Pregnancy-associated breast cancer: the influence of gestational age

2021 ◽  
Author(s):  
Britt Berendine Maria Suelmann ◽  
Carmen van Dooijeweert ◽  
Carsten Bakhuis ◽  
Sabine Linn ◽  
Elsken van der Wall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gestational Age ◽  
Age At Diagnosis ◽  
Her2 Status ◽  
Third Trimester ◽  
The Common ◽  
Negative Phenotype ◽  
Histopathologic Features ◽  
Grade Iii

Whether PABC tumors arise before or during pregnancy and whether histopathology is affected by gestational age is currently unclear. The present study assesses the influence of gestational age and lactation on the histopathologic profile of PABC. We identified 744 patients with PABC (defined as breast cancer during pregnancy or 6-months following delivery). Histopathologic features were compared between pregnant and postpartum patients. Median age at diagnosis was 34.2 years and majority of cancers were diagnosed during pregnancy (71.3%). Within pregnant patients, tumors were significantly more often ER-negative in second and third trimesters (57.4%), as compared to first trimesters (41.9%) (p=0.036). Similarly, a PR-negative status was reported significantly less often within first trimesters (38.0%) compared to second and third trimesters (57.1%) (p=0.032). For HER2 status no significant differences were observed between gestational trimesters or lactating versus non-lactating patients. In postpartum patients, grade III tumors were found in over 80%, with high percentages of ER-negative tumors reaching 63% in those lactating versus 49% in non-lactating patients. This study demonstrates the varying histopathologic profile of PABC by gestational age and lactation status. Second and third trimester cancers display most typically the common ER/PR-negative phenotype, which is commonly reported in literature. The increased ER-negative status and percentage grade III tumors in lactating versus non-lactating patients also suggest presence of additional factors further diversify histology. This indicates the need for clear definitions of PABC and the role of potential subgroups, which may provide a stepping stone for further in-depth research into PABC-carcinogenesis.

scholarly journals Chemotherapy for breast cancer during pregnancy induces vascular alterations and impaired development of placental villi: a preliminary histopathological study.

2019 ◽  
Author(s):  
Alessandro Del Gobbo ◽  
Giovanna Scarfone ◽  
Fedro Alessandro Peccatori ◽  
Antonella Villa ◽  
Wally Ossola ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Birth Weight ◽  
Pregnant Women ◽  
Gestational Age ◽  
First Trimester ◽  
Histopathological Study ◽  
Third Trimester ◽  
Significant Difference ◽  
Placental Villi ◽  
Fetal Malformations

Abstract Breast cancer is diagnosed in approximately 1/3000 pregnant women. Chemotherapy may be administered after the first trimester, with improved maternal outcome and relatively few pregnancy and offspring complications. Nonetheless, no information about the effects of different chemotherapy regimens on placenta architecture and vasculature are available. Methods To evaluate histological alterations in placentas of women affected by breast cancer and treated with chemotherapy during pregnancy, we retrospectively analyzed 23 placentas of patients affected by breast cancer and treated with chemotherapy during pregnancy and 23 control placentas of women without breast cancer and with physiological pregnancies of the same gestational age. Results All the patients had breast ductal infiltrating carcinoma, 19 of 23 cases had a G3 cancer. All patients were treated with 2-6 cycles of chemotherapy starting after 16 weeks of gestation, with different protocols. No hypertensive complications and no pre-eclampsia episodes were observed; birth weight was consistent with gestational age in all babies in both group with no uneventful outcomes and no perinatal mortality or fetal malformations. Twenty out of 23 cases (86%) showed hypoxia-induced villous alterations, including increased syncytial knotting (Tenney-Parker changes), perivillar fibrin deposits, distal villous hypoplasia or accelerated maturation and focal villous chorangiosis. These alterations were found in 19 out of 23 controls (83%), with no statistically significant difference between the two groups. Conclusions These results shows that chemotherapy in the second and third trimester of pregnancy may lead to non-specific alterations in placental vasculature and morphology.

Metastatic breast cancer and the elderly: A single institution, retrospective review.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 55-55
Author(s):  
Michael Kidd ◽  
Nina J. Karlin ◽  
Amylou C. Dueck
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cox Regression ◽  
Age Groups ◽  
Metastatic Breast ◽  
Age At Diagnosis ◽  
Her2 Status ◽  
P Value ◽  
Cox Regression Analysis ◽  
Hormone Status

55 Background: The aim of this retrospective study was to examine the overall survival (OS) of metastatic breast cancer patients over a decade and assess for any differences with respect to age, tumor characteristics, and ECOG status. Methods: Data on metastatic breast cancer cases from 1999-2010 were retrieved from the institutional cancer registry and linked to electronic medical records. Through chart review of 240 metastatic breast cancer cases, we determined hormone receptor (HR), HER2/neu (HER2), ECOG, age at diagnosis of metastatic cancer and mortality data. Kaplan-Meier survival curves for OS were used and compared between HR status, HER2 status, ECOG, and age at diagnosis using log-rank regression and Cox Regression analysis was performed to control for these variables. A 95% confidence interval (CI) was used. Results: The median OS of the sampled cases was 2.2 years (CI: 1.8-2.5 years). Analysis for overall survival by pre-determined age groups demonstrated no significant difference between the age groups (p value 0.46), but did yield a statistical difference based on ECOG status (p value 0.0001). Cox regression analysis showed consistent findings where survival was significantly affected by HR, HER2 status and ECOG but not age (HR: p value <0.0001; HER2: p value 0.0132; ECOG: p value <0.0001; age at diagnosis: p value 0.8462). Analysis for OS based on HR yielded a median survival of 1.4 years (CI: 0.9-1.6 years) for HR negative and 2.5 years (CI: 2.2-3.0 years) for HR positive (p value 0.0018). HER2 yielded a median survival of 1.8 years (CI: 1.4-2.3 years) for no amplification and 3.0 years (CI: 2.5 - 3.4 years) for amplification (p-value 0.0043). HR negative, HER2 non-amplified tumors had the poorest median OS at 0.7 years (CI: 0.5 - 1.1 years) whereas those tumors with HR positive, HER2 amplified had the best median OS at 3.0 years (CI: 2.5 - 4.7 years) with a p value < 0.0001. Conclusions: In this retrospective analysis, there was no significant survival difference with respect to age. Age continued to have no significant effect on survival when adjusting for ECOG, hormone status, and HER2/neu status. Those factors that did act as determinants of survival were ECOG status, hormone status and HER2/neu status of the tumor.

scholarly journals Circulating Tumor Cells in Breast Cancer Patients: An Evolving Role in Patient Prognosis and Disease Progression

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Holly Graves ◽  
Brian J. Czerniecki
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Early Breast Cancer ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Neoplastic Process

In this paper, we examine the role of circulating tumor cells (CTCs) in breast cancer. CTCs are tumor cells present in the peripheral blood. They are found in many different carcinomas but are not present in patients with benign disease. Recent advances in theories regarding metastasis support the role of early release of tumor cells in the neoplastic process. Furthermore, it has been found that phenotypic variation exists between the primary tumor and CTCs. Of particular interest is the incongruency found between primary tumor and CTC HER2 status in both metastatic and early breast cancer. Overall, CTCs have been shown to be a poor prognostic marker in metastatic breast cancer. CTCs in early breast cancer are not as well studied, however, several studies suggest that the presence of CTCs in early breast cancer may also suggest a poorer prognosis. Studies are currently underway looking at the use of CTC level monitoring in order to guide changes in therapy.

Impact of endocrine therapy on overall survival in ER negative/PR positive locoregional breast cancer: An analysis of the National Cancer Database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 545-545
Author(s):  
Vidya Kollu ◽  
Kohei Osterloth ◽  
Andrew J. Borgert ◽  
Susan M. Frankki ◽  
Benjamin Marshall Parsons
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Endocrine Therapy ◽  
Stage I ◽  
Her2 Status ◽  
Matched Cohort ◽  
Cancer Data ◽  
Her2 Breast Cancer ◽  
Definitive Surgery

545 Background: Breast cancer expressing PR, but not ER (ER-/PR+) are uncommon, comprising 2–8% of breast cancers, with less known about their characteristics and responsiveness to therapy. The role of adjuvant endocrine therapy (ET) in ER-/PR+ locoregional breast cancer is unclear as these patients have been largely excluded from prospective clinical trials. Despite a lack of data patients are often treated with adjuvant ET due to perceived possible benefit. We used the National Cancer Data Base (NCDB) to assess role of adjuvant ET in ER-/PR + breast cancer. Methods: Using the NCDB, we included adults ≥ 18 and ≤ 70 years old in order to minimize the non-cancer related deaths. We selected only female patients with stage I, II, and III. Patients have received definitive surgery (lumpectomy with radiation or mastectomy) with negative margins. Systemic therapy (ST) was defined as receipt of chemotherapy and/or immunotherapy. We excluded those who had unknown ST status, unknown ET status, unknown HER 2 status, who did not receive definitive surgery and those whose survival time was missing. Patients were stratified into four groups based on HER2 status and receipt of ET. Both Multivariable Cox proportional hazards regression modeling was utilized to determine predictors of overall survival (OS). A propensity score matched cohort was developed based on relevant demographic and clinical factors. The primary endpoint assessed was OS. All analyses were performed using SAS 9.4. Results: We identified 5344 patients (74% were Caucasian, 20% were African American and 6% were others) with ER-/PR+(74% were HER2 - and 26% were HER2 +) locoregional breast cancer (51% were Stage I, 38 % were stage II and 11% were stage III). Grade 1 cancer was seen in 2%, grade 2 in 18%, and majority being grade 3 in 80%. Of which 3093 (58%) patients received ET and 4462 (83%) received ST. Majority of patients were in age group 50-70 comprising of 69% patients, 8 % in age 18—39, 23% in age 40-49 with Charlson-Deyo Score of 0 in 83%, 1 in13%, 2-3 in 4%. In a propensity matched cohort (N=3980), ET was not significantly associated with OS among HER2 negative (HER2-) patients (HR=1.05, 95% CI 0.86-1.28, p=0.63). In HER2+ patient ET was associated with significantly improved OS (HR=0.65, 95% CI 0.42-0.99, p=.047). Conclusions: Receiving ET was not associated with improved OS in locoregional ER-/PR+/HER2- breast cancer based on our study using a propensity matched cohort in the NCDB. However, was frequently administered. Interestingly, improved OS was seen in locoregional ER-/PR+/HER2+ breast cancer with adjuvant ET.

scholarly journals Predictive role of HER2-status on the effectiveness of endocrine adjuvant treatment in postmenopausal breast cancer patients: a population-based cohort study

2020 ◽  
Author(s):  
Aglaia Schiza ◽  
Davide Mauri ◽  
Irma Fredriksson ◽  
Anna-Karin Wennstig ◽  
Antonios Valachis
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Endocrine Therapy ◽  
Population Based ◽  
Her2 Status ◽  
Her2 Positive ◽  
Study Results

Abstract Purpose There are conflicting results on the potential role of HER2-status on the efficacy of aromatase inhibitors (AIs) and tamoxifen (TAM) in patients with hormone receptor (HR)-positive breast cancer (BC). The purpose of this population-based cohort study was to investigate the potential benefit of AIs compared to TAM as adjuvant therapy in postmenopausal BC patients by HER2-status in the era of modern therapy with HER2-blockade. Methods A population-based cohort study was performed including all postmenopausal women diagnosed with HR-positive BC without distant metastasis between 2007 and 2012 in three healthcare regions in Sweden. We analyzed the breast cancer-specific survival (BCSS) and overall survival (OS) in two distinct cohorts (HER2-negative, HER2-positive) based on the type of endocrine therapy (ET) used. A propensity score matching was performed separately in the HER2-negative and HER2-positive cohorts, respectively. Results After propensity score matching, 4368 patients with HER2-negative and 214 patients with HER2-positive BC were available for analysis. In the HER2-negative cohort, an improved BCSS [Hazard Ratio (HR): 0.51; 95% confidence interval (CI): 0.34–0.77, p value < 0.001] and a trend toward improved OS (HR: 0.66; 95% CI: 0.41–1.08, p value = 0.093) in favor of AI-based therapy was observed. In the HER2-positive cohort, no statistically significant difference between AI-based ET and TAM was found in terms of either BCSS or OS, although the direction of HR was similar as in the HER2-negative cohort (HR for BCSS: 0.84; 95% CI: 0.14–5.04, p = 0.849; HR for OS: 0.62; 95% CI: 0.10–3.38, p = 0.345). Conclusion Our study results, based on propensity-matched cohorts, did not support any predictive value of HER2-status on endocrine therapy in postmenopausal BC patients. AI-based ET remains the treatment of choice for postmenopausal BC patients with HR-positive disease in the modern era of HER2-directed therapy irrespective of HER2-status.

Genetic variants of kinases suppressors of ras (KSR1) to predict survival in patients with ER-alpha positive metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11018-e11018
Author(s):  
Wu Zhang ◽  
Leonor Benhaim ◽  
Dongyun Yang ◽  
Armin Gerger ◽  
Pierre Oliver Bohanes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor Alpha ◽  
Mapk Pathway ◽  
Univariate Analysis ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Lymph Node Status ◽  
Nucleotide Polymorphisms ◽  
Potential Marker

e11018 Background: In addition to its activating role of MAPK pathway, the protein kinase suppressor of ras 1 (KSR1) has been identified as a novel modulator of estrogen receptor alpha (ERα), as silencing of KSR1 in ERα+ breast cancer (BC) cells lines resulted in dowregulation of ERα transcriptional activity in the presence of oestradiol. Our previously data revealed the existence of single nucleotide polymorphisms (SNPs) in EGFR and ERα pathway genes that may predict clinical outcome in ERα positive metastatic BC (mBC) patients. With respect to those findings we aimed to evaluate the clinical implication of KSR1 SNPs on survival in patients with primary ERα+ mBC treated with tamoxifen. Methods: Tumoral DNA was obtained from 222 patients treated with tamoxifen withERα+ invasive BC who had undergone surgery between 1981 and 2003 (median age 56 [28-90]). Three relevant KSR1 SNPs were selected based on public literature resources and databases, including 2 SNPs localised in the regulating 3’untranslated region (rs224190, rs 1075952) and 1 non-synonymous SNP localised in the coding exon 7 region (rs2293180). All SNP were analysed using DNA sequencing with OS and DFS as primary endpoint. Results: The overall median follow-up was 6.4 years.In univariate analysis the rs2241906 SNP was significantly associated with DFS and OS and patients with the TT genotypedemonstrated shorter DFS (2.1 vs. 7.1 months, p=0.005) and OS ( 2.6 vs. 8.4 months p=0.002) than patients with the x/C genotypes. The associations remained significant in the multivariate analysis adjusting age, lymph node status and HER2 status (HR (95%CI): 4.81 (2.00-11.59) and 5.74 (2.29-14.43), for DFS and OS, respectively). The same significant correlation was retrieved with the SNP rs1075952 in linkage disequilibrium with rs2241906 that was used as a control. No relationship was shown between rs2293180 and survival. Conclusions: Our findings demonstrated that KSR1 polymorphisms could arise as a potential marker to predict survival in patients with mBC treated with tamoxifen. The putative role of KSR1 as a modulator of ERα activity could functionally explain our results yielding insight for further studies.

scholarly journals Chemoresistance is associated with overexpression of HAX-1, inhibition of which resensitizes drug-resistant breast cancer cells to chemotherapy

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769222 ◽  
Author(s):  
Ji Yang ◽  
Yue Wu ◽  
Xiao Wang ◽  
Liqian Xu ◽  
Xiaohong Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Breast Cancer Cells ◽  
Acquired Resistance ◽  
Specific Protein ◽  
Drug Resistant ◽  
Standard Chemotherapy ◽  
Protein X ◽  
The Common

Acquired resistance to standard chemotherapy is the common and critical limitation for cancer therapy. Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) has been reported to be upregulated in numerous cancers. However, the role of HAX-1 in oncotherapy remains unclear. In this study, we established MDA-MB-231 cell lines which were resistant to cisplatin (MDA-MB-231/CR) or doxorubicin (MDA-MB-231/DR) to study the chemoresistance in breast cancer. As a result, the HAX-1 which is an apoptosis-associated protein was observed to be overexpressed in both MDA-MB-231/CR and MDA-MB-231/DR compared with the routine MDA-MB-231 cells. Moreover, knockdown of HAX-1 via RNA interference decreased IC50 level of cisplatin by 70.91% in MDA-MB-231/CR cells, and the IC50 level of doxorubicin was decreased by 76.46% in MDA-MB-231/DR cells when the HAX-1 was downregulated. Additionally, we found that the knockdown of HAX-1 induced the release of cytochrome C from mitochondria, resulting in the activation of caspases. Taken together, our study indicates that the overexpression of HAX-1 is essential in the development of chemoresistance in breast cancer. Furthermore, we identify that HAX-1 may become the target for cancer therapy.

scholarly journals The Role of Fetal Kidney Length and Fetal Transverse Diameter of Heart in Prediction of Gestational Age

2020 ◽  
Vol 5 (04) ◽  
Author(s):  
Panda Subrat ◽  
Rudrapal Gouri Sankar ◽  
Das Ananya ◽  
Ray Baruah Surajit ◽  
Sharma Nalini
Keyword(s):  
Gestational Age ◽  
First Trimester ◽  
Accurate Estimation ◽  
Transverse Diameter ◽  
Second Trimester ◽  
Fetal Kidney ◽  
Third Trimester ◽  
Kidney Length ◽  
Singleton Pregnancies

Objective: Currently there is no single ultrasonological parameter for accurate estimation of gestational age in third trimester. The present study is undertaken to validate the fetal kidney length and fetal transverse diameter of heart measurement as a measurement of fetal growth with less variability. Materials & Methods: It is a cohort study conducted in Department of Obstetrics and Gynaecology, NEIGRIHMS from 2015 to 2016. 224 women with singleton pregnancies and sure of LMP were enrolled. Each woman underwent minimum three ultrasonographic measurements- at first trimester for gestational age by CRL, at second trimester with fetal conventional biometry, at third trimester with Fetal kidney length, transverse diameter of heart and fetal conventional biometric parameters and analysed with SPSS Version22. Results: The gestational age with CRL was within three days of the menstrual age. In second trimester, conventional parameter (BPD,HC,AC,FL) were better parameters. Conventional parameter did not correspond to gestational age calculated from LMP. (BPD, R2= 0.4819, HC R2- 0.507, AC R2- 0.5175, FL R2-0.5243, Combined Conventional parameter R2- 0.5888). Fetal kidney length (R2-0.8356) and transverse diameter of heart (R2-0.8795) better correlated with gestational age. Conclusion: Kidney length and transverse diameter of heart are better predictors of gestational age in third trimester.

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