ABSTRACT
PURPOSE: The incidence rate of inflammatory breast cancer (IBC) is higher among non-Hispanic Black (NHB) than non-Hispanic White (NHW) women. We examined the differences in treatment and outcomes between NHB and NHW women with IBC, accounting for demographic, clinicopathological, and socioeconomic factors. METHODS: We collected data from the Surveillance, Epidemiology, and End Results database for NHB and NHW women with IBC diagnosed between 2010-2016. We analyzed the odds of receiving chemotherapy, radiation, and surgery between NHB and NHW women. We evaluated overall survival (OS) with Kaplan-Meier methods and Cox proportional hazards methods. Competing risk analysis was used to compare the risk of breast cancer death between NHB and NHW women. We also evaluated the magnitude of survival disparities within the strata of demographic, socioeconomic, and treatment factors. RESULTS: Among 1,652 NHW and 371 NHB women with IBC, the odds of receiving chemotherapy, surgery, and radiation were similar for NHB and NHW. After 39-month follow-up, the median OS was 40 and 81 months for NHB and NHW, respectively (p < 0.0001). The risk of breast cancer death was higher for NHB than NHW women (5-year risk of breast cancer death, 51% vs. 35%, p < 0.0001). CONCLUSION: After adjustment for demographic, clinicopathological, and socioeconomic factors; NHB women with IBC had similar odds of receiving surgery, chemotherapy, and radiation therapy, but were more likely to die of the disease compared to their NHW counterparts. Our findings suggest the presence of masked tumor biology, treatment, or socioeconomic factors associated with race that can lead to worse IBC outcomes.
Subject(s)
Breast Neoplasms , Healthcare Disparities , Inflammatory Breast Neoplasms , Female , Humans , Black or African American , Breast Neoplasms/epidemiology , Breast Neoplasms/ethnology , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/ethnology , Inflammatory Breast Neoplasms/mortality , Inflammatory Breast Neoplasms/therapy , Treatment Outcome , White People , Healthcare Disparities/ethnology , Healthcare Disparities/statistics & numerical data , United States/epidemiology , SEER Program/statistics & numerical data , Survival Analysis , RiskABSTRACT
PURPOSE: The real-time prognosis of patients with inflammatory breast cancer (IBC) after surviving for several years was unclear. We aimed to estimate survival over time in IBC using conditional survival (CS) and annual hazard functions. PATIENTS AND METHODS: This study recruited 679 patients diagnosed with IBC between 2010 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. We used the Kaplan-Meier method to estimate overall survival (OS). CS was the probability of surviving for another y years after surviving for x years after the diagnosis, and the annual hazard rate was the cumulative mortality rate of follow-up patients. Cox regression analyses were used to identify prognostic factors, and changes in real-time survival and immediate mortality in surviving patients were assessed within these prognostic factors. RESULTS: CS analysis showed real-time improvement in survival, with 5-year OS updated annually from the initial 43.5% to 52.2%, 65.3%, 78.5%, and 89.0% (surviving 1-4 years, respectively). However, this improvement was relatively small in the first two years after diagnosis, and the smoothed annual hazard rate curve showed increasing mortality during this period. Cox regression identified seven unfavorable factors at diagnosis, but only distant metastases remained after five years of survival. Analysis of the annual hazard rate curves showed that mortality continued to decrease for most survivors, except for metastatic IBC. CONCLUSION: Real-time survival of IBC improved dynamically over time, and the magnitude of this improvement was non-linear, depending on survival time and clinicopathological characteristics.
Subject(s)
Inflammatory Breast Neoplasms , Humans , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/therapy , Inflammatory Breast Neoplasms/diagnosis , Survival Analysis , Prognosis , Risk Assessment , Probability , SEER Program , Survival RateABSTRACT
BACKGROUND: Conditional survival takes into account the time that has elapsed since diagnosis and may have additional informative value. Compared with the static traditional survival evaluation method, conditional survival predictions can be adapted to incorporate the dynamic changes during the disease and provide a more suitable way of identifying time-evolved prognoses. METHODS: Of 3333 patients diagnosed with inflammatory breast cancer between 2010 and 2016 were extracted from the Surveillance, Epidemiology, and End Results database. The trend of the hazard rate over time was represented by the kernel density smoothing curve. The traditional cancer-specific survival (CSS) rate was estimated by the Kaplan-Meier method. Conditional CSS assessment was defined as the probability that a patient will survive y years given the x years who already survived after diagnosis, and the formula is as follows: CS(y)=CSS(x + y)/CSS(x). 3-year cancer-specific survival (CSS3) and 3-year conditional cancer-specific survival (CS3) were estimated. The Fine-Gray proportional subdistribution hazard model was constructed to screen for time-dependent risk factors associated with cancer-specific death. Subsequently, a nomogram was applied to predict a 5-year survival rate based on the number of years already survived. RESULTS: Of 3333 patients, the cancer-specific survival (CSS) rate decreased from 57% in the 4th year to 49% in the 6th year, while the comparable 3-year CS (CS3) rate improved from 65% in the first year to 76% in the third year. Overall, the CS3 rate was superior to actuarial cancer-specific survival, which was also found in subgroup analysis, especially in patients with high-risk characteristics. The Fine-Gray's model indicated that remote organ metastasis (M stage), lymph node metastasis (N stage), and surgery all significantly impacted the prognosis for cancer-specific survival. The Fine-Gray's model-based nomogram was constructed to predict 5-year cancer-specific survival immediately after diagnosis and given survival for 1, 2, 3, and 4 years after diagnosis. CONCLUSION: High-risk patients had a significantly improved cancer-specific survival prognosis after surviving for 1 or more years after diagnosis with inflammatory breast cancer. The probability of reaching 5-year cancer-specific survival following diagnosis improves with each additional year survived. More effective follow-up is required for patients diagnosed at an advanced N stage, remote organ metastasis, or not received surgery. Additionally, a nomogram and web-based calculator may be helpful for patients with inflammatory breast cancer during follow-up counseling (https://ibccondsurv.shinyapps.io/dynnomapp/).
Subject(s)
Inflammatory Breast Neoplasms , Humans , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/therapy , Prognosis , Nomograms , Proportional Hazards Models , Risk Factors , SEER ProgramABSTRACT
BACKGROUND: Patients with inflammatory breast cancer (IBC) have a high risk of central nervous system metastasis (mCNS). The purpose of this study was to quantify the incidence of and identify risk factors for mCNS in patients with IBC. METHODS: The authors retrospectively reviewed patients diagnosed with IBC between 1997 and 2019. mCNS-free survival time was defined as the date from the diagnosis of IBC to the date of diagnosis of mCNS or the date of death, whichever occurred first. A competing risks hazard model was used to evaluate risk factors for mCNS. RESULTS: A total of 531 patients were identified; 372 patients with stage III and 159 patients with de novo stage IV disease. During the study, there were a total of 124 patients who had mCNS. The 1-, 2-, and 5-year incidence of mCNS was 5%, 9%, and 18% in stage III patients (median follow-up: 5.6 years) and 17%, 30%, and 42% in stage IV patients (1.8 years). Multivariate analysis identified triple-negative tumor subtype as a significant risk factor for mCNS for stage III patients. For patients diagnosed with metastatic disease, visceral metastasis as first metastatic site, triple-negative subtype, and younger age at diagnosis of metastases were risk factors for mCNS. CONCLUSIONS: Patients with IBC, particularly those with triple-negative IBC, visceral metastasis, and those at a younger age at diagnosis of metastatic disease, are at significant risk of developing mCNS. Further investigation into prevention of mCNS and whether early detection of mCNS is associated with improved IBC patient outcomes is warranted.
Subject(s)
Breast Neoplasms , Central Nervous System Neoplasms , Inflammatory Breast Neoplasms , Humans , Female , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/therapy , Incidence , Retrospective Studies , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Central Nervous System Neoplasms/epidemiology , Central Nervous System Neoplasms/therapy , Central Nervous System/pathologyABSTRACT
PURPOSE: Inflammatory breast cancer is a deadly and aggressive type of breast cancer. A key challenge relates to the need for a more detailed, formal, objective definition of IBC, the lack of which compromises clinical care, hampers the conduct of clinical trials, and hinders the search for IBC-specific biomarkers and treatments because of the heterogeneity of patients considered to have IBC. METHODS: Susan G. Komen, the Inflammatory Breast Cancer Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to review the state of IBC and to propose initiatives to advance the field. After literature review of the defining clinical, pathologic, and imaging characteristics of IBC, the experts developed a novel quantitative scoring system for diagnosis. RESULTS: The experts identified through consensus several "defining characteristics" of IBC, including factors related to timing of onset and specific symptoms. These reflect common pathophysiologic changes, sometimes detectable on biopsy in the form of dermal lymphovascular tumor emboli and often reflected in imaging findings. Based on the importance and extent of these characteristics, the experts developed a scoring scale that yields a continuous score from 0 to 48 and proposed cut-points for categorization that can be tested in subsequent validation studies. CONCLUSION: To move beyond subjective 'clinical diagnosis' of IBC, we propose a quantitative scoring system to define IBC, based on clinical, pathologic, and imaging features. This system is intended to predict outcome and biology, guide treatment decisions and inclusion in clinical trials, and increase diagnostic accuracy to aid basic research; future validation studies are necessary to evaluate its performance.
Subject(s)
Breast Neoplasms , Inflammatory Breast Neoplasms , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Female , Humans , Inflammatory Breast Neoplasms/diagnosis , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/therapyABSTRACT
BACKGROUND: Primary inflammatory breast cancer (IBC) is a rare and aggressive entity whose prognosis has been improved by multimodal therapy. However, 5-year overall survival (OS) remains poor. Given its low incidence, the prognosis of IBC at metastatic stage is poorly described. MATERIALS AND METHODS: This study aimed to compare OS calculated from the diagnosis of metastatic disease between IBC patients and non-IBC patients in the Epidemiological Strategy and Medical Economics database (N = 16 702 patients). Secondary objectives included progression-free survival (PFS) after first-line metastatic treatment, identification of prognostic factors for OS and PFS, and evolution of survival during the study period. RESULTS: From 2008 to 2014, 7465 patients with metastatic breast cancer and known clinical status of their primary tumor (T) were identified (582 IBC and 6883 non-IBC). Compared with metastatic non-IBC, metastatic IBC was associated with less hormone receptor-positive (44% versus 65.6%), more human epidermal growth factor receptor 2-positive (30% versus 18.6%), and more triple-negative (25.9% versus 15.8%) cases, more frequent de novo M1 stage (53.3% versus 27.7%; P < 0.001), and shorter median disease-free interval (2.02 years versus 4.9 years; P < 0.001). With a median follow-up of 50.2 months, median OS was 28.4 months [95% confidence interval (CI) 24.1-33.8 months] versus 37.2 months (95% CI 36.1-38.5 months) in metastatic IBC and non-IBC cases, respectively (P < 0.0001, log-rank test). By multivariate analysis, OS was significantly shorter in the metastatic IBC group compared with the metastatic non-IBC group [hazard ratio = 1.27 (95% CI 1.1-1.4); P = 0.0001]. Survival of metastatic IBC patients improved over the study period: median OS was 24 months (95% CI 20-31.9 months), 29 months (95% CI 21.7-39.9 months), and 36 months (95% CI 27.9-not estimable months) if diagnosis of metastatic disease was carried out until 2010, between 2011 and 2012, and from 2013, respectively (P = 0.003). CONCLUSION: IBC is independently associated with adverse outcome when compared with non-IBC in the metastatic setting.
Subject(s)
Inflammatory Breast Neoplasms , Cohort Studies , Humans , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/therapy , Prognosis , Progression-Free Survival , Retrospective StudiesABSTRACT
The survival after the diagnosis of inflammatory breast cancer (IBC) has been steadily improving for the past few decades. This has been due to advances in the knowledge of IBC in a number of fields, including epidemiology, molecular biology, and medical management. In this review we summarize some of the most important recent advances in these fields and suggest possible opportunities for continued improvement.
Subject(s)
Inflammatory Breast Neoplasms/classification , Inflammatory Breast Neoplasms/epidemiology , Female , Humans , Inflammatory Breast Neoplasms/etiology , Inflammatory Breast Neoplasms/physiopathology , Risk Factors , Tunisia/epidemiology , United States/epidemiologyABSTRACT
PURPOSE: Inflammatory breast cancer (IBC) is a rare type of breast cancer with poor prognosis. IBC patients with bone metastasis (BM) often suffer from many complications. This study was performed to identify risk factors with strong capability of predicting high BM risk for IBC patients and find prognostic factors for those patients. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to collect the clinicopathological and survival information of IBC patients. 966 IBC patients diagnosed between 2010 and 2015 were included to study the risk factors for developing BM by using Multivariable logistic regression. A total of 194 and 176 patients were included to analyze independent prognostic factors for overall survival (OS) and cancer specific survival (CSS) of IBC patients with BM respectively. RESULTS: Of the 966 IBC patients, 194 (20.1%) patients were with BM. The risk factors for developing BM in IBC patients included unmarried marital status, double breast tumor, N1 stage, N3 stage, and liver metastases had higher risk of BM, while those of uninsured status and triple negative breast cancer (TNBC) were less likely to have BM. Analysis of prognostic factors for OS and CSS of IBC patients with BM showed that TNBC subtype and liver metastases were independently significantly associated with poorer OS and CSS of BM patients, while chemotherapy could serve as an independent prognostic factor for better OS and CSS of BM patients. CONCLUSION: Marital status, double breast tumor, N1 stage, N3 stage, and liver metastases should be considered for prediction of BM in IBC patients. TNBC subtype and liver metastases may indicate poor survival and chemotherapy can indicate improved survival for IBC patients with BM.
Subject(s)
Bone Neoplasms , Inflammatory Breast Neoplasms , Bone Neoplasms/epidemiology , Humans , Inflammatory Breast Neoplasms/epidemiology , Prognosis , Risk FactorsABSTRACT
Inflammatory breast cancer is a rare and aggressive malignancy that is often initially misdiagnosed because of its similar presentation to more benign breast pathologies such as mastitis, resulting in treatment delays. Presenting symptoms of inflammatory breast cancer include erythema, skin changes such as peau d' orange or nipple inversion, edema, and warmth of the affected breast. The average age at diagnosis is younger than in noninflammatory breast cancer cases. Known risk factors include African American race and obesity. Diagnostic criteria include erythema occupying at least one-third of the breast, edema, peau d' orange, and/or warmth, with or without an underlying mass; a rapid onset of <3 months; and pathologic confirmation of invasive carcinoma. Treatment of inflammatory breast cancer includes trimodal therapy with chemotherapy, surgery, and radiation. An aggressive surgical approach that includes a modified radical mastectomy enhances survival outcomes. Although the outcomes for patients with inflammatory breast cancer are poor compared with those of patients with noninflammatory breast cancer, patients with inflammatory breast cancer who complete trimodal therapy have a favorable locoregional control rate, underscoring the importance of a prompt diagnosis of this serious but treatable disease. Obstetrician-gynecologists and other primary care providers must recognize the signs and symptoms of inflammatory breast cancer to make a timely diagnosis and referral for specialized care.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy, Adjuvant , Inflammatory Breast Neoplasms/therapy , Lymph Node Excision , Mastectomy, Modified Radical , Neoadjuvant Therapy , Black or African American/statistics & numerical data , Alcohol Drinking/epidemiology , Axilla/surgery , Contraceptives, Oral/therapeutic use , Diagnosis, Differential , Early Diagnosis , Early Medical Intervention , Granulomatous Mastitis/diagnosis , Hispanic or Latino/statistics & numerical data , Humans , Inflammatory Breast Neoplasms/diagnosis , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/pathology , Mastitis/diagnosis , Neoplasm Staging , Obesity/epidemiology , Risk Factors , White People/statistics & numerical dataABSTRACT
BACKGROUND & AIMS: It is currently unclear whether reported changes in the gut microbiome are cause or consequence of inflammatory bowel disease (IBD). Therefore, we studied the gut microbiome of IBD-discordant and -concordant twin pairs, which offers the unique opportunity to assess individuals at increased risk of developing IBD, namely healthy cotwins from IBD-discordant twin pairs. METHODS: Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex-, and body mass index-matched controls, and 99 unrelated patients with IBD. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared among healthy cotwins, IBD-twins, unrelated patients with IBD, and healthy controls with multivariable (ie, adjusted for potential confounding) generalized linear models. RESULTS: No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate <0.10). Compared with healthy controls, 13, 19, and 18 species, and 78, 105, and 153 pathways were found to be differentially abundant in healthy cotwins, IBD-twins, and unrelated patients with IBD, respectively (false discovery rate <0.10). Of these, 8 (42.1%) of 19 and 1 (5.6%) of 18 species, and 37 (35.2%) of 105 and 30 (19.6%) of 153 pathways overlapped between healthy cotwins and IBD-twins, and healthy cotwins and unrelated patients with IBD, respectively. Many of the shared species and pathways have previously been associated with IBD. The shared pathways include potentially inflammation-related pathways, for example, an increase in propionate degradation and L-arginine degradation pathways. CONCLUSIONS: The gut microbiome of healthy cotwins from IBD-discordant twin pairs displays IBD-like signatures. These IBD-like microbiome signatures might precede the onset of IBD. However, longitudinal follow-up studies are needed to infer a causal relationship.
Subject(s)
Gastrointestinal Microbiome , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/microbiology , Adult , Antigens, Bacterial/biosynthesis , Case-Control Studies , Cross-Sectional Studies , Feces/microbiology , Female , Gastrointestinal Microbiome/physiology , Humans , Male , Metagenomics , Middle Aged , Netherlands/epidemiology , Phenotype , Risk Factors , Siderophores/biosynthesis , Twins, Dizygotic , Twins, Monozygotic , Young AdultABSTRACT
PURPOSE: Inflammatory breast cancer (IBC) is an aggressive variant characterized by erythema, edema, and "peau d'orange" of the skin progressing within 6 months. We assessed the incidence and survival of IBC in the US over four decades. METHODS: Using SEER*Stat, a case list of IBC patients diagnosed between 1973 and 2015 (n = 29,718) was extracted from SEER 18 registries by using a combination of morphology, stage, and extent of disease criteria. M1 and M0 patients were included. Age-adjusted incidence rates, relative survival rates, and mean survival time were calculated. Significance was determined as non-overlapping 95% confidence intervals. RESULTS: The overall incidence of IBC from 1973 to 2015 is 2.76 (2.73, 2.79) cases per 100,000 people, with white patients having an incidence rate of 2.63 (2.60, 2.67), black patients 4.52 (4.39, 4.65), and patients of other race 1.84 (1.76, 1.93). The overall IBC relative 5-year survival rate is 40.5% (39.0%, 42.0%), 42.5% (40.7%, 44.3%), and 29.9% (26.6%, 33.3%) for white patients and black patients, respectively. Patients diagnosed in 1978-1982 have a mean survival time of 62.3 (52.0, 72.6) months, while those diagnosed in 2008-2012 have mean survival time of 99.4 (96.4, 102.4) months. There is no significant difference in survival time between T4D patients and patients with other T staging and extent of disease coding consistent with clinical IBC presentation. CONCLUSIONS: IBC survival has increased over four decades. Despite the improvement in survival for all racial groups, a persistent survival disparity that has not narrowed over two decades remains between white and black patients.
Subject(s)
Breast Neoplasms , Inflammatory Breast Neoplasms , Black or African American , Breast Neoplasms/epidemiology , Female , Humans , Incidence , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/pathology , Neoplasm Staging , SEER Program , Survival Rate , White PeopleABSTRACT
There are scant data identifying epidemiologic characteristics among individuals diagnosed with inflammatory breast cancer (IBC), which is considered the most aggressive subtype of breast cancer. The purpose of this study was to evaluate the epidemiologic features among patients seen at a dedicated IBC program, to elucidate the potential causes of this disease and guide prevention strategies. We reviewed retrospective data from 447 patients enrolled in an IRB-approved IBC registry through Dana-Farber Cancer Institute from 1997 to 2016. The data examined included the following: demographics, medical, reproductive and family history, duration of symptoms prior to the diagnosis of IBC, pathologic characteristics, and clinical outcome. JMP statistical software was used to compile the data. Descriptive statistics were used to evaluate the data. The majority of patients (66.0%) were overweight or obese (body mass index [BMI] ≥25) at the time of diagnosis. Fifty patients (11.1%) had "secondary" IBC, defined as developing IBC after a previous history of non-IBC breast cancer in an ipsilateral breast. Of those patients with secondary IBC, 60% were also overweight or obese at the time of IBC diagnosis. Approximately 58% of IBC patients had a family history of breast or ovarian cancer, including first- and second-degree relatives. This analysis suggested a high frequency of familial breast/ovarian cancer among IBC patients which supports further evaluating genetic risks. This may have implications for screening and prevention strategies as well as insight into additional contributing risk factors. The prevalence of a high BMI among both pre- and postmenopausal women with IBC, including those diagnosed with secondary IBC, warrants focusing on strategies targeting the obesity crisis as a potential means of reducing the risk of developing this disease.
Subject(s)
Breast Neoplasms , Inflammatory Breast Neoplasms , Body Mass Index , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Case-Control Studies , Female , Humans , Inflammatory Breast Neoplasms/diagnosis , Inflammatory Breast Neoplasms/epidemiology , Retrospective Studies , Risk FactorsABSTRACT
PURPOSE: Studies of the etiology of inflammatory breast cancer (IBC), a rare but aggressive breast cancer, have been hampered by limited risk factor information. We extend previous studies by evaluating a broader range of risk factors. METHODS: Between 2009 and 2015, we conducted a case-control study of IBC at six centers in Egypt, Tunisia, and Morocco; enrolled were 267 IBC cases and for comparison 274 non-IBC cases and 275 controls, both matched on age and geographic area to the IBC cases. We administered questionnaires and collected anthropometric measurements for all study subjects. We used multiple imputation methods to account for missing values and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using polytomous logistic regression comparing each of the two case groups to the controls, with statistical tests for the difference between the coefficients for the two case groups. RESULTS: After multivariable adjustment, a livebirth within the previous 2 years (OR 4.6; 95% CI 1.8 to 11.7) and diabetes (OR 1.8; 95% CI 1.1 to 3.0) were associated with increased risk of IBC, but not non-IBC (OR 0.9; 95% CI 0.3 to 2.5 and OR 0.9; 95% CI 0.5 to 1.6 for livebirth and diabetes, respectively). A family history of breast cancer, inflammatory-like breast problems, breast trauma, and low socioeconomic status were associated with increased risk of both tumor types. CONCLUSIONS: We identified novel risk factors for IBC and non-IBC, some of which preferentially increased risk of IBC compared to non-IBC. Upon confirmation, these findings could help illuminate the etiology and aid in prevention of this aggressive cancer.
Subject(s)
Breast Neoplasms , Inflammatory Breast Neoplasms , Breast Neoplasms/epidemiology , Breast Neoplasms/etiology , Case-Control Studies , Egypt , Female , Humans , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/etiology , Morocco , Risk Factors , TunisiaABSTRACT
Evidence has emerged implicating epigenetic alterations in inflammatory breast cancer (IBC) origin and progression. IBC is a rare and rapidly progressing disease, considered the most aggressive type of breast cancer (BC). At clinical presentation, IBC is characterized by diffuse erythema, skin ridging, dermal lymphatic invasion, and peau d'orange aspect. The widespread distribution of the tumor as emboli throughout the breast and intra- and intertumor heterogeneity is associated with its poor prognosis. In this review, we highlighted studies documenting the essential roles of epigenetic mechanisms in remodeling chromatin and modulating gene expression during mammary gland differentiation and the development of IBC. Compiling evidence has emerged implicating epigenetic changes as a common denominator linking the main risk factors (socioeconomic status, environmental exposure to endocrine disruptors, racial disparities, and obesity) with IBC development. DNA methylation changes and their impact on the diagnosis, prognosis, and treatment of IBC are also described. Recent studies are focusing on the use of histone deacetylase inhibitors as promising epigenetic drugs for treating IBC. All efforts must be undertaken to unravel the epigenetic marks that drive this disease and how this knowledge could impact strategies to reduce the risk of IBC development and progression.
Subject(s)
Epigenesis, Genetic , Inflammatory Breast Neoplasms/genetics , Inflammatory Breast Neoplasms/therapy , Carcinogenesis/genetics , Carcinogenesis/pathology , Cell Differentiation/genetics , DNA Methylation/genetics , Female , Humans , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/pathology , Tumor MicroenvironmentABSTRACT
OBJECTIVE: We evaluated the risk factors of inflammatory breast cancer (IBC) compared to non-IBC and according to histological subtype. METHODS: Cases of IBC (n = 160) and controls of non-IBC (n = 580) were collected from the cohort of breast cancer patients treated in two oncology centers matched based on age at cohort entry. Data about breast cancer risk factors were collected. We evaluated correlation and ORs using conditional logistic regression analysis for each case group versus the control group. We also evaluated those factors in three further subgroups: luminal (HR+, HER2-), HER2-overexpressing (HER2+, HR-), and triple-negative (TN) patients. RESULTS: Long duration of breastfeeding of ≥12 months (OR = 4.64, 95% CI 2.97-7.26), body mass index ≤25 (OR = 2.48, 95% CI 1.71-3.58), and use of oral contraceptives (OR = 2.48, 95% CI 1.62-3.84) were the most significant risk factors in favor of IBC compared to non-IBC. There was no impact of contraceptives use in the luminal subgroup and no impact of long duration of breastfeeding in the TN subgroup. The role of socioeconomic and educational levels was unclear. Age at menarche, age at first pregnancy, and age at menopause were nonsignificant risk factors of IBC. CONCLUSION: Reproductive risk factors were distinct in IBC patients reflecting the clinical entity of IBC.
Subject(s)
Inflammatory Breast Neoplasms/epidemiology , Receptor, ErbB-2/metabolism , Triple Negative Breast Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Body Mass Index , Breast Feeding , Case-Control Studies , Contraceptives, Oral/therapeutic use , Educational Status , Female , Humans , Menarche , Middle Aged , Pregnancy , Receptors, Estrogen/metabolism , Reproductive Physiological Phenomena , Risk Factors , Socioeconomic Factors , Young AdultABSTRACT
OBJECTIVES: The aim of this analysis was to study the impact of marital status on inflammatory breast cancer (IBC) patients, as the prognostic impact is yet to be studied in detail. METHODS: Data of IBC patients from 2004 to 2010 were sorted out from the database of surveillance, epidemiology, and end results (SEER), and overall survival (OS) rates and breast cancer-specific survival (CSS) rates were compared between a group of married and unmarried patients. The comparison was performed by Kaplan-Meier method with log-rank test, and multivariate survival analysis of CSS and OS was performed using the Cox proportional hazard model. RESULTS: Data of 1342 patients were collected from the SEER database, on an average 52% of married patients (n = 698, 52.01%) and 48% of unmarried patients (n = 644, 47.99%) for this analysis. Married patients were more likely to be more younger (aged ≤ 56) (52.44% vs. 43.94%), white ethnicity (83.24% vs. 71.58%), HoR positive (48.28% vs. 41.61%), more patients received surgery (78.51% vs. 64.60%), chemotherapy (90.69% vs. 80.12%) and radiotherapy (53.44% vs. 44.41%) compared to unmarried group, and less likely to be AJCC stage IV (26.22% vs. 35.40%) (All P Ë 0.05). Married patients had better 5-year CSS (74.90% vs. 65.55%, P < 0.0001) and OS rates (45.43% vs. 33.11%, P < 0.0001). The multivariate analysis revealed that marital status is an independent prognostic factor, whereas the data of unmarried patients showed worse CSS (HR 1.188; 95% CI 1.033-1.367; P = 0.016) and OS rates (HR 1.245; 95% CI 1.090-1.421; P = 0.001).The subgroup analysis further revealed that the OS and CSS rates in the married group were better than the unmarried group, regardless of different AJCC stages. CONCLUSION: Marital status was an independent prognostic indicator in IBC patients. As the study reveals, the CSS and OS rates of the married patients were better than those of the unmarried patients.
Subject(s)
Inflammatory Breast Neoplasms/epidemiology , Marital Status , Adult , Aged , Aged, 80 and over , Animals , Databases, Factual , Disease Models, Animal , Disease Susceptibility , Female , Humans , Inflammatory Breast Neoplasms/diagnosis , Inflammatory Breast Neoplasms/mortality , Inflammatory Breast Neoplasms/therapy , Kaplan-Meier Estimate , Middle Aged , Neoplasm Grading , Neoplasm Staging , Population Surveillance , Prognosis , Proportional Hazards Models , Risk Assessment , Risk Factors , SEER Program , Young AdultABSTRACT
INTRODUCTION: Inflammatory Breast Cancer (IBC) is a distinct and rare type of breast cancer accounting for up to 6% of all breast cancer cases in Europe. The aim of this study was to investigate diagnostic methods, treatments, and outcome after IBC in patients treated at a single institution in Denmark. METHOD: All patients treated for IBC at Aarhus University Hospital between 2000 and 2014 were identified and included in the cohort. Survival was assessed using Kaplan-Meier curves and log-rank statistics. RESULTS: A total of 89 patients were identified with a median follow up of 3.6 years. The overall survival at 5 and 10 years were 41% and 18%, respectively. The disease free survival at 5 and 10 years were 47% and 27%, respectively. Thirty-four percent had distant metastasis at time of diagnosis. Patients with ER positive tumors had a significantly better overall survival than patients with ER negative tumors (p = 0.01). CONCLUSION: Despite a more aggressive systemic and loco-regional treatment today, IBC is still a very serious disease with a high mortality.
Subject(s)
Inflammatory Breast Neoplasms/diagnostic imaging , Inflammatory Breast Neoplasms/drug therapy , Registries , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biopsy, Needle , Denmark/epidemiology , Disease-Free Survival , Female , Humans , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/secondary , Magnetic Resonance Imaging , Mammography , Middle Aged , Neoplasm Metastasis , Receptors, Estrogen/genetics , Retrospective Studies , Skin/pathology , Survival RateABSTRACT
BACKGROUND: The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype. METHODS: By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives. RESULTS: The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n = 178], lobular [n = 1688], and mucinous [n = 542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P = .011) as well as for inflammatory breast cancers (P = .024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P = .03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P < .001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P = .00021) subtypes. CONCLUSIONS: These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.