein.

JAMA Oncology, Aug 1, 2022

Patients selected to receive neoadjuvant chemotherapy (NAC) are usually those at higher risk of r... more Patients selected to receive neoadjuvant chemotherapy (NAC) are usually those at higher risk of relapse, and there is a need to find better therapeutic options for these patients. OBJECTIVE To determine the efficacy and safety outcomes for patients with hormone receptor (HR)-positive, ERBB2 (formerly HER2)-, high-risk early breast cancer enrolled in the randomized clinical trial monarchE who received NAC. DESIGN, SETTING, AND PARTICIPANTS The monarchE randomized clinical trial was a multicenter, phase 3, open-label study that evaluated adjuvant treatment with abemaciclib plus endocrine therapy (ET) compared with ET alone in patients with HR + , ERBB2-, and node-positive early breast cancer who were at high risk of recurrence. Patients were recruited between July 2017 and August 2019 from 603 sites in 38 countries. This subgroup analysis was performed with primary outcome data, with a cutoff date of July 8, 2020. INTERVENTION Enrolled patients were randomized (1:1) to receive standard of care ET for at least 5 years with or without treatment with abemaciclib (150 mg, twice daily) for 2 years (treatment period) or until criteria were met for discontinuation. MAIN OUTCOMES AND MEASURES Prior chemotherapy (NAC vs adjuvant vs none) was a stratification factor in monarchE, and and a prespecified exploratory analysis included outcomes in patients who received NAC. The data presented in this article are from the primary outcome analysis (395 invasive disease-free survival [IDFS] events; cutoff date, July 8, 2020; median follow-up 19 months [IQR, 15.6-23.9 months]). Invasive disease-free survival (the primary end point of monarchE) and distant relapse-free survival (DRFS) were evaluated using the Cox proportional hazard model and Kaplan-Meier method. RESULTS Of the 5637 patients (mean [SD] age, 49.9 [10.6] years; 2046 women [99.5%]; 462 Asian [22.8%], 54 Black [2.7%], and 1473 White participants [70.8%]) enrolled in monarchE, 2056 (37%) received treatment with NAC. In this subgroup, treatment with abemaciclib and ET demonstrated clinically meaningful benefit in IDFS (hazard ratio, 0.61; 95% CI, 0.47-0.80) and DRFS (hazard ratio, 0.61; 95% CI, 0.46-0.81), which corresponded with an absolute improvement of 6.6% in 2-year IDFS rates and 6.7% in 2-year DRFS rates. A consistent treatment benefit was observed across subgroups of pathological breast tumor size or number of positive lymph nodes at surgery. CONCLUSIONS AND RELEVANCE In the randomized clinical trial monarchE, treatment with adjuvant abemaciclib combined with ET demonstrated a clinically meaningful improvement in IDFS and DRFS for patients with HR + , ERBB2 − , node-positive, high-risk early breast cancer who received NAC before trial enrollment.

Cancer Genomics - Proteomics

Background/Aim: The use of multi-gene panels for germline testing in breast cancer enables the es... more Background/Aim: The use of multi-gene panels for germline testing in breast cancer enables the estimation of cancer risk and guides risk-reducing management options. The aim of this study was to present data that demonstrate the different levels of actionability for multi-gene panels used in genetic testing of breast cancer patients and their family members. Materials and Methods: We performed an analysis in our clinical database to identify breast cancer patients undergoing genetic testing. We reviewed positive results in respect of risk estimation and management, cascade family testing, secondary findings and information for treatment decision-making. Results: A total of 415 positive test reports were identified with 57.1%, 18.1%, 10.8% and 13.5% of individuals having pathogenic/likely pathogenic variants in high, moderate, low and with insufficient evidence for breast cancer risk genes, respectively. Six point seven percent of 60 This article is freely accessible online.

Cancer Diagnosis & Prognosis

Background/Aim: A possible role of antibody-drug conjugates against tumors with low HER2-expressi... more Background/Aim: A possible role of antibody-drug conjugates against tumors with low HER2-expression, leads to the emergence of a new “low-HER2” classification in breast cancer, encompassing tumors from the hormonal-receptor-positive and the triple-negative subgroups. There is a need for data (clinical trial data and real-world evidence) that will accurately describe this population, the risk of recurrence and the possible benefit of HER2 targeted therapies. Patients and Methods: We retrospectively analyzed 949 patients from our Department databases, with hormonal receptor-positive and HER2-negative early breast cancer, for whom detailed data for immunohistochemical HER2-staining could be retrieved. Results: HER2-low expression was detected in 66.6% of patients (472 IHC +1 and 160 IHC +2 and ISH-negative). Lobular, or mixed lobular and ductal cancers had a statistically significantly lower chance of being HER2-low when compared to pure infiltrative ductal carcinomas (53.1% vs. 69.3% ...

Cancer Research, 2022

Background: Breast cancer is the most frequently diagnosed cancer in women and about 10% of breas... more Background: Breast cancer is the most frequently diagnosed cancer in women and about 10% of breast cancer cases are hereditary. BRCA1 and BRCA2 are the genes most frequently associated with Hereditary Breast Cancer, although there are numerous other genes, such as PALB2, CHEK2 and ATM, that require to be considered as well. Germline Copy Number Variation (CNV) is one mutation type that is an important contributor to hereditary breast cancer. Nowadays, next-generation sequencing (NGS) technologies has contributed to multi-gene panel analysis used in clinical practice. Methods: In total, 1418 individuals were tested for breast cancer predisposition, using a solution-based capture approach. Targeted NGS was performed with a panel of 36 genes. The capture-based approach allowed for computational analysis of CNVs from NGS data. Results: We investigate the performance of the CNV module of the commercial software suite SeqPilot (JSI Medical Systems) and the non-commercial tool panelcn.MOPS...

Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 2021

PURPOSE Early-stage, HER2-positive breast cancer is increasingly treated with neoadjuvant chemoth... more PURPOSE Early-stage, HER2-positive breast cancer is increasingly treated with neoadjuvant chemotherapy (NAC). After the positive results of the Neosphere trial, the standard of care has been the combination of chemotherapy with two anti-HER2 agents, trastuzumab and pertuzumab. Many oncologists use the sequence of four cycles of anthracycline-containing regimen followed by four cycles of taxane with the two monoclonals. We report here the cardiac safety of four cycles of epirubicin with cyclophosphamide followed by four cycles of docetaxel with trastuzumab and pertuzumab, given at the neoadjuvant setting in early, HER2-positive breast cancer. METHODS We retrospectively collected data from the medical records of patients treated at our clinic between 2014 and 2020. RESULTS It total, 55 patients treated with the same regimen were identified. There were 20 estrogen receptor (ER)-negative and 35 ER-positive patients. Complete pathologic response was observed in 64.8% of the patients. Aft...