Ductal Carcinoma Of Breast Research Articles

A dedicated structured data set for reporting of invasive carcinoma of the breast in the setting of neoadjuvant therapy: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations, is an initiative aimed at providing a unified international approach to reporting cancer. ICCR recently published new data sets for the reporting of invasive breast carcinoma, surgically removed lymph nodes for breast tumours and ductal carcinoma in situ, variants of lobular carcinoma in situ and low-grade lesions. The data set in this paper addresses the neoadjuvant setting. The aim is to promote high-quality, standardised reporting of tumour response and residual disease after neoadjuvant treatment that can be used for subsequent management decisions for each patient. The ICCR convened expert panels of breast pathologists with a representative surgeon and oncologist to critically review and discuss current evidence. Feedback from the international public consultation was critical in the development of this data set. The expert panel concluded that a dedicated data set was required for reporting of breast specimens post-neoadjuvant therapy with inclusion of data elements specific to the neoadjuvant setting as core or non-core elements. This data set proposes a practical approach for handling and reporting breast resection specimens following neoadjuvant therapy. The comments for each data element clarify terminology, discuss available evidence and highlight areas with limited evidence that need further study. This data set overlaps with, and should be used in conjunction with, the data sets for the reporting of invasive breast carcinoma and surgically removed lymph nodes from patients with breast tumours, as appropriate. Key issues specific to the neoadjuvant setting are included in this paper. The entire data set is freely available on the ICCR website. High-quality, standardised reporting of tumour response and residual disease after neoadjuvant treatment are critical for subsequent management decisions for each patient.

Resección de metástasis pancreáticas: análisis de resultados quirúrgicos y oncológicos. Estudio de cohorte retrospectiva.

Background: Pancreatic metastases are rare but are likely to be diagnosed more frequently in the future due to the increase in oncology surveillance programs. Objective: The aim of this study was to describe the surgical and oncologic outcomes of a series of patients undergoing surgery for pancreatic metastases. Materials and methods: We conducted a retrospective, descriptive, and multicenter cohort study on patients who underwent pancreatic resections for metastases in the pancreas by the same surgical group between January 2016 and December 2022 in three healthcare providers. Results: A total of 19 patients were operated on, mean age was 59 years (45-79), and 11 were women with good performance status and no other evidence of oncologic disease. Clear cell renal cell carcinoma was the primary tumor in 14 cases (7 diagnosed during surveillance), and the remaining primary tumors were one case of breast ductal carcinoma, one testicular cancer, one colorectal cancer, one melanoma and one cervical cancer. The surgical techniques used were pancreatectomies and splenectomies in 7 patients (5 via laparoscopy and 2 conventional procedures), 4 enucleations (3 conventional procedures and 1 laparoscopic surgery), 3 conventional cephalic pancreaticoduodenectomies, 2 conventional central pancreatectomies and one spleen-preserving distal pancreatectomy. No deaths were reported within 90 days of surgery, and overall survival and disease-free survival were 58 and 53 months, respectively. Conclusion: Resection of pancreatic metastases is safe and provides good oncologic outcomes and overall survival when performed with a multidisciplinary approach in centers with a high volume of hepatobiliary and pancreatic surgeries and in selected cases

A Rare Combination of Breast, and Thyroid Carcinoma, with Superadded COVID-19 Infection in Mother: Struggle of a Doctor as a Daughter – Case Report

Introduction: COVID-19 pandemic has severely affected the diagnosis and management of cancer patients to a large extent, with many patients being diagnosed at a later stage, and many are not able to get appropriate treatment. Furthermore, cancer patients are more prone to suffer from severe COVID-19 infection and its associated morbidity and mortality. Breast cancer is one of the commonest cancers affecting women worldwide and its number is projected to increase sharply in the post- COVID-19 era due to a serious fall in screening modalities, as patients stopped reporting to the hospital because of lockdown, movement restrictions, and fear of contracting the infection. Case Presentation: The present case report briefs a mother's sufferings and the impact it has on a daughter who is a doctor herself. It reports a rare combination of two primaries in the breast and thyroid in an asymptomatic patient with a rare mutation of the BLM gene detected incidentally. The patient was successfully operated on for stage IB ductal carcinoma breast with hemithyroidectomy and was put on chemotherapy with Cyclophosphamide 1000mg (600mg/m2) and Doxorubicin 100 mg (60mg/m2) per cycle on day one every fortnightly followed by four cycles of Paclitaxel 175mg/m2 every fortnightly. After the second cycle, the patient developed severe neutropenia and COVID-19 infection with atypical symptoms that severely involved her lungs, leading to the loss of the patient. Conclusion: With the onset of the COVID-19 pandemic, thousands of cancer patients have lost their lives, not due to cancer directly but due to failed early detection, treatment, loss of follow-up, and superadded severe COVID-19 infection.

TransNeT-CGP: A cluster-based comorbid gene prioritization by integrating transcriptomics and network-topological features

The local disruptions caused by the genes of one disease can influence the pathways associated with the other diseases resulting in comorbidity. For gene therapies, it is necessary to prioritize the key genes that regulate common biological mechanisms to tackle the issues caused by overlapping diseases. This work proposes a clustering-based computational approach for prioritising the comorbid genes within the overlapping disease modules by analyzing Protein-Protein Interaction networks. For this, a sub-network with gene interactions of the disease pair was extracted from the interactome. The edge weights are assigned by combining the pairwise gene expression correlation and betweenness centrality scores. Further, a weighted graph clustering algorithm is applied and dominant nodes of high-density clusters are ranked based on clustering coefficients and neighborhood connectivity. Case studies based on neurodegenerative diseases such as Amyotrophic Lateral Sclerosis- Spinal Muscular Atrophy (ALS-SMA) pair and cancers such as Ovarian Carcinoma-Invasive Ductal Breast Carcinoma (OC-IDBC) pair were conducted to examine the efficacy of the proposed method. To identify the mechanistic role of top-ranked genes, we used Functional and Pathway enrichment analysis, connectivity analysis with leave-one-out (LOO) method, analysis of associated disease-related protein complexes, and prioritization tools such as TOPPGENE and Heml2.0. From pathway analysis, it was observed that the top 10 genes obtained using the proposed method were associated with 10 pathways in ALS-SMA comorbidity and 15 in the case of OC-IDBC, while that in similar methods like SAPDSB and S2B were 4, 6 respectively for ALS-SMA and 9, 10 respectively for OC-IDBC. In both case studies, 70 % of the disease-specific benchmark protein complexes were linked to top-ranked genes of the proposed method while that of SAPDSB and S2B were 55 % and 60 % respectively. Additionally, it was found that the removal of the top 10 genes disconnect the network into 14 distinct components in the case of ALS-SMA and 9 in the case of OC-IDBC. The experimental results shows that the proposed method can be effectively used for identifying key genes in comorbidity and can offer insights about the intricate molecular relationship driving comorbid diseases.

Uncommon Metachronicity: Breast and Endometrial Carcinomas in a Young Woman with No Familial Cancer History - A Case Report

Background: Worldwide, breast and endometrial carcinomas are the two most common cancers of women, but their coexistence in a woman <40 years of age is a rare event. The risk of developing a new second primary cancer is higher in cancer survivors compared to those without a history of cancer. The exact pathogenesis of two different primary malignancies is not clear. Still, the coexistence of breast and endometrial carcinoma may be due to germline mutations of p53, BRCA 1, and BRCA 2 genes, environmental, hereditary, and immune-mediated factors. Case Presentation: The present case report briefs the finding of a 37-year-old woman who presented to the Gynecological outpatient department with complaints of abnormal uterine bleeding and a solid irregular lump in the upper outer quadrant of the right breast and the right axilla. She had a history of modified radical mastectomy for left breast ductal carcinoma five years back. She was diagnosed as a case of metachronous endometrial carcinoma (stage IA) with a recurrence of invasive ductal carcinoma in the right breast with metastasis to the right axillary lymph node. Conclusion: The metachronous development of breast and endometrial carcinoma in young women is relatively rare. In young patients <40 years of age with gynecological or breast carcinoma, a thorough work-up, including genetic testing and follow-up, should be done for early diagnosis of metachronous or synchronous primary malignancies of other organs.

Synchronous double primary small cell lung cancer and invasive ductal breast carcinoma: a case report

BackgroundAlthough lung and breast cancers are common malignancies, the occurrence of primary synchronous neoplasms involving these organs has been rarely reported in literature.Case presentationA 75-year-old female patient presented at a local hospital with a ten-day history of dizziness and slurred speech. A CT contrast-enhanced scan revealed a 4.2 cm mass in the lower lobe of the right lung and a 3.8 cm space-occupying lesion in the right breast. Subsequent breast ultrasound identified a hypoechoic lesion measuring5.41 × 4.75 × 3.06 cm in the right breast, and an ultrasound-guided biopsy confirmed the presence of infiltrating ductal carcinoma of the right breast. The immunohistochemistry analysis of the breast mass revealed positive staining for ER, PR, HER-2, AR and Ki67 in the tumor cells, while negative staining was observed for P63, Calponin, CK5/6 and CK14. MR imaging of the head detected abnormal signals in the right frontal lobe (3.6 cm×2.9 cm in size), left cerebellar hemisphere, and punctate enhancement in the left temporal lobe, indicating potential metastasis. Pathological examination of a lung biopsy specimen confirmed the presence of small cell lung cancer (SCLC). Furthermore, immunohistochemistry analysis of the lung lesions demonstrated positive staining for TTF-1, CK-Pan, Syn, CgA, CD56, P53 (90%) and Ki67 (70%), and negative staining for NapsinA and P40 in the tumor cells. The patient’s diagnosis of SCLC with stage cT2bN0M1c IVB and brain metastases (BM), as well as invasive ductal breast carcinoma (IDC), was confirmed based on the aforementioned results. Whereupon we proposed a treatment plan consisting of whole-brain radiation (40 Gy/20fractions), focal radiotherapy (60 Gy/20fractions), and adjuvant concurrent chemotherapy with oral etoposide (50 mg on days 1 to 20).ConclusionsTo the best of our knowledge, the present case is the first of its kind to describe the synchronous double cancer, consisting of primary SCLC and IDC.

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.

Breast cancer characteristics in elderly women: A comprehensive cohort study of 7,965 patients

Purpose Breast cancer in older women is a major public health issue as there is an age-related excess mortality. Our aim was to study the tumor characteristics at diagnosis, treatment and outcomes in order to identify possible ways of improving breast cancer management in elderly women.Methods We conducted a single-institution retrospective analysis on a cohort of 7,965 women with invasive breast cancer or Ductal Carcinoma in situ (DCIS) who were treated between 2001 and 2017. This cohort was constituted with a machine learning-based tool called SENOMETRY (NCT02810093) which allowed us to extract structured data from unstructured Electronic Health Records. Patients were divided in 3 groups according to the age at diagnosis: younger (< 49, N = 2001), middle-aged (50 to 74, N = 4859) and elderly (≥ 75, N = 1105).Results In elderly women breast cancer had more favorable predictive factors (more estrogen receptors P < 0.001, less Human Epidermal growth-factor Receptor 2 overexpression P = 0.009) and prognostic factors (less Ki67 > 30 %, P = 0.001) factors. Tumors were diagnosed at a more advanced local stage (P < 0.001). Lymph node involvement decreased before 70 (ρ -0.033, P = 0.027) and increased again after this threshold (ρ +0.065, P = 0.021). Older women underwent heavier surgical procedures (P < 0.001 to 0.049) and more surgical abstention (P < 0.001) for invasive carcinomas while no difference was noted for patients with DCIS only (P ranged from 0.280 to 0.440). Older women had less chemotherapy (P < 0.001). Elderly women had higher overall mortality and lower locoregional recurrence (P < 0.001). Specific mortality increased with age after 75 (P = 0.042). No difference of relapse-free or overall survival was noted for axillary lymph node dissection compared to sentinel lymph node biopsy in elderly women, after adjustement on tumor size and lymph node involvement.Conclusion Our findings suggest that axillary surgery de-escalation and earlier diagnosis would be and accessible way of improving breast cancer management in older women.

Are better AI algorithms for breast cancer detection also better at predicting risk? A paired case–control study

BackgroundThere is increasing evidence that artificial intelligence (AI) breast cancer risk evaluation tools using digital mammograms are highly informative for 1–6 years following a negative screening examination. We hypothesized that algorithms that have previously been shown to work well for cancer detection will also work well for risk assessment and that performance of algorithms for detection and risk assessment is correlated.MethodsTo evaluate our hypothesis, we designed a case-control study using paired mammograms at diagnosis and at the previous screening visit. The study included n = 3386 women from the OPTIMAM registry, that includes mammograms from women diagnosed with breast cancer in the English breast screening program 2010–2019. Cases were diagnosed with invasive breast cancer or ductal carcinoma in situ at screening and were selected if they had a mammogram available at the screening examination that led to detection, and a paired mammogram at their previous screening visit 3y prior to detection when no cancer was detected. Controls without cancer were matched 1:1 to cases based on age (year), screening site, and mammography machine type. Risk assessment was conducted using a deep-learning model designed for breast cancer risk assessment (Mirai), and three open-source deep-learning algorithms designed for breast cancer detection. Discrimination was assessed using a matched area under the curve (AUC) statistic.ResultsOverall performance using the paired mammograms followed the same order by algorithm for risk assessment (AUC range 0.59–0.67) and detection (AUC 0.81–0.89), with Mirai performing best for both. There was also a correlation in performance for risk and detection within algorithms by cancer size, with much greater accuracy for large cancers (30 mm+, detection AUC: 0.88–0.92; risk AUC: 0.64–0.74) than smaller cancers (0 to < 10 mm, detection AUC: 0.73–0.86, risk AUC: 0.54–0.64). Mirai was relatively strong for risk assessment of smaller cancers (0 to < 10 mm, risk, Mirai AUC: 0.64 (95% CI 0.57 to 0.70); other algorithms AUC 0.54–0.56).ConclusionsImprovements in risk assessment could stem from enhancing cancer detection capabilities of smaller cancers. Other state-of-the-art AI detection algorithms with high performance for smaller cancers might achieve relatively high performance for risk assessment.

The type 2 inflammatory response favors recognition of tumor antigens by IgE in breast cancer.

Several studies describe an inverse statistical relationship between the presence of an allergy and development of cancer. However, the immunological mechanism involved in the relationship between these two degenerative diseases has not been explored. The main objective of this study was to explore the possibility that the lymphocyte T helper (Th) 2 response, a characteristic of allergy, induces recognition of tumor antigens. Patients with a clinical diagnosis of breast ductal carcinoma were included. Histopathological markers related to proliferation of tumor cells were determined (Her-2-neu, Ki-67, estrogen receptor, and progesterone receptor). IHC was performed using IgE antibodies purified from an allergy patient and from each biopsy donor patient. Serum concentrations of cytokines representative of Th1 and Th2 inflammatory responses were determined. A total of 14 patients with a confirmed diagnosis of breast ductal carcinoma were included. IHC performed on biopsies showed a weak response when using purified IgE antibodies from an allergy patient; however, IHC using the IgE of each patient as the primary antibody showed an intense and highly specific signal. Serum concentrations of cytokines of the Th2 response, that is, IL-4 (130.5 pg/mL (116-135 pg/mL)), IL-5 (202 pg/mL (191-213 pg/mL)), and IL-13 (105.5 pg/mL (98-117 pg/mL)), were significantly higher than those of the Th1 response, that is, IL-6 (86 pg/mL (79-90 pg/mL)) and INF-γ (93 pg/mL (79-99 pg/mL)). Purified IgE antibodies specifically recognize tumor cells in breast ductal carcinoma.

Complex breast reconstruction using bilateral profunda artery perforator-free-flaps in a resource-limited setting: a case report

Interestingly, the current shift in mastectomy patterns and advances in reconstruction techniques have contributed to an increasing number of patients requesting breast reconstruction postmastectomy every year. Depending on available expertise, patients can access breast reconstruction options (immediate or delayed), autologous, or implant-based. We present a case of a 36-year-old female patient 5 years into remission, having undergone mastectomy for invasive ductal carcinoma of the right breast and now preferred risk reduction surgery (prophylactic mastectomy) of her left unaffected breast with immediate reconstruction. The microsurgical technique utilized bilateral profunda artery perforator flaps from both thighs for (immediate and delayed) breast reconstruction. In our scenario, the authors had an unfavorable outcome on the side of delayed breast reconstruction (right) with a venous insufficiency diagnosis leading to unilateral complete flap loss, which was subsequently debrided and reconstructed with an obliquely-oriented pedicled Latissimus dorsi flap. In contrast, following risk reduction surgery and immediate reconstruction on the left side, the buried flap was a complete success, with the free nipple graft doing well postoperatively.

Nuclear anaplasia of positive and negative hormonal receptor (estrogen and progesterone receptor) in breast cancer cytology

Background: Breast epithelial duct cells show response to sex hormone such as estrogen and progesterone since they have receptor for estrogen and progesterone. Consequently, malignant cells from breast epithelial ductuli (Breast Ductal Carcinoma) show positivity for estrogen and progesterone receptor (ER and PR). However, when this neoplasm becomes poorly differentiated, they lost these characteristics and became ER and PR negative. On the other hand, poorly differentiated cancer cells show more nuclear enlargement that was accompanied by increase nuclear pleomorphism. This study wants to compare area of breast cancer cells nuclei and nuclear pleiomorphism in positive and negative ER and PR. Material and method: Positive and negative ER and PR breast cancer cases were collected from archive of Anatomic Pathology Department each consisting of ten to fourteen cases. Image analysis was made from each case to measure the area, diameter, and nuclear pleiomorphism. Result and discussion: There were no differences in nuclear size and pleomorphism of breast cancer cells with positive and negative ER and PR. This result show that poorly differentiated cancer cells did not accompany by increase of nuclear anaplasia. Conclusion: There is no difference of cancer cells morphology in positive and negative ER and PR. Hormonal status and anaplasia of cell nuclei can be used as independent prognostic factor to breast cancer progression.

Prognostic analysis of cT1-3N1M0 breast cancer patients who have responded to neoadjuvant therapy undergoing various axillary surgery and breast surgery based on propensity score matching and competitive risk model.

Sentinel lymph node biopsy (SLNB) in breast cancer patients with positive clinical axillary lymph nodes (cN1+) remains a topic of controversy. The aim of this study is to assess the influence of various axillary and breast surgery approaches on the survival of cN1+ breast cancer patients who have responded positively to neoadjuvant therapy (NAT). Patients diagnosed with pathologically confirmed invasive ductal carcinoma of breast between 2010 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. To mitigate confounding bias, propensity score matching (PSM) analysis was employed. Prognostic factors for both overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated through COX regression risk analysis. Survival curves were generated using the Kaplan-Meier method. Furthermore, cumulative incidence and independent prognostic factors were assessed using a competing risk model. The PSM analysis matched 4,890 patients. Overall survival (OS) and BCSS were slightly worse in the axillary lymph node dissection (ALND) group (HR = 1.10, 95% CI 0.91-1.31, p = 0.322 vs. HR = 1.06, 95% CI 0.87-1.29, p = 0.545). The mastectomy (MAST) group exhibited significantly worse OS and BCSS outcomes (HR = 1.25, 95% CI 1.04-1.50, p = 0.018 vs. HR = 1.37, 95% CI 1.12-1.68, p = 0.002). The combination of different axillary and breast surgery did not significantly affect OS (p = 0.083) but did have a significant impact on BCSS (p = 0.019). Competing risk model analysis revealed no significant difference in the cumulative incidence of breast cancer-specific death (BCSD) in the axillary surgery group (Grey's test, p = 0.232), but it showed a higher cumulative incidence of BCSD in the MAST group (Grey's test, p = 0.001). Multivariate analysis demonstrated that age ≥ 70 years, black race, T3 stage, ER-negative expression, HER2-negative expression, and MAST were independent prognostic risk factors for both OS and BCSS (all p < 0.05). For cN1+ breast cancer patients who respond positive to NAT, the optimal surgical approach is combining breast-conserving surgery (BCS) with SLNB. This procedure improves quality of life and long-term survival outcomes.

Retracted: Clinicopathological Features of 166 Cases of Invasive Ductal Breast Carcinoma and Effect of Primary Tumor Location on Prognosis after Modified Radical Mastectomy.

[This retracts the article DOI: 10.1155/2022/3158956.].

Case Presentation where MRI shows Superiority as A Modality for Breast Cancer Screening

Background: Common modalities for breast cancer screening include regular clinical breast exams (73%), annual breast sonograms (73%) for high-risk groups, and mammograms (71.5%) recommended every 3 years for high-risk groups. Despite a higher sensitivity of 89.4%, MRI is underutilized, especially among high-risk groups with the means for the test. Kenyan guidelines recommend mammography for normal-risk populations, omitting MRI for routine screening in average-risk populations. This study explores an intriguing case of a 60-year-old post-menopausal lady, with no hormone replacement history, three parities, and a smoking habit. She presented with a left-sided benign cyst but revealed an ominous, undetected lesion on the right breast, emphasizing the limitations of conventional screening modalities. Method: The patient was admitted for abdominal pain due to gastroenteritis and a breast lump on the left breast for 3 months with a strong family history of breast cancer, so she requested screening for the same. In the process, we found axillary and mediastinal lymph nodes, but the left breast showed a simple harmless cystic lesion. The right breast confirmed a lesion with irregular borders that looked suspicious, and a biopsy confirmed ductal carcinoma of the right breast. Results: The right breast that had no symptoms or signs, and no abnormality on mammogram, ultrasound, or CT scan, had a grade 3a Ductal Cancer in its initial stage that was seen on a simultaneous MRI. Conclusion: MRI could be a better choice for screening early breast cancer in high-risk groups and in those who can afford the test.

Abstract B012: Pedigree and multi-omics analyses implicate nucleotide excision repair genes, XPA, ERCC6, and ERCC8, in susceptibility to breast cancer

Abstract Background: The majority of low- and moderate-risk [odds ratios (OR) ≤ 3] susceptibility genes for peri- and post-menopausal breast cancer (≥50 years of age), particularly those with minor allele frequency (MAF) of &amp;lt;30%, have not yet been identified and/or validated. We used a hypothesis-driven integrative approach to identify breast cancer susceptibility genes by analyzing pedigree and multi-omics (genomics, transcriptomics, mutation landscape) data. Methods: We conducted pedigree analysis in 31 families with DNA repair disorders, xeroderma pigmentosum (XP), trichothiodystrophy (TTD), Cockayne syndrome (CS), XP/TTD and XP/CS. These disorders can be caused by mutations in genes involved in the nucleotide excision repair (NER) pathway such as XPA-XPG, ERCC6 and ERCC8. We estimated the frequency of hereditary breast cancer, defined as the presence of at least two cases of premenopausal breast cancer (diagnosed &amp;lt;50 years of age) or one case of premenopausal breast cancer and one case of ovarian cancer in one side of the family, in our study. Furthermore, we conducted individual analysis of four genome-wide association studies (GWAS) datasets (totaling 2961 cases and 4335 controls), individual and meta-analysis of two gene expression microarray datasets (98 cases and 163 controls), and targeted analysis of The Cancer Genome Atlas (TCGA) (522 breast cancers). All analyses involved invasive ductal breast carcinoma in women diagnosed at ≥50 years of age. Results: In an XP family with causative mutations in XPA, there were four cases of premenopausal breast cancer (including heterozygote mutation carriers), one case of ovarian cancer, and one case of prostate cancer. Comprehensive sequencing failed to identify a BRCA1 or BRCA2 mutation in this family. Overall, 7 of 31 (22.6%) families with DNA repair disorders had a family history that was compatible with hereditary breast cancer. Hence, we selected a panel of NER genes as candidates for association studies with breast cancer. Our candidate-gene association analysis of GWAS datasets suggested an increased risk of breast cancer with ERCC6 (main effect:1.29 ≤ OR ≤ 2.91, 0.005 ≤ p ≤ 0.04, 11.8 ≤ MAF ≤ 29.7%) and implicated its interaction with ERCC8 (joint effect:3.03 ≤ OR ≤ 5.31, 0.01 ≤ pinteraction ≤ 0.03). Our transcriptomics analysis identified significant upregulation of ERCC6 (p=7.95 × 10–6) and ERCC8 (p=4.67 × 10–6) in breast cancer. Our analysis of TCGA breast tumor data showed similar mutation frequency of ERCC6 (1.8%) and ERCC8 (0.3%) as known breast cancer susceptibility genes such as BLM (1.9%) and LSP1 (0.3%). Conclusion: Our integrative analyses suggest that ERCC6 may be a previously unreported low- to moderate-risk breast cancer susceptibility gene, which may also interact with ERCC8. ERCC6 and ERCC8 code for the main components of the transcription-coupled (TC) repair sub-pathway of the NER. TC-NER protects against genotoxic agents, such as free radicals and reactive oxygen species. Our results provide a deeper biologic insight and leads for prevention of common breast cancer. Citation Format: Roxana Moslehi, Amiran Dzutsev. Pedigree and multi-omics analyses implicate nucleotide excision repair genes, XPA, ERCC6, and ERCC8, in susceptibility to breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B012.

Association of integrin expression in tumor tissue with hematogenic metastasis of breast cancer

Background. Distant hematogenous metastasis is the leading cause of tumor-related death from breast cancer. To prevent metastasis, prognostic markers for predicting the risk and location of hematogenous metastases are required. In this regard, it is of great importance to study the expression of integrins involved in the most important processes that determine the progression of cancer.The objective of the study was to investigate the association of integrin expression in tumor tissue with hematogenous metastasis of patients with breast cancer.Material and Methods. The study included 72 patients (average age – 51 ± 12 years) with stage T1–4N0–3M0–1 unspecifed invasive ductal breast carcinoma, with all molecular biological subtypes (luminal A, luminal B, HER2-positive and triple negative). The biopsy material was examined before the start of antitumor treatment. Expression of integrins in tumor cells was assessed by immunohistochemical methods. Antibodies CD61 (integrin β3, Invitrogen, USA), CD104 (integrin β4, Invitrogen, USA), CD51 (integrin αV, Invitrogen, USA) were used.Results. In patients with hematogenous metastases, cytoplasmic rather than cytoplasmic/membrane colocalization, CD61 expression was more often detected (p=0.036). Cytoplasmic and membrane colocalization of CD104 was more frequently detected in brain metastases compared to lung (p=0.026) and bone (p=0.036) metastases. Expression of CD51 integrin was more often associated with lung metastases than with bone metastases (p=0.045).Conclusion. The frequency and localization of hematogenous metastases in breast cancer patients are associated with the presence and localization of CD61, CD104 and CD51 expression in the tumor cell.

Zosteriform cutaneous metastases: A rare occurrence in ductal carcinoma breast after mastectomy

Zosteriform cutaneous metastases: A rare occurrence in ductal carcinoma breast after mastectomy

Evaluating Treatment Response in Breast Cancer: A Case Report on Static Metastatic Disease on Bone Scans

Background: We report a case of a 54-year-old female patient with carcinoma of the left breast with persistent methylene diphosphonate (MDP) uptake in sclerotic osseous lesions. These lesions were finally declared treated osseous metastatic lesions due to non-avidity on the F18 FDG PET-CT scan, normalization of CA-15.3, and resolution of bone pains. To the best of our knowledge, this has not been reported previously. Case presentation: A 54-year-old woman with persistent backache was referred for further evaluation by a Tc99m MDP bone scan. A Tc-99mmMDP bone scan showed wide-spread skeletal metastatic disease. Magnetic resonance imaging (MRI) showed extensive marrow disease involving the spine and iliac bones. A bone marrow biopsy revealed metastatic carcinoma with a tumor phenotype favoring breast primary. On further workup, the patient was diagnosed with invasive ductal carcinoma of the left breast and was treated with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors along with hormone therapy and bisphosphonates, followed by radiation therapy for bone metastasis. The skeletal metastatic disease remains static on three consecutive Tc99m MDP bone scans, despite the clinical improvement and decreased tumor marker levels. The F18-FDG-FDG-CT scan done for monitoring treatment response revealed multiple non-avid sclerotic osseous lesions, favoring treatment response. The patient was continued with the same treatment, and a follow-up Tc99m MDP bone scan after 6 months revealed no interval change in the reported lesions compared to the initial scan. However, a synergistically performed F18 FDG PET-CT scan again showed multiple non-avid sclerotic osseous lesions suggestive of treated metastasis. Conclusion: This case highlights the importance of 18F-FDG PET-CT in evaluating the treatment response, especially in patients with symptomatic improvement and falling tumor marker levels with static disease on repeated Tc99m MDP bone scans.

Total laparoscopic curative resection of a rare pan-necrotic solid pseudopapillary pancreatic tumor in a child

Abstract: Tumor necrosis is purportedly related to an aggressive tumor phenotype in few solid tumors such as pancreatic ductal carcinoma, breast and bladder carcinomas. We hereby report a unique pan-necrotic (98% of tumor) pseudopapillary pancreatic tumor in a 13-year-old child who underwent laparoscopic subtotal pancreatectomy and curative resection. To our knowledge, this is the first account of complete tumor necrosis in a pancreatic neoplasm with curative laparoscopic resection. This case report has discussed the literary background of various mechanisms of cell death in solid tumors to explain the plausible cause of unique pan-tumor necrosis.