Prognostic and predictive factors are well established in early-stage breast cancer, but less is known about which metastatic sites will be affected.
Patients with early-stage breast cancer diagnosed ...between 1986 and 1992 with archival tissue were included. Subtypes were defined as luminal A, luminal B, luminal/human epidermal growth factor receptor 2 (HER2), HER2 enriched, basal-like, and triple negative (TN) nonbasal. Distant sites were classified as brain, liver, lung, bone, distant nodal, pleural/peritoneal, and other. Cumulative incidence curves were estimated for each site according to competing risks methods. Association between the site of relapse and subtype was assessed in multivariate models using logistic regression.
Median follow-up time among 3,726 eligible patients was 14.8 years. Median durations of survival with distant metastasis were 2.2 (luminal A), 1.6 (luminal B), 1.3 (luminal/HER2), 0.7 (HER2 enriched), and 0.5 years (basal-like; P < .001). Bone was the most common metastatic site in all subtypes except basal-like tumors. In multivariate analysis, compared with luminal A tumors, luminal/HER2 and HER2-enriched tumors were associated with a significantly higher rate of brain, liver, and lung metastases. Basal-like tumors had a higher rate of brain, lung, and distant nodal metastases but a significantly lower rate of liver and bone metastases. TN nonbasal tumors demonstrated a similar pattern but were not associated with fewer liver metastases.
Breast cancer subtypes are associated with distinct patterns of metastatic spread with notable differences in survival after relapse.
Purpose
We hypothesized different Overall Survival (OS) in metastatic breast cancer (MBC) after relapse vs de novo presentation.
Methods
We identified women in British Columbia with MBC diagnosed ...between 01/2001 and 12/2009. OS from MBC was calculated for relapsed vs de novo cohorts in 3 subgroups, based on hormone receptors (HR) and HER2 status. Age at MBC, disease-free interval (DFI), de novo vs relapsed, year of MBC diagnosis, and systemic treatment were entered into univariable and multivariable analyses.
Results
We identified 3645 pts with known HR of which 2796 had known HER2. Median follow-up was 91 months. Median OS was longer for de novo vs relapsed MBC: HR+/HER2- 34 versus 23 months (mos) (
p
< 0.0001), HR−/HER2- (TN) 11 versus 8 mos (
p
= 0.02), HER2+ 29 versus 15 mos (
p
< 0.0001). For TN disease, no variable independently discriminated a group with increased risk of death. For both the HR +/HER2- and the HER2 + groups, relapsed vs de novo status (HzR 1.4 95% CI 1.2–1.5;
p
< 0.0001, and HzR 1.6 95% CI 1.4–1.9;
p
< 0.0001, respectively) and age >50 (HzR 1.2 95% CI 1.1–1.4;
p
= 0.001 and HzR 1.3 95% CI 1.1–1.5;
p
= 0.01, respectively) were associated with increased risk of death on multivariable analysis.
Conclusion
These data provide information that may guide discussions about prognosis between physicians and patients with MBC. In addition, it highlights the importance of stratifying for initial stage at diagnosis in future MBC therapeutic trials.
To determine whether the patterns of relapse according to estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status changed in the contemporary era.
Female patients referred ...to the British Columbia Cancer Agency with biopsy-proven stage I to III breast cancer (BC), diagnosed between 1986 and 1992 (cohort 1 C1) and between mid-2004 and 2008 (cohort 2 C2), and with known ER and HER2 status were eligible. Data were prospectively collected. C2 patients were matched to C1 patients for stage, grade, and ER and HER2 status. The primary end point was hazard rate of relapse (HRR) for BC by study cohort according to biomarker status. Secondary outcomes included HRR according to stage, grade, and age and hazard rate of death (HRD).
After matching, 7,178 patients were included (3,589 patients in each cohort). BC subtype distribution was as following ER positive/HER2 negative, 70.8%; ER positive/HER2 positive, 6.9%; ER negative/HER2 positive, 6.6%; and ER negative/HER2 negative, 15.8%. For the overall population, the HRR approximately halved in all yearly intervals to year 9 in C2 compared with C1. Differences in HRR between cohorts were greater in the initial five intervals for HER2-positive and ER-negative/HER2-negative BC. The HRR decreased in C2 compared with C1 for all disease stages and grades. The HRD in C2 also decreased compared with C1, although to a lesser extent.
Although the pattern of relapse remains similar, there has been a significant improvement in BC relapse-free survival. Outcomes have improved for all BC subtypes, especially HER2-positive and ER-negative/HER2-negative BC, with the early spike in disease recurrence markedly decreased. These contemporary hazard rates are important for treatment decisions, patient discussions, and planning clinical trials of early BC.
Adjuvant! (www.adjuvantonline.com) is a web-based tool that predicts 10-year breast cancer outcomes with and without adjuvant systemic therapy, but it has not been independently validated.
Using the ...British Columbia Breast Cancer Outcomes Unit (BCOU) database, demographic, pathologic, staging, and treatment data on 4,083 women diagnosed between 1989 and 1993 in British Columbia with T1-2, N0-1, M0 breast cancer were abstracted and entered into Adjuvant! to calculate predicted 10-year overall survival (OS), breast cancer-specific survival (BCSS), and event-free survival (EFS) for each patient. Individual BCOU observed outcomes at 10 years were independently determined. Predicted and observed outcomes were compared.
Across all 4,083 patients, 10-year predicted and observed outcomes were within 1% for OS, BCSS, and EFS (all P > .05). Predicted and observed outcomes were within 2% for most demographic, pathologic, and treatment-defined subgroups. Adjuvant! overestimated OS, BCSS, and EFS in women younger than age 35 years (predicted-observed = 8.6%, 9.6%, and 13.6%, respectively; all P < .001) or with lymphatic or vascular invasion (LVI; predicted-observed = 3.6%, 3.8%, and 4.2%, respectively; all P < .05); these two prognostic factors were not automatically incorporated within the Adjuvant! algorithm. After adjusting for the distribution of LVI, using the prognostic factor impact calculator in Adjuvant!, 10-year predicted and observed outcomes were no longer significantly different.
Adjuvant! performed reliably. Patients younger than age 35 or with known additional adverse prognostic factors such as LVI require adjustment of risks to derive reliable predictions of prognosis without adjuvant systemic therapy and the absolute benefits of adjuvant systemic therapy.
BACKGROUND:Optimal management of rectal neuroendocrine tumors is not yet well defined. Various pathologic factors, particularly tumor size, have been proposed as prognostic markers.
OBJECTIVE:We ...characterized sequential patients diagnosed with rectal neuroendocrine tumors in a population-based setting to determine whether tumor size and other pathologic markers could be useful in guiding locoregional management.
DESIGN:This study is a retrospective analysis of data from the British Columbia provincial cancer registry.
SETTINGS:The study was conducted at a tertiary care center.
PATIENTS:Sequential patients diagnosed with rectal neuroendocrine tumors between 1999 and 2011 were identified. Neuroendocrine tumors were classified as G1 and G2 tumors with a Ki-67 ≤20% and/or mitotic count ≤20 per high-power field.
MAIN OUTCOME MEASURES:Baseline clinicopathologic data including TNM staging, depth of invasion, tumor size, treatment modalities, and outcomes including survival data were measured.
RESULTS:Of 91 rectal neuroendocrine tumors, the median patient age was 58 years, and 35 were men. Median tumor size was 6 mm. Median length of follow-up was 58.1 months, with 3 patients presenting with stage IV disease. Treatment included local ablation (n = 5), local excision (n = 79), surgical resection (n = 4), and pelvic radiation (n = 1; T3N1 tumor). Final margin status was positive in 17 cases. Local relapse occurred in 8 cases and 1 relapse to bone 13 months after T3N1 tumor resection. Univariate analysis demonstrated an association between local relapse and Ki-67, mitotic count, grade, and lymphovascular invasion (p < 0.01). Larger tumor size was associated with decreased disease-free survival.
LIMITATIONS:Sample size was 91 patients in the whole provincial population over a 13-year time period because of the low incidence of rectal neuroendocrine tumors.
CONCLUSIONS:In this population-based cohort, rectal neuroendocrine tumors generally presented with small, early tumors and were treated with local excision or surgical resection without pelvic radiation. Pathologic markers play a role in risk stratification and prognostication. See Video Abstract at http://links.lww.com/DCR/A514.
Estrogen receptor (ER) expression predicts improved breast cancer-specific survival and reduced risk of recurrence and is targeted in breast cancer therapy. A high-quality antibody to identify ...ER-positive patients plays an important role in clinical decision making for women with breast cancer. This study evaluates immunohistochemistry using two anti-ER antibodies, a new rabbit monoclonal antibody (SP1) and the mouse monoclonal antibody (1D5), in relation to biochemical ER assay results and clinical data on survival and adjuvant systemic therapy.
A population-based tissue microarray series of 4,150 invasive breast cancers was constructed. All patients had staging, pathology, treatment, and follow-up information. The median follow-up was 12.4 years and the median age at diagnosis 60 years. Survival analysis and log-rank tests were used to evaluate the prognostic value of ER status and correlations with clinical data.
Among the 4,105 samples interpretable for both antibodies, SP1 detected ER positivity in 69.5% and 1D5 in 63.1% of cases. Both monoclonal antibodies are demonstrated to be good prognostic indictors for breast cancer-specific and relapse-free survival. In multivariate analysis, including age, tumor size, grade, and lymphovascular and nodal status, SP1 was a better independent prognostic factor than 1D5. Among patients with discrepant ER results, the 8% of patients who were SP1 positive/1D5 negative showed good outcomes, and the 2% SP1-negative/1D5 positive had poor outcomes. Maintaining the same 92% specificity and 98% positive predictive value, SP1 is 8% more sensitive than 1D5 using biochemical assay as gold standard.
SP1 represents an improved standard for ER immunohistochemistry assessment in breast cancer.
In an evaluation of the prognostic role of sex on colorectal cancer (CRC)-specific outcomes, we reviewed all patients with resected stage I to III colorectal cancer referred to cancer centers in a ...large, representative Canadian province. Men had worse overall and recurrence-free survival compared to women; however, CRC-specific survival and time to recurrence did not differ significantly between men and women. This suggests that the trajectory of CRC is similar irrespective of sex when noncancer causes of death are excluded.
Women have been shown to experience longer overall survival after colorectal cancer (CRC) diagnosis than men even after adjusting for disease stage and management. However, the etiology of this observation is not well understood, and the impact of non-CRC health conditions on survival has not been described. We aimed to evaluate the prognostic role of sex on CRC-specific outcomes.
All patients who underwent primary resection of stage I to III CRC from 2001 to 2005, and who were referred to cancer centers in a large, representative Canadian province were reviewed. Baseline patient characteristics, including common comorbidities, were compared between men and women. Multivariable analysis was used to evaluate the associations between sex and survival outcomes.
We identified 1837 patients. Median age was 69 (interquartile range 60-76) years, and there were 867 women (47%) and 970 men (53%). Men were more likely to report ischemic heart disease, diabetes, dyslipidemia, and obesity (all P < .001). On multivariable analysis, men had worse overall and recurrence-free survival compared to women (hazard ratio HR = 1.38, 95% confidence interval CI 1.15-1.64; and HR = 1.40, 95% CI, 1.18-1.67, respectively). However, CRC-specific outcomes, including CRC-specific survival and time to recurrence, did not differ significantly between men and women (HR = 1.15, 95% CI, 0.91-1.45; and HR = 1.12, 95% CI, 0.90-1.40, respectively).
Women diagnosed with early stage CRC lived longer and had better general health than men. When noncancer causes of death were excluded, however, the trajectory of CRC appeared similar irrespective of sex. Early identification and better management of comorbidities may narrow the survival gap between men and women.
We investigated the impact of new systemic therapies approved in Canada for colorectal cancer on the frequency, intensity and duration of oncology clinic and infusion visits over five treatment ...phases from diagnosis (P1, P3) to treatment (P2, P4) of primary and metastatic disease, respectively, and during the last 6 months of life (P5). In total, 15,157 adult patients with newly diagnosed colorectal cancer and referred between 2000 and 2012 to any cancer clinic in British Columbia, Canada, were included. Frequency, intensity and duration of medical oncology clinic visits (CVs), oncology infusions (OIs) and oncology prescriptions (OPs) were measured by treatment phase. Mean, total and adjusted total duration for CVs increased for P1–5. CVs increased in P1–5, and in P1–4 when adjusted by treatment length. Adjusted and unadjusted OIs decreased in P1 coinciding with the introduction of an oral treatment option, but increased in P2–5. Mean OI duration increased in P1–5, while total and adjusted total decreased in P1 and increased in P2–5. OPs increased in P2–4, but were unchanged in P1 and P5. Multi‐fold increases in resources and time required per patient were also observed, which have significant implications for demand projections in cancer care planning and delivery. In conclusion, patients required more visits in almost all treatment phases, visits on average took longer and patients were in treatment for longer periods of time.
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