Patterns of HER2 testing in the management of primary breast cancer

Background: Women with invasive breast cancer should be tested for human epidermal growth factor receptor-2 (HER2) status at the time of diagnosis. To date, no population-based patterns of use studies have examined demographic and clinicopathologic factors associated with decisions by clinicians to test patients. Methods: We reviewed summary pathology reports submitted to the Connecticut Tumor Registry for all Black/African American (B/AA) women (n = 644) and a 7% random sample (n = 720) of White women diagnosed in 2000–2003 with primary invasive breast carcinoma. Receipt of a HER2 test (yes vs. no) was examined in relation to patient race, age, socioeconomic status, year of diagnosis, estrogen receptor (ER) status, tumor grade, lymph node status, size and stage at diagnosis. Results: A greater proportion of tumors from B/AA patients were tested compared to those of White women (69.5% vs. 61.9%, p < 0.05). Tumors of patients under the age of 60 were 1.50-times more likely than older women to have been tested, and B/AA women were 1.40-times more likely than White patients to be tested. HER2 testing was more likely to be observed when information also was reported about ER status (OR = 15.9, p < 0.001), tumor grade (OR = 2.28, p < 0.05), tumor size (OR = 2.16, p < 0.05), and lymph node status (OR = 2.06, p < 0.05). Conclusions: Variation in which breast cancer patients received HER2 testing appears to reflect expectations about a woman's prognosis. Discrepancies in receipt of testing deserve further study as current guidelines call for all tumors to be assessed in order to adequately characterize prognosis and determine eligibility for HER2-targeted therapy.     

Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas

Gliomas are the most important group of malignant primary brain tumors and one of the most aggressive forms of cancer. During the last years, several studies have demonstrated that cannabinoids induce apoptosis of glioma cells and inhibit angiogenesis of gliomas in vivo. As the effects of cannabinoids rely on CB₁ and CB₂ receptors activation, the aim of the present study was to investigate both receptors protein expression in cellular membrane homogenates of human glial tumors using specific antibodies raised against these proteins. Additionally, we studied the functionality of the cannabinoid receptors in glioblastomas by using WIN 55,212-2 stimulated [³⁵S]GTPγS binding.Western blot analysis showed that CB₁ receptor immunoreactivity was significantly lower in glioblastoma multiforme (?43%, n = 10; p < 0.05) than in normal post-mortem brain tissue (n = 16). No significant differences were found for astrocytoma (n = 6) and meningioma (n = 8) samples. Conversely, CB₂ receptor immunoreactivity was significantly greater in membranes of glioblastoma multiforme (765%, n = 9; p < 0.05) and astrocytoma (471%, n = 4; p < 0.05) than in control brain tissue (n = 10). Finally, the maximal stimulation of [³⁵S]GTPγS binding by WIN 55,212-2 was significantly lower in glioblastomas (134 ± 4%) than in control membranes (183 ± 2%; p < 0.05). The basal [³⁵S]GTPγS binding and the EC₅₀ values were not significantly different between both groups.The present results demonstrate opposite changes in CB₁ and CB₂ receptor protein expression in human gliomas. These changes may be of interest for further research about the therapeutic effects of cannabinoids in glial tumors.     

Luminal (Her2 negative) prognostic index and survival of breast cancer patients

PurposeThe group of luminal (Her2 negative) is distinguished from other subtypes of breast cancer. We aimed to produce a prognostic index specific for luminal (Her2 negative) subtype breast cancer that could assist clinical treatment.MethodsThe test set comprised 406 consecutive luminal (Her2 negative) breast cancer patients. The relationship of 11 clinicopathologic factors including survivin with the 5-year disease-free survival was analyzed.ResultsIn univariate analysis, TNM stage, surgery, tumor size, lymph node involvement, and survivin expression were prognostic factors. In multivariate analysis, tumor size [HR (95% CI): 1.98 (1.12–3.49), p = 0.019], the number of lymph node metastasis [HR (95% CI): 1.75 (1.33–2.29), p < 0.0001] and the expression of progesterone receptor [HR (95% CI): 0.58 (0.36–0.95), p = 0.029] can independently predict prognosis. Prognostic index (PI) was calculated as 0.68 × tumor size + 0.56 × the number of lymph node metastasis − 0.54 × PR. According to the PI, patients were categorized into three groups: low, middle, and high risk group with the 5-year disease-free survival rates of 91.91%, 84.97% and 70.47%, respectively (P < 0.001). In the validation set, the luminal prognostic index (LPI) remained significant.ConclusionThe LPI may be a useful tool for evaluating the outcome of patients with luminal (Her-2 negative) breast cancer.     

Does consanguinity lead to decreased incidence of breast cancer?

Background: In the Middle East region, consanguinity remains to be a central feature where it has shown an increasing trend. Breast cancer is an extremely complex disease, characterized by a progressive multistep process caused by interactions of both environmental and genetic factors. Aim: The aim of this study was to examine the possible effect of consanguinity on the risk of breast cancer in a population with a high rate of consanguinity and find the associated risk-modifying factors. Subjects and methods: The study included 167 Qatari and other Arab expatriates women with breast cancer and 341 age and ethnicity matched control women. A questionnaire that included the socio-demographic information, type of consanguinity, medical history, life style habits, dietary intake and tumor grade was designed to collect, the information of cases and controls. A total number of 214 breast cancer patients were approached and 167 cases completed the questionnaires with a response rate of 78%. Of the 417 healthy women who agreed to participate in this study, 341 responded to the questionnaire (81.8%). Results: The study revealed that the rate of parental consanguinity was lower in breast cancer patients (24%) than in controls (32.3%) (p = 0.062). Female controls were slightly younger (46.5 ± 11.9) than breast cancer patients (48.4 ± 10.7). Breast cancer incidence was significantly higher in Qatari women (34.1%) compared to other Arab women (65.9%) (p = 0.034). A significant difference was noted only in occupation of the studied women between cases and controls (p < 0.001). Overweight (46.7%) and obesity (32.9%) were significantly higher in female breast cancer patients compared to controls (p = 0.028). Overall, the mean coefficient of consanguinity was lower in breast cancer patients (0.014) than in controls (0.018) (p = 0.0125). Family history of breast cancer was significantly more often in breast cancer patients (14.4%) than in controls (6.2%) (p = 0.002). However, the family history of breast cancer was more often positive in cases of non-consanguineous parents (15.7%) than cases of consanguineous parents (10.0%). Conclusion: The present study revealed the lack of association between of breast cancer and the parental consanguinity in Arab women residing in Qatar. The family history of breast cancer and the body mass index (BMI) are highly associated with breast cancer.     

Association of physical activity and polymorphisms in FGFR2 and DNA methylation related genes with breast cancer risk

PurposePhysical activity, a protective factor for breast cancer, increases the level of DNA methylation. Fibroblast growth factor receptor 2 (FGFR2), a confirmed breast cancer susceptibility gene, is predisposed to be methylated. Therefore, DNA methylation related genes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and DNA methyltransferase (DNMT), together with physical activity and FGFR2, may interact with each other to effect breast cancer risk.MethodsA total of 839 incident breast cancer cases and 863 age-matched controls from Guangzhou, China were included in this study. We used questionnaires to assess physical activity in metabolic equivalent (MET)-h/week/year and a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform to ascertain genotypes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models.ResultsExercise activity and FGFR2 rs2981582 were confirmed to be associated with breast cancer risk, and were found to significantly interact (P for multiplicative and additive interactions = 0.045 and 0.021, respectively). Women who had CT/TT genotypes of FGFR2 rs2981582 and experienced exercise activity <3 MET-h/week/year had significantly increased risk (OR = 3.15, 95% CI = 2.28–4.35) compared to women with CC genotype and ≥3 MET-h/week/year. There was also a significant interaction between FGFR2 rs2981582 and MTHFR rs1801133 on breast cancer risk (P for multiplicative and additive interactions = 0.039 and 0.023, respectively).ConclusionWe found both a gene–environment (FGFR2-exercise activity) and a gene–gene (FGFR2–MTHFR) interaction on breast cancer risk. Our results suggest that environmental factors, such as physical activity, may be able to counteract genetic susceptibility to breast cancer.     

Assessment of RNA in human breast tissue sampled by random periareolar fine needle aspiration and ductal lavage and processed as fixed or frozen specimens

Ductal lavage (DL) and random periareolar fine needle aspiration (RPFNA) have both been proposed as minimally invasive techniques to sample breast tissue during breast cancer prevention trials. Laser capture microdissection (LCM), linear RNA amplification and quantitative real-time polymerase chain reaction (qPCR) theoretically overcome the limitations of small specimen size obtained with DL and RPFNA. In order to test the yield, relative stability and amplifiability of RNA from fixed and archived RPFNA and DL specimens, breast tissue was sampled from individual high risk women (n = 9) by both DL and RPFNA. RPFNA samples showed good RNA/cDNA yield and amplification while only 2 of 9 of the paired DL specimens had cDNA of adequate quality for subsequent PCR. One and two rounds of linear amplification provided approximately a 200- and 20,000-fold enrichment of RNA, respectively. PCR analysis consistently detected ER and COX-1 mRNA in the majority of RPFNA samples examined while pS2, PCNA, VEGF and survivin expression varied with subject. RNA yield and/or stability was greater for fixed and archived RPFNA than DL specimens of breast tissue. In a subsequent study examining an expanded biomarker gene panel in fixed vs. frozen RPFNA samples, mRNA profiles and ranked relative mRNA abundance were similar (r = 0.89) for frozen and fixed RPFNA specimens. In summary, frozen RPFNA samples may be optimal for RNA endpoints in human breast cancer prevention trials but fixed RPFNA specimens allow similar analyses with greater convenience.     

Survivin and its spliced isoform gene expression is associated with proliferation of renal cancer cells and clinical stage of renal cancer

Background: Survivin has been implicated in inhibition of apoptosis. To date, alternatively spliced isoforms, Survivin-2α, -2B, -ΔEx3, -3B, have been described. We assessed the effect of survivin gene expression on the proliferation of renal cancer (RCC) cells, and studied the association of survivin and its spliced isoform gene expression levels with the clinical stage of RCC. Methods: Gene expression of survivin and its spliced isoform in RCC cells, Caki-1, were performed by RT-PCR. We knocked down the gene expression of Survivin using small interfering RNA (siRNA), and assessed the cell proliferation by MTS assay. Next, we quantified the gene expression levels of survivin and its isoform in nephrectomy samples using quantitative real-time PCR. Results: In Caki-1 cells, survivin and survivin-2α, -2B were expressed higher than survivin-ΔEx3. Decrease of Survivin gene expression by transfection of siRNA was accompanied by inhibition of the proliferation of Caki-1 cell with 36% decrease in comparison with negative control transfected cells (p < 0.01). In clinical RCC tissues, survivin expression levels in metastatic stage were significantly higher compared with those in distant metastasis stage (M0:M1 = 1:4.81, p = 0.014); survivin 2B gene expression levels in pT3 tumors were associated significantly higher than those in pT1 (pT1:pT3 = 1:4.50, p = 0.043). No significant differences were found in survivin-2α expression levels and the ratio of survivin-2B/survivin gene expression levels among any clinical stages. Conclusion: We first demonstrated the gene expression of survivin-2α in renal cancer cells, and also showed that survivin and its spliced isoforms had associations with renal cancer cell proliferation and distant metastases.     

Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women?

Introduction: Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. Methods: Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Results: Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r = ?0.26, p-value = 0.033; r = 0.42, p = 0.0003), decreasing levels of sex hormone binding globulin (r = 0.38, p = 0.0013; r = ?0.32, p = 0.0076), and increasing body mass index (BMI) (r = ?0.31, p =  < 0.0001; r = 0.39, p =  < 0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p = 0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend = 0.43), aPAI-1 (p = 0.78), or resistin (p = 0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p > 0.05). The lack of association with risk may be due to measurement error of the laboratory assays. Discussion: lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk.     

Haplotype analysis of p53 polymorphisms: Arg72Pro,Ins16bp and G13964C in Tunisian patients with familial or sporadic breast cancer

Background: The p53 polymorphisms have been extensively studied as putative breast cancer susceptibility variants. The present study was undertaken to investigate the association of p53 Arg72Pro, Ins16bp and G13964C polymorphisms and their haplotypes with breast cancer risk in Tunisian women. Methods: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 159 patients and 132 controls. Results: The G13964C intronic variant was significantly associated with familial breast cancer risk (p = 0.0018) while the genotypic distribution was similar for p53 Arg72Pro and Ins16bp in patients and controls. Moreover, the (NoIns-C), (Arg-C) and (NoIns-Arg-C) haplotypes were significantly associated with familial breast cancer risk (p = 0.0021, p = 0.0096 and p = 0.0084, respectively) while there was a trend of association between the (Ins-Arg) and (Ins-Arg-G) haplotypes and the risk of sporadic breast cancer. Only the G/C genotype as well as the (NoIns-C) haplotype remained significant after correction for multiple testing. Conclusion: Our data revealed an association between the G/C genotype and the (NoIns-C) haplotype and the risk of familial breast cancer in Tunisian women. However, these observations need to be confirmed due to the limited statistical power of our study and the small number of cases.     

Breast cancer susceptibility loci in association with age at menarche,age at natural menopause and the reproductive lifespan

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Some of these loci have unknown functional significance and may mediate the effects of hormonal exposures on breast cancer risk. We examined relationships between breast cancer susceptibility variants and menstrual/reproductive factors using data from two population-based studies. Methods: The first analysis was based on a sample of 1328 women age 20–74 who participated as controls in a case–control study of breast cancer conducted in three U.S. states. We evaluated the associations between age at menarche, age at natural menopause and the reproductive lifespan with 13 previously identified breast cancer variants. Associations were also examined with a genetic score created as the sum of at-risk alleles across the 13 variants. For validation, significant results were evaluated in a second dataset comprised 1353 women age 43–86 recruited as part of a cohort study in Wisconsin. Results: Neither the genetic score nor any of the 13 variants considered individually were associated with age at menarche or reproductive lifespan. Two SNPs were associated with age at natural menopause; every increase in the minor allele (A) of rs17468277 (CASP8) was associated with a 1.12 year decrease in menopause age (p = 0.02). The minor allele (G) of rs10941679 (5p12) was associated with a 1.01 year increase in age at natural menopause (p = 0.01). The results were not replicated in the validation cohort (B = −0.61, p = 0.14 and B = −0.01, p = .0.98, respectively). Conclusions: The evaluated variants and reproductive experiences may work through separate pathways to influence breast cancer risk.     

Prognostic Value of Molecular Breast Cancer Subtypes based on Her2, ESR1, PGR and Ki67 mRNA-Expression in Muscle Invasive Bladder Cancer

INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n = 57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P = 0.0009) and ESR1 (P = 0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR = 2.11, CI 1.11-4.21, P = 0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P = 0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR = 4.41, CI 1.53-18.71, P = 0.004) and Luminal B (HR = 1.96, CI 0.99-4.08, P = 0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.     

Extracellular matrix metalloproteinase inducer expression has an impact on survival in human bladder cancer

Aim: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote tumor invasion and metastasis via stimulating matrix metalloproteinase synthesis in neighboring fibroblasts, to enhance angiogenesis via vascular endothelial growth factor, to induce chemoresistant tumor cells via the production of hyaluronan, and to confer resistance of cancer cells to anoikis through inhibition of Bim. The purpose of this study was to investigate the expression of EMMPRIN in human primary bladder cancer and to evaluate its prognostic value. Methods: EMMPRIN expression patterns were detected by immunohistochemistry. In order to determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: Of the 101 cases with bladder cancers, 68 (67.3%) cases were positive for EMMPRIN expression. When categorized into negative vs. positive expression, EMMPRIN was associated with the stage (p = 0.006), the grade (p = 0.002), carcinoma in situ (p = 0.01), the recurrence (p = 0.009), the progression (p = 0.009), and the death (p = 0.01) of patients with bladder cancer. Moreover, positive EMMPRIN expression clearly predicted poorer PFS (p = 0.008) and OS (p = 0.006). In the multivariate analysis, positive EMMPRIN expression was an independent prognostic factor for PFS (p = 0.03) and OS (p = 0.03). Conclusion: EMMPRIN expression was greater in bladder cancers than in the adjacent normal tissues and may be a useful prognostic marker for patients with bladder cancer.     

Diabetes,physical activity and breast cancer among Hispanic women

Purpose: We assessed the association between diabetes and breast cancer and whether physical activity modified the effect of diabetes on breast cancer in Hispanic women. Methods: We used data from a case-control study of breast cancer among Hispanic women aged 30–79 conducted between 2003 and 2008 on the Texas–Mexico border. In-person interviews were completed with 190 incident breast cancer cases ascertained through surgeons and oncologists, and 979 controls who were designated as both high-risk (n = 511) and low-risk (N = 468) for breast cancer (with respective response rates of 97%, 83% and 74%). Results: After adjustment for menopausal status and mammography screening, there was no effect of diabetes on breast cancer risk (high-risk control group odds ratio [OR] 1.02, 95% confidence interval [CI] 0.71–1.48; low-risk control group OR 0.87, 0.58–1.30). Women who had a diabetes history and did not exercise were at no risk of breast cancer (OR 0.96, 95% CI 0.63–1.48) or a slightly reduced breast cancer risk (low-risk control group OR 0.72, 95% CI 0.46–1.15) depending on the control group used, while women with diabetes who did exercise had significantly reduced breast cancer risk (OR 0.41, 95% CI 0.21–0.83) regardless of the control group used (high-risk control group p-value for interaction = 0.013, low-risk control group p-value for interaction 0.183). Conclusions: Should other studies confirm our results, physical activity should be explored as a means of reducing breast cancer risk in diabetic women.     

Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes

Introduction/objectivesThe role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic.The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls.MethodsPRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n = 8) at delivery and compared to controls (n = 5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n = 5) or nicotinamide (NCT) plus STZ (n = 9) or vehicle (n = 9). Placental whole-genome gene expression and PRL western blots were performed at birth.ResultsIn human placentas, PRL (p < 0.05) and BMP-1 (p < 0.01) gene expressions were increased with a higher amount of cleaved PRL (p < 0.05) in T1D than controls. In rats, diabetes was more pronounced in STZ than in NCT–STZ group with intra-uterine growth restriction. Decidual prolactin-related protein (Dprp) (p < 0.01) and Bmp-1 (p < 0.001) genes were up-regulated in both diabetic groups, with an increased cleaved PRL amount in the STZ (p < 0.05) and NCT–STZ (p < 0.05) groups compared to controls. No difference in CTSD gene expression was observed in rats or women.ConclusionsAlterations in the levels of the PRL family are associated with maternal diabetes in both rats and T1D women suggesting that placental changes in these hormones impact on fetal development.     

Valeur de la TEP-FDG dans la détection précoce des métastases osseuses : étude d’une série de 20 cas

FDG-PET is useful for metabolic analysis of metastatic cells. Based on a retrospective study relating to 20 cases of osseous metastases (MO), and a literature review, we will try to specify the main characteristics of bone metastases detected with FDG-PET. In our study, the primary malignant findings included lymphoma (n = 7), lung cancer (n = 5), breast cancer (n = 4), colon cancer (n = 2), melanoma (n = 1), and nasopharyngeal cancer (n = 1). On FDG-PET, 4 patients had a solitary metastatic focus (20%), 1 patient had two metastatic focuses (5%) and 15 patients had multiple lesions (75%). Most of the lesions showed intense abnormal uptake with SUVmax > 4.0 (14 patients, 70%); 6 patients had both intense and moderate FDG uptake with SUVmax > 2.1. Only 6 patients had MO diagnosed with standard diagnostic procedures (SDP) before FDG-PET. However, FDG-PET consistently revealed more metastatic foci missed by SDP. We conclude that FDG-PET is better than SDP in detecting all bone metastases at all sites of the skeleton according to the data of the literature.     

CHEK2 gene alterations in the forkhead-associated domain, 1100delC and del5395 do not modify the risk of sporadic pancreatic cancer

Checkpoint kinase 2 gene (CHEK2) alterations increase risk of several cancer types. We analyzed selected CHEK2 alterations in 270 Czech pancreatic cancer patients and in 683 healthy controls. The pancreatic cancer risk was higher in individuals who inherited rare alterations in CHEK2 region involving forkhead-associated domain other than I157T (OR = 5.14; 95% CI = 0.94–28.23) but the observed association was non-significant (p = 0.057). The most frequent I157T mutation did not alter the pancreatic cancer risk and neither the followed deletion of 5395 bp nor c.1100delC were found in any of pancreatic cases. We conclude that the I157T, other alterations in its proximity, del5395 and c.1100delC in CHEK2 do not predispose to pancreatic cancer risk in the Czech population.     

Clinical and radiological features of breast tumors according to history of false-positive results in mammography screening

BackgroundWomen with a false-positive result after a screening mammogram have an increased risk of cancer detection in subsequent participations, especially after assessments involving cytology or biopsy. We aimed to compare women's personal characteristics, tumoral features and the radiological appearance of cancers with and without a previous false-positive result generated by additional imaging or invasive procedures.MethodsFrom 1996 to 2007, 111,098 women aged 45–69 years participated in four population-based breast cancer screening programs in Spain, and 1281 cancers were detected. We included all cancers detected in subsequent screenings (n = 703) and explored the occurrence of previous false-positive results. We identified false-positives requiring additional imaging or invasive procedures. Differences on tumoral features (invasiveness, tumor size, and lymph node status) and radiological appearance were assessed by Chi-square test, and agreement between the location of cancer and prior suspicious by Cohen's kappa coefficient. A multivariate analysis was preformed to evaluate the effect of previous screening results and age on the odds of presenting an in situ carcinoma.ResultsAmong the 703 cancers detected in subsequent screenings, 148 women (21.1%) had a previous false-positive result. Of these, 105 were by additional imaging and 43 by invasive procedures. Women with prior false-positive result requiring invasive assessment, compared to women with negative tests, and women with prior false-positive requiring additional imaging, had a higher proportion of in situ carcinomas (31.7%, 15.3%, 12.9%, respectively; p = 0.014) and microcalcifications (37.2%, 20.2%, 9.5%, respectively; p = 0.003). The proportion of in situ carcinomas was even higher in women over 60 years (39.2%, 12.5%, 13.0%, respectively; p = 0.001). Ipsilateral cancer was observed in 65.7% of cases with prior cytology or biopsy (k = 0.479; 95%CI: 0.330–0.794).ConclusionA large number of in situ malignancies and calcification patterns were found among women with prior false-positive result in mammography screening requiring cytology or biopsies, suggesting progression from a previously benign lesion.