Qualitative age interactions (or effect modification) suggest divergent pathways for early-onset and late-onset breast cancers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21036-21036 ◽  
Author(s):  
W. F. Anderson ◽  
L. A. Brinton ◽  
B. Chen ◽  
S. S. Devesa
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Early Onset ◽  
Late Onset ◽  
Breast Cancer Incidence ◽  
Temporal Trends ◽  
Effect Modification ◽  
Low Grade ◽  
High Grade ◽  
Breast Cancers

21036 Background: Notwithstanding some recent declines, breast cancer incidence rates have risen for decades, though not equally for all age groups. We used the National Cancer Institute's SEER program to further explore the effect of aging upon breast cancer incidence. Materials and Methods: The SEER program collected data on n=494,543 in-situ + invasive female breast cancer cases, newly diagnosed during 1974–2003. Temporal trends by race, stage, and grade were stratified by age at diagnosis in decades: 20–29 to 80+ years. Results: We observed age interactions over time. For example, as the specification of grade improved from 1974–2003, temporal trends for high and low grade tumors varied with age. Among women ages <40 years, high grade lesions were more common than low grade tumors for all time periods. Among women ages 40+ years, high grade lesions were more common during the early years, and then rates crossed, after which low-grade tumors were more common than high grade lesions. Conclusion: Age at diagnosis was both a quantitative (non- crossover) and qualitative (crossover) effect modifier. The crossing of rates from high to low grade tumors among women ages 40+ years in the 1980s is consistent with more aggressive breast cancer screening, with mammography preferentially detecting low grade tumors among women targeted for screening, i.e., ages 40–80 years. Though once thought to be rare or artifactual, qualitative interactions or effect modification suggest etiologic heterogeneity in an otherwise homogeneous disease process. Indeed, if true, qualitative age interactions imply divergent pathways for early-onset and late-onset breast cancers. No significant financial relationships to disclose.

scholarly journals Diabetes, Metformin, and Breast Cancer in Postmenopausal Women

2012 ◽  
Vol 30 (23) ◽  
pp. 2844-2852 ◽  
Author(s):  
Rowan T. Chlebowski ◽  
Anne McTiernan ◽  
Jean Wactawski-Wende ◽  
JoAnn E. Manson ◽  
Aaron K. Aragaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Cancer Incidence ◽  
Proportional Hazards ◽  
Breast Cancer Incidence ◽  
Cox Proportional Hazards ◽  
Diabetes Incidence ◽  
Breast Cancers ◽  
Cancer Risk Factors ◽  
Cancer Management

Purpose Emerging evidence suggests that metformin may reduce breast cancer incidence, but reports are mixed and few provide information on tumor characteristics. Therefore, we assessed associations among diabetes, metformin use, and breast cancer in postmenopausal women participating in Women's Health Initiative clinical trials. Patients and Methods In all, 68,019 postmenopausal women, including 3,401 with diabetes at study entry, were observed over a mean of 11.8 years with 3,273 invasive breast cancers diagnosed. Diabetes incidence status was collected throughout follow-up, with medication information collected at baseline and years 1, 3, 6, and 9. Breast cancers were confirmed by review of central medical records and pathology reports. Cox proportional hazards regression, adjusted for breast cancer risk factors, compared breast cancer incidence in women with diabetes who were metformin users or nonusers with breast cancer incidence in women without diabetes. Results Compared with that in women without diabetes, breast cancer incidence in women with diabetes differed by diabetes medication type (P = .04). Women with diabetes receiving medications other than metformin had a slightly higher incidence of breast cancer (hazard ratio [HR], 1.16; 95% CI, 0.93 to 1.45), and women with diabetes who were given metformin had lower breast cancer incidence (HR, 0.75; 95% CI, 0.57 to 0.99). The association was observed for cancers positive for both estrogen receptor and progesterone receptor and those that were negative for human epidermal growth factor receptor 2. Conclusion Metformin use in postmenopausal women with diabetes was associated with lower incidence of invasive breast cancer. These results can inform future studies evaluating metformin use in breast cancer management and prevention.

Bimodal breast cancer incidence patterns provide support for a dualistic model of mammary carcinogenesis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 595-595 ◽  
Author(s):  
W. F. Anderson ◽  
R. M. Pfeiffer ◽  
G. M. Dores ◽  
M. E. Sherman
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Early Onset ◽  
Late Onset ◽  
Mammary Carcinogenesis ◽  
Breast Cancers ◽  
Breast Carcinomas ◽  
Cellular Origin ◽  
Causal Pathways ◽  
Er Expression

595 Background: Although breast cancers are extremely heterogeneous with respect to clinical presentation, histopathological appearance, and molecular alterations; breast cancer is often viewed as a single biologic entity with common etiology and unified pathogenesis. Accumulating data has challenged this view, demonstrating that the stratification of tumors by gene expression profiles, immunohistochemical (IHC) staining patterns, and other techniques may permit the categorization of breast cancers into two main pathways of mammary carcinogenesis. Based upon cellular origin and/or estrogen receptor (ER) expression there are 1) tumors from stem cells committed to luminal differentiation and ER expression and 2) neoplasms from stem cells programmed to display basal differentiation and lacking ER expression. If confirmed, these observations may form the basis for revised conceptual frameworks. Methods:: We applied age-at-diagnosis density plots and a two component statistical mixture model to breast cancer cases overall (n=270,124) in the SEER program. These age distributions were reevaluated after stratification by histopathologic type, race, and ER. Results: A bimodal distribution provided a better fit for the age distribution patterns than a single distribution for breast cancers overall and for all histologic types, except medullary carcinoma. However, the proportion of early-onset and late-onset tumors varied: ductal and tubular carcinomas demonstrated relatively equal proportions; lobular, papillary and mucinous tumors were associated with late-onset populations; and inflammatory and medullary tumors were more related to early-onset disease. Medullary carcinomas were exceptional in showing a single distribution irrespective of race and/or ER status. Of note, medullary breast carcinomas are rare tumors that are associated with germline mutations in BRCA1. Conclusion: Most histopathologic types of breast carcinomas demonstrated a bimodal mixture of early- and late-onset cancer populations, possibly representing two major age-related causal pathways. These population-based results seem consistent with emerging molecular data, showing two main classes of breast cancer based upon cellular origin and ER expression. No significant financial relationships to disclose.

scholarly journals Distinct temporal trends in breast cancer incidence from 1997 to 2016 by molecular subtypes: A population-based study of Scottish cancer registry data

2019 ◽  
Author(s):  
Ines Mesa-Eguiagaray ◽  
Sarah H Wild ◽  
Philip S. Rosenberg ◽  
Sheila M Bird ◽  
David H Brewster ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Registry ◽  
Cancer Incidence ◽  
Molecular Subtypes ◽  
Breast Cancer Incidence ◽  
Temporal Trends ◽  
Population Based ◽  
Registry Data ◽  
Cancer Registry Data ◽  
Er Status

AbstractBackgroundStrategies for breast cancer prevention are informed by assessing whether incidence differs by tumour biology. We describe temporal trends of breast cancer incidence by molecular subtypes in Scotland.MethodsPopulation-based cancer registry data on 72,217 women diagnosed with incident primary breast cancer from 1997 to 2016 were analysed. Age-standardised rates (ASR) and age-specific incidence were estimated by tumour subtype after imputing the 8% of missing oestrogen receptor (ER) status. Joinpoint regression and age- period- cohort models were used to assess whether significant differences were observed in incidence trends by ER status.ResultsER positive tumour incidence steadily increased particularly for women of screening age 50 to 69 years from 1997 till around 2011 (1.6%/year, 95%CI: 1.2 to 2.1). ER negative incidence decreased among all ages at a consistent rate of −0.7%/year (95%CI: −1.5, 0) from around 2000-2016. Compared to the 1941-1959 central birth cohort, women born 1912-1940 had lower incidence rate ratios (IRR) for ER+ tumours and women born 1960- 1986 had higher IRR for ER- tumours.ConclusionsWe show evidence of aetiologic heterogeneity of breast cancer. Future incidence and survival reporting should be monitored by molecular subtypes.

scholarly journals Effect of Changing Breast Cancer Incidence Rates on the Calibration of the Gail Model

2010 ◽  
Vol 28 (14) ◽  
pp. 2411-2417 ◽  
Author(s):  
Sara J. Schonfeld ◽  
David Pee ◽  
Robert T. Greenlee ◽  
Patricia Hartge ◽  
James V. Lacey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Invasive Breast Cancer ◽  
Clinical Decision Making ◽  
Prediction Models ◽  
Breast Cancer Incidence ◽  
Incidence Rates ◽  
Breast Cancers ◽  
Gail Model ◽  
Cancer Incidence Rates

Purpose The Gail model combines relative risks (RRs) for five breast cancer risk factors with age-specific breast cancer incidence rates and competing mortality rates from the Surveillance, Epidemiology, and End Results (SEER) program from 1983 to 1987 to predict risk of invasive breast cancer over a given time period. Motivated by changes in breast cancer incidence during the 1990s, we evaluated the model's calibration in two recent cohorts. Methods We included white, postmenopausal women from the National Institutes of Health (NIH) –AARP Diet and Health Study (NIH-AARP, 1995 to 2003), and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO, 1993 to 2006). Calibration was assessed by comparing the number of breast cancers expected from the Gail model with that observed. We then evaluated calibration by using an updated model that combined Gail model RRs with 1995 to 2003 SEER invasive breast cancer incidence rates. Results Overall, the Gail model significantly underpredicted the number of invasive breast cancers in NIH-AARP, with an expected-to-observed ratio of 0.87 (95% CI, 0.85 to 0.89), and in PLCO, with an expected-to-observed ratio of 0.86 (95% CI, 0.82 to 0.90). The updated model was well-calibrated overall, with an expected-to-observed ratio of 1.03 (95% CI, 1.00 to 1.05) in NIH-AARP and an expected-to-observed ratio of 1.01 (95% CI: 0.97 to 1.06) in PLCO. Of women age 50 to 55 years at baseline, 13% to 14% had a projected Gail model 5-year risk lower than the recommended threshold of 1.66% for use of tamoxifen or raloxifene but ≥ 1.66% when using the updated model. The Gail model was well calibrated in PLCO when the prediction period was restricted to 2003 to 2006. Conclusion This study highlights that model calibration is important to ensure the usefulness of risk prediction models for clinical decision making.

Qualitative age interactions (or effect modification) suggest different cancer pathways for early-onset and late-onset breast cancers

2007 ◽  
Vol 18 (10) ◽  
pp. 1187-1198 ◽  
Author(s):  
William F. Anderson ◽  
Bingshu E. Chen ◽  
Louise A. Brinton ◽  
Susan S. Devesa
Keyword(s):  
Early Onset ◽  
Late Onset ◽  
Effect Modification ◽  
Breast Cancers ◽  
Cancer Pathways

scholarly journals Temporal Trends in Geographic Disparities in Small-Area Breast Cancer Incidence and Mortality, 1988 to 2005

2010 ◽  
Vol 19 (4) ◽  
pp. 1122-1131 ◽  
Author(s):  
Mario Schootman ◽  
Min Lian ◽  
Anjali D. Deshpande ◽  
Elizabeth A. Baker ◽  
Sandi L. Pruitt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Small Area ◽  
Breast Cancer Incidence ◽  
Temporal Trends ◽  
Geographic Disparities ◽  
Incidence And Mortality

scholarly journals Characterization of Potential Driver Genes Involved in Human Breast Cancer in Maysan Province, Iraq

2021 ◽  
Author(s):  
Zainab Zamil gataa Allami ◽  
Maytham A Dragh
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Breast Cancer Incidence ◽  
Brca1 Gene ◽  
Receptor Expression ◽  
Breast Cancers ◽  
Driver Genes ◽  
Healthy Control ◽  
Hormone Receptor Expression ◽  
The Relationship

Abstract Background: Breast cancer is a heterogeneous disease regarding its morphology, invasive behaviour, metastatic capacity, hormone receptor expression and clinical outcome. There are many risk factors for breast cancer, including genetic factors that account for 25-30% of the incidence; from this percentage, only 15-30% of the heritable component of breast cancer is due to known familiar highly penetrating genes, and the others are sporadic.Methods: This study was the first to include amplified genes as PCR templates to determine the relationship between their polymorphism and breast cancer incidence using RAPD of amplified genes. The study was designed first to evaluate the association of ABCG2, ABCB1 and BRCA1 gene polymorphisms in addition to miRNA-152 and ER-a using the RAPD technique with breast cancer incidence in Maysan Province women and second to use those genes as indicators for breast cancer prediction and diagnosis. The study included 100 patients with breast cancer and 30 healthy control women, and then all samples were amplified by conventional PCR with specific F and R primers for ABCG2, ABCB1, BRCA1, ER-α, and miRNA-152 genes. Then, the best PCR product (20) was chosen as the template for the RAPD technique.Results: The results revealed that all RAPD primers showed polymorphisms with higher values and more specific bands in patient samples. Our study proved the relationship between genetic polymorphisms of breast cancer-related genes and a higher incidence of cancer.Conclusion: The current study recommends employing these results for the future prediction and diagnosis of breast cancers.

scholarly journals Breast Cancer beyond the Age of Mutation

Gerontology ◽  
2015 ◽  
Vol 62 (4) ◽  
pp. 434-442 ◽  
Author(s):  
Mark A. LaBarge ◽  
E. Lorena Mora-Blanco ◽  
Susan Samson ◽  
Masaru Miyano
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Breast Tissue ◽  
Breast Cancer Incidence ◽  
Epigenetic Changes ◽  
Breast Cancers ◽  
Age Related ◽  
Age Dependent ◽  
Tissue Changes ◽  
Cellular Phenotypes

Age is the greatest risk factor for breast cancer, but the reasons underlying this association are unclear. While there is undeniably a genetic component to all cancers, the accumulation of mutations with age is insufficient to explain the age-dependent increase in breast cancer incidence. In this viewpoint, we propose a multilevel framework to better understand the respective roles played by somatic mutation, microenvironment, and epigenetics making women more susceptible to breast cancer with age. The process of aging is associated with gradual breast tissue changes that not only corrupt the tumor-suppressive activity of normal tissue but also impose age-specific epigenetic changes that alter gene expression, thus reinforcing cellular phenotypes that are associated with a continuum of age-related tissue microenvironments. The evidence discussed here suggests that while the riddle of whether epigenetics drives microenvironmental changes, or whether changes in the microenvironment alter heritable cellular memory has not been solved, a path has been cleared enabling functional analysis leading to the prediction of key nodes in the network that link the microenvironment with the epigenome. The hypothesis that the accumulation of somatic mutations with age drives the age-related increase in breast cancer incidence, if correct, has a somewhat nihilistic conclusion, namely that cancers will be impossible to avoid. Alternatively, if microenvironment-driven epigenetic changes are the key to explaining susceptibility to age-related breast cancers, then there is hope that primary prevention is possible because epigenomes are relatively malleable.

scholarly journals The Potential Contribution of BRCA Mutations to Early Onset and Familial Breast Cancer in Uzbekistan

2016 ◽  
Vol 5 (1) ◽  
Author(s):  
Abdulla Abdikhakimov ◽  
Mukaddas Tukhtaboeva ◽  
Bakhtiyar Adilov ◽  
Shahlo Turdikulova
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Early Onset ◽  
Breast Cancer Incidence ◽  
Potential Contribution ◽  
Brca1 And Brca2 ◽  
Screening Programs ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations ◽  
Disease Free

Introuduction: Breast cancer is the most common malignancy in women and affects approximately 1 out of 8 females in the US. Risk of developing breast cancer is strongly influenced by genetic factors. Germ-line mutations in BRCA1 and BRCA2 genes are associated with 5–10% of breast cancer incidence. To reduce the risk of developing cancer and to increase the likelihood of early detection, carriers of BRCA1 or BRCA2 mutations are offered surveillance programs and effective preventive medical interventions. Identification of founder mutations of BRCA1/2 in high risk communities can have a significant impact on the management of hereditary cancer at the level of the national healthcare systems, making genetic testing more affordable and cost-effective. BRCA1 and BRCA2 mutations in breast cancer patients have not been characterized in the Uzbek population. This pilot study aimed to investigate the contribution of BRCA1 and BRCA2 mutation to early onset and familial cases of breast cancer in Uzbekistan.Methods: A total of 67 patients with breast cancer and 103 age-matched disease free controls were included in this study. Utilizing SYBR Green based real-time allele-specific PCR, we have analyzed DNA samples of  patients with breast cancer and disease free controls to identify the following BRCA1 and BRCA2 mutations: BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT.Results: Three unrelated samples (4.5%) were found to be positive for the heterozygous 5382insCBRCA1 mutation, representing a possible founder mutation in the Uzbek population, supporting the need for larger studies examining the contribution of this mutation to breast cancer incidence in Uzbekistan.We did not findBRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, and BRCA2 6174delT mutations.Conclusion: This preliminary evidence suggests a potential contribution of BRCA1 5382insC mutation to breast cancer development in Uzbek population. Taking into account a high disease penetrance in carriers of BRCA1 mutation, it seems reasonable to recommend inclusion of the 5382insC mutation test in future research on the development of screening programs for breast cancer prevention in Uzbekistan.

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