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
2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21036-21036 ◽  
Author(s):  
W. F. Anderson ◽  
L. A. Brinton ◽  
B. Chen ◽  
S. S. Devesa

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.


2020 ◽  
Vol 9 (3) ◽  
pp. 853 ◽  
Author(s):  
Léo Partouche ◽  
Radjiv Goulabchand ◽  
Alexandre Thibault Jacques Maria ◽  
Sophie Rivière ◽  
Christian Jorgensen ◽  
...  

Cancer among patients with systemic sclerosis (SSc) would appear to be more prevalent than in the general population. Pathophysiological hypotheses are multiple, involving intertwined factors such as immune system antitumoral response, oxygen species dysregulation, and immunosuppressive treatments. We aimed to identify SSc patients with cancer monitored at our center, describing their clinical and immunological characteristics, such as cancer-specific outcomes. We focused in particular on the temporal relationships between cancer onset and SSc diagnosis. A retrospective study was conducted on SSc patients from Montpellier University Hospital from 2003 to 2018. Clinical characteristics and outcomes of each SSc patient with cancer were recorded. Fifty-five patients with SSc and at least one cancer was included (median age 56 years (47–66)), with a median follow-up time of 11 years (4–15). Sixty-four metachronous malignancies were identified (12 patients had two cancers). Among them, early-onset cancer occurrences (±5 years from SSc diagnosis) included 23 cancers (39% breast cancers, 13% lung cancers, and 13% gastro-intestinal tract cancers). Twenty-two cancers occurred 10 years (±5 years) after SSc diagnosis (14% breast cancers, 23% gastrointestinal (GI) tract cancers, and 18% lung cancers). Patients without any of the two autoantibodies (anti-centromere (ACA) and anti-topoisomerase (ATA-scl70) antibodies) were more prevalent in the early-onset cancer subgroup (14 vs. 6, p = 0.02). This study brought to light two peaks of cancer occurrence in SSc patients. Early-onset cancers were associated with SSc with a specific immunological signature. Late-onset cancers might be the consequence of a subtle interplay between repeated target organ inflammation, immunosuppressant use, mesenchymal cell dysfunction and subsequent genetic alterations.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 595-595 ◽  
Author(s):  
W. F. Anderson ◽  
R. M. Pfeiffer ◽  
G. M. Dores ◽  
M. E. Sherman

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.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9079-9079
Author(s):  
W. F. Anderson ◽  
R. M. Pfeiffer ◽  
M. A. Tucker ◽  
P. S. Rosenberg

9079 Background: Emerging data suggest that cutaneous malignant melanomas (CMM) may arise through divergent cancer pathways, linked to intermittent versus accumulated sun exposure. However, numerous questions remain regarding the timing and/or age of exposure. Methods: We, therefore, systematically examined the effect of aging upon CMM incidence in the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Standard descriptive epidemiology was supplemented with mathematical models. The impact of advancing age upon CMM incidence was assessed by gender, histopathological subtype (superficial spreading melanoma (SSM) or lentigo maligna melanoma [LMM]), and anatomic site (face, head, and neck [FHN] or lower extremity [LE]). Results: Gender, histopathological and anatomic site were age-specific effect modifiers for CMM, showing divergent (or bimodal) early- and late-onset cancer pathways. Early-onset melanomas were predominantly associated with female gender, SSM, and LE. Late- onset melanomas were correlated with male gender, LMM, and FHN. Early- and late-onset melanoma populations were confirmed with age-period-cohort models (adjusted for period and cohort effects) and two-component mixture models. Conclusions: These results are consistent with a divergent and age-dependent solar hypothesis for CMM. Early-onset melanomas may represent gene-sun exposure interactions occurring early (and/or intermittently) in life among susceptible individuals. Late-onset melanomas possibly reflect accumulated lifelong sun exposure in comparatively less susceptible individuals. Future analytical studies should be adequately powered to account for this age-dependent effect modification for acknowledged (gender, histopathology, and anatomic site) as well as suspected melanoma risk factors such as constituent genetic variants. No significant financial relationships to disclose.


Cancer ◽  
2009 ◽  
Vol 115 (18) ◽  
pp. 4176-4185 ◽  
Author(s):  
William F. Anderson ◽  
Ruth M. Pfeiffer ◽  
Margaret A. Tucker ◽  
Philip S. Rosenberg

Cancer ◽  
2010 ◽  
pp. NA-NA
Author(s):  
William F. Anderson ◽  
Margaret A. Tucker ◽  
Philip S. Rosenberg

Cancer ◽  
2010 ◽  
pp. NA-NA
Author(s):  
Beatriz Pérez-Gomez ◽  
Nuria Aragonés ◽  
Marina Pollan

Author(s):  
Pramod P. Singhavi

Introduction: India has the highest incidence of clinical sepsis i.e.17,000/ 1,00,000 live births. In Neonatal sepsis septicaemia, pneumonia, meningitis, osteomyelitis, arthritis and urinary tract infections can be included. Mortality in the neonatal period each year account for 41% (3.6 million) of all deaths in children under 5 years and most of these deaths occur in low income countries and about one million of these deaths are due to infectious causes including neonatal sepsis, meningitis, and pneumonia. In early onset neonatal sepsis (EOS) Clinical features are non-specific and are inefficient for identifying neonates with early-onset sepsis. Culture results take up to 48 hours and may give false-positive or low-yield results because of the antenatal antibiotic exposure. Reviews of risk factors has been used globally to guide the development of management guidelines for neonatal sepsis, and it is similarly recommended that such evidence be used to inform guideline development for management of neonatal sepsis. Material and Methods: This study was carried out using institution based cross section study . The total number neonates admitted in the hospital in given study period was 644, of which 234 were diagnosed for neonatal sepsis by the treating pediatrician based on the signs and symptoms during admission. The data was collected: Sociodemographic characteristics; maternal information; and neonatal information for neonatal sepsis like neonatal age on admission, sex, gestational age, birth weight, crying immediately at birth, and resuscitation at birth. Results: Out of 644 neonates admitted 234 (36.34%) were diagnosed for neonatal sepsis by the paediatrician based on the signs and symptoms during admission. Of the 234 neonates, 189 (80.77%) infants were in the age range of 0 to 7 days (Early onset sepsis) while 45 (19.23%) were aged between 8 and 28 days (Late onset sepsis). Male to female ratio in our study was 53.8% and 46% respectively. Out of total 126 male neonates 91(72.2%) were having early onset sepsis while 35 (27.8%) were late onset type. Out of total 108 female neonates 89(82.4%) were having early onset sepsis while 19 (17.6%) were late onset type. Maternal risk factors were identified in 103(57.2%) of early onset sepsis cases while in late onset sepsis cases were 11(20.4%). Foul smelling liquor in early onset sepsis and in late onset sepsis was 10(5.56%) and 2 (3.70%) respectively. In early onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 21(11.67%), 19 (10.56%), 20(11.11%) and 33 (18.33%) cases respectively. In late onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 2 (3.70%), 1(1.85%), 3 (5.56%) and 3 (5.56%) cases respectively. Conclusion: Maternal risk identification may help in the early identification and empirical antibiotic treatment in neonatal sepsis and thus mortality and morbidity can be reduced.


Sign in / Sign up

Export Citation Format

Share Document