American Joint Committee on Cancer PS offers superior prognostic stratification compared to UICC AS in high-risk luminal breast cancer, and incorporation into clinical practice may enable more personalized treatment approaches, particularly when identifying candidates for adjuvant abemaciclib therapy.
Abstract
Introduction: Breast cancer remains the most prevalent malignancy among women worldwide, with prognostic outcomes and therapeutic responses differing considerably across subtypes. The conventional staging framework developed by the Union for International Cancer Control (UICC), based on the Tumor, Node, Metastasis classification, reflects anatomical stage (AS) but overlooks biological characteristics. To address this limitation, the American Joint Committee on Cancer (AJCC) introduced the Prognostic Stage (PS) in its 8th edition, which integrates biomarkers including estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and histological grade (HG). This study aimed to assess and compare the prognostic utility of UICC AS and AJCC PS in patients with high-risk luminal breast cancer. Methods: This retrospective study included patients who underwent surgery for ER-positive, HER2-negative breast cancer at Tokyo Metropolitan Komagome Hospital from 2011 to 2018. High-risk classification was defined based on MonarchE trial criteria: axillary lymph node metastasis, tumor diameter ≥5 cm, HG3, or Ki-67 ≥20%. Staging was performed using both UICC AS and AJCC PS, and prognostic values were evaluated via Kaplan-Meier survival analysis. Results: Among 105 eligible cases, 43 (41%) were downstaged when reclassified from UICC AS to AJCC PS. While UICC AS failed to yield significant stratification in terms of invasive disease-free survival (IDFS) and distant recurrence-free survival (DRFS), AJCC PS demonstrated significant prognostic discrimination (IDFS p = 0.014; DRFS p = 0.004). Conclusions: American Joint Committee on Cancer PS offers superior prognostic stratification compared to UICC AS in high-risk luminal breast cancer. Its incorporation into clinical practice may enable more personalized treatment approaches, particularly when identifying candidates for adjuvant abemaciclib therapy. Further validation through larger, prospective studies is warranted.
Background: Breast cancer is the most frequently diagnosed malignancy among women and a significant health burden in South Africa. The American Joint Committee on Cancer (AJCC) 8th Edition incorporates biological markers (oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2] status and tumour grade) into conventional tumour, node, metastasis staging. Evidence from low-income and middle-income settings with high HIV prevalence remains limited.
Aim: We compared the anatomical staging (AJCC 7th Edition) with the clinical prognostic staging (AJCC 8th Edition) at a South African tertiary centre, and evaluated stage migration by tumour biology, HIV status and demographics.
Setting: Charlotte Maxeke Johannesburg Academic Hospital (CMJAH).
Methods: We conducted a retrospective review of 524 newly diagnosed patients with breast cancer at CMJAH. Clinical records, pathology, and imaging were used to assign anatomical and clinical prognostic stages. Associations among stage migration and molecular subtype, HIV status, and age were assessed.
Results: Overall, 33.8% of patients experienced stage migration. Downstaging was most frequent in Luminal A (28.1%) and Luminal B HER2+ (34.1%); upstaging predominated in triple-negative breast cancer (69.4%). Application of the clinical prognostic model reclassified an additional 8% as Stage I, with a 5% and 2% decline in Stage II and Stage III disease, respectively. Stage IV disease did not change. HIV prevalence was 15.65% and showed no association with migration (p > 0.05).
Conclusion: Incorporating biological markers substantially reclassifies patients, especially among hormone receptor-positive and triple-negative subtypes, with direct implications for treatment planning.
Contribution: These findings support routine adoption of biologically informed staging in South Africa.
Rahmiz R. Thomas, Tahlia Naidoo, Uchechukwu A. N. Izegbu et al.· South African Journal of Onc...· 0 citations
Breast cancer survival is shaped by a complex interaction of tumor-specific, biological, and patient-related factors. Stage at diagnosis remains the strongest predictor of outcome. Tumor size, nodal involvement, and histologic grade further aid in prognostic prediction by reflecting the biological aggressiveness of the disease. Since the early 2000s, molecular characteristics gained importance in risk stratification. Hormone receptor-positive cancers generally respond well to endocrine therapy, while HER2-positive tumors, once associated with poor outcomes, now benefit from targeted therapy. Newer agents and combinations such as CDK4/6 and PI3K/AKT/mTOR inhibitors are being investigated recently. Patient factors, including age, comorbidities, and overall health, also influence outcome and treatment tolerance. Cardiovascular toxicity from chemotherapy and radiotherapy has become an important consideration, particularly in the elderly. Although modern radiotherapy techniques have reduced cardiac risks, long-term cardiovascular mortality remains a competing cause of death in many survivors. Studies comparing breast-conserving therapy with mastectomy suggest improved overall survival with the former, partly due to reduced treatment morbidity. Early detection through mammography, ultrasound, and awareness campaigns greatly improves survival, yet access remains unequal in low-resource settings. Strengthening healthcare systems, tailoring treatments, expanding multidisciplinary care and improving public education are essential. Affordable personalized therapies, better infrastructure, and international collaboration can reduce disparities and enhance global breast cancer outcomes. Our international team researched literature information as well as summarizing up-to-date opinions from global experts, including those with limited resources and war-torn regions.
Lorent Sijarina, O. Alqaisi, Drilon Bytyçi et al.· Exploration of Medicine· 0 citations
Background Breast cancer (BC) mortality risk extends over decades; yet, the temporal prognostic patterns of histological grade across subtypes and stages remain unclear. Patients and methods Women with stage I-III BC diagnosed between 2000 and 2018 were identified from Surveillance, Epidemiology, and End Results registries (N = 767 218). Breast cancer-specific mortality (BCSM), as the primary endpoint, was analyzed using cumulative incidence functions including competing risk and annual hazard rates stratified by grade, estrogen receptor (ER) status, stage, and adjuvant chemotherapy. Restricted mean survival time differences were calculated to quantify absolute survival differences across follow-up intervals. Landmark survival analyses were carried out for 0 to <60, 60 to <120, and 120 to <180 months from diagnosis. Time-varying effects of grade were assessed through interval-specific modeling to evaluate nonproportional hazards. Results Overall, 23%, 44%, and 33% of cancers were grades 1, 2, and 3, respectively, accounting for 8%, 35%, and 57% of BC deaths. In each consecutive follow-up period, the contribution of grade 1 cancers to BCSM increased, and the contribution of grade 3 cancers decreased. Overall, 59% and 30% of deaths from grades 1 and 3 cancers, respectively, occurred after 5 years. In ER-positive disease, grade 3 tumors showed peak annual hazards between years 3 and 5, whereas grade 1 tumors had lower but sustained hazards extending beyond 10 years; the hazard curves converged between years 10 and 12. In ER-negative disease, early hazards were higher, and convergence also started earlier at years 5-8. Absolute risk was influenced by nodal status and tumor stage within each grade category and follow-up interval. Conclusion Grade 1 cancers show sustained risk beyond 10 years, whereas grade 3 cancers exhibit front-loaded risk. These temporal risk patterns, together with other clinical and genomic data, could inform extended endocrine therapy decisions and surveillance strategies.
M. Mariani, M. Ochocki, G. Bianchini et al.· ESMO Open· 0 citations
Background: Risk stratification after curative resection remains challenging in stage II-III colorectal cancer (CRC). The cancer inflammation prognostic index (CIPI) has been proposed as a novel prognostic marker; however, whether high-risk stage II disease, as defined by CIPI, has outcomes comparable to those of stage III CRC remains unclear, particularly in patients with normal carbohydrate antigen 19-9 (CA19-9) levels. Patients and Methods: We retrospectively analyzed 654 patients with pathological stage II-III CRC and normal preoperative CA19-9 who underwent curative resection between 2008 and 2018. Patients were stratified using a validated CIPI cutoff (56.9). Disease-free (DFS) and overall (OS) survival were evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Results: A high CIPI was significantly associated with poor DFS and OS (both log-rank p<0.01). In multivariate analysis, CIPI ≥56.9 independently predicted worse DFS (hazard ratio=1.91, 95% confidence interval=1.25-2.91; p<0.01) and OS (hazard ratio=2.57, 95% confidence interval=1.42-4.64; p<0.01). Among patients with stage II disease, those with a high CIPI demonstrated DFS and OS comparable to those with stage III CRC (DFS: p=0.31; OS: p=0.49). Conclusion: CIPI identifies biologically high-risk stage II CRC with long-term outcomes comparable to stage III disease among patients with normal CA19-9 levels, supporting its role as a complementary prognostic tool beyond conventional pathological staging.
Traditional pathological markers remain relevant in prognostic assessment for solid tumors, but their clinical value may differ according to tumor biological context. This study evaluated the prognostic significance of Ki-67, histological grade, and vascular invasion (VI) in breast and colorectal cancer, with emphasis on subtype-specific differences. This single-center retrospective cohort included 846 patients with breast cancer or colorectal cancer who underwent curative-intent surgery between 2015 and 2022. Ki-67 expression, histological grade, and VI were extracted from pathological records. The pooled analysis was designed as an exploratory cross-cancer comparison of shared pathological features rather than as an assumption of biological equivalence between the 2 malignancies; cancer-specific and molecular-context analyses were therefore emphasized. Overall survival was assessed using Cox proportional hazards regression, with subgroup analyses according to breast cancer surrogate molecular subtype and colorectal cancer mismatch repair status. A simple Ki-67/VI score was explored for risk stratification. In multivariable analysis, increased age, stage III disease, high Ki-67 expression, and VI were independently associated with worse overall survival, whereas histological grade was not retained as an independent predictor. In breast cancer, the prognostic effect of Ki-67 was evident in luminal B and triple-negative subtypes but not in luminal A disease. In colorectal cancer, VI showed stronger prognostic value in proficient mismatch repair tumors than in deficient mismatch repair tumors. The combined Ki-67/VI score provided incremental prognostic stratification and showed better discriminatory performance than any single marker alone. Ki-67 and VI were associated with prognosis in this retrospective cohort, and the magnitude of these associations varied according to tumor biological context. The Ki-67/VI score should be regarded as exploratory and hypothesis-generating pending internal optimism correction and external validation. Interpretation of conventional pathological indicators should therefore remain cancer- and subtype-specific.
Hong-Yan Ji, Bin-Zheng Liu, Li-Sha Xie· Medicine· 0 citations
BACKGROUND
Stage at diagnosis, histologic grade, and molecular subtypes are established prognostic indicators for women with breast cancer (BC), but their impact on population-based survival estimates is poorly documented. This study assessed long-term BC survival trends according to these factors.
METHODS
We identified women aged <75 years diagnosed with stage I-IV invasive BC between 2004 and 2014 from the Friuli Venezia Giulia (North Eastern Italy) Cancer Registry (N = 10,476). Follow-up through 2023 was used to estimate overall and net survival (NS) according to combinations of prognostic factors.
RESULTS
The highest 10-year NS (10-NS) was observed in women with stage I HR+/HER2- subtype (98.8%), while it was 35.1% for stage III triple-negative (TN) subtype. Among women with stage IV BC, 10-NS was 18.9% for those HR-/HER2+, 11.5% for those HR+/HER2+, 8.3% for HR+/HER2-, and 6.7% for TN. For each stage, NS decreased with increasing grade. Comparing period of diagnosis (2004-2009 vs 2010-2014), 10-NS remained >90% for women with stage I BC, but improved for stage III and aggressive subtypes (HR-/HER2+ and TN). In women with stage III HR-/HER2+ BC, 10-NS increased from 48.6% to 87.9% (+39 percentage points), while when diagnosis was stage III TN BC it rose from 28.8% to 42.3.
CONCLUSION
Population-based estimates of long-term BC survival by combined stage, grade, and molecular subtype can inform the interpretation of evolving therapeutic strategies and improve risk stratification for patient follow-up.
Fabiola Giudici, D. Serraino, F. Puglisi et al.· The Oncologist· 0 citations
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