Metachronous Breast Cancer Research Articles

Germline DNA Damage Repair Gene Alterations in Patients with Metachronous Breast and Colorectal Cancer.

A hereditary component of breast (BC) and colorectal cancer (CRC) has been described in approximately one-third of these tumor types. BC patients have an increased risk of developing CRC as a second primary tumor and vice versa. Germline genomic variants (NextSeq550, Illumina) were investigated in 24 unrelated BC and/or CRC patients and 7 relatives from 3 index patients. Fifty-six pathogenic or likely pathogenic variants were identified in 19 of 24 patients. We detected single-nucleotide variants (SNVs) in CRC predisposition genes (MLH1 and MUTYH) and other promising candidates (CDK5RAP3, MAD1L1, NOS3, and POLM). Eighteen patients presented SNVs or copy number variants (CNVs) in DNA damage repair genes. We also identified SNVs recently associated with BC or CRC predisposition (PABPC1, TYRO3, MAP3K1, SLC15A4, and LAMA1). The PABPC1c.1255C>T variant was detected in nine unrelated patients. Each patient presented at least one SNV/CNV in a candidate gene, and most had alterations in more than one gene, reinforcing a polygenic model for BC/CRC predisposition. A significant fraction of BC/CRC patients with a family history of these tumors harbored deleterious germline variants in DNA repair genes. Our findings can lead to strategies to improve the diagnosis, genetic counseling, and treatment of patients and their relatives.

Survival analysis for patients with metachronous contralateral breast cancer: Insights from a retrospective study.

Continued advances in the diagnosis and treatment of breast cancer (BC) have led to an increase in the number of long-term BC survivors and an increase in the incidence of metachronous BC in the contralateral breast. Therefore, it is important to understand the factors that influence the development of metachronous BC; however, the impact of the laterality of the initial ipsilateral (I)BC as a risk factor for the development of metachronous contralateral (MC)BC has not been extensively investigated. The present study included 17,082 female patients with stage 0-3 IBC from the prospectively maintained Korean Breast Cancer Registry from 1989-2013 and divided them into two groups: Patients with MCBC (n=88) and those without MCBC (n=16,994). Risk factors that present at the initial BC diagnosis that could significantly influence the development of MCBC were screened for and risks were evaluated using the Fine-Gray subdistribution hazard model. Significant differences in baseline characteristics between MCBC and non-MCBC groups were demonstrated. Patients aged <40 years, those with histological and nuclear grade 3 tumors, and those with the triple-negative BC subtype were significantly more prevalent in the MCBC group than in the non-MCBC group. Additionally, the cumulative incidence of MCBC increased over time, with a notable increase from 0.1% in year 1 to 1.6% in year 10. Survival analysis revealed no significant differences in overall or BC-specific survival between the two groups. Key predictive factors identified for MCBC included an age of <40 years at initial diagnosis, a negative progesterone receptor status, and a Ki-67 score of >14%. Overall, the present study revealed several factors associated with MCBC and emphasized the need for long-term monitoring of BC survivors, considering these newly identified risk factors.

Synchronous or metachronous breast and colorectal cancers in younger-than-average-age patients: a case series.

The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care.

Comparison of Clinicopathological Features of Pleomorphic and Invasive Lobular Breast Carcinomas.

Accounting for about 15% of invasive lobular carcinomas and 1% of breast carcinomas, pleomorphic lobular carcinoma is known to be a rare histological subtype of invasive lobular carcinoma. Yet, it is more aggressive and produces a worse prognosis than other breast cancers. Ultimately, the present study compares the clinicopathological features of pleomorphic and invasive lobular breast carcinomas. In the study, we retrospectively evaluated the data of 262 patients with histological subtypes of classical and pleomorphic lobular cancers having been recruited for surgical operations. After resorting to Kolmogorov-Smirnov and Shapiro-Wilk tests to check the normality of distribution, the categorical and continuous variables were compared between the groups using the chi-square test and independent samples t test, respectively. In all analyses, we considered a P-value of <.05 to be statistically significant. Our findings revealed that the groups with lobular and pleomorphic groups significantly differed by Ki-67 value, estrogen receptor negativity, grade, multicentricity, multifocality, surgical margin positivity, completion mastectomy, and metachronous contralateral tumor (P < .05). We discovered that pleomorphic type was associated with higher grades, estrogen receptor negativity, and Ki-67 expression. The incidence of metachronous breast cancer was high in the pleomorphic group, which may be a noteworthy finding to be considered in follow-ups. In addition, the high rates of multicentricity and multifocality of tumors in the pleomorphic group may be associated with increased surgical margin positivity and a higher likelihood of mastectomy. In a nutshell, our findings may guide patients and surgeons regarding the type of intervention and reconstruction options to be adopted in prospective surgeries.

Post burn and bilateral inflammatory breast cancer: Three case reports from one patient

Inflammatory Breast Cancer (IBC) is the most aggressive form of primary breast cancer. IBC has an incidence of approximately 2.5 cases per 100,000 women. Malignant neoplasms arising from burn scars are well-known but rarely encountered. The subject was reviewed in a comprehensive publication that reviewed the literature between 1923 and 2007 and found 412 well-documented cases of squamous cell carcinoma (71%), basal cell carcinoma (12%), melanoma (6%), sarcoma (5%), other neoplasms (4%), squamo-basal cell carcinoma (1%), and squamous cell-melanoma (1%). In 2008, two cases were reported by Losanof, et al. both female, who were diagnosed with advanced breast cancer many years after severe thermal injury to their breasts. Bilateral synchronous or metachronous breast cancer is well-known and documented except for IBC. To our knowledge, our search using Medline and other searches did not reveal any post-burn IBC or bilateral IBC cases reported in the literature that occurred till 2006. There are only 2 cases reported in 2010 and 2016. We report our 3 case reports presented from one patient; who was diagnosed in 2006; a case of post-burn breast cancer, and to our knowledge the first case report of post-burn IBC type and a rare case report of bilateral metachronous IBC.

Primary fallopian tube cancer followed by primary breast cancer in RAD51C mutation carrier treated with niraparib as first line maintenance therapy: a case report

Given the rarity of RAD51C mutations, the risk and treatment of metachronous breast cancer after the diagnosis of ovarian cancer in RAD51C mutation carriers is not clear, especially for those who have received PARPi treatment. We report the case of a 65-year-old woman diagnosed with stage IIIC high-grade serous primary fallopian tube cancer. The patient had no family history of breast or ovarian cancer. The patient received three cycles of neoadjuvant chemotherapy with paclitaxel and carboplatin and achieved a complete response. After interval debulking surgery, the patient received three cycles of adjuvant chemotherapy. Collection and extraction of saliva DNA for next-generation sequencing identified a RAD51C mutation c.838-2 A > G. The patient received niraparib as front-line maintenance treatment. After 36 months of niraparib treatment, the patient had grade II invasive ductal carcinoma of the left breast that was positive for estrogen receptor (90%) and Ki-67 (30%) and negative for progesterone receptor and human epidermal growth factor receptor 2. Computed tomography revealed the absence of distant metastases. Modified radical mastectomy and axillary lymph node dissection were then performed. The final pathological report of the breast showed a 1.8 cm Bloom-Richardson grade II invasive ductal carcinoma in the left breast with axillary lymph node metastasis (1/21). Finally, the breast cancer was stage IIA, pT1cN1M0. The metachronous breast cancer in this case may be the first report of second primary cancer in fallopian tube cancer patient harboring a RAD51C mutation during niraparib treatment. Further studies are required to determine optimal treatment.

Metachronous breast cancer in a BRCA1 mutation carrier

Metachronous breast cancer in a BRCA1 mutation carrier

Optimal tactics of ovarian and metachronous breast cancer treatment in &lt;i&gt;BRCA&lt;/i&gt; mutations carriers

Treatment of patients with multiple primary malignant neoplasms caused by genetic mutations requires correct priorities from the clinician in selection of the most effective therapeutic tactics. An important aspect in this case is the identification of the neoplasm determining patient’s survival. The main goal is to achieve maximal treatment effect for this tumor and use therapy methods for control of other synchronous and metachronous tumors.The article presents a clinical case of a patient with BRCA1 mutation-associated recurrent ovarian cancer and de novo breast cancer of negative subtype. Combination multidisciplinary and personalized approach to treatment which led to the maximally effective result is described. Personalized approach to prescription of antitumor drug therapy, timing of surgical intervention and subsequent targeted therapy allowed to realize maximal antitumor effect and increase the patient’s lifespan.

Clinical Trials of Carbon Ion Radiotherapy for Early-Stage Breast Cancer

Our institute conducted a clinical trial of curative partial breast irradiation using carbon ion radiotherapy (CIRT) to patients with stage 0 and I breast cancer since 2013. The purpose of this report is to evaluate treatment outcomes up to now. To date, we have conducted three clinical trials and one advanced medical treatment (NIRS 9404 Comprehensive Research). The first study (UMIN000010848: commonly known as Breast I trial) was 4-split irradiation for stage I low-risk patients aged 60 years or older, and the next clinical study (UMIN000029478: commonly known as Breast II trial) was for Tis-1N0M0 cases of 2 cm or less. On the other hand, 4-split irradiation using standard adjuvant drug therapy according to risk combined with whole breast irradiation by X-ray, the latest clinical trial (UMIN000046859: commonly known as Breast III trial) is a single irradiation for Tis-1N0M0 patients aged 50 years or older. be. In each phase I, the dose increase test was performed, and in phase II, treatment was performed with the recommended dose determined in phase I. Advanced medical care was provided in parallel with breast I for stage I breast cancer that was difficult or rejected to participate in breast I trial. By January 2023, 60 cases were enrolled. A total of 19 were enrolled In Breast I, 7 in Phase I, 12 in Phase II of the recommended dose of 60.0 Gy (RBE). A total of 14 were enrolled in the 9404 Comprehensive Research. A total of 17 were enrolled In Breast II, 5 cases in Phase I, 12 cases in Phase II of recommended dose 60.0 Gy (RBE). A total of 10 were enrolled in Breast III, 6 cases in Phase I, and 4 in Phase II of recommended dose 50.0 Gy (RBE). As acute adverse events, grade 2 of acute radiation dermatitis were observed in 1 case, grade 1 of acute radiation dermatitis was observed in 31 cases, and grade 1 of mastitis was observed in 6 cases. As a late adverse event, grade 3 of pneumonia of unknown causality were observed in one case, but there were no other problematic adverse events, and breast cosmetic outcome was excellent in all cases. Tumor disappearance after CIRT took 3 to 24 months. Local recurrence and axillary lymph node metastasis were observed in one high-risk case of advanced medical treatment who refused any other therapy. Two cases had ipsilateral intramammary metachronous breast cancer with different subtypes. To date, no other recurrences or metastases have been observed. CIRT for early-stage breast cancer is expected to be effective with mild adverse events, and it is considered meaningful to continue research.

Synchronous and Metachronous Breast and Ovarian Cancers: Experience from a Single Tertiary Care Cancer Centre in India.

Women with either breast cancer (BC) or ovarian cancer (OC) have a 1.5-2 times higher risk of developing the other. Discerning discrete primaries versus metastases from either can be challenging. Clinico-pathological and outcome details of patients diagnosed with both BC and OC from December 1994 to August 2018 were retrospectively evaluated at a single tertiary cancer centre. We report the pattern of presentation and recurrences with case-based illustrations.Out of 139 patients, presentation was BC-first in 66.2%, OC-first in 24.5% and synchronous cancers (SC) in 9.3% of women. The median age at diagnosis in BC-first, OC-first and SC was 42years, 48years and 49 years, respectively. The most common histological subtype was invasive breast carcinoma-no special type (74.8%) in BC and serous cystadenocarcinoma (81.3%) in OC. BC presented at an early stage in 67.6% while OC presented at an advanced stage in 48.2% of patients. Germline mutation results were available in 82% with 61.4% of the cohort exhibiting a mutation- BRCA1 mutationbeing the most common. The median time to development of second cancer was 77.4months and 39.4months in BC-first and OC-first, respectively. At a median follow-up of 9.47years, disease-free survival was 32.6%, 32.4% and 30.8% in BC-first, OC-first and SC, respectively (p < 0.001). In hereditary breast and ovarian cancer, BC-first patients have a better prognosis while synchronous malignancies have worse oncological outcomes. Deaths are mainly due to OC progression. Appropriate surveillance and prophylactic intervention in young patients with breast cancer may improve overall outcomes.

Treatment and treatment-related toxicity following subsequent breast cancer: A report from the Childhood Cancer Survivor Study (CCSS).

10051 Background: Long-term survivors of childhood cancer are at high risk for treatment-related breast cancer and have elevated mortality risk after a breast cancer diagnosis than the general population. There is no standard of care for women with treatment-related breast cancer, and treatment patterns and risk for toxicity are not known. Methods: Female survivors in CCSS diagnosed and treated for childhood cancer between 1970-1999 who developed a subsequent breast cancer (N = 344) were matched with females with sporadic breast cancer (multi-institution sampling; 1:1 matching ratio) on age at breast cancer diagnosis, breast cancer treatment decade, race/ethnicity, histology, and hormone receptor status. Conditional logistic regression evaluated univariate associations with treatments, toxicities, and synchronous breast cancer (≤12 months from diagnosis). Hazard ratios (HR) for metachronous disease risk ( &gt; 12 months from diagnosis) were estimated using proportional hazard models with robust variance estimation. Results: Among survivors, the median time between the primary cancer and initial breast cancer diagnosis at median age 40 years (IQR 35-45) was 26 years (IQR 21-30). Two-thirds received chest radiation therapy (RT) and 44% were treated with anthracyclines for their childhood cancer. In the matched sample, breast cancer clinical features were similar between survivors vs. controls, but the odds of synchronous bilateral disease at diagnosis was 4.8-fold greater (95% CI 2.2-10.2) among survivors. Surgical interventions (99% vs. 98%, P = 0.22) and treatment with chemotherapy (46% vs. 45%, P = 0.43) were similar between groups. However, women with sporadic breast cancers were more likely to receive RT (OR 4.4, 95% CI 2.9-6.8) or anthracyclines (OR 2.4, 95% CI 1.5-3.8). Survivors were more likely to undergo mastectomy (OR 3.0, 95% CI 2.1-4.2) and experience surgical complications (OR 2.2, 95% CI 1.4-3.4), and had 1.4-fold greater odds (95% CI 1.01-1.98) of experiencing any treatment-related toxicity compared to controls. The 15-year cumulative incidence of developing a metachronous breast cancer was 20% (95% CI 13-25%) in survivors versus 9% (95% CI 5-13%) in controls (P &lt; 0.001). Risk of metachronous disease remained higher among survivors (HR 2.4, 95% CI 1.5-4.0) after adjusting for breast cancer treatments (mastectomy, RT, and anthracyclines). Conclusions: Female survivors of childhood cancer who develop subsequent treatment-related breast cancer are more likely to develop synchronous and metachronous breast cancer compared to controls. Despite similar biologic characteristics, survivors are treated differently from females with sporadic breast cancer and are more likely to experience treatment-related toxicities. Further study of how treatment of subsequent breast cancers and corresponding toxicities impact prognosis and survival is needed.

Tertiary Autologous Breast Reconstruction After Implant-Based Reconstruction: Safety and Patient-Related Outcomes

Silicone breast implants are popularly used for breast reconstruction. As more patients receive long-term silicone breast implants, the number of replacement operations will also increase, and some patients prefer to change from silicone breast implantation to tertiary autologous reconstruction. We evaluated the safety of tertiary reconstruction and assessed patient views regarding the two reconstruction methods. We retrospectively analyzed patient backgrounds, surgical characteristics, and silicone breast implantation retention periods until tertiary reconstruction. We designed an original questionnaire to assess patient opinion regarding silicone breast implantation and tertiary reconstruction. Twenty-three patients (24 breasts) with decisive factors of patient-initiated elective surgery (n=16), contralateral breast cancer occurrence (n=5), or late-onset infection (n=2) underwent tertiary reconstruction. The median time from silicone breast implantation to tertiary reconstruction was significantly shorter in patients with metachronous cancer (47 months) than that in those undergoing elective surgery (92 months). Complications included partial flap loss (n=1), seroma (n=6), hematoma (n=5), and infection (n=1). Total necrosis did not occur. Twenty-one patients responded to the questionnaire. The satisfaction score was significantly higher for abdominal flaps than for silicone breast implants. When presented with the option to select the initial reconstruction method again, 13 of 21 respondents chose silicone breast implantation. Tertiary reconstruction is beneficial because it reduces clinical symptoms and cosmetic complaints and is recommended as a bilateral reconstruction method, especially for patients with metachronous breast cancer. However, silicone breast implants, which are minimally invasive and associated with shorter hospital stays, were simultaneously found to be sufficiently attractive to patients.

S2221 A Rare Case of Triple Synchronous Colon and Metachronous Breast Cancer in an Elderly Male

S2221 A Rare Case of Triple Synchronous Colon and Metachronous Breast Cancer in an Elderly Male

Білатеральний синхронний і метахронний рак грудної залози: особливості топографії, етіологія, патогенез, чинники ризику, діагностика і прогноз

The purpose of the study was to analyze the data of the domestic and foreign specialized literature, which are devoted to the pathogenesis, features of the topography, risk factors, prognosis of the course of bilateral synchronous and metachronous breast cancer. Materials and methods. Analytical and bibliosemantic methods were used in the research. The search for scientific information on bilateral synchronous and metachronous breast cancer for the period from 1990 to 2021 was conducted in databases of electronic searching systems. Results and discussion. Bilateral cancer can be either primary or metastatic to the contralateral breast. Primary one, depending on the time of tumor development in the contralateral breast gland, is divided into synchronous (development interval up to 6 months) and metachronous (development interval more than 6 months). Synchronous tumors of the breast glands are found significantly less frequently (22.7%) than metachronous tumors (69.6%). Relative risk factors for the occurrence of bilateral metachronous breast cancer are the presence of a BRCA1 and BRCA2 gene mutation, a heavy family history of breast cancer in blood relatives, and a young age of up to 45 years. A higher risk was established in patients with a lobular histological type of carcinoma compared to ductal carcinoma and with the absence of expression of steroid hormone receptors in the tumor. Bilateral synchronous tumors are very often characterized by the same visual manifestations during mammography, and their location in the breast glands is a "mirror image". Metachronous tumors are characterized by a smaller size, with rare involvement of axillary lymph nodes. A peculiarity of the topography of metachronous breast cancer is the presence, mainly in the upper outer quadrants of the breast gland, of a fixed or slow-moving nodule of rounded or star shape with unclear contours. Magnetic resonance mammography of the glands is an effective method of comprehensive diagnosis of breast pathology and is performed when other imaging methods are ineffective (sensitivity 99.2%, specificity 97.9%, accuracy 98.9%). The duration of the recurrence-free period in patients with synchronous tumor was 126.3 months, while in patients with metachronous tumor it was 243.7 months. Conclusion. The problem of bilateral breast cancer remains complex and far from fully understood. There are many controversial issues related to the pathogenesis, risk factors, features of the topography, clinical and morphological manifestations, diagnosis, recurrence-free and overall survival of bilateral breast carcinoma, which is important for determining and evaluating the prognosis, as well as the choice of management tactics for such patients

Metachronous Breast Cancer- A Case Report

Metachronous Breast Cancer- A Case Report

Abstract 70: Metastatic versus primary: Genomic analysis suggests a metastatic origin for breast cancer previously diagnosed as metachronous vulvar ectopic breast cancer

Abstract Introduction: Accessory breast tissue is a rare finding in the general population with an incidence of 1-2%. Ectopic mammary tissue may occur anywhere along the milk line, from the axilla to the groin. Thus, breast cancer present in the vulva may arise as a primary breast adenocarcinoma or distant metastasis. Differentiating the two can be clinically challenging but is critically important as it impacts prognosis and treatment. Using genomic and bioinformatic approaches, we re-evaluated a previously histopathologically diagnosed rare case of metachronous vulvar ectopic breast cancer. Methods: Two biobanked breast tumor samples were obtained from a 43-year-old woman diagnosed with in situ breast cancer 17 months prior to her presentation and diagnosis with vulvar ectopic breast carcinoma. Whole exome (WES) and whole transcriptomic sequencing (RNAseq) were performed on all breast and vulvar tumor samples. Bioinformatics analysis was performed using the QIAGEN software suite (CLC Genomic Workbench, QCI-T) and Ingenuity Pathway Analysis (IPA). Sequence variants with &amp;gt;10 reads and 5% AF were selected for analysis. Results: We performed detailed molecular characterization of breast and vulvar tumor samples. WES profiles revealed, respectively, 4904 and 166 somatic mutations from primary breast and vulva tumor tissues. Among these mutations, 60 mutations were shared between primary breast and vulva tumors. Given the length of the WES target (~54MB). We calculated the probability that the shared mutations could occur by chance alone. To estimate this likelihood, we made the assumption that all positions interrogated by WES could be mutated with equal probability. Under this assumption, it is highly unlikely that the 60 identical mutations identified in multiple samples would occur by chance alone (Fisher exact test - p &amp;lt;10100) Beyond these shared mutations, we identified a number of known breast cancer functional variants including variants in TP53, KMT2D, MET and an additional 32 likely pathogenic genes in the vulvar tumor that were not shared with the patient’s original breast tumor tissues. Similarly, we also identified a pathogenic variant in PRKAR1A and an additional 95 likely pathogenic variants in genes including ATRX, ATXN3, CTBP2, SCN2A only in the breast tumor. Conclusion: This illustrative case provides an interesting resolution to a clinically difficult question: differentiating synchronous or metachronous breast carcinoma in the vulva. While unusual, answering this question correctly significantly impacts staging and treatment for that patient. Citation Format: Sabina Swierczek, Deep Pandya, Jean-Noel Billaud, Boris Reva, Magdalena Swierczek, Matthew Reeves, Sara Farisello, Steven Sieber, Anya Laibangyang, Vaagn Andikyan, John A. Martignetti, Linus Chuang. Metastatic versus primary: Genomic analysis suggests a metastatic origin for breast cancer previously diagnosed as metachronous vulvar ectopic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 70.

Time Intervals between Double Primary Breast and Ovarian Cancers and Survival Outcomes of Patients with Both Cancers: A SEER Database Analysis.

Background The time interval rules and survival outcomes of individuals with synchronous and metachronous breast cancer (BC) and ovarian cancer (OC) were examined in this retrospective population-based investigation. Methods The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to create a cohort of people diagnosed with BC and OC between 1973 and 2015. Patients were separated into three groups: those with main BC followed by primary OC (group 1), those with synchronous primary breast and ovarian cancer (group 2), and those with OC prior to BC (group 3). The Kaplan-Meier technique was used to assess overall survival (OS) and cancer-specific survival (CSS). Results A total of 4,975 patients were identified: 2,929 patients in group 1, 680 patients in group 2, and 1,366 patients in group 3. The average duration between these tumors was 60 months (range 0–499). Approximately 50% of second primary cancer cases occurred during the first 60 months of the first primary cancer diagnosis, and more than 70% occurred within the first 120 months. The median survival time for 4,975 individuals was 140 months. Group 2 had the smallest median OS (35 months), whereas group 3 had the longest (45 months) (239 months). Conclusions The majority of second primary cancer cases occurred during the first 120 months following the diagnosis of the first original malignancy. Individuals who had primary OC prior to BC had better prognoses, whereas patients who had synchronous BC and OC had worse prognoses.

Study of the level of tumor markers and mutations in the BRCA1/2 genes in breast cancer patients with metachronous tumors.

e12563 Background: Primary multiple malignant tumors are more common in women with breast cancer (BC). However, the difference in the frequency of mutations in the BRCA1/2 genes in metachronous BC tumors has not been fully studied, and there are also conflicting data on the increase in the level of specific tumor markers in this category of patients. Methods: The survey included 58 patients with BC with II-III clinical stages of the disease, of which metachronous tumors in terms of 6 months or more were found in 26 (44.8%) patients, among them metachronous cancer of the second breast - in 14 (53 .8%), cancer of the body of the uterus - in 7 (26.9%) and ovarian cancer - in 5 (19.2%) patients. In the control group of 32 (55.2%) patients with initially diagnosed BC, with the same stages of the disease. Tumor markers were determined in the peripheral venous blood of patients using reagent kits for ELISA analysis produced in Russia. The study of mutations in the BRCA1/2 genes was performed using sequencing on the Illumina MiSeq platform in tumor samples from waxed histological blocks. Library sequencing was performed using MiSeq Reagent Kit v2. Results: ELISA analysis of the level of tumor markers in patients with BC showed that with the development of metachronous cancer, the studied markers were more common than in the control group. In patients with metachronous tumors, elevated levels of CA-125 occurred in 10 (38.5%) patients, CA-15-3 - in 8 (30.8%), CA-19-9 - in 4 (15.4%), AFP - in 5 (19.2%), CEA - in 6 (23.1%). In the control group, CA-125 was found in 6 (18.8%) patients, CA-15-3 - in 5 (15.6%), CA-19-9 - in 2 (6.3%), AFP - in 1 (3.1%), CEA - in 2 (6.3%). Excess levels significant for diagnosis were observed for CA-125 and CA-15-3 in both groups of patients, but in the group of patients with BC with metachronous tumors, these figures were approximately 2 times higher. In the rest of the patients, the oncomarkers under consideration did not reach values significant for diagnosis. The total incidence of patients with clinically significant germline variants in the BRCA1/2 genes in the control group was 5 (15.6%), of which there were predominantly patients with an increased frequency in the population (5382insC, 4154del4, C61G). The total incidence of BC patients with metachronous tumors with germline and somatic variants in the BRCA1/2 genes was 16 (61.5%), with an increased frequency in the same population, mainly in patients with germline mutations. Conclusions: Dynamic study of the level of tumor markers CA-125 and CA-15-3 and CA-19-9 may be useful in the preventive examination of patients with a history of BC as an early diagnosis of the development of metachronous tumors in this category of patients. The most important diagnostic unfavorable factor in the development of metachronous tumors in the examined BC patients was germline mutations in the BRCA1/2 genes.

Outcome and risk factors for local recurrence after breast conserving surgery in patients affected by ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is a tumor with long term survival and low local recurrence rate. Although the progression of these lesions is rare, the current guidelines recommend breast conservating surgery (BCS) with adjuvant radio and/or endocrine therapy, often resulting in an overtreatment for patients. The aim of this single-center study was to evaluate the long-term outcome of the breast conservating surgery of DCIS followed by adjuvant radio and/or endocrine therapy and to identify prognostic factors associated with the risk of recurrence. Patients treated for DCIS with BCS and radiation therapy between March 2006 and January 2019 were retrospectively reviewed using a prospectively maintained database. Analysis of the potential risk factors was performed to evaluate the risk of subsequent ipsilateral and contralateral recurrence. Out of 2894 patients, two hundred eighty-eight (10%) patients were treated for DCIS. After a median follow-up of 85 months (IQR 27-124), the incidence of recurrence was 6% (18 patients). Nine of them (3%) had an ipsilateral local recurrence (LR) with a median disease-free survival of 19 months (IQR 12-35). The remaining nine patients had contralateral metachronous breast cancer (CBC) with a median DFS of 29 months (IQR 14-36). Margin status, multifocality, hormone receptor status and Her-2/Basal-like subtype were identified as risk factors for the local recurrence with a OR of 5.58 (1.44-21.54), 7.46(1.89-24.48) 0.25 (0.06-0.96) and 4.86 (1.26-18.71) respectively. DCIS had been confirmed to have long term survival. Margin status, multifocality, hormone receptor status and Her-2/Basal-like subtype could be identified as reliable risk factors for the progression of the disease.

BRCA 1–2 Incidence in Synchronous and Metachronous Breast Cancer: a Tertiary Center Study

BRCA 1–2 Incidence in Synchronous and Metachronous Breast Cancer: a Tertiary Center Study