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1.
Clin Imaging ; 111: 110189, 2024 Jul.
Article En | MEDLINE | ID: mdl-38759599

OBJECTIVES: Women harboring germline BRCA1/BRCA2 pathogenic sequence variants (PSVs) are at an increased risk for breast cancer. There are no established guidelines for screening during pregnancy and lactation in BRCA carriers. The aim of this study was to evaluate the utility of whole-breast ultrasound (US) screening in pregnant and lactating BRCA PSV carriers. METHODS: Data were retrospectively collected from medical records of BRCA PSV carriers between 2014 and 2020, with follow-up until 2021. Associations between imaging intervals, number of examinations performed and pregnancy-associated breast cancers (PABCs) were examined. PABCs and cancers diagnosed at follow-up were evaluated and characteristics were compared between the two groups. RESULTS: Overall 212 BRCA PSV carriers were included. Mean age was 33.6 years (SD 3.93, range 25-43 years). During 274 screening periods at pregnancy and lactation, eight (2.9 %) PABCs were diagnosed. An additional eight cancers were diagnosed at follow-up. Three out of eight (37.5 %) PABCs were diagnosed by US, whereas clinical breast examination (n = 3), mammography (n = 1) and MRI (n = 1) accounted for the other PACB diagnoses. One PABC was missed by US. The interval from negative imaging to cancer diagnosis was significantly shorter for PABCs compared with cancers diagnosed at follow-up (3.96 ± 2.14 vs. 11.2 ± 4.46 months, P = 0.002). CONCLUSION: In conclusion, pregnant BRCA PSV carriers should not delay screening despite challenges like altered breast tissue and hesitancy towards mammography. If no alternatives exist, whole-breast ultrasound can be used. For lactating and postpartum women, a regular screening routine alternating between mammography and MRI is recommended.


BRCA1 Protein , Breast Neoplasms , Early Detection of Cancer , Lactation , Ultrasonography, Mammary , Humans , Female , Pregnancy , Breast Neoplasms/genetics , Breast Neoplasms/diagnostic imaging , Adult , Retrospective Studies , Early Detection of Cancer/methods , Ultrasonography, Mammary/methods , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/diagnostic imaging , Mammography/methods , Heterozygote
5.
JAMA ; 331(1): 49-59, 2024 01 02.
Article En | MEDLINE | ID: mdl-38059899

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.


Breast Neoplasms , Genes, BRCA1 , Genes, BRCA2 , Pregnancy Complications, Neoplastic , Pregnancy Outcome , Adult , Female , Humans , Pregnancy , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Disease-Free Survival , Germ-Line Mutation , Retrospective Studies , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/mortality , Internationality
6.
Bioengineered ; 13(1): 291-307, 2022 01.
Article En | MEDLINE | ID: mdl-34974815

Breast cancer is the most common malignancy in females and poses a significant health threat to women. Pregnancy-associated plasma protein-A (PAPPA) is highly expressed in pregnancy-associated breast cancer (PABC) tissues. In this study, we investigated the functional role of PAPPA in regulating the malignant phenotype of breast cancer. We first examined the expression level of PAPPA in PABC tissue and breast cancer cell lines using quantitative real-time polymerase-chain reaction (qRT-PCR) and western blot. Next, the functional role of PAPPA in breast cancer cells was validated by overexpression and knockdown experiments. Cell counting kit-8 (CCK-8) proliferation assay, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, wound healing and transwell invasion assay were used to examine cell proliferation, migration, and invasion ability. We further identified the microRNA target regulating PAPPA and studied its functional role. Finally, we examined the impact of PAPPA on the tumorigenesis and metastasis of breast cancer in mice model. Our study revealed that PAPPA was upregulated in PABC tissues and breast cancer cells. Overexpression of PAPPA promoted cell proliferation, motility, invasion, and epithelial-mesenchymal transition (EMT). We further identified miR-497-5p as a negative regulator of PAPPA, which suppressed cell proliferation, migration, invasion, and EMT in breast cancer cells. We also validated the oncogenic role of PAPPA in the mouse xenograft model. Collectively, our study suggests that PAPPA is an oncogenic protein highly expressed in PABC tissues and promotes breast cancer progression, which could serve as a novel therapeutic target for breast cancer.


Breast Neoplasms/pathology , MicroRNAs/genetics , Pregnancy Complications, Neoplastic/pathology , Pregnancy-Associated Plasma Protein-A/genetics , Pregnancy-Associated Plasma Protein-A/metabolism , Up-Regulation , Animals , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Case-Control Studies , Cell Line, Tumor , Cell Movement , Cell Proliferation , Disease Progression , Epithelial-Mesenchymal Transition , Female , Gene Expression Regulation, Neoplastic , Humans , MCF-7 Cells , Mice , Neoplasm Metastasis , Neoplasm Transplantation , Pregnancy , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/metabolism
7.
BMC Cancer ; 21(1): 572, 2021 May 19.
Article En | MEDLINE | ID: mdl-34011307

BACKGROUND: Pregnancy-associated breast cancer (PABC) defined as breast cancer diagnosed during gestation, lactation or within 1 year after delivery, represents a truly challenging situation with significantly increasing incidence rate. The genomic background of PABC has only recently been addressed while the underlying mechanisms of the disease still remain unknown. This analysis aims to further elucidate the frequency of PABC cases attributable to genetic predisposition and identify specific cancer susceptibility genes characterizing PABC. METHODS: A comprehensive 94-cancer gene panel was implemented in a cohort of 20 PABC patients treated in our clinic and descriptive correlation was performed among the results and the patients' clinicopathological data. RESULTS: In the present study, 35% of PABC patients tested carried pathogenic mutations in two known cancer predisposition genes (BRCA1 and CHEK2). In total, 30% of the patients carried BRCA1 pathogenic variants. An additional 5% carried pathogenic variants in the CHEK2 gene. Variants of unknown/uncertain significance (VUS) in breast cancer susceptibility genes BRCA2, CHEK2 and BRIP1 were also identified in three different PABC patients (15%). Not all patients carrying germline mutations reported known family history of cancer. CONCLUSIONS: Genetic testing should be considered as an option for PABC patients since the disease is highly associated with genetic susceptibility among other predisposing factors. Germline mutation identification may further modify PABC management approach and improve the prognostic outcome.


Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Genetic Predisposition to Disease , Pregnancy Complications, Neoplastic/genetics , Adult , BRCA1 Protein/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Checkpoint Kinase 2/genetics , Cohort Studies , DNA Mutational Analysis , Fanconi Anemia Complementation Group Proteins/genetics , Female , Genetic Testing/statistics & numerical data , Germ-Line Mutation , Humans , Middle Aged , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/epidemiology , Prevalence , RNA Helicases/genetics
8.
Int J Surg Pathol ; 29(8): 882-886, 2021 Dec.
Article En | MEDLINE | ID: mdl-33827325

Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.


Biomarkers, Tumor/analysis , Breast/pathology , Carcinoma, Acinar Cell/diagnosis , Pregnancy Complications, Neoplastic/diagnosis , Triple Negative Breast Neoplasms/diagnosis , Adult , Anoctamin-1/analysis , Anoctamin-1/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Breast/surgery , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/pathology , DNA Mutational Analysis , Female , GATA3 Transcription Factor/analysis , GATA3 Transcription Factor/metabolism , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry , Mastectomy , Neoplasm Proteins/analysis , Neoplasm Proteins/metabolism , Polymorphism, Single Nucleotide , Pregnancy , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/pathology , Proto-Oncogene Proteins c-ret/genetics , Sentinel Lymph Node Biopsy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Tumor Suppressor Protein p53/genetics
9.
Breast Cancer Res Treat ; 186(3): 699-704, 2021 Apr.
Article En | MEDLINE | ID: mdl-33635448

PURPOSE: Breast cancer is the most common type of malignancy in pregnant women, occurring approximately once in every 3000 pregnancies. Pregnancy-associated breast cancer (PABC) is commonly defined as breast cancer diagnosed during or within one year after pregnancy, and it accounts for up to 6.9% of all breast cancers in women younger than 45 years old. Whether these cancers arise before or during pregnancy, and whether they are stimulated by the high hormonal environment of pregnancy, is currently unknown. This study assesses the histopathological profile of PABC in a large Dutch population-based cohort. METHODS: We identified 744 patients with PABC (in this cohort defined as breast cancer diagnosed during or within 6 months after pregnancy) diagnosed between 1988 and 2019, in the nationwide Dutch Pathology Registry (PALGA). An age-matched PALGA cohort of unselected breast cancer patients (≤ 45 years), diagnosed between 2013 and 2016, was used as a control. Histopathologic features of both cohorts were compared. RESULTS: The median age of PABC patients was 34.3 years old (range 19-45 years) and most breast cancers were diagnosed during pregnancy (74.2%). As compared to age-matched controls, PABC patients had tumors of higher Bloom-Richardson grade (grade I: 1.5% vs. 12.4%, grade II: 16.9% vs. 31.3%, grade III: 80.3% vs. 39.5%, p < 0.0001). Furthermore, estrogen (ER)- and progesterone (PR)-receptor expression was less frequently reported positive (ER: 38.9% vs. 68.2% and PR: 33.9% vs. 59.0%, p < 0.0001), while a higher percentage of PABC tumors overexpressed HER2 (20.0% vs. 10.0%, p < 0.0001). The most observed intrinsic subtype in PABC was triple-negative breast cancer (38.3% vs. 22.0%, p < 0.0001), whereas hormone-driven cancers were significantly less diagnosed (37.9% vs. 67.3%, p < 0.0001). CONCLUSION: This study, based on a large population-based cohort of 744 PABC Dutch patients, underlines the more aggressive histopathologic profile compared to age-matched breast cancer patients ≤ 45 years. Further in-depth genetic analysis will be performed to unravel the origin of this discriminating phenotype. It definitely calls for timely detection and optimal treatment of this small but delicate subgroup of breast cancer patients.


Breast Neoplasms , Pregnancy Complications, Neoplastic , Triple Negative Breast Neoplasms , Adult , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Cohort Studies , Female , Humans , Middle Aged , Pregnancy , Pregnancy Complications, Neoplastic/epidemiology , Pregnancy Complications, Neoplastic/genetics , Prognosis , Receptor, ErbB-2/genetics , Receptors, Progesterone/genetics , Young Adult
10.
Am J Hematol ; 96(3): 354-366, 2021 03 01.
Article En | MEDLINE | ID: mdl-33296529

Pregnancy in the context of myeloproliferative neoplasms (MPN) poses unique fetal and maternal challenges. Current literature in this regard mostly involves essential thrombocythemia (ET) and less so polycythemia vera (PV) or myelofibrosis. In ET, live birth rate is estimated at 70% with first trimester fetal loss (˜ 30%) as the major complication. Risk of pregnancy-associated complications is higher in PV, thus mandating a more aggressive treatment approach. Herein, we appraise the relevant literature, share our own experience and propose management recommendations. Aspirin therapy may offer protection against fetal loss; however the additive benefit of systemic anticoagulation or cytoreductive therapy, in the absence of high risk disease, is unclear. We recommend cytoreductive therapy in the form of interferon alpha in all high risk and select low-risk ET and PV patients with history of recurrent fetal loss, prominent splenomegaly or suboptimal hematocrit control with phlebotomy. In addition, all women with PV should maintain strict hematocrit control <45% with the aid of phlebotomy. Systemic anticoagulation with low molecular weight heparin is advised in patients with history of venous thrombosis. Further clarification awaits prospective clinical trials that implement risk adapted therapeutic interventions.


Myeloproliferative Disorders/therapy , Pregnancy Complications/therapy , Abortion, Habitual/etiology , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/prevention & control , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Combined Modality Therapy , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Infant, Low Birth Weight , Infant, Newborn , Interferon-alpha/therapeutic use , Live Birth , Multicenter Studies as Topic , Mutation , Myeloproliferative Disorders/drug therapy , Myeloproliferative Disorders/genetics , Phlebotomy , Platelet Count , Practice Guidelines as Topic , Preconception Care , Pregnancy , Pregnancy Complications/drug therapy , Pregnancy Complications/genetics , Pregnancy Complications, Neoplastic/drug therapy , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/therapy , Pregnancy Outcome , Prenatal Care , Puerperal Disorders/therapy , Retrospective Studies , Thrombophilia/drug therapy , Thrombophilia/etiology , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
12.
J Cutan Pathol ; 48(1): 86-89, 2021 Jan.
Article En | MEDLINE | ID: mdl-32640078

Clear-cell carcinoma (CCC) is an uncommon malignant tumor of minor salivary glands. It characteristically has a low-grade morphology and a favorable outcome by most reports. An EWSR1-ATF1 fusion can be detected in the majority of cases. We present a rare case of CCC, which had an aggressive course with the development of cutaneous metastases. Practicing dermatopathologists should be aware of this tumor given its low-grade appearance and histopathologic resemblance to other primary cutaneous adnexal and metastatic neoplasms.


Adenocarcinoma, Clear Cell/secondary , Head and Neck Neoplasms/secondary , Salivary Gland Neoplasms/pathology , Skin Neoplasms/secondary , Adenocarcinoma, Clear Cell/genetics , Adult , Female , Head and Neck Neoplasms/genetics , Humans , Oncogene Proteins, Fusion , Pregnancy , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/pathology , Salivary Gland Neoplasms/genetics , Salivary Glands, Minor/pathology , Scalp/pathology , Skin Neoplasms/genetics
13.
IEEE/ACM Trans Comput Biol Bioinform ; 18(3): 1035-1048, 2021.
Article En | MEDLINE | ID: mdl-32776880

Breast-cancer (BC) is the most common invasive cancer in women, with considerable death. Given that, BC is classified as a hormone-dependent cancer, when it collides with pregnancy, different questions may arise for which there are still no convincing answers. To deal with this issue, two new frameworks are proposed within this paper: CoRaM and Dist-CoRaM. The former is the first unified framework dedicated to the extraction of a generic basis of Correlated-Rare Association rules from gene expression data. The proposed approach has been successfully applied on a breast-cancer Gene Expression Matrix (GSE1379) with very promising results. The latter, the Dist-CoRaM approach, is a big-data processing based on Apache spark framework, dealing with correlation mining from micro-array pregnancy associated breast-cancer assays (PABC) data. It is successfully applied on the (GSE31192) gene expression matrix (GEM). The correlated patterns of gene-sets shed light on the fact that PABC exhibits heightened aggressiveness compared to cancers for Non-PABC women. Our findings suggest that higher levels of estrogen and progesterone hormones, unfortunately, are very keen to the increase of the tumor aggressiveness and the proliferation of the cancer.


Breast Neoplasms/genetics , Pregnancy Complications, Neoplastic/genetics , Transcriptome/genetics , Algorithms , Computational Biology , Data Mining , Female , Humans , Machine Learning , Pregnancy
14.
Hum Pathol ; 106: 62-73, 2020 12.
Article En | MEDLINE | ID: mdl-32971128

Inflammatory myofibroblastic tumors (IMTs) of the uterus are often associated with pregnancy and are delivered with the placenta. We describe the clinical, pathologic, and molecular findings in nine cases of placenta-associated IMT (PaIMT). All the lesions were incidentally discovered at delivery or on placental pathological examination. The maternal age ranged from 21 to 41 (mean = 30.6) years. Eight patients had high-risk pregnancies, and when known, all patients were multigravida. Macroscopically, eight tumors were well defined, ranging in size from 2 to 6 cm present at the maternal surface of the placenta (n = 3) and membranes (n = 4) or separately delivered with the placenta (n = 2). All nine lesions revealed classical IMT morphology with spindle cells associated with a lymphoplasmacytic infiltrate and thin elongated vessels. Five showed decidualization, and five showed coagulative necrosis. All tumors expressed CD10. Of the seven tumors that were anaplastic lymphoma kinase (ALK) positive, six were confirmed to have an ALK rearrangement by fluorescence in situ hybridization (FISH), whereas one failed FISH testing. Fusions included TIMP3-ALK (n = 3), THBS1-ALK (n = 2), and a novel SYN3-ALK fusion (n = 1). Clinical follow-up was available in three patients, with no recurrence reported. There appears to be an increased frequency of uterine IMTs in pregnancy and associated with the placenta. No PaIMT has behaved aggressively, although follow-up has been quite limited. This may speak to a specific behavior of these tumors when associated with pregnancy.


Myofibroblasts/pathology , Placenta/pathology , Pregnancy Complications, Neoplastic/pathology , Uterine Neoplasms/pathology , Adult , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Databases, Factual , Female , Gene Fusion , Humans , Hysterectomy , Incidental Findings , Myofibroblasts/chemistry , Placenta/chemistry , Pregnancy , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/metabolism , Pregnancy Complications, Neoplastic/surgery , Treatment Outcome , Tumor Burden , Uterine Neoplasms/chemistry , Uterine Neoplasms/genetics , Uterine Neoplasms/surgery , Young Adult
15.
Adv Exp Med Biol ; 1252: 129-132, 2020.
Article En | MEDLINE | ID: mdl-32816272

Genetic testing should be offered to all women less than 40 years of age who are diagnosed with breast cancer, and patients with PABC are generally among them. However, there is no specific study about these cases, and whether genetic testing should be carried out during or after pregnancy is not known. Generally, testing before delivery should only be performed if positive results change management plans, such as undergoing fetal testing and choosing mastectomy instead of breast conserving surgery.


Breast Neoplasms/genetics , Genetic Testing , Lactation , Pregnancy Complications, Neoplastic/genetics , Adult , Breast Neoplasms/diagnosis , Female , Humans , Mastectomy , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Prenatal Diagnosis
16.
J Assist Reprod Genet ; 37(9): 2273-2277, 2020 Sep.
Article En | MEDLINE | ID: mdl-32592075

Molar pregnancies are benign trophoblastic diseases associated with a risk of malignant transformation. If aetiology remains mostly unknown, the risk of recurrent molar pregnancy is around 1.5% after one molar pregnancy and around 25% after 2 molar pregnancies. In the later situation, genetic mutations have been described, increasing hugely this risk. In case of mutations, probability to obtain a normal pregnancy is estimated around 1.8%. We report the case of a Caucasian 30-year-old woman whose previous five spontaneous pregnancies had a negative outcome: a spontaneous miscarriage and then 4 complete hydatidiform moles. Genetic testing revealed that the patient carried two heterozygous mutations in the NLRP7 gene (c.2982-2A > G and Y318CfsX7). According to this, counselling was conducted to advocate for oocyte donation in order to obtain a normal pregnancy. This technique enabled a complication-free, singleton pregnancy that resulted in a healthy term live birth of a 2900 g female. Few months after delivery, the patient presented a new complete hydatidiform mole. Women presented with mutations in the NLRP7, KHDC3L or PADI6 genes are unlikely to obtain normal pregnancies, with a major risk of reproductive failure. In such a context, oocyte donation may be the best option. Only 4 normal pregnancies and deliveries have been published in this situation through this technique to our knowledge.


Adaptor Proteins, Signal Transducing/genetics , Hydatidiform Mole/genetics , Neoplasm Recurrence, Local/genetics , Pregnancy Complications, Neoplastic/genetics , Abortion, Spontaneous/genetics , Abortion, Spontaneous/physiopathology , Adult , Female , Humans , Hydatidiform Mole/pathology , Mutation/genetics , Neoplasm Recurrence, Local/pathology , Neoplasms/genetics , Neoplasms/pathology , Oocyte Donation/methods , Pregnancy , Pregnancy Complications, Neoplastic/pathology
17.
J Genet Couns ; 29(6): 1200-1209, 2020 12.
Article En | MEDLINE | ID: mdl-32384214

We conducted a test of concept study to explore feasibility, face validity, and sensitivity of an interactive web-based video tool designed to assess communication practices of genetic counselors in response to standardized video prompts. A convenience sample of genetic counselors was recruited from the National Society of Genetic Counselors to respond verbally to a set of brief standardized video prompts from a virtual client in a prenatal genetic counseling session and a cancer genetic counseling session, embedded in an interactive online platform. Participant verbal responses to prompts were captured through a secure voicemail service. A total of 89 participants attempted to use the online tool and 51 (57%) successfully completed the simulation and produced an audio record of their responses. The average length of recordings was 12.2 min. Face validity was high; participants rated the virtual client as similar to clients seen in practice (75% agree; 12% strongly agree, 7% neutral, 6% disagree) and rated their own responses to the virtual client prompts as similar to those in practice (63% agree; 19% strongly agree; 12% neutral, 6% disagree). Feasibility was assessed by ratings of ease of use (57% agreed, 24% strongly agreed, 17% were neutral, and none disagreed). Content checklists showed that the tool was sensitive enough to detect variation in frequency of certain topics discussed by participants that was similar to previous descriptive studies. The test of concept demonstrated feasibility, face validity, and sensitivity of this communication tool with possible applications in research, training, and program evaluation.


Communication , Genetic Counseling/methods , Internet , Neoplasms/genetics , Adult , Feasibility Studies , Female , Humans , Male , Pregnancy , Pregnancy Complications, Neoplastic/genetics , Program Evaluation , Reproducibility of Results
18.
Am J Surg Pathol ; 44(7): 970-981, 2020 07.
Article En | MEDLINE | ID: mdl-32271187

As inflammatory myofibroblastic tumors (IMTs) have become more widely recognized in the female genital tract, an intriguing subset of uterine tumors associated with pregnancy has emerged. Whether uterine IMTs occurring in the setting of pregnancy are clinically or biologically distinct from other uterine IMTs is unknown. Furthermore, little is known about the perinatal factors that may influence the development of these tumors. Here, we report the largest case series of 8 pregnancy-associated IMTs. All pregnancy-associated IMTs in this series occurred in association with pregnancy complications, including abnormal implantation (n=1), gestational diabetes (n=2), preeclampsia and/or HELLP syndrome (n=2), antiphospholipid syndrome (n=1), premature rupture of membranes (n=1), and hepatitis B (n=1). Notably, all IMTs were expelled at the time of delivery or immediately postpartum and were either adherent to the placenta or presented as separate, detached tissue. Tumors ranged from 2.0 to 6.0 cm (median, 3.9 cm), were well-circumscribed and showed classic histologic features of IMTs, including myxoid stroma and a lymphoplasmacytic infiltrate. Seven of 8 cases were positive by ALK immunohistochemistry and confirmed to have an ALK gene rearrangement by fluorescent in situ hybridization and RNA sequencing. The ALK-rearranged IMTs were found to be particularly enriched for TIMP3-ALK (n=5) and THBS1-ALK (n=2) fusions. The single case that was negative for an ALK rearrangement exhibited the classic morphology of an IMT. None of the 4 cases with available clinical follow-up recurred. The clinicopathologic features of pregnancy-associated IMTs in this series in conjunction with those reported in the literature suggests that these may be transient tumors that develop during pregnancy and shed at parturition; they appear to have a relatively indolent clinical course and favorable outcome, although studies with a longer duration of follow-up are still required.


Anaplastic Lymphoma Kinase/genetics , Neoplasms, Muscle Tissue/diagnosis , Oncogene Proteins, Fusion/genetics , Pregnancy Complications, Neoplastic/diagnosis , Thrombospondin 1/genetics , Tissue Inhibitor of Metalloproteinase-3/genetics , Uterine Neoplasms/diagnosis , Adult , Anaplastic Lymphoma Kinase/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Female , Follow-Up Studies , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Neoplasms, Muscle Tissue/genetics , Neoplasms, Muscle Tissue/pathology , Oncogene Fusion , Oncogene Proteins, Fusion/metabolism , Pregnancy , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/pathology , Sequence Analysis, RNA , Thrombospondin 1/metabolism , Tissue Inhibitor of Metalloproteinase-3/metabolism , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology
19.
Fam Cancer ; 19(4): 311-314, 2020 10.
Article En | MEDLINE | ID: mdl-32281046

Desmoid tumors are a manifestation of familial adenomatous polyposis (FAP), associated with mutation of the APC gene. Although considered benign tumors, desmoids can be aggressive and cause considerable morbidity. Known risk factors for desmoid tumor growth include location of mutations within the APC gene, family history of desmoid tumors, previous surgery, female gender, and pregnancy. Desmoids occur at diverse sites, commonly within the abdomen or at sites of previous surgery; thoracic desmoids are relatively uncommon. Reported here is a highly desmoid tumor-prone FAP family with a truncating mutation in the APC gene at codon 1550 (c.4648G>T) in which female siblings developed remarkably similar thoracic desmoids with highly aggressive tumor behavior during the onset of puberty, throughout adolescence, and in one sibling during and following pregnancy. Both siblings had a fatal outcome. This case underscores the potential for aggressive behavior of desmoids during adolescence and the need for close vigilance during the adolescent and young adult (AYA) age range in desmoid-prone FAP kindreds.


Adenomatous Polyposis Coli/genetics , Fibromatosis, Aggressive/genetics , Genes, APC , Siblings , Thoracic Neoplasms/genetics , Adenomatous Polyposis Coli/complications , Adolescent , Child, Preschool , Combined Modality Therapy/methods , Fatal Outcome , Female , Fibromatosis, Aggressive/pathology , Fibromatosis, Aggressive/therapy , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Humans , Mutation , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Pedigree , Pregnancy , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/pathology , Risk Factors , Thoracic Neoplasms/pathology , Thoracic Neoplasms/therapy , Young Adult
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