Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

Abstract

BackgroundStage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit.MethodsIn a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes.ResultsScreen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05).ConclusionsMolecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially.Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology.

Emerging Trends in Family History of Breast Cancer and Associated Risk

“…For instance, among women with invasive breast cancer at diagnosis, women with a positive family history tended to have smaller tumors with more favorable prognostic outcomes (39, 40); however, results have been mixed with other studies suggesting no relationship with stage of disease (41, 42). Stage at diagnosis could be related to family history through mechanisms working in different ways; women undergoing routine mammography screening are more likely to be diagnosed with breast cancer at an earlier stage, whereas breast cancer tumors with more aggressive features tend to be diagnosed at later stages (43). In the CBCS, family history was more common in earlier as compared with later staged breast cancer.…”

Molecular Subtypes of Breast Cancer: Long-term Incidence Trends and Prognostic Differences

“…This increase could probably be attributed to longer survival among Luminal A patients diagnosed in 1995 or later. Since Luminal tumours are more likely to be detected by screening (34)(35)(36), it is plausible that the longer survival among many Luminal A cases diagnosed after 1995 may be due to earlier detection by mammography (lead-time bias). Aggressive subtypes, such as the Basal phenotype or the HER2 type, are more likely to present clinically, and lead-time bias may be a negligible issue for these subtypes (34)(35)(36)(37).…”

Breast cancer screening, body mass index and prognosis benefit

“…Detailed eligibility criteria are reported elsewhere. 7 BMI was categorized as: normal weight (<25 kg/m 2 ), overweight (25-29 kg/m 2 ) and obese (530 kg/m 2 ). Tumours were considered screen-detected if suspicious findings were first detected by breast imaging within the routine national screening programme.…”