scholarly journals Breast Cancer—Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies—An Updated Review

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4287
Author(s):  
Sergiusz Łukasiewicz ◽  
Marcin Czeczelewski ◽  
Alicja Forma ◽  
Jacek Baj ◽  
Robert Sitarz ◽  
...  

Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide with more than 2 million new cases in 2020. Its incidence and death rates have increased over the last three decades due to the change in risk factor profiles, better cancer registration, and cancer detection. The number of risk factors of BC is significant and includes both the modifiable factors and non-modifiable factors. Currently, about 80% of patients with BC are individuals aged >50. Survival depends on both stage and molecular subtype. Invasive BCs comprise wide spectrum tumors that show a variation concerning their clinical presentation, behavior, and morphology. Based on mRNA gene expression levels, BC can be divided into molecular subtypes (Luminal A, Luminal B, HER2-enriched, and basal-like). The molecular subtypes provide insights into new treatment strategies and patient stratifications that impact the management of BC patients. The eighth edition of TNM classification outlines a new staging system for BC that, in addition to anatomical features, acknowledges biological factors. Treatment of breast cancer is complex and involves a combination of different modalities including surgery, radiotherapy, chemotherapy, hormonal therapy, or biological therapies delivered in diverse sequences.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tomi Akinyemiju ◽  
Kelley Jones ◽  
Anjali Gupta ◽  
Taofik Oyekunle ◽  
Veeral Saraiya ◽  
...  

Abstract Background The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women. Methods We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between measures of body composition and BC and molecular subtypes among 419 histologically confirmed cases of BC and 286 healthy controls from the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) case-control study. Results Higher BMI (aOR: 0.79; 95% CI: 0.67, 0.95) and weight (aOR: 0.83; 95% CI: 0.69, 0.98) were associated with reduced odds of BC in adjusted models, while height was associated with non-statistically significant increased odds of BC (aOR: 1.07, 95% CI: 0.90, 1.28). In pre/peri-menopausal, but not post-menopausal women, both higher BMI and weight were significantly associated with reduced odds of BC. Further, higher BMI was associated with reduced odds of Luminal A, Luminal B, and HER2-enriched BC among pre/peri-menopausal women, and reduced odds of triple-negative BC among post-menopausal women. Conclusions Higher BMI and weight were associated with reduced odds of BC overall and by molecular subtype among West African women. Larger studies of women of African descent are needed to definitively characterize these associations and inform cancer prevention strategies.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 572-572
Author(s):  
Yunan Han ◽  
Shuai Xu ◽  
Graham A. Colditz ◽  
Adetunji T. Toriola

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p<0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p<0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p<0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12575-e12575 ◽  
Author(s):  
Ramses F. Sadek ◽  
Li fang Zhang ◽  
Houssein Talal Abdul Sater

e12575 Background: Breast Cancer (BC) has been classified into four subtypes: Luminal A (LABC), Luminal B (LBBC), Triple negative (TNBC) and HER2-enriched (HER2e). BC mortality in Black women is significantly higher than in Whites and Asians. BC in Blacks has been characterized by higher grade and later stage. Causes of the Black-White BC survival disparity have been investigated, including differences in: diagnostic stage, socioeconomics, and comorbidities. These have led researchers to investigate the differences in tumor molecular subtype and their association with clinical outcomes and races. Methods: This study used the Surveillance, Epidemiology, and End Results – 18 (SEER-18) Registries research data between 2010 and 2013 that included over 212,000 patients. Descriptive statistics, Odds ratios (OR) and 95%Confidence intervals (CI) were used to study the association between BC stage, grade, and mortality and BC molecular subtypes across different races. We employed Cox regression models to explore the race disparity in BC mortality before and after controlling for BC molecular subtype and other clinical and social factors. Results: TNBC had more high grade cancer compared to HER2e subtype (OR, 1.5; CI, 1.3 - 1.8), LBBC (OR, 4.5; CI, 4.0 - 5.0) and LABC (OR, 12.2; CI, 11.2 – 13.3) for Black. BC mortality was higher in TNBC subtype compared to HER2e subtype (OR, 1.3; CI, 1.1 - 1.6), LBBC (OR, 2.4; CI, 2.0 - 2.9), and LABC (OR, 2.8; CI, 2.4 – 3.2) for Blacks. Results are consistent for all races. HER2e subtype had more late cancer stage compare to LBBC (OR, 1.2; CI, 1.0 - 1.4), TNBC (OR, 1.4; CI, 1.2 - 1.6) and LABC (OR, 2.1; CI, 1.8 - 2.4) in Blacks with similar results in all races. BC mortality in Blacks was higher compare with Whites (HR, 1.9; CI, 1.8 - 2.0) and Asian (HR, 2.7; CI, 2.5 - 3.0). After controlling for cancer subtype and other factors in the Cox regression model, the corresponding HRs ware significantly decreased to 1.2 (CI, 1.1 -1.3) and 1.6 (9CI, 1.5 -1.8). Blacks have heighst percent in stage IV and grade higer grade of disease. Conclusions: Molecular subtypes of BC contribute differently to risks of late cancer stage, high cancer grade and BC specific mortality. These differences are consistent in all races. The molecular subtypes and other social and clinical factors may explain part of the BC mortality race disparity.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13075-e13075
Author(s):  
Lúcio Lara Santos ◽  
Fernando Miguel ◽  
Lygia Vieira Lopes ◽  
Julio Oliveira ◽  
Eduardo Ferreira ◽  
...  

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.


Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 157
Author(s):  
Henry J. Thompson ◽  
Elizabeth S. Neil ◽  
John N. McGinley ◽  
Vanessa K. Fitzgerald ◽  
Karam El Bayoumy ◽  
...  

In vivo evidence of heterogeneous effects of n-3 fatty acids (N3FA) on cell signaling pathways associated with the reduced growth of breast cancer has been reported and is consistent with the expectation that N3FA will not exert uniform effects on all molecular subtypes of the disease. Similarly, available evidence indicates that many metabolites of N3FA are synthesized by mammalian cells and that they exert metabolite-specific biological activities. To begin to unravel the complex relationships among molecular subtypes and effects exerted by specific N3FA metabolites on those pathways, proof-of-concept experiments were conducted using cell lines representative of common molecular subtypes of human breast cancer. N3FA differed in anticancer activity with docosahexaenoic acid (DHA) having greater anticancer activity than eicosapentaenoic acid. 4-oxo-docosahexaenoic (4-oxo-DHA), a penultimate metabolite of 5-lipoxygenase mediated DHA metabolism, induced dose-dependent inhibition of cell number accumulation with apoptosis as a primary effector mechanism. Interrogation of protein expression data using the Ingenuity Pathway Analysis (IPA) bioinformatics platform indicated that 4-oxo-DHA differentially impacted six canonical pathways and the cellular functions they regulate across common molecular subtypes of breast cancer. This included the endocannabinoid pathway for cancer inhibition that has not been previously reported. These findings provide a rationale for juxtaposing molecular subtype targeted treatment strategies with the adjuvant use of specific N3FA metabolites as an example of precision onco-nutrition (PON) for the management and control of breast cancer.


Biomedicine ◽  
2021 ◽  
Vol 41 (1) ◽  
pp. 75-81
Author(s):  
N. Priyathersini ◽  
J. Thanka ◽  
B Jayashree

Introduction and Aim: Breast cancer is the most common malignancy in females worldwide. Almost 1.4 million new cases have been diagnosed with breast cancer every year. This aims to study the clinicopathological profile and molecular subtypes of invasive breast carcinoma in resected mastectomy specimens over a period of 5 years. Materials and Methods:A retrospective study of 90 mastectomy and wide local resection specimens received during the period of January 2012 to June 2017 were analyzed. The clinical data of patients including age, gender, and stage of the diseasewere obtained from the medical records section. Immunohistochemical staining for Estrogen Receptor [ER], Progesterone Receptor[PR] and Human Epidermal Growth Factor Receptor 2HER2neu were done.The cases were classified according to the molecular classification based on the ER, PR and HER2 receptor status. Results: The peak incidence of breast carcinoma was in the age group 50 to 60 years. Invasive ductal carcinoma,Not otherwise specified[NOS] accounted for the most common histologic type. There was higher incidence of pT2 tumors in our study. The most common molecular subtype was luminal A, followed by triple negative tumors. These molecular subtypes associated well with Tumor grade and HGDCIS with a statistically significant p value of 0.001 and 0.015 respectively. An increased proportion of Grade 3 tumors were Triple Negative tumors. Conclusion:In breast carcinomas the routine histopathological features provide inexpensive method for understanding tumour biology and prognosis. It`s essential in areas with poor resources. ER, PR and HER2 assessment helps in identifying hormonal status and enables for hormone therapy and anti HER2 therapy.  


2020 ◽  
pp. 848-859
Author(s):  
Max Klebe ◽  
Carlo Fremd ◽  
Mark Kriegsmann ◽  
Katharina Kriegsmann ◽  
Thomas Albrecht ◽  
...  

PURPOSE Conversion of tumor subtype frequently occurs in the course of metastatic breast cancer but is a poorly understood phenomenon. This study aims to compare molecular subtypes with subsequent lung or pleural metastasis. PATIENTS AND METHODS In a cohort of 57 patients with breast cancer and lung or pleural metastasis (BCLPM), we investigated paired primary and metastatic tissues for differential gene expression of 269 breast cancer genes. The PAM50 classifier was applied to identify intrinsic subtypes, and differential gene expression and cluster analysis were used to further characterize subtypes and tumors with subtype conversion. RESULTS In primary breast cancer, the most frequent molecular subtype was luminal A (lumA; 49.1%); it was luminal B (lumB) in BCLPM (38.6%). Subtype conversion occurred predominantly in lumA breast cancers compared with other molecular subtypes (57.1% v 27.6%). In lumA cancers, 62 genes were identified with differential expression in metastatic versus primary disease, compared with only 10 differentially expressed genes in lumB, human epidermal growth factor receptor 2 (HER2)–enriched, and basal subtypes combined. Gene expression changes in lumA cancers affected not only the repression of the estrogen receptor pathway and cell cycle–related genes but also the WNT pathway, proteinases ( MME, MMP11), and motility-associated cytoskeletal proteins (CK5, CK14, CK17). Subtype-switched lumA cancers were further characterized by cell proliferation and cell cycle checkpoint gene upregulation and dysregulation of the p53 pathway. This involved 83 notable gene expression changes. CONCLUSION Our results indicate that gene expression changes and subsequent subtype conversion occur on a large scale in metastatic luminal A–type breast cancer compared with other molecular subtypes. This underlines the significance of molecular changes in metastatic disease, especially in tumors of initially low aggressive potential.


2021 ◽  
Author(s):  
Shahin Sayed ◽  
Shaoqi Fan ◽  
Zahir Moloo ◽  
Ronald Wasike ◽  
Peter Bird ◽  
...  

Abstract BackgroundFew studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. MethodsWe conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors.ResultsThe median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3 and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and Triple Negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER positive tumors, ER negative patients were more likely to have higher parity (OR=2.03, 95% CI= (1.11, 3.72), p=0.021, comparing ≥5 to <2 children) and younger age at first pregnancy (ORtrend=0.77, 95% CItrend=0.61, 0.98, Ptrend=0.032, comparing older to younger age). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR=0.45, 95% CI= 0.23, 0.87, p=0.018, comparing ≥5 to <2 children); HER2-enriched patients were less likely to be obese (OR=0.36, 95% CI=0.16, 0.81, p=0.013) or older age at menopause (OR=0.38, 95% CI=0.15, 0.997, p=0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. Conclusions In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies are needed to develop population and subtype specific risk prediction/prevention strategies.


2018 ◽  
Vol 6 (1) ◽  
pp. 9-17
Author(s):  
Avisak Bhattacharjee ◽  
AFM Anwar Hossain ◽  
Shahanara Yeasmin ◽  
Tangera Akter

Background: Molecular subtype determination of breast carcinoma is still an enigma in our perspective. We are far behind the genetic analysis but immunohistochemistry is commonly ensured now a days.Objective: To observe the incidence, epidemiological and clinico-pathological status of different molecular subtypes of breast cancer patients.Materials and method: At first 141 patients were enrolled by purposive sampling. Among them 138 patients were finalized according to the eligibility criteria. A pre-structured, peer reviewed, properly tested, interview and observation based data collection sheet was prepared. Data regarding epidemiological profile, clinical profile and histopathological profile were collected, compiled, edited and analyzed. Mean, frequency, chi-square test were adopted for analysis. Statistics were found significant at <0.05.Results: Mean age of patients was 43.20±9.69 years. Mean BMI was 25.26±13.47. Out of 138 patients, only 4.34% had positive family history, 64.49% and 35.5% had left and right sided breast cancer respectively, 65.2% had tumour size 2-5cm which was followed by 27.53% cases with >5cm sized tumour in maximum diameter. Among the five major molecular subtypes both luminal A and triple negative breast cancer (TNBC) showed high prevalence (27.53%). Association of molecular subtypes with histopathological grading revealed TNBC was the most aggressive among all molecular subtypes. Axillary lymphadenopathy was present in almost all cases.Conclusion: Luminal A and TNBC were positive in most of the cases whereas TNBC showed higher association with advance histopathological grade. Clinical status was almost similar in all subtypes.Delta Med Col J. Jan 2018 6(1): 9-17


2013 ◽  
Vol 20 (3) ◽  
pp. 339-348 ◽  
Author(s):  
Sewha Kim ◽  
Do Hee Kim ◽  
Woo-Hee Jung ◽  
Ja Seung Koo

The aim of this study was to investigate the expression of glutamine metabolism-related proteins to determine whether glutamine is metabolized differently according to breast cancer molecular subtype. We generated a tissue microarray of 702 breast cancer patients and performed immunohistochemical staining for glutamine metabolism-related proteins, including glutaminase 1 (GLS1 (GLS)), glutamate dehydrogenase (GDH (H6PD)), and amino acid transporter-2 (ASCT2 (SLC1A5)), which were separately evaluated in tumor and stroma compartments and then analyzed by breast cancer molecular subtypes. Breast cancers were classified as follows: 293 luminal A (41.7%), 166 luminal B (23.6%), 67 HER2 type (9.6%), and 176 TNBC (25.1%). HER2 type showed the highest stromal GLS1 (P=0.001), tumoral GDH (P=0.001), stromal GDH (P<0.001), and tumoral ASCT (P<0.001) expression. We identified differential expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. The highest glutamine metabolic activity was seen in HER2-type breast cancer.


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