Impact of new cancer therapies on outpatient treatment delivery for colorectal cancer: A population-based study.

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.

Comparison of Treatment, Cost, and Survival in Patients With Metastatic Colorectal Cancer in Western Washington, United States, and British Columbia, Canada.

PURPOSE: Few studies have directly compared health care utilization, costs, and outcomes between patients treated in the US multipayer health system and Canada's single-payer system. Using cancer registry and claims data, we assessed treatment types, costs, and survival for patients with metastatic colorectal cancer (mCRC) in Western Washington State (WW) and British Columbia (BC). MATERIALS AND METHODS: Patients age ≥ 18 years diagnosed with mCRC in 2010 and later were identified from the BC Cancer database and a regional database linking WW SEER to claims from Medicare and two large commercial insurers. Demographics, treatment characteristics, costs of systemic therapy, and survival data were obtained from these databases and compared between the two regions. RESULTS: A total of 1,592 patients from BC and 901 from WW were included in the study. Median age was similar (BC, 66 years; WW, 63 years), but patients in BC were more likely to be male (57.1% v 51.2%; P ≤ .01) and to have de novo metastatic disease (61.0% v 38.3%; P ≤ .01). The use of radiation therapy was similar between regions (BC, 31.2%; WW, 33.9%; P = .18), but primary tumor resection was more common in BC (74.1% v 66.3%; P ≤ .01) as was hepatic metastasectomy (12.4% v 2.3%; P ≤ .01). Similar percentages of patients received systemic therapy (BC, 68.8%; WW, 67.1%; P = .40), but costs were significantly higher for first-line systemic therapy in WW ($6,226 v $15,792 per patient per month; P ≤ .01). Median overall survival was similar (BC, 16.9 months; WW, 18 months). CONCLUSION: Cost of systemic therapy for mCRC was significantly higher for patients in WW than in BC, but this did not translate to a difference in overall survival.

Sex Disparities in Outcomes of Early Stage Colorectal Cancer: A Population-Based Study.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Prognostic Factors for Locoregional Recurrence in Neuroendocrine Tumors of the Rectum.

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.

Real-World Effect of Maintenance and Intermittent Chemotherapy on Survival in Metastatic Colorectal Cancer.

BACKGROUND: With improved survival and longer duration of treatment, clinicians managing metastatic colorectal cancer (mCRC) increasingly consider intermittent (IC) or maintenance chemotherapy (MC), but the effect of these treatment modifications on real-world outcomes is unclear. PATIENTS AND METHODS: Using a population-based cohort of mCRC patients who received combination chemotherapy, we aimed to describe the use of IC/MC and their effect on overall survival (OS). RESULTS: Among 617 patients, 120 (19%) had periods of IC, 67 (11%) had periods of MC, and 53 (9%) had periods of both. Most (85.5%) modifications occurred in the first-line setting. The receipt of IC (median OS [mOS], 37 vs. 21 months; P < .0001) or MC (mOS, 36 vs. 24 months; P = .0015) was associated with improved mOS compared with continuous combination therapy. In multivariate analysis adjusting for age, sex, and regimen used at the time of treatment modification, IC (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.42-0.65; P < .0001), MC (HR, 0.71; 95% CI, 0.58-0.88; P = .002), and the combination (HR, 0.45; 95% CI, 0.33-0.63; P < .0001) were all associated with improved mOS. Among patients receiving MC, individuals with (HR, 0.69; 95% CI, 0.53-0.90; P = .005) and without (HR, 0.74; 95% CI, 0.55-1.00; P = .048) re-escalation to their original cytotoxic regimen had improved mOS compared with continuous therapy. The use of IC was associated with an improved OS compared with MC (HR, 0.65; 95% CI, 0.47-0.90; P = .009). CONCLUSION: In patients with mCRC, IC and MC are reasonable options to maintain quality of life and do not appear to negatively affect OS in carefully selected patients.

Impact of Duration of Neoadjuvant Radiation on Rectal Cancer Survival: A Real World Multi-center Retrospective Cohort Study.

BACKGROUND: The utility of neoadjuvant radiotherapy (nRT) for the treatment of stage II and III rectal cancer is well-established. However, the optimal duration of nRT in this setting remains controversial. Using a population-based cohort of patients with stage II and III rectal cancer (RC) treated with curative intent, our aims were to (1) examine the patterns of nRT use and (2) explore the relationship between different nRT schedules and survival in the real-world setting. METHODS: This is a multi-center retrospective cohort study based on population-based data from 5 regional comprehensive cancer centers in British Columbia, Canada. We analyzed patients diagnosed with clinical stage II or III RC from 2006 to 2010 and treated with either short-course (SC) or long-course (LC) nRT prior to curative intent surgery. Logistic regression models were constructed to determine the factors associated with the course of nRT delivered to patients. Kaplan-Meier methods and Cox regression that accounted for known prognostic factors were used to evaluate the relationship between nRT schedule and overall (OS), disease-free (DFS), local recurrence-free (LRFS), and distant recurrence-free survival (DRFS). RESULTS: We identified 427 patients: the median age was 65 years (range, 31 to 94 years), 67% were men, 87% had T3 or T4 tumors, and 74% had N1 or N2 disease. Among them, 241 (56%) received SC and 186 (44%) received LC. Adjusting for confounders, patients with N1 or N2 disease were more likely to undergo LC (odds ratio [OR], 5.08; 95% confidence interval [CI], 2.51-11.22; P < .0001 and OR, 8.35; 95% CI, 3.35-22.39; P < .0001, respectively), whereas older age patients were less likely to receive LC (OR, 0.95; 95% CI, 0.94-0.98; P < .0001). In Kaplan-Meier analysis, there were no significant differences observed in OS, DFS, LRFS, and DRFS between SC and LC. Likewise, multivariate analyses demonstrated that OS (hazard ratio [HR], 0.91; 95% CI, 0.61-1.37; P = .66), DFS (HR, 1.06; 95% CI, 0.68-1.64; P = .80), LRFS (HR, 0.79; 95% CI, 0.39-1.57; P = .50) and DRFS (HR, 0.99; 95% CI, 0.60-1.61; P = .95) were similar regardless of nRT schedules. Additional baseline clinical and tumor characteristics did not influence outcomes (all P > .05). CONCLUSION: Appropriate preoperative selection of SC versus LC nRT for locally advanced RC based on patient and tumor characteristics was not associated with differences in survival outcomes in the real-world setting.

The utility of abbreviated patient-reported outcomes for predicting survival in early stage colorectal cancer.

BACKGROUND: Patient-reported outcomes (PROs) are increasingly used in clinical settings. Prior research suggests that PROs collected at baseline may be associated with cancer survival, but most of those studies were conducted in patients with breast or lung cancer. The objective of this study was to determine the correlation between prospectively collected PROs and cancer-specific outcomes in patients with early stage colorectal cancer. METHODS: Patients who had newly diagnosed stage II or III colorectal cancer from 2009 to 2010 and had a consultation at the British Columbia Cancer Agency completed the brief Psychosocial Screen for Cancer (PSSCAN) questionnaire, which collects data on patients' perceived social supports, quality of life (QOL), anxiety and depression, and general health. PROs from the PSSCAN were linked with the Gastrointestinal Cancers Outcomes Database, which contains information on patient and tumor characteristics, treatment details, and cancer outcomes. Cox regression models were constructed for overall survival (OS), and Fine and Gray regression models were developed for disease-specific survival (DSS). RESULTS: In total, 692 patients were included. The median patient age was 67 years (range, 26-95 years), and the majority had colon cancer (61%), were diagnosed with stage III disease (54%), and received chemotherapy (58%). In general, patients felt well supported and reported good overall health and QOL. On multivariate analysis, increased fatigue was associated with worse OS (hazard ratio [HR], 1.99; P = .00007) and DSS (HR, 1.63; P = .03), as was lack of emotional support (OS: HR, 4.36; P = .0003; DSS: HR, 1.92; P = .02). CONCLUSIONS: Although most patients described good overall health and QOL and indicated that they were generally well supported, patients who experienced more pronounced fatigue or lacked emotional support had a higher likelihood of worse OS and DSS. These findings suggest that abbreviated PROs can inform and assist clinicians to identify patients who have a worse prognosis and may need more vigilant follow-up. Cancer 2017;123:1839-1847. © 2017 American Cancer Society.

Population-Based Patterns and Factors Associated With Underuse of Palliative Systemic Therapy in Elderly Patients With Metastatic Colon Cancer.

BACKGROUND: We compared the patterns and factors associated with chemotherapy and bevacizumab use in elderly versus young patients with metastatic colon cancer (mCC) and determined the effect of systemic therapy on overall survival (OS) according to age. MATERIALS AND METHODS: Patients diagnosed with mCC from 2009 to 2010 in British Columbia, Canada were reviewed and categorized as elderly patients (age ≥ 70 years) and young patients (age < 70 years). Cox regression models adjusted for age and confounders were used to determine the effect of systemic therapy on OS. RESULTS: We identified 1013 patients with a median age of 67 years. Of the 1013 patients, 42% were elderly and 58% were young; 57% were men; and 66% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Fewer elderly patients were offered systemic therapy compared with young patients (48% vs. 77%; P < .001). Among those treated, elderly patients were less likely than young patients to receive combination chemotherapy (47% vs. 81%; P < .0001) and bevacizumab (19% vs. 47%; P < .0001). The most common reasons for no treatment were similar for the elderly and young patients: patient choice, poor ECOG PS, and significant comorbidities. Advanced age alone was also cited as a reason for elderly but not for young patients (7% vs. 0%). When treated, the risk of adverse events and treatment interruptions was comparable between age groups. The receipt of systemic therapy was associated with improved OS in both elderly (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.37-0.56; P < .0001) and young (HR, 0.43; 95% CI, 0.35-0.53; P < .0001) patients, regardless of age (interaction P > .05). CONCLUSION: In carefully selected elderly patients, the outcomes from systemic therapy were comparable to those for young patients. Thus, age alone should not be a barrier to treatment of mCC.

Survival with metastatic breast cancer based on initial presentation, de novo versus relapsed.

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.

Impact of Travel Distance and Urban-Rural Status on the Multidisciplinary Management of Rectal Cancer.

OBJECTIVES: Optimal treatment of rectal cancer (RC) requires multidisciplinary care. We examined whether distance to treatment center or community size impacts access to multimodality care and population-based outcomes in RC. METHODS: Patients diagnosed with stage II/III RC from 1999 to 2009 and treated at 1 of 6 regional cancer centers in British Columbia were reviewed. Distance to treatment center was determined for each patient. Communities were classified as rural, small, medium, and large population centers. Logistic and Cox regression models assessed associations of distance and community size with treatment received as well as cancer-specific (CSS) and overall survival (OS). RESULTS: Of 3,158 patients, 93.6% underwent surgery, 86.3% received radiotherapy, and 51.3% were treated with adjuvant chemotherapy (AC). Median time from diagnosis to oncologic consultation was longer for those >100 km from a treatment center or residing in medium/rural communities. Logistic regression demonstrated no correlation between distance or community size and receipt of treatment modality. Univariate analysis showed similar CSS (P = .18, .88) and OS (P = .36, .47) based on community size and distance, respectively. In multivariate analysis, distance >100 km had inferior CSS (Hazard Ratio [HR] 1.39, 95% CI: 1.03-1.88; P = .031). There was no consistent trend between decreasing community size and outcomes; however, living in a small center was associated with improved OS (HR 0.58, 95% CI: 0.38-0.88; P = .011) and CSS (HR 0.42, 95% CI: 0.25-0.70; P = .001). CONCLUSIONS: In this population-based study, there were no urban-rural differences in access to multidisciplinary care, but increased distance may be associated with worse cancer-specific outcomes.

Effect of Adjuvant Chemotherapy on Stage II Rectal Cancer Outcomes After Preoperative Short-Course Radiotherapy.

BACKGROUND: Adjuvant chemotherapy (AC) is offered to patients with stage II rectal cancer, but its use is controversial. We examined population-based outcomes of patients with pathologic stage II rectal cancer treated with AC after preoperative short-course radiotherapy. MATERIALS AND METHODS: We included patients diagnosed with pathologic stage II tumors from 1999 to 2009 in British Columbia. The disease-specific survival (DSS), relapse-free (RFS), and overall survival (OS) were assessed. Multivariate models adjusting for age, gender, Eastern Cooperative Oncology Group, and high-risk features (ie, pT4, poor differentiation, < 12 lymph nodes removed, lymphovascular invasion, perineural invasion, or obstruction or perforation) were constructed. RESULTS: Of 851 patients reviewed, 330 had received preoperative short-course radiotherapy, of whom 123 (37%) subsequently received AC. Patients treated with AC were younger (median age 61 vs. 73 years; P < .0001), reported better Eastern Cooperative Oncology Group status (P < .0001), and had more high-risk features (P < .0001). On univariate analysis, AC was associated with improved DSS (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.36-0.94; P = .028), RFS (HR, 0.62; 95% CI, 0.39-0.98; P = .043), and OS (HR, 0.42; 95% CI, 0.30-0.59; P < .0001). On multivariate analysis, these outcomes were not significant (DSS HR, 0.83; 95% CI, 0.43-1.61; P = .58; RFS HR, 0.82; 95% CI, 0.44-1.50; P = .51; OS HR, 0.62; 95% CI, 0.37-1.03; P = .064). Subgroup analysis suggested AC improved DSS (HR, 0.25; 95% CI, 0.07-0.89; P = .033), RFS (HR, 0.24; 95% CI, 0.07-0.85; P = .027), and OS (HR, 0.22; 95% CI, 0.069-0.70; P = .011) only in patients with ≥ 2-high risk features. CONCLUSION: In the present population-based cohort of patients with stage II rectal cancer, AC did not improve the outcomes in unselected patients. In a small subgroup of patients with ≥ 2 risk factors, we noted improved outcomes with AC use.

Effect of Adjuvant FOLFOX Chemotherapy Duration on Outcomes of Patients With Stage III Colon Cancer.

BACKGROUND: Studies have demonstrated that patients with stage III colon cancer who receive adjuvant FOLFOX (5-fluorouracil and oxaliplatin) chemotherapy experience an improved disease-free (DFS) and overall survival (OS). However, the magnitude of benefit among patients who discontinue FOLFOX early is not well known. We sought to examine the rate of FOLFOX treatment completion, determine the factors associated with adherence, and explore the relationship between duration of FOLFOX treatment and survival. PATIENTS AND METHODS: We analyzed patients diagnosed with stage III colon cancer from 2006 to 2010 and initiated at least 1 cycle of adjuvant FOLFOX at any 1 of 5 regional cancer centers in British Columbia. Logistic regression models were constructed to determine the clinical factors associated with treatment completion, which was defined as receipt of ≥ 10 cycles of FOLFOX. Kaplan-Meier methods and Cox regression that accounted for known prognostic factors were used to evaluate the relationship between early FOLFOX discontinuation and DFS and OS. RESULTS: We identified 616 patients: median age of 62 years (range, 26-80), 321 (52%) men, 536 (87%) with T3/4 tumors, and 245 (40%) with N2 disease. Among them, 183 (30%) received < 10 and 433 (70%) received ≥ 10 cycles. Adjusting for covariates, female sex and the absence of obstruction or perforation were each associated with receiving ≥ 10 cycles of FOLFOX (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.12-2.32; P = .01 and OR, 1.82; 95% CI, 1.08-3.05; P = .02, respectively). In multivariate analyses, early discontinuation of FOLFOX did not affect DFS or OS (hazard ratio [HR], 1.16; 95% CI, 0.82-1.63; P = .40 and HR, 1.07; 95% CI, 0.70-1.61; P = .76, respectively). CONCLUSION: Early discontinuation of FOLFOX was not associated with differences in survival outcomes, lending support to clinical trials that are under way to evaluate the efficacy of shorter durations of therapy.

Comparison of breast cancer recurrence and outcome patterns between patients treated from 1986 to 1992 and from 2004 to 2008.

PURPOSE: 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. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Contemporary systemic therapy for male breast cancer.

BACKGROUND: The use, effectiveness, and tolerability of tamoxifen, aromatase inhibitors, and trastuzumab in early and advanced male breast cancer were examined at a population level. PATIENTS AND METHODS: A total of 158 consecutively referred men with invasive breast cancer diagnosed between 2000 and 2010 were identified. Stage and prognostic factors were compared with a random sample of contemporary female patients. Survival outcomes were compared with a separate female cohort matched 2:1 by prognostic and treatment factors. RESULTS: Men were older (median 69.5 years) than women (median 60 years) and presented with more advanced stage disease. Estrogen receptor was positive in 96% (n = 152) of cases. Tamoxifen was more commonly used than aromatase inhibitors in the curative and metastatic settings. Adherence to adjuvant tamoxifen therapy was generally adequate with estimated actuarial rates of persistence at 1 year and 3.5 years of 89% and 70%, respectively. For the 146 men treated with curative intent, 5-year overall survival, breast cancer-specific survival and progression-free survival were 72%, 86%, and 62%, respectively. Outcomes were similar to matched female patients in univariate and multivariate analyses. CONCLUSIONS: In this large population-based study, outcomes appear similar between male and risk-matched female patients with breast cancer. Side effect profiles, tolerance, adherence, and outcomes after tamoxifen, aromatase inhibitors, and trastuzumab in men appear comparable with those described in the literature for women.

Impact of routine pathology review on treatment for node-negative breast cancer.

PURPOSE: Routine secondary pathology review influences diagnosis and treatment among patients diagnosed with breast cancer. The impact of review on patients with node-negative breast cancer and the nature of the pathology elements leading to management changes are not well described. METHODS: Patients with node-negative, invasive, or in situ breast cancer and evaluable nodes referred to the British Columbia Cancer Agency during two time periods between 2004 and 2007 were included. Pathologists with expertise in breast cancer reviewed the original reports and slides. Biomarker testing was not routinely repeated. Medical record review was conducted to determine whether original pathology was changed and whether recommended therapy was affected. RESULTS: Among 906 eligible patients, 405 (45%) received a pathology review. Univariate comparisons revealed that reviewed patients were younger (P < .001) and more likely to have close margins (P < .001), whereas other characteristics were similar. A total of 102 pathology changes were documented among 81 patients (20%). The most frequently changed elements were grade (40%) and lymphovascular (26%), nodal (15%), and margin (12%) status. These changes resulted in 27 treatment modifications among 25 patients (6%). Treatment changes were primarily related to nodal and margin status, and only two of 27 were related to measurement of tumor biology in women with estrogen receptor-positive, node-negative breast cancer. CONCLUSION: Reported rates of change are significant and warrant routine secondary pathology review among patients with node-negative breast cancer or ductal carcinoma in situ before final treatment is recommended. Review remains relevant in the era of gene expression signatures to determine margin and nodal status.

Outcomes of node-negative breast cancer 5 centimeters and larger treated with and without postmastectomy radiotherapy.

PURPOSE: The role of adjuvant postmastectomy radiotherapy (PMRT) remains controversial for the rare presentation of pT3pN0cM0 breast cancer. The present analysis examined locoregional recurrence (LRR) and breast cancer-specific survival (BCSS) in pT2 = 5.0-cm and pT3 >5.0-cm tumors treated with mastectomy, stratified by PMRT use. MATERIALS AND METHODS: Between January 1, 1989 and December 31, 2000, the British Columbia provincial database yielded 100 node-negative patients with tumors ≥ 5 cm of 19,846 nonmetastatic breast cancer patients (0.5%). Of these 100 patients, 44 (44%) had received adjuvant PMRT. RESULTS: The PMRT group contained significantly more pT3 >5-cm cases (p = 0.001) and margin-positive cases (p = .03). With a median follow-up of 10 years, the cumulative 10-year LRR rate was 2.3% (95% confidence interval, 0.2-10.5) in the PMRT group vs. 8.9% (95% confidence interval, 3.2-18.2) in the no-PMRT group (p = .2). Regarding LRR in the no-PMRT group, all patients had Grade 3 histologic features (LRR 17%, 5 of 29) and had not received hormonal therapy (LRR 15%, 5 of 34). The 10-year breast cancer-specific survival rate was 85.8% (95% confidence interval 71.0-93.4) in the PMRT group vs. 74.6% (95% confidence interval 59.9-84.5) in the no-PMRT group (p = .2). On multivariate analysis, adjusted for the prognostic and predictive variables, PMRT did not significantly improve the LRR or breast cancer-specific survival rates. CONCLUSION: The present study demonstrated a low LRR rate for node-negative breast cancer ≥ 5 cm. Our results indicate that PMRT should be considered for Grade 3 histologic features and patients not undergoing hormonal therapy.

Increased use of regional radiotherapy is associated with improved outcome in a population-based cohort of women with breast cancer with 1-3 positive nodes.

PURPOSE: To examine use of and outcomes from adjuvant locoregional radiotherapy (LRRT) after breast-conserving surgery (BCS) for women with breast cancer with 1-3 positive nodes (1-3N+) before and after the 1997 publication of randomised trial evidence of a survival advantage from post-mastectomy LRRT. METHODS: Data were analysed for 2768 women diagnosed between 1989 and 2005 and referred to the British Columbia Cancer Agency with newly diagnosed pT1-3 breast cancer with 1-3N+, treated with BCS and RT. LRRT use was analysed over time. Ten-year Kaplan-Meier locoregional control (LRC), breast cancer-specific survival (BCSS) and overall survival (OS) curves were compared using the log-rank test. Cox regression modeling of LRC and BCSS were performed. RESULTS: LRRT use in patients with 1-3N+ increased from 23% before 1997 to 57% after 1997. LRRT was associated with significant improvements in LRC, but not in DRFS, BCSS, or OS. 10--year LRC was 89% with local RT alone and 93% with LRRT (p=0.006). On multivariable analysis, LRRT was associated with improved LRC compared to local RT alone (HR 0.55, 95% CI: 0.40-0.77), but not with significant BCSS differences. Margin status, grade, % positive nodes, and hormonal therapy were significant predictors for LRC, while tumour size, grade, % positive nodes, and hormonal therapy significantly affected BCSS. CONCLUSION: Post-BCS LRRT use in British Columbia increased almost threefold in patients with 1-3N+ after 1997. Adjuvant LRRT was associated with improved LRC, but not with improved BCSS compared to breast RT alone.

Metastatic behavior of breast cancer subtypes.

PURPOSE: Prognostic and predictive factors are well established in early-stage breast cancer, but less is known about which metastatic sites will be affected. METHODS: 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. RESULTS: 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. CONCLUSION: Breast cancer subtypes are associated with distinct patterns of metastatic spread with notable differences in survival after relapse.

Micrometastatic node-positive breast cancer: long-term outcomes and identification of high-risk subsets in a large population-based series.

PURPOSE: The prognostic implication of breast cancer with nodal micrometastases measuring >0.2 mm but < or =2 mm (pNmic) is unclear. This study evaluates survival in pNmic relative to node-negative (N0) and macroscopic node-positive (pNmac) disease in a large population-based series. METHODS: Subjects were 9,637 women diagnosed between 1989 and 1999, referred to the British Columbia Cancer Agency with pT1-2, node-negative and node-positive, M0 breast cancer. Kaplan-Meier breast-cancer-specific survival (BCSS) and overall survival (OS) were compared between patients with pN0 (n = 7,988), pNmic (n = 491), and pNmac disease (n = 1,158), according to the number of positive nodes and the lymph node ratio (LNR) of positive to excised nodes. Cox regression and recursive partitioning analyses were performed to identify significant factors associated with survival. RESULTS: Median follow-up was 8.2 years. Patients with pNmic disease had significantly poorer outcomes compared with pN0 cancers, with progressively lower BCSS and OS with increasing number of positive nodes and with LNR > 0.25. On multivariable analysis, histologic subtype, T stage, number of positive nodes, LNR, grade, lymphovascular invasion, estrogen receptor status, and systemic therapy use were factors significantly associated with BCSS and OS. Recursive partitioning trees for BCSS and OS both selected the pN/LNR variable at the first split, indicating that this variable provided the strongest prognostic separation. CONCLUSION: Patients with nodal micrometastases are a heterogeneous population with varying breast cancer mortality risks. The number of positive nodes and the LNR should be considered in conjunction with tumor factors in risk estimates and treatment decisions for patients with nodal micrometastatic breast cancer.