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Zimovjanova, M., P. Tesarova, B. Konopasek, J. Barkmanova, P. Brabec, J. Novotny, D. Pavlista, and L. B. Petruzelka. "Pregnancy-associated breast cancer (PABC): Czech Young Breast Cancer Study Group Project 35." Journal of Clinical Oncology 29, no. 27_suppl (September 20, 2011): 265. http://dx.doi.org/10.1200/jco.2011.29.27_suppl.265.
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265 Background: Breast cancer (BC) is the most common cancer in women. 12% of BC occur in women age 20–34. BC is classified as “pregnancy associated” if it is diagnosed during pregnancy or within one year after the delivery (PABC). We propose two distinct subtypes of PABC: BC diagnosed during pregnancy and BC diagnosed post-partum. This distinction is important because epidemiologic data highlights worsened outcomes specific to post-partum cases. The safety of pregnancy after treatment of BC is an important issue for many young women. Current research does not indicate that pregnancy negatively affects survival. Methods: There are about 95 young women being diagnosed each year with BC in the Czech Republic. A project of clinical registry named “Project 35” was launched in 2005 with the aim to collect data on epidemiology of the disease in young women. The standardization of the multidisciplinary medical treatment, genetic counselling and psychosocial support should result in better clinical outcomes and improve the quality of life. Results: In our project (n=225) were referred 25 women with PABC, 9 patients with the diagnosis of breast cancer during the pregnancy, 16 patients within one year after the delivery. 2 patients underwent termination of the pregnancy (first trimester) before oncological treatment, in 2 patients anthracycline-based chemotherapy was administered (second trimester), and in 5 patients were induced preterm delivery (third trimester). After delivery we followed standard therapeutic guidelines. All patients are alive but three of them have metastatic disease. From 16 women treated for post-partum BC, 11 patients have complete remission, 2 are alive with metastatic disease, 1 is recovering after the surgery for local recurrence and 2 patients died due to progressive disease. 8 women are BRCA1/2 carriers. 8 women after the successful treatment of breast cancer have delivered of healthy children and are in a complete remission, despite 1 of them with local reccurence of breast cancer. Conclusions: PABC is rare situation, which needs to be managed individually. These patients should be treated under the supervision of the Oncological Centres. Project 35 is useful framework for the counselling in PABC.
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Zhang, Zhenzhen, Shangyuan Ye, Sarah M. Bernhardt, Heidi D. Nelson, Ellen M. Velie, Virginia F. Borges, Emma R. Woodward, D. Gareth R. Evans, and Pepper J. Schedin. "Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants." JAMA Network Open 7, no. 4 (April 19, 2024): e247421. http://dx.doi.org/10.1001/jamanetworkopen.2024.7421.
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ImportanceIn young-onset breast cancer (YOBC), a diagnosis within 5 to 10 years of childbirth is associated with increased mortality. Women with germline BRCA1/2 pathogenic variants (PVs) are more likely to be diagnosed with BC at younger ages, but the impact of childbirth on mortality is unknown.ObjectiveTo determine whether time between most recent childbirth and BC diagnosis is associated with mortality among patients with YOBC and germline BRCA1/2 PVs.Design, Setting, and ParticipantsThis prospective cohort study included women with germline BRCA1/2 PVs diagnosed with stage I to III BC at age 45 years or younger between 1950 and 2021 in the United Kingdom, who were followed up until November 2021. Data were analyzed from December 3, 2021, to November 29, 2023.ExposureTime between most recent childbirth and subsequent BC diagnosis, with recent childbirth defined as 0 to less than 10 years, further delineated to 0 to less than 5 years and 5 to less than 10 years.Main Outcomes and MeasuresThe primary outcome was all-cause mortality, censored at 20 years after YOBC diagnosis. Mortality of nulliparous women was compared with the recent post partum groups and the 10 or more years post partum group. Cox proportional hazards regression analyses were adjusted for age, tumor stage, and further stratified by tumor estrogen receptor (ER) and BRCA gene status.ResultsAmong 903 women with BRCA PVs (mean [SD] age at diagnosis, 34.7 [6.1] years; mean [SD] follow-up, 10.8 [9.8] years), 419 received a BC diagnosis 0 to less than 10 years after childbirth, including 228 women diagnosed less than 5 years after childbirth and 191 women diagnosed 5 to less than 10 years after childbirth. Increased all-cause mortality was observed in women diagnosed within 5 to less than 10 years post partum (hazard ratio [HR], 1.56 [95% CI, 1.05-2.30]) compared with nulliparous women and women diagnosed 10 or more years after childbirth, suggesting a transient duration of postpartum risk. Risk of mortality was greater for women with ER-positive BC in the less than 5 years post partum group (HR, 2.35 [95% CI, 1.02-5.42]) and ER-negative BC in the 5 to less than 10 years post partum group (HR, 3.12 [95% CI, 1.22-7.97]) compared with the nulliparous group. Delineated by BRCA1 or BRCA2, mortality in the 5 to less than 10 years post partum group was significantly increased, but only for BRCA1 carriers (HR, 2.03 [95% CI, 1.15-3.58]).Conclusions and RelevanceThese findings suggest that YOBC with germline BRCA PVs was associated with increased risk for all-cause mortality if diagnosed within 10 years after last childbirth, with risk highest for ER-positive BC diagnosed less than 5 years post partum, and for ER-negative BC diagnosed 5 to less than 10 years post partum. BRCA1 carriers were at highest risk for poor prognosis when diagnosed at 5 to less than 10 years post partum. No such associations were observed for BRCA2 carriers. These results should inform genetic counseling, prevention, and treatment strategies for BRCA PV carriers.
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Oktaviani, Ika, Sri Widiyas, and Hellen Anggranis. "ANALISIS IBU POSTPARTUM DENGAN BENDUNGAN ASI LITERATURE VIEW." Prosiding Simposium Nasional Multidisiplin (SinaMu) 4 (February 6, 2023): 310. http://dx.doi.org/10.31000/sinamu.v4i1.7891.
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AbstrakAsi merupakan makanan yang paling sempurna bagi bayi, dimana kandungan gizi sesuai kebutuhan pertumbuhan dan perkembangan yang optimal. Asi mengandung zat untuk perkembangan kecerdasan, zat kekebalan (mencegah tubuh dari berbagai penyakit) dan dapat menjalani hubungan cinta kasih antara ibu dan bayi. Manfaat menyusui bagi ibu dapat mengurangi perdarahan setelah melahirkan, mempercepat pemulihan ibu, seperti involusi Rahim, menunda kehamilan dan mengurangi resiko terkena kanker payudara. Asi yang tidak sering dikeluarkan dapat berkembang menjadi bendungan asi, payudara terisi sangat penuh dengan asi aliran susu menjadi terhambat dan akan menyebabkan payudara bengkak. Tujuan : Menganalisis ibu postpartum dengan bedungan asi. Metode : pencarian artikel ini menggunakan google scholar, pudmed, science direck, kemudian ditemukan 10 artikel sesuai kriteria inklusi dan eklusi yang selanjutnya dilakukan review. Hasil : berdasarkan 10 jurnal artikel secara umum menyatakan bahwa faktor-faktor yang mempengaruhi ibu postpartum dengan bendungan asi disebabkan oleh umur, pendidikan, perawatan payudara. Kesimpulan : Analisis ibu postpartum dengan bendungan asi yaitu, umur, pendidikan, perawatan payudaraKata Kunci: Ibu postpartum, Kejadian Bendungan Asi, PengetahuanAbstractBreast milk is the most perfect food for babies, where the nutritional content is according the needs of optimal growth and development. Breast milk contains subtances of the development of intelligence immune subtances (prevents the body from various diseaces) and can undergo a loving relationship between mother and baby. The benefits of breast feeding of mothers can reduce bleedinh after childbirth, accelerate the speed of recovery of the mother such as uterine involution, delay pregnancy and reduce the risk of breast cancer. Breast milk that is not often expelled can development breast milk dams, the breasts are very full with milk the flow of milk becomes blocked and wiil cause the breasts to swell. Desination : analysis post partum mothers with breast milk Method : searching for this article using google scholar, pudmed, science director, then found 10 articles according to tehe criteria which were then reviewed. Results : Based on 10 jurnal articles, it is generally stated that the Analysis of post partum mother with breast milk are coused by the influence of age, education, breast care Conclusion : Description of the analysis of post partum mothers with breast milk, age,education, breast careKeywords : Post partum mother, Breast milk dam incident, Knowledge
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Lue, Jaida, Derek Radisky, Mark Sherman, Amy Degnim, Stacey Windam, Morian Curtis, and Melody Stallings-Mann. "396 Unraveling the Immunological Basis of Lobular Involution in Breast Cancer Development." Journal of Clinical and Translational Science 8, s1 (April 2024): 118. http://dx.doi.org/10.1017/cts.2024.346.
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OBJECTIVES/GOALS: Reveal common immune mechanisms in dysregulated age-related lobular involution (ARLI) and post-partum lobular involution (PPLI) to understand their link to increased breast cancer risk, challenging the traditional view of their distinctiveness. Ultimately, to improve breast cancer risk assessment and personalized prevention METHODS/STUDY POPULATION: The Mayo Clinic Benign Breast Disease (BBD) cohort comprises of ~20,000 women with benign biopsies, including ~1000 women with sequential benign biopsies. Lobular involution (LI) status was assessed by selecting perimenopausal women, ages 45-55, with sequential biopsies, comparing acini number and lobule size between initial and subsequent biopsies. NanoString IO360/ BC360 RNA profiling identified differentially expressed genes associated with dysregulated LI. Using multiplex immunofluorescence (mIF), I'll analyze and spatially map immune biomarkers related to dysregulated ARLI and PPLI in BBD tissue from perimenopausal women who did or did not go on to develop breast cancer, assessing the commonality of ARLI and PPLI markers and exploring their potential as risk biomarkers for breast cancer. RESULTS/ANTICIPATED RESULTS: Preliminary findings link patients who display dysregulated ARLI with an increased breast cancer risk and identify vital PPLI biomarkers in perimenopausal women. I expect the biopsies of women who developed post-menopausal breast cancer (PMBC) and post-partum breast cancer (PPBC) to exhibit elevated levels of dysregulated ARLI immune biomarkers and PPLI biomarkers. Spatially mapping these markers promises to provide a more comprehensive understanding of their interactions, potentially revealing common immunological pathways. These findings could transform our current paradigm of ARLI and PPLI as distinct processes and demonstrate their interconnection in shaping breast cancer risk. DISCUSSION/SIGNIFICANCE: PMBC and PPBC dominate majority of breast cancer cases. Both involve activation of the understudied process of lobular involution, which has been shown to have pro-tumorigenic traits. Elucidating these mechanisms will aid more efficient risk stratification and personalized prevention to reduce incidence and mortality of breast cancer.
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Menes, Tehillah S., Tal Sella, and Gabriel Chodick. "Time to cancer diagnosis in young women presenting to surgeons with breast-related symptoms: A population-based cohort study." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e13099-e13099. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e13099.
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e13099 Background: Reports on delay to diagnosis of cancer in young women are based on retrospective studies and conflicting. The purpose of this study was to investigate time to cancer diagnosis in women presenting to a surgeon with breast-related complaints; and particularly, the role of age. Methods: A population-based cohort study including all women aged 18 to 44 presenting to a surgeon with a breast-related complaint between 2005 and 2015 in a large Israeli healthcare plan (N = 157,264). We collected data including demographics, diagnosis codes, breast imaging and biopsies. Breast cancer diagnosis within one year of the visit was ascertained from the national cancer registry. Time to breast imaging and biopsy was compared between the different age groups. Logistic regression analysis was used to determine the association between age and delay to biopsy while adjusting for possible confounders. Results: During the first year after the visit, 45,434 (29%) women had a breast imaging study; 5,767 (3.7%) women had a breast biopsy; and 676 (0.43%) were diagnosed with breast cancer. Overall, time to first breast imaging (mean, 53 days) and biopsy (mean, 68 days) did not differ significantly between the age groups. Non-specific visit codes (other than breast mass) were associated with delays to imaging and biopsy. This was more pronounced in the women ultimately diagnosed with breast cancer. Among women diagnosed with breast cancer, age under 40 (OR 2.3, 95% CI 1.4; 3.9), being post-partum (OR 2.6, 95% CI 1.1; 5.9) and a non-specific visit code (OR-8.3, 95% CI 4.9; 14.2) were associated with delay to biopsy. Conclusions: Symptomatic women with lower a-priori likelihood of breast malignancy (younger age, post-partum, or non-specific visit code) are at a significantly greater risk of delayed diagnosis of cancer. Physicians should be aware of the challenging diagnosis in young women with non-specific symptoms.
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Panchal, Hiral. "A Study to Identify Problems of Lactation Among Postnatal Mothers During Early Post-Partum Period at Selected Hospitals of Bardoli Taluka of Surat District, Gujarat." Nursing Journal of India CXII, no. 06 (2021): 283–88. http://dx.doi.org/10.48029/nji.2021.cxii607.
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Post-partum period is the period following child birth which lasts for 6 weeks. Early post-partum period lasts from child birth to 7 days. Breast feeding is universally recognised as the best way to feed an infant. Lactational problems are the complaints during initial puerperium which hinders breast feeding. Mother who is failing to breast feed is associated with increased risk of premenopausal breast cancer, ovarian cancer, type 2 diabetes & metabolic syndrome. The main objective of the study was to identify problems of lactation among the post-natal mothers during early post-partum period at selected hospitals of Surat district, Gujarat. Quantitativedescriptive research method was used for the study. Total 30 postnatal mothers irrespective of their gravidity, parity, mode of delivery, any complications in present pregnancy were selected by non-probability convenient sampling technique. Tool for the data collection comprises of questionnaire for socio demographic information and observation & inventory checklist for assessment of lactational problems. The data were collected by interview method and analysed with the help of descriptive statistics. Findings of the study revealed that 66.67 percent belonged to the age group of 21-30 years, 56.6 percent were following mixed diet pattern, 80 percent were primi gravida & para, 56.67 percent were having caesarian delivery, 83.33 percent were in the gestational age of 38-42 weeks, 43.33 percent were having 2nd postnatal day & 93.33 percent have initiated breast feeding after 30 min. With regards to the 'Agrave; ndings of lactational problems, 20 percent mothers had redness, 33.34 percent had swelling, 100 percent had tenderness, 56.67 percent had excessive hotness, 86.66 percent had hard mass, 19.99 percent had rashes on breast, 9.99 percent had inverted nipple, 58.89 percent mothers had pain in breast, 100 percent had heaviness in breast, 6.66 percent had burning sensation, 20 percent had itching on breast, 70 percent had breast discomfort, 100 percent had insuf'Agrave;cient milk supply and 6.66 percent had over stretching of breast. Study 'Agrave;ndings concluded that lactational problems are common in post-natal period. Identi'Agrave;cation of problems at earliest and helping the mother to deal with them is major responsibility of nurse.
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Faccio, Flavia, Chiara Ionio, Eleonora Mascheroni, Fedro Peccatori, Giulia Ongaro, Elena Cattaneo, Camilla Pisoni, et al. "Risk factors in pregnant women with an oncological diagnosis and their impact in the post-partum period." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e23166-e23166. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e23166.
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e23166 Background: An oncological diagnosis during pregnancy, or the choice of motherhood following cancer may be accompanied by anxiety, distress and depression. The aim of the study is to explore the possible risk factors in the perinatal period in women who experienced an oncological diagnosis before or during pregnancy. Methods: 32 pregnant women (25 breast, 3 cervix, 1 lung, 1 Hodgkin's lymphoma, 1 perivascular epithelial cell neoplasia, 1 epatic PEComa) were assessed during their 3rd trimester (T1) and three months’ post-partum (T2). At T1 mood states and post-traumatic symptoms were evaluated, at T2 parenting stress and perceived quality of life (QoL). Results: Depression, anger and anxiety correlated with lower physical and psychological QoL in the post-partum. Moreover, mothers who expressed higher levels of fatigue and confusion during pregnancy are associated to lower levels of perceived psychological QoL. Women who manifested hypervigilance and hyperarousal during pregnancy were more likely to perceive lower psychological QoL three months after birth. Finally, post-traumatic symptoms of intrusiveness during pregnancy correlated with higher levels of parenting stress and higher risk of dysfunctional parenting, together with a stronger perception of having a child with a difficult temperament in the post-partum period. Conclusions: Mood states and post-traumatic symptoms can decrease the mother’s quality of life and heighten parental distress. These preliminary results suggest implementing psychological support for women with current or previous oncological diagnosis during pregnancy in order to prevent the onset of dysfunctional parenting and/or problem behaviours in their children. [Table: see text]
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Altshuler, Ellery, Sarah Wheeler, and Karen Daily. "Bilateral primary breast Burkitt’s lymphoma in pregnancy." BMJ Case Reports 16, no. 1 (January 2023): e251896. http://dx.doi.org/10.1136/bcr-2022-251896.
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Pregnancy-associated cancer is defined as malignancy diagnosed during gestation or up to 1 year post partum. Treatment of cancer during pregnancy is complicated by the risk of harm to the fetus and limitations in safety data. Postpartum patients receiving chemotherapy, tyrosine-kinase inhibitors or hormonal agents should avoid breast feeding to avoid drug excretion in breast milk. Patients who will receive cytotoxic chemotherapy should be advised of the potential impact on their future fertility and offered fertility-preservation options. Breast cancer is the most common pregnancy-associated malignancy and is most frequently either invasive ductal or lobular carcinoma. Breast lymphoma is an exceedingly rare diagnosis that typically presents with unilateral disease in the seventh decade of life. Here, we present the case of a woman who presented with bilateral breast masses during the second trimester of pregnancy and was ultimately diagnosed with primary breast Burkitt’s lymphoma.
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Poorvu, Philip D., Yue Zheng, Tal Sella, Shoshana M. Rosenberg, Kathryn Jean Ruddy, Shari I. Gelber, Rulla M. Tamimi, et al. "Diagnostic and treatment delays in young women with breast cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 6575. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.6575.
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6575 Background: Delays in diagnosis (dx) and treatment (tx) affect breast cancer (BC) outcomes. We sought to identify factors associated with delays among young women, who do not undergo routine screening and often have pregnancy or breastfeeding-related breast changes that may mask a BC. Methods: The Young Women’s Breast Cancer Study is a multicenter, prospective cohort that enrolled 1302 women with newly dx BC age ≤40 between 2006-2016. Women reported the method and timing of cancer detection on the baseline survey. 231 were ineligible or excluded due to missing information. Among those reporting self-detected cancers, using multivariable regression we evaluated factors associated with delays ≥90 days (d) from symptom to presentation (self delay) and presentation to dx (care delay); in stage 0-III BC we evaluated delays ≥60d from dx to tx (tx delay). Results: 1071 eligible women had median age at dx of 37 yrs (17-40) and 74% reported self-detected cancers. Self delay or care delay ≥90d was reported in 17% and 13%, respectively. Factors inversely associated with self delay included pregnancy at dx (vs nulliparous, OR 0.10, CI 0.01-0.78) and perceived financial comfort (vs not, OR 0.62, CI 0.41-0.93). Women dx ≤1 year post-partum who breastfed (vs nulliparous, OR 2.60, CI 1.14-5.93) and those with a family history of breast/ovarian cancer (vs none, OR 1.79, CI 1.00-3.19) were more likely to have a care delay. Age was inversely associated with care delays (OR 0.94, CI 0.89-0.99). Tx delay was reported by 10% (105/1015), and associated with being single (vs partnered, OR 1.61, CI 1.02-2.56 ), non-white (vs white, OR 1.85, CI 1.09-3.13) and having Stage 0 BC (vs stage 1, OR: 3.08, CI 1.65-5.77); women with stage 3 BC (vs stage 1, OR 0.13, CI 0.03-0.56) were less likely to have a tx delay. Conclusions: In this cohort, most young women with BC underwent timely dx and tx initiation. Women dx ≤1 year post-partum who breastfed were more likely to experience a care delay, likely because lactational changes may mask BC signs and symptoms. The associations of perceived financial status with self delay and non-white race with tx delay underscore the need for additional support to ensure timely care for underserved populations with the goal of eliminating disparities in outcomes.
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Van Der Hock, Sarah, Alekhya Chintamani, Gabriella Bulloch, Ishith Seth, and Nita Dhupar. "Pregnancy-associated breast cancer: a case report and literature review." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 12, no. 10 (September 28, 2023): 3177–80. http://dx.doi.org/10.18203/2320-1770.ijrcog20232968.
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Pregnancy-associated breast cancer (PABC) is a rare, yet significant clinical entity which presents itself during pregnancy or within one year postpartum. This case report and literature review discusses the case of a 33-year-old G1P0 woman diagnosed with PABC at 38 weeks’ gestation with an uncomplicated pregnancy and no significant risk factors. Fine needle aspiration revealed a left-sided metaplastic grade 3 invasive ductal carcinoma with heterogeneous mesenchymal differentiation and focal ductal carcinoma in situ, and an uncomplicated nipple-sparing mastectomy was undertaken at three weeks’ post-partum. This case report emphasises the need for early diagnosis and the importance of screening for breast cancer during pregnancy, and advocates for a low threshold to screen for PABC in all pregnancies. The literature review also provides updated insights into the presentation, diagnosis, and management of PABC. We explore the diagnostic challenges associated with PABC, including physiological changes in breast tissue during pregnancy, limitations of imaging modalities, and the importance of considering PABC as a differential diagnosis.
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O’Sullivan, Ciara C., Sheeba Irshad, Zheyu Wang, Zhuojun Tang, Christopher Umbricht, Gary L. Rosner, Mindy S. Christianson, Vered Stearns, and Karen Lisa Smith. "Clinico-pathologic features, treatment and outcomes of breast cancer during pregnancy or the post-partum period." Breast Cancer Research and Treatment 180, no. 3 (March 11, 2020): 695–706. http://dx.doi.org/10.1007/s10549-020-05585-7.
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Felcher, Carla M., Emilia S. Bogni, and Edith C. Kordon. "IL-6 Cytokine Family: A Putative Target for Breast Cancer Prevention and Treatment." International Journal of Molecular Sciences 23, no. 3 (February 5, 2022): 1809. http://dx.doi.org/10.3390/ijms23031809.
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The IL-6 cytokine family is a group of signaling molecules with wide expression and function across vertebrates. Each member of the family signals by binding to its specific receptor and at least one molecule of gp130, which is the common transmembrane receptor subunit for the whole group. Signal transduction upon stimulation of the receptor complex results in the activation of multiple downstream cascades, among which, in mammary cells, the JAK-STAT3 pathway plays a central role. In this review, we summarize the role of the IL-6 cytokine family—specifically IL-6 itself, LIF, OSM, and IL-11—as relevant players during breast cancer progression. We have compiled evidence indicating that this group of soluble factors may be used for early and more precise breast cancer diagnosis and to design targeted therapy to treat or even prevent metastasis development, particularly to the bone. Expression profiles and possible therapeutic use of their specific receptors in the different breast cancer subtypes are also described. In addition, participation of these cytokines in pathologies of the breast linked to lactation and involution of the gland, as post-partum breast cancer and mastitis, is discussed.
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Jenkins, Edmund Charles, Samantha O. Brown, and Doris Germain. "The Multi-Faced Role of PAPP-A in Post-Partum Breast Cancer: IGF-Signaling is Only the Beginning." Journal of Mammary Gland Biology and Neoplasia 25, no. 3 (September 2020): 181–89. http://dx.doi.org/10.1007/s10911-020-09456-1.
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Walsh, Elaine, Grainne O'Kane, Karen Anne Cadoo, Donna M. Graham, Grzegorz Korpanty, Derek Gerard Power, and Desmond Carney. "Cancer in pregnancy: To treat or not?" Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e12533-e12533. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e12533.
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e12533 Background: Cancer in pregnancy accounts for ~1 in 1,000 pregnancies. Studies show that cytotoxic agents are safe from the second trimester. Long-term follow up has not shown increased malformations or malignancies in children exposed to chemotherapy in utero. There is no evidence of worse outcomes among women diagnosed in pregnancy. Methods: We retrospectively identified women diagnosed with cancer in pregnancy over a 25-year period. Medical records were reviewed for demographics, diagnosis, gestation, timing of treatment and outcomes. We assessed if all cancers need to be treated in pregnancy or if treatment could be safely deferred to allow normal delivery. Results: Twenty-five women were diagnosed with cancer in pregnancy and referred to medical oncology. Of 25 women, 16 (64%) received chemotherapy during pregnancy. These included 13 cases of breast cancer, one Ewing’s sarcoma, one ovarian cancer, and one small cell of cervix. All 16 women received doxorubicin and cyclophosphamide. There were 15 live births and no abnormalities seen in children who received chemotherapy in utero. At a median follow-up of 6 years 11 mothers (69%) are disease free and 4 (25%) have recurrent disease. Of nine mothers who did not receive chemotherapy in pregnancy, seven received chemotherapy immediately post-partum. Six (86%) were diagnosed in early pregnancy (median gestation 13 weeks). There were three cases of Hodgkin lymphoma, two breast cancers, and one ovarian cancer. At a median follow-up of 12 years, all mothers remain disease free. There were no abnormalities seen in these children. Conclusions: We did not identify any adverse outcomes in mothers or infants exposed to chemotherapy during pregnancy. We identified a cohort of patients that do not need immediate treatment during pregnancy. In selected cases, it is safe and appropriate to delay chemotherapy until delivery of the baby. There were no adverse outcomes to mothers due to delayed treatment and no adverse outcomes to babies not exposed to chemotherapy in utero. A multi-disciplinary team is essential to individualize treatment planning. [Table: see text]
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Borges, V. F., T. Lyons, J. O'Brien, T. Russell, H. Martinson, P. Keely, and P. J. Schedin. "The role of collagen and COX-2 in post-partum breast involution on the progression of pregnancy-associated breast cancer and its inhibition by NSAIDs." Journal of Clinical Oncology 29, no. 15_suppl (May 20, 2011): e11117-e11117. http://dx.doi.org/10.1200/jco.2011.29.15_suppl.e11117.
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Ramaswamy, Bhuvaneswari, Neelam Shinde, Gary K. Gray, Resham Mawalkar, Allen Zhang, Mustafa Basree, Xiaoli Zhang, et al. "Abstract 11: Prophylactic use of tamoxifen could reduce the risk of breast cancer in women who do not breast feed postpartum." Cancer Research 82, no. 12_Supplement (June 15, 2022): 11. http://dx.doi.org/10.1158/1538-7445.am2022-11.
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Abstract Background: Triple negative breast cancer (TNBC) is associated with poor survival, particularly affecting African American women (AAW). Epidemiological studies indicate prolonged breast feeding reduces breast cancer (BC) risk, including TNBC. AAW have significantly lower rates of breast feeding compared to Caucasian women. To understand this link we developed a mouse model mimicking abrupt (AI) and gradual involution (GI). AI led to increased estrogen signaling, cell proliferation and chronic inflammation, which was followed by hyperplasia and squamous metaplasia in mammary glands1. There was an increase in the luminal progenitor (LP) cell population, the cells of origin of TNBC, and a decrease in mature luminal (ML) cells in AI glands. In this study, we sought to determine if blocking estrogen signaling with tamoxifen (TAM) could revert the negative effects of AI, and if so, could be a prophylactic option to reduce BC risk in women who do not breast feed. Methods: Uniparous FVB/N mice (~8 weeks) were allowed to nurse six pups per dam at partum. To induce AI, all pups were removed on postpartum (PP) day 7 (d7). For TAM treatment, 5mg sustained release TAM citrate pellet or placebo was implanted in the subscapular region on PP d8. Mammary glands were harvested on PP d28 and d120. FFPE sections were used for histology and immunohistochemistry. Single cell suspensions were analyzed for mammary epithelial subpopulations using Fluorescence Activated Cell Sorting. Affymetrix and qPCR were used for gene expression analysis. Mass cytometry was performed on mammary glands harvested at PP d120. Results: TAM treatment for 21 days completely abrogated hyperplastic and metaplastic changes in AI glands harvested on d120. Treatment initiation on PP d8, d15 and d35 had the same effect. TAM treatment reduced the cell proliferation and collagen deposition in AI glands. De-enrichment of estrogen signaling pathways and decrease in Elf5 expression, a luminal progenitor marker, were observed upon TAM treatment in d28 glands. Mass cytometry revealed a marked reduction in LP population and a significant increase in ML population in TAM treated AI glands on d120, restoring to the levels in age matched virgin mice. Significant increases in progenitor-like markers TSPAN8, Ly6D, CD200 and decreases in CD49f and CD47 expression in LP cells were observed, indicating return to a normal uniparous LP state. Expression of Ly-6D in ML cells, a ML cell marker, was also rescued upon TAM treatment. Conclusion: Using our mouse model of AI and GI, we show that suppression of estrogen signaling after initiation of AI offered marked protection against precancerous changes. TAM restored the balance of epithelial lineages and normalized the LP and basal cells in AI glands to the post-involution phenotype. Our data provide a rationale for considering short-term TAM treatment for women who do not breastfeed to reduce risk of BC. 1. Basree et.al. PMID 31315645 Citation Format: Bhuvaneswari Ramaswamy, Neelam Shinde, Gary K. Gray, Resham Mawalkar, Allen Zhang, Mustafa Basree, Xiaoli Zhang, Ramesh Ganju, Gina M. Sizemore, Joan S. Brugge, Sarmila Majumder. Prophylactic use of tamoxifen could reduce the risk of breast cancer in women who do not breast feed postpartum [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 11.
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Vianzon, Vianca, Ishita Garg, Kara Greenfield, Kathryn Knoop, and Laura Rogers. "511 Tumor immune microenvironment in adult mice asynchronously cross-fostered as pups." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A547. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0511.
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BackgroundImmune responses to cancer are highly variable and influenced by genetic and environmental factors.1 Syngeneic tumor models in mice with intact immune systems are required to study anti-tumor immune responses but are unable to adequately model varied immune responses. Classically, different mouse strain backgrounds have been used to compare different immune responses to cancer immunotherapy, but this approach is limited by the inability to administer identical tumor cell lines, keeping constant the tumor while experimentally varying the immune response. Proper establishment of the immune system begins in early life and is regulated by environmental cues from maternal breast milk and the developing microbiota. To disrupt these cues prior to weaning, newborn pups can be cross-fostered to dams that delivered their litters asynchronously, either 2 weeks earlier or later, a model referred to as asynchronous cross-foster (ACF).2 We previously demonstrated that ACF can profoundly skew the immune profile of genetically identical offspring.2 Young ACF mice exhibited enhanced Th2 immunologic skewing and reduced peripheral tolerance in response to antigen, which resulted from impaired development of peripherally-induced regulatory T cells (pTreg). Adult mice that underwent ACF also exhibited altered systemic cytokine expression even in the absence of immunologic stimuli, suggesting that ACF has lasting impact on the immune system. Because peripheral tolerance and immune skewing directly impact anti-tumor immunity,3 we hypothesized that ACF would also impact the immune response to tumor growth.MethodsTo measure impact of ACF on tumor growth and tumor infiltration, we introduced EL4 lymphoma cells into 7-week-old mice with the following foster schemes: conventionally reared mice, 1-day-old pups cross-fostered with 10-day post-partum dam (ACF1 to ppd10), and 13-day-old pups cross-fostered with 1-day post-partum dams (ACF13 to ppd1). Immune infiltration at tumor endpoint was measured using flow cytometry.ResultsEL4 tumor growth was increased in ACF mice compared to conventionally-reared controls. Further, the immune infiltrate at endpoint was altered, with ACF mice having fewer natural killer (NK) cells, dendritic cells, and activated cytotoxic CD8+ T cells in the tumor microenvironment.ConclusionsOur observations support the hypothesis that ACF impacts tumor growth and immune infiltration. Future directions include phenotyping the immune infiltrate with finer resolution, the study of additional tumor models, and investigation of the effects of ACF on spontaneous tumor incidence and immunotherapy efficacy. Development of this novel model could provide valuable insight into early life factors that influence anti-tumor immunity.Ethics ApprovalThe study was approved by Mayo Clinic’s IACUC approved all uses in this study, approval number A00004845.ReferenceRadiloff DR, Rinella ES, and Threadgill DW. Modeling cancer patient populations in mice: complex genetic and environmental factors. Drug Discov Today Dis Models 2008; 4:83–88.Knoop KA, McDonald KG, Coughlin PE, et al. Synchronization of mothers and offspring promotes tolerance and limits allergy. JCI Insight. 2020; 5.3. Hedge UP, Jellison ER, and Chakraborty NG. pTregs or iTregs are the potent tolerance inducer for the growth and Metastasis of cancer. Int J Immunol Immunother 2018:5.
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De Sancho, Maria Teresa, and Sana Khalid. "Outcomes in Pregnant Women Exposed to Low Molecular Weight Heparin." Blood 114, no. 22 (November 20, 2009): 4168. http://dx.doi.org/10.1182/blood.v114.22.4168.4168.
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Abstract Abstract 4168 Objective To evaluate the efficacy of low molecular weight heparin (LMWH) in a heterogeneous population of pregnant women. Methods Using hospital databases, we retrospectively evaluated the records of all women who were managed with LMWH during pregnancy and referred to our hematology clinic at a tertiary center between January 2001 and August 2009. Data collected included age, rate of live births, indications for using LMWH, type of thrombophilia, need to adjust LMWH dose, incidence of adverse outcomes of pregnancy (AOP), maternal complications, and complications related to use of LMWH. Results There were a total of 64 pregnancies in 57 women whose mean age was 25 years (range, 23 to 48). The rate of live births was 97%. Indications for LMWH included: deep venous thrombosis (DVT) (n=11), pulmonary embolism (PE) (n=10), combined DVT and PE (n=5), cerebrovascular accident (n=7), prosthetic mechanical heart valves (n=1), and upper extremity arterial thrombosis (n=1). Of the 57 women, 7 had a history of intrauterine growth restriction (IUGR), 6 had a history of preeclampsia, 3 had a history of HELLP syndrome and 1 had a history of placental abruption. In 31 of the pregnancies women had a prior history of spontaneous pregnancy loss (23 recurrent first trimester losses, 5 second trimester and 3 stillborn). There were 7 women with history of unexplained infertility. Seventeen women had factor V Leiden, 15 had prothrombin G20210 mutation, 11 had antiphospholipid antibodies IgG isotype, 8 had IgM isotype, 5 had lupus anticoagulant (LAC), 3 had hereditary antithrombin (AT) deficiency, and 1 protein S deficiency. Twenty women had less important thrombophilias. 14 pregnancies (22%) were managed with treatment doses of LMWH while 50 pregnancies (78%) were managed with preventive doses. LMWH dose adjustment was required in 11 pregnancies on treatment doses and in 23 pregnancies on preventive doses. Six pregnancies were complicated with IUGR and 3 with other complications (diaphragmatic hernia, congenital heart defect and death). Six women had documented bone loss and 1 had an allergic reaction. 15 had other complications (4 hypertension, 2 anemia, 1 subchorionic hematoma, 1 preterm labor, 1 proteinuria, 1 preeclampsia, 1 cholecystitis, 1 transient visual loss, 1 headaches 1 was diagnosed of breast cancer after completion of the post-partum period and 1 had amniotic fluid leak after amniocentesis. 14 pregnancies (22%) were managed with treatment doses of LMWH while 50 pregnancies (78%) were managed with preventive doses. LMWH dose adjustment was required in 11 pregnancies on treatment doses and in 23 pregnancies on preventive doses. Six pregnancies were complicated with IUGR and 3 with other complications (diaphragmatic hernia, congenital heart defect and death). Six women had documented bone loss and 1 had an allergic reaction. 15 had other complications (4 hypertension, 2 anemia, 1 subchorionic hematoma, 1 preterm labor, 1 proteinuria, 1 preeclampsia, 1 cholecystitis, 1 transient visual loss, 1 headaches 1 was diagnosed of breast cancer after completion of the post-partum period and 1 had amniotic fluid leak after amniocentesis. Conclusion Almost all pregnant women exposed to LMWH in our series had live births. Dose adjustments in LMWH were required for both treatment and prophylactic dosages. Complications related to use of LMWH were minimal. Disclosures: No relevant conflicts of interest to declare.
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Rostom, Hussam, Xin Meng, Helen Price, Alexandria Fry, Taha Elajnaf, Robert Humphrey, Nishan Guha, Tim James, Stephen H. Kennedy, and Fadil M. Hannan. "Protocol for an observational study investigating hormones triggering the onset of sustained lactation: the INSIGHT study." BMJ Open 12, no. 8 (August 2022): e062478. http://dx.doi.org/10.1136/bmjopen-2022-062478.
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IntroductionLactation is a hormonally controlled process that promotes infant growth and neurodevelopment and reduces the long-term maternal risk of diabetes, cardiovascular disease and breast cancer. Hormones, such as prolactin and progesterone, mediate mammary development during pregnancy and are critical for initiating copious milk secretion within 24–72 hours post partum. However, the hormone concentrations mediating lactation onset are ill defined.Methods and analysisThe primary objective of the investigating hormones triggering the onset of sustained lactation study is to establish reference intervals for the circulating hormone concentrations initiating postpartum milk secretion. The study will also assess how maternal factors such as parity, pregnancy comorbidities and complications during labour and delivery, which are known to delay lactation, may affect hormone concentrations. This single-centre observational study will recruit up to 1068 pregnant women over a 3-year period. A baseline blood sample will be obtained at 36 weeks’ gestation. Participants will be monitored during postpartum days 1–4. Lactation onset will be reported using a validated breast fullness scale. Blood samples will be collected before and after a breastfeed on up to two occasions per day during postpartum days 1–4. Colostrum, milk and spot urine samples will be obtained on a single occasion. Serum hormone reference intervals will be calculated as mean±1.96 SD, with 90% CIs determined for the upper and lower reference limits. Differences in hormone values between healthy breastfeeding women and those at risk of delayed onset of lactation will be assessed by repeated measures two-way analysis of variance or a mixed linear model. Correlations between serum hormone concentrations and milk composition and volume will provide insights into the endocrine regulation of milk synthesis.Ethics and disseminationApproval for this study had been granted by the East of England—Cambridgeshire and Hertfordshire Research Ethics Committee (REC No. 20/EE/0172), by the Health Research Authority (HRA), and by the Oxford University Hospitals National Health Service Foundation Trust. The findings will be published in high-ranking journals and presented at national and international conferences.Trial registration numberISRCTN12667795.
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Tolcher, Anthony W., Funda Meric-Bernstam, Meredith McKean, Roger R. Beerli, Lorenz Waldmeier, Rémy Gebleux, Ina Hellmann, Pawel Chrom, and Ulf Grawunder. "NBE-002: A novel anthracycline-based antibody-drug conjugate (ADC) targeting ROR1 for the treatment of advanced solid tumors—A phase 1/2 clinical trial." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): TPS1108. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.tps1108.
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TPS1108 Background: The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is highly expressed during embryonic development, but is minimally present or absent on post-partum healthy tissues. ROR1 is expressed in a variety of hematological and solid tumors and is associated with aggressive cancer phenotype and poor clinical outcomes. NBE-002 is an ADC targeting ROR1, obtained by site-specific, enzymatic conjugation of the anthracycline-derivative PNU-159682, modified with a non-cleavable linker to a humanized recombinant IgG1 monoclonal antibody, based on a novel anti-human ROR1 monoclonal antibody XBR1-402 (Peng et al. (2017) J. Mol. Biol. 429: 2954-73). Direct anti-tumor activity of NBE-002 was evaluated in immunodeficient, ROR1 expression-low/-intermediate/-high PDX models of several carcinoma and sarcoma subtypes. The most pronounced anti-tumor effect was achieved in triple-negative breast cancer (TNBC), at doses as low as 0.033 mg/kg, suggesting a best-in-class therapeutic index in light of the high tolerability in preclinical toxicology models. Administration in a fully immune competent setting (EMT6/ROR1 orthotopic breast cancer model) led to a strong anti-tumor response and a long-lasting anti-tumor immune protection dependent on CD8 T cells. Methods: NBE-002-01 (NCT04441099) is a first-in-human, open-label, multi-center, phase (Ph) 1/2 study of NBE-002 in adult patients with advanced solid tumors. Ph 1 of the study consists of a Dose Escalation Cohort (DEC), utilizing an accelerated titration design, followed by a traditional 3+3 design, and an optional Safety Expansion Cohort (SEC). Ph 2 will include two parallel Expansion Cohorts (EC), enrolling patients with advanced TNBC (EC1) or other solid tumors (EC2), with Simon’s two-stage design. Key eligibility criteria include Eastern Cooperative Oncology Group performance status of 0-2 (Ph 1) or 0-1 (Ph 2), adequate organ function defined as: hemoglobin ≥9.0 g/dL, neutrophils ≥1500 /µL, platelets ≥100000/µL, aspartate and alanine aminotransferases ≤2.5x the upper limit of normal (ULN), total bilirubin ≤1.5x ULN, creatinine ≤1.5x ULN, left ventricular ejection fraction ≥50%. The primary objectives are to assess safety and tolerability and to establish the recommended dose for further development (Ph 1), and to evaluate anti-tumor activity of (Ph 2). Secondary and exploratory objectives include characterization of immunogenicity as well as pharmacokinetic and pharmacodynamic profiles. NBE-002 is given intravenously once every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specific criteria are met. Ph 1 dose escalation was initiated on 17 JULY 2020 and is still recruiting in the US. Ph 2 is planned to be initiated in 2022. Clinical trial information: NCT04441099 .
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Borges, V. F., E. Shagisultanova, J. O'Shaughnessy, A. M. Brufsky, R. Mahtani, K. Hoskins, H. Linden, et al. "32P Genomic risk classification and whole transcriptome analysis of HR+/HER2- post-partum breast cancers: A FLEX sub study." ESMO Open 9 (May 2024): 103040. http://dx.doi.org/10.1016/j.esmoop.2024.103040.
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Wang, Michael, Anissa Cyhaniuk, David L. Cooper, and Neeraj N. Iyer. "Identification of Persons with Acquired Hemophilia in a Large Electronic Health Record Database." Blood 126, no. 23 (December 3, 2015): 3271. http://dx.doi.org/10.1182/blood.v126.23.3271.3271.
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Abstract Background: Electronic health records (EHR) capture rich clinical information on a patient's encounter with their health care system. Studying national EHRs has the potential to provide epidemiological and granular clinical insights of the patient's diagnosis, treatment patterns and clinical outcomes. Acquired hemophilia (AH) occurs in 1:1-1.5 million people and is characterized by anti-factor VIII autoantibodies, and bleeding in elderly and post-partum patients often in the absence of prior bleeding history. The AH literature includes case reports and registries of known patients; no study to date has attempted to extract population-level information using a large EHR. Objective: This study aimed to identify patients with AH using a large EHR for the purposes of studying treatment patterns. Methods: This retrospective study attempts to identify AH patients by combining standard identification methods used in secondary database analysis along with clinical information from the EHR, and a text search of physician notes using Natural Language Processing (NLP) output. Records were accessed from a large, national, de-identified, longitudinal EHR database (Humedica) between January 1, 2007 and July 31, 2013. Given the rare nature of the disease, broader selection criteria were initially applied by using an ICD-9 code for hemorrhagic disorder due to intrinsic circulating anticoagulants (286.5 and all sub-codes), and confirmation of records in the EHR, 6 months before and 12 months after first (index) diagnosis. Additional selection criteria were: no anticoagulant use, not having a diagnosis of systemic lupus erythematosus, accessible physician notes, membership in an integrated delivery network (IDN), mention of "bleeding" within physician notes, and a normal prothrombin test (PT) but an elevated activated partial thromboplastin time (aPTT). Results: From 6,348 patients with a diagnosis code of 286.5 or any sub-codes, there were 20 males and 18 females who met selection criteria. The median age was 78.5 years (age top coded at 89 years). Table 1.Total usable patients13,000,000100%ICD-9 286.5*6,3480.049%With pre/post diagnosis records4,2120.032%Without anticoagulant1,1670.009%Without lupus/SLE1,1250.009%With physician notes and IDN3990.003%NLP "Bleeding"2550.002%NLP "Bleeding" and PT/aPTT1140.001%NLP "Bleeding" and normal PT/elevated aPTT380.0003% All 38 had a note for "pain" (most commonly chest [66%] and back [50%]), 21 (55%) had a note for "bruising", while none of the females had an ICD-9 code for abnormal menstruation or pregnancy. All 286* diagnoses for the 38 patients included: Table 2.286.0Congenital hemophilia A3 (8%)286.5Hemorrhagic disorder due to intrinsic circulating anticoagulants26 (68%)286.52Acquired hemophilia1 (3%)286.59Other intrinsic anticoagulant, antibody or inhibitor5 (13%)286.7Acquired factor deficiency3 (8%)286.9Other and unspecified5 (13%) No patients received typical AH treatment for bleeding (factor VIII, bypassing agent or DDAVP). The most common prescriptions were azithromycin (34%) and prednisone (32%). Data review: Individual Signs, Diseases, and Symptoms (SDS) associated with the patient via NLP key word extracts were randomly reviewed to validate if the identified cohort indeed had AH. (1) >89-year-old male; ~6 months of bruising and ecchymoses, "suspect" "clotting factor deficiency". (2) 70-year-old female breast cancer patient; isolated mention of hematemasis from Mallory-Weiss tear, multiple mentions of hematuria, hemorrhagic cystitis, and paradoxically a renal pelvis blood clot in the SDS on the same date. (3) A 32-year-old pregnant female reports bruising and irregular menses, and conflicting mention of venous thrombosis and blot clots. NLP output included FVIII deficiency, and there was mention of congenital and FVIII inhibitor. All 3 had bleeding symptoms, normal PT and elevated aPTT, but none had AH diagnosis or hemostatic treatment. Conclusions: NLP approaches to analysis of EHRs hold promise and have demonstrated utility in population-based studies for some disorders. However, in this study, ICD-9 codes, lab results, NLP output, and treatments were not consistently aligned. This study highlights that in ultra-rare disorders, ICD-9 coding alone may not be sufficient to identify cohorts, and multimodal analysis combined with in-depth reviews of physician notes might be more effective. Disclosures Wang: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Biogen: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees. Cyhaniuk:Novo Nordisk Inc.: Consultancy. Cooper:Novo Nordisk Inc.: Employment. Iyer:Novo Nordisk Inc.: Employment.
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Cui, Bing, George F. Widhopf, Charles E. Prussak, Christina C. N. Wu, Anil Sadarangani, Suping Zhang, Fitzgerald Lao, Catriona HM Jamieson, Dennis A. Carson, and Thomas J. Kipps. "Cirmtuzumab Vedotin (UC-961ADC3), An Anti-ROR1-Monomethyl Auristatin E Antibody-Drug Conjugate, Is a Potential Treatment For ROR1-Positive Leukemia and Solid Tumors." Blood 122, no. 21 (November 15, 2013): 1637. http://dx.doi.org/10.1182/blood.v122.21.1637.1637.
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Abstract ROR1 is an onco-embryonic antigen that is expressed on the neoplastic cells of patients with chronic lymphocytic leukemia (CLL), other B-cell lymphomas, acute leukemias, or many different solid-tumors, but not on non-neoplastic post-partum tissues, except for the uncommon precursor B cells known as hematogones. Because of its restricted expression on human malignancies, we have generated a series of monoclonal antibodies (mAb) against the extracellular domain of human ROR1 and are advancing our lead candidate mAb UC-961 (cirmtuzumab) into human clinical trials. Along with the anti-leukemia activity of this mAb, we have also shown that the UC-961 anti-ROR1 antibody is internalized by CLL B cells, and by several B cell leukemia and lymphoma cell lines, at a greater rate and degree than other anti-ROR1 mAb that bind other epitopes of the extracellular domain of ROR1. As such, we speculated that cirmtuzumab may have an enhanced specific cytotoxic activity when employed as an antibody-drug-conjugate (ADC). To test this hypothesis, we generated a series of cirmtuzumab ADCs using proprietary (Concortis Biosystems, San Diego) linkers and toxins. We examined the cytotoxic activity of each of the various cirmtuzumab-ADC against ROR1 expressing cells (e.g. CLL cells, JeKo-1 cells, or solid tumor cells) or ROR1-negative cells (e.g. Ramos and Jurkat cells). Cirmtuzumab stably bound to a modified monomethyl auristatin E (MMAE) through a light chain, constant region, lysine-linker with an antibody-drug ratio (ADR) of 2.5 (designated UC-961ADC3) showed the highest specific activity for killing ROR1+ cells without generating any toxic activities on ROR1-Neg cells in vitro. For example, UC-961ADC3 kills ROR1+ JeKo-1 (LD 50=1.4 μg/ml) or primary CLL cells (LD 50=39.9 μg/ml) in a dose dependent manner, but had no or low cytotoxicity for ROR1-Neg cell lines, Ramos (LD 50>200 μg/ml) or Jurkat (LD50> 95 μg/ml). To expand these findings, we examined the specific activity of UC-961ADC3 in clearing ROR1+ JeKo-1 cells engrafted in immune deficient Rag-2-/-/γc-/- mice. In these studies, groups of animals were given intravenous injections of 1 x 105 JeKo-1 cells. Three weeks after transfer, each mouse cohort was treated with weekly injections of 10 mg/kg UC-961ADC3, or control IgG antibody. Six weeks after adoptive transfer, the animals were sacrificed and spleens analyzed for the presence of the leukemic cells. Animals treated with UC-961ADC3 had a 5-fold lower median number of leukemia JeKo-1 cells in the spleen than animals treated with control IgG (p<0.001). We also tested the activity of UC-961ADC3 in a murine in vivo human primary CLL xenograph, niche-dependent model. In a representative experiment, control and test mouse cohorts were intraperitoneal implanted on day 0 with 2 x 107 primary human CLL cells. On day 1 the animals were treated with a single 1mg/kg i.p. injection of either UC-961ADC3 or control antibody. One week after implantation the animals were sacrificed and the residual CLL cells determined. In mice treated with UC-961ADC3 only an average of 3 ± 2 x 103 CLL cells were harvested. This number of cells was significantly less than the average number of CLL cells harvested from control IgG treated mice (9.3 ± 3.3 x 105, p <0.01). Finally, we have also demonstrated that UC-961ADC3 also could induce specific killing of ROR1-expressing adenocarcinomas of the breast or pancreas. These studies indicate that a cirmtuzumab-ADC can directly target and kill ROR1-expressing cancer cells in vitro and in vivo without detectable cytotoxicity for ROR1 negative cells. Because of the restricted expression of ROR1 on human malignancies, we propose that UC-961ADC3 might have potential utility in the treatment of patients with ROR1 positive leukemias and solid tumors with an enhanced therapeutic index relative to other therapies. Disclosures: No relevant conflicts of interest to declare.
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Samayoa-Reyes, Gabriela, Sidney O. Ogolla, Ibrahim I. Daud, Conner Jackson, Katherine R. Sabourin, Arlene Dent, and Rosemary Rochford. "Maternal HIV Infection as a Risk Factor for Primary Epstein-Barr Virus Infection in Kenyan Infants." Frontiers in Oncology 11 (January 12, 2022). http://dx.doi.org/10.3389/fonc.2021.805145.
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Human immunodeficiency virus (HIV) infection is known to be associated with EBV shedding in saliva suggesting an increased risk of EBV transmission to infants born to mothers with HIV at an earlier age. In this study we investigated (i) whether maternal HIV status was a risk factor for EBV in blood at delivery or for shedding in saliva and breast milk of 6- and 10-weeks post-partum mothers, (ii) if there was a difference in EBV strains shed between HIV+ and HIV- mothers, and (iii) if maternal HIV status was a determinant of EBV viral load in their infants. Samples were collected as part of a prospective cohort study that followed HIV-positive (HIV+) and HIV-negative (HIV-) pregnant women in Western Kenya through delivery and post-partum period. EBV viral load in blood was found to be significantly higher in mothers with HIV (p-value = 0.04). Additionally, a statistically significant difference was observed between EBV viral load in saliva samples and HIV status where HIV+ mothers had a higher EBV viral load in saliva at 6-weeks post-partum compared to HIV- mothers (p-value < 0.01). The difference in EBV shedding in breast milk was not found to be statistically significant. Furthermore, no difference in frequency of EBV strain was attributable to HIV- or HIV+ mothers. Interestingly, we found that infants born to HIV+ mothers had a higher EBV viral load at the time of their first EBV detection in blood than infants born to HIV- mothers and this was independent of age at detection. Overall, our study suggests that HIV infected mothers shed more virus in saliva than HIV-negative mothers and infants born to HIV+ mothers were at risk for loss of control of primary EBV infection as evidenced by higher EBV viral load following primary infection.
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Li, Yuechong, Yingjiao Wang, Qiang Sun, and Songjie Shen. "Clinicopathologic features, treatment, and prognosis of pregnancy-associated breast cancer." Frontiers in Oncology 12 (December 14, 2022). http://dx.doi.org/10.3389/fonc.2022.978671.
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PurposeTo identify the clinicopathological features, treatment, and prognosis of patients with breast cancer, who were diagnosed during and after pregnancy.MethodsWe searched for patients with pregnancy-associated breast cancer (PABC) using the big data query and analysis system of Peking Union Medical College Hospital from between January 1, 2013, and December 31, 2021, and matched each patient with two non-PABC patients by age at diagnosis, year at diagnosis, and tumor stage. The clinicopathologic features, treatment, and outcomes of breast cancer during pregnancy (BC-P) and breast cancer during the first-year post-partum (BC-PP) were examined retrospectively in two case-control studies.ResultsEighteen BC-P cases, 36 controls for BC-P cases, 62 BC-PP cases, and 124 controls for BC-PP cases were enrolled in our study. The expression of HER-2 and Ki-67 was higher in BC-PP cases than in its controls (P=0.01, 0.018, respectively). Patients with BC-PP were more likely to choose mastectomy than breast-conserving surgery (P=0.001). There were no significant differences in event-free survival (EFS) between patients with BC-P and BC-PP and their controls.ConclusionBC-P and BC-PP patients displayed adverse clinicopathological features in our population. However, when matched by age at diagnosis, year of diagnosis, and tumor stage, BC-P and BC-PP patients did not show inferior outcomes to controls, probably due to aggressive multimodality therapy.
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Callaway, Mackenzie K., and Camila O. dos Santos. "Gestational Breast Cancer – a Review of Outcomes, Pathophysiology, and Model Systems." Journal of Mammary Gland Biology and Neoplasia 28, no. 1 (July 14, 2023). http://dx.doi.org/10.1007/s10911-023-09546-w.
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AbstractThe onset of pregnancy marks the start of offspring development, and represents the key physiological event that induces re-organization and specialization of breast tissue. Such drastic tissue remodeling has also been linked to epithelial cell transformation and the establishment of breast cancer (BC). While patient outcomes for BC overall continue to improve across subtypes, prognosis remains dismal for patients with gestational breast cancer (GBC) and post-partum breast cancer (PPBC), as pregnancy and lactation pose additional complications and barriers to several gold standard clinical approaches. Moreover, delayed diagnosis and treatment, coupled with the aggressive time-scale in which GBC metastasizes, inevitably contributes to the higher incidence of disease recurrence and patient mortality. Therefore, there is an urgent and evident need to better understand the factors contributing to the establishment and spreading of BC during pregnancy. In this review, we provide a literature-based overview of the diagnostics and treatments available to patients with BC more broadly, and highlight the treatment deficit patients face due to gestational status. Further, we review the current understanding of the molecular and cellular mechanisms driving GBC, and discuss recent advances in model systems that may support the identification of targetable approaches to block BC development and dissemination during pregnancy. Our goal is to provide an updated perspective on GBC, and to inform critical areas needing further exploration to improve disease outcome.
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Lim, Chew Leng, Yu Zuan Or, Zoe Ong, Hwa Hwa Chung, Hirohito Hayashi, Smeeta Shrestha, Shunsuke Chiba, Feng Lin, and Valerie Chun Ling Lin. "Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism." eLife 9 (July 24, 2020). http://dx.doi.org/10.7554/elife.57274.
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There is strong evidence that the pro-inflammatory microenvironment during post-partum mammary involution promotes parity-associated breast cancer. Estrogen exposure during mammary involution drives tumor growth through neutrophils’ activity. However, how estrogen and neutrophils influence mammary involution are unknown. Combined analysis of transcriptomic, protein, and immunohistochemical data in BALB/c mice showed that estrogen promotes involution by exacerbating inflammation, cell death and adipocytes repopulation. Remarkably, 88% of estrogen-regulated genes in mammary tissue were mediated through neutrophils, which were recruited through estrogen-induced CXCR2 signalling in an autocrine fashion. While neutrophils mediate estrogen-induced inflammation and adipocytes repopulation, estrogen-induced mammary cell death was via lysosome-mediated programmed cell death through upregulation of cathepsin B, Tnf and Bid in a neutrophil-independent manner. Notably, these multifaceted effects of estrogen are mostly mediated by ERα and unique to the phase of mammary involution. These findings are important for the development of intervention strategies for parity-associated breast cancer.
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Jerzak, Katarzyna J., Nechama Lipton, Sharon Nofech-Mozes, Dina Boles, Elzbieta Slodkowska, Gregory R. Pond, and Ellen Warner. "Clinical outcomes and prognostic biomarkers among pregnant, post-partum and nulliparous women with breast cancer: a prospective cohort study." Breast Cancer Research and Treatment, July 27, 2021. http://dx.doi.org/10.1007/s10549-021-06327-z.
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Nimbalkar, Vidya P., V. P. Snijesh, Savitha Rajarajan, Annie Alexander, Rohini Kaluve, Rakesh Ramesh, B. S. Srinath, and Jyothi S. Prabhu. "Premenopausal women with breast cancer in the early post-partum period show molecular profiles of invasion and are associated with poor prognosis." Breast Cancer Research and Treatment, May 9, 2023. http://dx.doi.org/10.1007/s10549-023-06956-6.
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Abstract Purpose Young premenopausal women develop breast cancer (BC) within 5–10 years of the last childbirth, known as post-partum breast cancers (PPBC), often present with aggressive disease. The exact mechanisms that lead to poor prognosis in these patients are largely unknown. Methods We have evaluated the association of clinical and reproductive factors with BC in a cohort of women ≤ 45 years (N = 155) with long-term follow-up. Based on duration since last childbirth (LCB), grouped patients into PPBC1 (LCB ≤ 5 years), PPBC2 (LCB between 6 and 10 years), PPBC3 (LCB > 10 years), and NPBC (age-matched nulliparous BC patients). We compared disease-free survival and hazard associated with recurrence/metastasis between the groups. RNA sequencing of tumor samples was performed from three parous groups (n = 10), and transcriptomic data were analyzed for differentially expressed genes and altered pathways. Results Women in the PPBC1 group had an early menarche and late age at first and last childbirth compared to other groups. Survival analysis within lymph node-positive tumors showed that PPBC1 tumors had a worse prognosis than PPBC2 and NPBC tumors (p = 0.015 and p = 0.026, respectively). Clustering of the differentially expressed genes between the groups showed distinct expression in early PPBC (E-PPBC) tumors. Pathway analysis revealed upregulation of invasive-related pathways along with T cell exhaustion, extracellular matrix remodeling, angiogenesis, and epithelial-to-mesenchymal transition in E-PPBC tumors. Conclusion Early PPBC is a unique subtype with aggressive clinical features and distinct biology. Further research is needed to accurately project the risk of recurrence and optimal treatment strategies in these young patients.
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Sushma. "CRITICAL ANALYSIS OF SUTIKA PARICHARYA AND ITS SIGNIFICANCE IN MODERN ERA IN SAFE MOTHERHOOD." International Journal of Ayurveda and Pharma Research, November 29, 2020, 71–76. http://dx.doi.org/10.47070/ijapr.v8isupply2.1599.
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Mortality and morbidity of mother are most challenging problems of our country. In our day to day life, we see many mothers complaining of increase in their physical problems like back-ache, anemia, joint pains and many other infections after puerperium. Frequent post-partum morbidity and its association with adverse perinatal outcome suggest the need for post-partum care in developing countries for both mother and baby. Lady after delivery of placenta is called as Sutika (puerperal woman). Sutikakala (duration of puerperium) is the period following childbirth during which all body tissues revert back approximately to a pre-pregnant state. Duration of this period varies according to different Ayurvedic classics. It is well known that certain psycho-somatic changes take place during Sutikakala such as loss of weight, loss of body fluid, lacerated genital tract, constipation, mental stress etc. Most of these changes lead to ati-aptarparpana (emaciation) of mother during Sutikakala. This status causes Vata-vriddhi which is responsible for different types of health problems such as puerperal sepsis, Stanyadushti (vitiated breast milk), anaemia, prolapse of uterus etc. According to Kashyapa Samhita, treatment of Sutika is as difficult as cleaning of unclean, tattered and old cloth. In olden days, ladies used to follow strict guidelines during early postpartum days i.e. in Sutikakala, which helped them for early recovery from stress and strain caused during delivery. It also improves the quality and quantity of breast milk and it also avoids various neonatal infections. Mothers who breast feed their babies are at low risk for breast cancer. In modern era due to changing lifestyle and Mithya aahaar-vihaar (abnormal dietetics and mode of Life), pregnant lady is usually prone to Vataprakopa. Many modern Sutika feel ancient guidelines during early puerperal days as age old and time consuming to follow. Hence, guided Sutika paricharya with logical use of classical referenced medicine would be the proper solution to avoid psycho-somatic disorders in order to promote early recovery of mother.
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Cardoso, Grasiela Benini dos Santos. "Oregnancy-associated breast cancer: Analysis of cases in the mastology service of hospital santa marcelina de itaquera, são paulo, from 2014 to 2019." Mastology 30, Suppl 1 (2020). http://dx.doi.org/10.29289/259453942020v30s1087.
Full textAbstract:
Thirty-one year old, median gestational age of 28 weeks. Four of our patients were primiparous with less than 20 years of age, and two between the ages of 30 and 34, with median of secundiparous patients (50%). By analyzing the obesity and BMI (body mass index) factors, we concluded that 3 patients were mildly obese, and one presented with morbid obesity at the time of diagnosis. Our BMI mean was 29. Considering histology and immunohistochemical, eight patients were diagnosed with ductal invasive carcinoma, without other specifications; one was diagnosed with fusiform cell carcinoma, and one with mucinous carcinoma. The histological subtypes found were luminal B (4 cases) and triple negative (6 cases). These results were compatible with a French retrospective study from 2017. The pregnant woman, or in the puerperium, with breast cancer may present the same symptoms as the other patients with the disease, but diagnosis can be delayed due to the physiological changes in breast tissue in the pregnancy-puerperal period. In our study, all patients were diagnosed at advanced clinical staging (IIIA, IIIB and IV). The treatment follows the same protocols as for non-pregnant patients, considering not only the type of tumor and disease staging, but also gestational age. The most used therapy for our group was neoadjuvant chemotherapy, followed by radical modified mastectomy. This was owed to the advanced stage of the disease. The sentinel lymph node biopsy was performed in two patients. One was diagnosed in the post-partum period, and the other was diagnosed while pregnant of 34 weeks. The latter received surgical treatment after the pregnancy. Chemotherapics are relatively safe when applied after the second trimester. During the patients’ follow-up, one of them presented with progression of the disease to the brain (this patient was in stage IV, with lung metastasis); one presented with bone and hepatic metastasis; and the other one had plastron recurrence. Until the conclusion of this study, four patients died. Conclusions: Pregnancy-associated breast cancer is a condition that should be observed by health teams, since its early diagnosis enables an approach that minimizes damages for the maternal-fetal binomial. Besides, detecting this disease in its early stages is the main factor that impacts the disease-free survival.