Does age affect outcome with breast cancer?

Prior data about the influence of age at diagnosis of breast cancer on patient outcomes and survival has been conflicting. Using the Breast Cancer Outcomes Unit database at BC Cancer, this retrospective population-based study identified a cohort of 24,469 patients diagnosed with invasive breast cancer between 2005 and 2014. Median follow-up was 11.5 years. We analyzed clinical and pathological features at diagnosis and treatment specific variables compared across the following age cohorts: <35, 35-39, 40-49, 50-59, 60-69, 70-79, and 80 years of age and older. We assessed the impact of age on breast cancer specific survival (BCSS) and overall survival (OS) by age and subtype. There were distinct clinical-pathological and treatment pattern differences at both extremes of age at diagnosis. Patients <35 and 35-39 years old were more likely to present with higher risk features, HER2 positive or triple-negative biomarkers, and more advanced TNM stage at diagnosis. They were more likely to undergo treatment with mastectomy, axillary lymph node dissection, radiotherapy and chemotherapy. Conversely, patients ≥80 years old were generally more likely to have hormone-sensitive HER2-negative disease, and lower TNM stage at diagnosis. They were less likely to undergo surgery or be treated with radiotherapy and chemotherapy. Both younger and elderly age at breast cancer diagnosis were independent risk factors for poorer prognosis after controlling for subtype, LVI, stage, and treatment factors. This work will help clinicians to more accurately estimate patient outcomes, patterns of relapse, and provide evidence-based treatment recommendations.

Treatment Patterns and Outcomes of Preoperative Neoadjuvant Radiotherapy in Patients with Early-onset Rectal Cancer.

Preoperative radiotherapy for early-stage rectal cancer has risks and benefits that may impact treatment choice in young patients. We reviewed radiotherapy use and outcomes for rectal cancer by age. Patients with early-stage rectal cancer in the Canadian province of British Columbia from 2002 to 2016 were identified (n = 6,232). Baseline characteristics, treatment response, overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and locoregional recurrence rate (LRR) were compared between patients <50 (early-onset; n = 532) and ≥50 years old (average-onset; n = 5,700). Early-onset patients were more likely to receive preoperative chemoradiotherapy than short-course radiotherapy [OR, 2.20; 95% confidence interval (CI), 1.67-2.89; P < 0.0001], but also had higher nodal (P = 0.00096) and overall clinical staging (P = 0.033). Cancer downstaging and pathologic complete response rates were similar in those receiving neoadjuvant chemoradiotherapy by age. Early-onset and average-onset patients had similar DSS (P = 0.91) and DFS (P = 0.27) in multivariate analysis unless non-colorectal deaths, which were higher in older patients, were censored in the DFS model (HR, 1.30; 95% CI, 1.01-1.68; P = 0.042). LRR also did not differ between age groups (P = 0.88). Outcomes did not differ based on radiotherapy type. Young patients with rectal cancer are more likely to present with higher staging and receive long-course chemoradiotherapy. DSS did not differ by age group; however, young patients had worse DFS when we censored competing risks of death in older patients. Significance: This population-based study suggests younger patients are more likely to receive chemoradiotherapy, potentially due to higher stage at diagnosis, and response is comparable by age.

Locoregional Recurrence and Survival Outcomes in Breast Cancer Treated With Modern Neoadjuvant Chemotherapy: A Contemporary Population-based Analysis.

BACKGROUND: Data guiding radiotherapy (RT) decisions after neoadjuvant chemotherapy (NAC) is largely retrospective, based on older treatment approaches without molecular subtype information. This study evaluated outcomes in breast cancer patients treated with modern NAC by molecular subtype and locoregional treatment. MATERIALS AND METHODS: There were 949 patients diagnosed between 2005 and 2016 treated with NAC followed by surgery ± locoregional radiotherapy (LRRT). Outcomes were 7-year locoregional relapse-free survival (LRRFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: Median follow-up was 6.5 years, 92% had cT2-4 and 72% cN1-3 disease. Subtypes were: 21% Luminal A, 18% Luminal B, 35% Her2+, and 21% triple-negative breast cancer (TNBC). Combined taxane and anthracycline-based NAC was used in 91.7% of cases. All patients with Her2+ disease received anti-Her2 therapy. After NAC, the majority (84.9%) underwent mastectomy, and received LRRT (86.1%). Only 11% had mastectomy without RT. Pathologic complete response (pCR) rates were 2.5% for Luminal A, 14.4% Luminal B, 27% TNBC, and 35.1% Her2+. Overall, adjuvant LRRT was associated with improved outcomes but was most significant for improved LRRFS in TNBC (92.5% vs. 68.5%, P < .001; Her2+ 95.4% vs. 93.6%, P = .81; Luminal A 97.4% vs. 100%, P = .49; Luminal B 89.7% vs. 100%, P = .17). On multivariable analysis, factors associated with reduced LRRFS were grade 3 histology (HR 4.96, P = .009) and no pCR (HR 7.0, P = .0008). Predictors of lower BCSS and OS were age >50, grade 3, cT3-4, lack of pCR, LRRT omission, and TNBC and Her2+ subtypes. CONCLUSION: In this analysis of patients treated with modern NAC, pCR rates varied by molecular subtype. Patients who did not receive LRRT, particularly those with TNBC, had lower survival compared to those treated with LRRT. These findings support the need for prospective studies to evaluate the safety of de-escalating RT after NAC.

Characterizing the KRAS G12C mutation in metastatic colorectal cancer: a population-based cohort and assessment of expression differences in The Cancer Genome Atlas.

Introduction: In metastatic colorectal cancer (mCRC), RAS mutations impart inferior survival and resistance to anti-epidermal growth factor receptor (EGFR) antibodies. KRAS G12C inhibitors have been developed and we evaluated how KRAS G12C differs from other RAS mutations. Patients and Methods: This retrospective review evaluated patients in British Columbia, Canada with mCRC and RAS testing performed between 1 January 2016 and 31 December 2018. Sequencing information from The Cancer Genome Analysis (TCGA) was also obtained and analysed. Results: Age at diagnosis, sex, anatomic location and stage at diagnosis did not differ by RAS mutation type. Progression free survival on first chemotherapy for patients with metastatic KRAS G12C tumours was 11 months. Median overall survival did not differ by RAS mutation type but was worse for both KRAS G12C (27 months) and non-G12C alterations (29 months) than wildtype (43 months) (p = 0.01). Within the TCGA, there was no differential gene expression between KRAS G12C and other RAS mutations. However, eight genes with copy number differences between the G12C and non-G12C RAS mutant groups were identified after adjusting for multiple comparisons (FITM2, PDRG1, POFUT1, ERGIC3, EDEM2, PIGU, MANBAL and PXMP4). We also noted that other RAS mutant mCRCs had a higher tumour mutation burden than those with KRAS G12C mutations (median 3.05 vs 2.06 muts/Mb, p = 4.2e-3) and that KRAS G12C/other RAS had differing consensus molecular subtype distribution from wildtype colorectal cancer (CRC) (p < 0.0001) but not each other (p = 0.14). Conclusion: KRAS G12C tumours have similar clinical presentation to other RAS mutant tumours, however, are associated with differential copy number alterations.

pN0(i+) and pN1mi Breast Cancer: Treatment and Outcomes in Comparison With pN0 and pN1a in the Modern Era.

PURPOSE: Locoregional recurrence risk and the role of locoregional radiation therapy (LRRT) in pN0(i+) and pN1mi breast cancer are unclear. This study compares locoregional relapse-free survival (LRRFS) in patients with pN0(i+) and pN1mi relative to pN0 and pN1a disease and evaluates LRRFS according to locoregional treatment. METHODS AND MATERIALS: We studied 10,271 patients referred between 2006 and 2011 with newly diagnosed pT1-T2, pN0, pN0(i+), pN1mi, or pN1a, M0 breast cancer. Outcomes were 10-year Kaplan-Meier LRRFS, relapse-free survival (RFS), distant relapse-free survival, and breast cancer-specific survival. Multivariable analysis of LRRFS and RFS was performed in pN0(i+) and pN1mi cohorts. RESULTS: Median follow-up was 9.3 years. In patients with pN0 (n = 7492), pN0(i+) (n = 305), pN1mi (n = 619), and pN1a (n = 1855) disease, LRRT was used in 1.1%, 24.3%, 45.7%, and 71.1%, respectively. Ten-year outcomes were LRRFS 96%, 92%, 97%, and 96% (P < .001), distant RFS 94%, 91%, 90%, and 84% (P < .001), and breast cancer-specific survival 95%, 90%, 93%, and 87% (P < .001), respectively. Ten-year LRRFS for patients treated with breast-conserving surgery alone, with breast RT, and with LRRT were 81%, 93%, and 91% for patients with pN0(i+) (P = .16) and 94%, 96%, and 100% for patients with pN1mi (P = .02), respectively. Among patients treated with mastectomy, 10-year LRRFS with surgery alone and with LRRT were 93% and 100% for patients with pN0(i+) (P = .12) and 95% and 99% for patients with pN1mi (P = .09). On multivariable analysis of patients with pN0(i+) and pN1mi, systemic therapy was associated with improved LRRFS in patients with pN0(i+) (hazard ratio [HR], 0.2; [0.06-0.6]; P = .005) and patients with pN1mi (HR, 0.1; [0.03-0.5]; P = .006). In patients with pN1mi, LRRT was associated with a trend toward increased LRRFS (HR, 0.2; [0.03-1.1]; P = .07). LRRT was not significantly associated with improved RFS in pN0(i+) or pN1mi disease. CONCLUSIONS: In the era of sentinel node staging and modern systemic therapy, patients with pN0(i+) and PN1mi treated with LRRT experienced 10-year LRR risks ≤10% after breast-conserving surgery or mastectomy and RT. LRRT was associated with a trend toward increased LRRFS in pN1mi but not pN0(i+) disease.

Impact of Tumor Location on Patient Outcomes in Small Bowel Cancers.

BACKGROUND: Small bowel cancers are rare gastrointestinal malignancies and tumor location impact on outcomes is unclear. MATERIAL AND METHODS: A retrospective review was performed on stage I to IV small bowel cancer cases from 2000 to 2017 in British Columbia, Canada. Baseline patient characteristics, disease-free survival (DFS) and overall survival (OS) were evaluated by tumor location and systemic therapy use patterns were summarized. RESULTS: Of 340 patients included, primary tumor distribution was: duodenum (51.2%), ileum (19.1%), jejunum (18.5%), and unspecified (11.2%). Median DFS for stage I to III disease was 37.7, 49.1, and 26.7 months for duodenal, jejunal, and ileal tumors (P = .018). Median OS was 9.6, 35.2, and 20.1 months for duodenal, jejunal, and ileal tumors (P < .0001). Compared to duodenal primaries, both jejunal and ileal tumors were associated with significantly improved OS (HR 0.43, P < .001 for jejunal; HR 0.71, P = .035 for ileal). Adjuvant therapy was given to 21.6% of stage II and 50.6% of stage III cancers. Among patients with metastatic disease, median OS was 4.2, 11.4, and 6.9 months for duodenal, jejunal, and ileal tumors (P = .0019). Jejunal tumors had the best prognosis (HR 0.48, P = .001 vs. duodenum). CONCLUSION: Survival differences exist when small bowel cancers were assessed by tumor location, and jejunal tumors portended better prognosis overall.

Impact of TAILORx on chemotherapy prescribing and 21-gene recurrence score-guided treatment costs in a population-based cohort of patients with breast cancer.

BACKGROUND: The trial assigning individualized options for treatment (Rx) (TAILORx) confirmed the predictive value of the 21-gene recurrence score (RS) assay in hormone receptor (HR)-positive, HER2-negative, node-negative breast cancer and established thresholds for chemotherapy benefit in younger and older patients. Real-world chemotherapy use and RS-guided treatment costs in British Columbia post-TAILORx were examined. METHODS: The authors assembled 3 cohorts of HR-positive, HER2-negative, node-negative patients with breast cancer defined by diagnosis: before RS funding (cohort 1 [C1]: January 2013-December 2013), after introduction of public RS funding (cohort 2 [C2]: July 2015-June 2016), and after TAILORx results (cohort 3 [C3]: July 2018-June 2019). Chemotherapy use was compared between cohorts by age and RS. Budgetary impacts of RS testing on chemotherapy costs were evaluated pre- and post-TAILORx. RESULTS: Among the 2066 patients included, chemotherapy use declined by 19% after RS funding was introduced and by an additional 23% after TAILORx publication (P = .001). Reduction in chemotherapy use was significant for RS 11-20 tumors (C3 vs C2, P = .004). There was no significant change in chemotherapy use in patients >50 years old (C2:12% vs C3:10%, P = .22). RS testing was associated with higher cost savings post-TAILORx, except in patients 70 to 80 years old, where testing led to excess costs when adjusting for the low rate of RS-concordant chemotherapy prescribed. CONCLUSIONS: TAILORx has had population-based impacts on chemotherapy prescribing in intermediate RS tumors and patients ≤50 years old. The lower clinical use of RS and increased spending in patients 70-80 years old highlights the importance of careful selection of older candidates for high-cost genomic testing. LAY SUMMARY: The 21-gene recurrence score (RS) test helps predict whether patients with hormone-positive, HER2-negative, lymph node-negative breast cancer are likely to benefit from chemotherapy. The recent trial assigning individualized options for treatment (Rx) (TAILORx) found that patients with intermediate RS tumors did not benefit from chemotherapy. The authors assessed whether TAILORx results translated to real-world changes in chemotherapy prescribing patterns. In this study, chemotherapy use decreased by 23% after TAILORx, with the greatest reductions seen among intermediate RS tumors and younger patients. In contrast, RS testing had lower clinical value and increased treatment costs in elderly patients, which requires further study to ensure optimal care for this age group.

Association Between Regional Nodal Irradiation and Breast Cancer Recurrence-Free Interval for Patients With Low-Risk, Node-Positive Breast Cancer.

PURPOSE: Randomized clinical trials have shown that regional nodal irradiation (RNI) in patients with unselected N1 breast cancer improves breast cancer-specific survival. However, the benefit of RNI in women with biologically low-risk N1 breast cancer is uncertain. We conducted a population-based study to determine whether RNI is associated with improved breast cancer recurrence-free interval (BCRFI) in this population. METHODS AND MATERIALS: Patients aged 40 to 79 years with pT1-2 pN1 (node-positive) breast cancer diagnosed between 2005 and 2014 were identified. The inclusion criteria were modeled off of the TAILOR RT study, which is a randomized noninferiority clinical trial designed to assess the value of RNI in patients with low-risk N1 disease. Eligible patients had breast-conserving surgery or mastectomy and axillary lymph node dissection with 1 to 3 positive nodes, breast-conserving surgery and sentinel lymph node biopsy with 1 to 2 positive nodes, or mastectomy and sentinel lymph node biopsy with 1 positive node. Additionally, patients had luminal A breast cancers, as approximated by estrogen receptor positive (Allred 6-8/8), progesterone receptor (PR) positive (Allred 6-8/8), human epidermal growth factor receptor 2-negative, and grade 1 to 2 immunohistochemical testing. All patients were prescribed hormonal treatment. The primary endpoint of BCRFI, the time to any breast cancer recurrence or breast cancer-related death, was analyzed using a multivariate competing risks analysis. RESULTS: The cohort included 1169 women with a median follow-up of 9.2 years. Radiation treatments were not performed in 151 women treated with mastectomy alone, were delivered to the breast only in 133 women, and were delivered locoregionally in 885 women. Patients undergoing RNI were younger (median age: 58 vs 62 years), more likely to have 2 to 3 macroscopic lymph nodes involved, and more often received chemotherapy (all P < .05). The 10-year estimate of BCRFI was 90% without RNI versus 90% with RNI (P = .5). On multivariable analysis, RNI was not a significant predictor of BCRFI (hazard ratio: 1.0; P = .9). CONCLUSIONS: In this retrospective analysis, RNI was not associated with improved BCRFI for women with biologically low-risk N1 breast cancer. We advocate accrual to the ongoing TAILOR RT study.

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.

Breast Tangent Beam Energy, Surgical Bed-to-Skin Distance and Local Recurrence After Breast-Conserving Treatment.

PURPOSE: Higher energy (>6 MV) photons reduce dose inhomogeneity with breast tangent beams, thereby reducing late breast toxicity, but skin and superficial tissue sparing by higher energy beams raises concerns about local recurrence (LR) risk. This study aimed to determine whether beam energy and surgical bed-to-skin distance affect LR. METHODS AND MATERIALS: This population-based study included newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with breast-conserving surgery and adjuvant whole breast radiation therapy without bolus or beam spoilers. The primary endpoint was the cumulative incidence of LR (CILR). Multivariable analysis (MVA) included mean beam energy, age, T-stage, nodal status, overall stage, lymphovascular invasion (LVI), grade, margin status, extensive intraductal component (EIC), breast cancer subtype, hormone therapy, and chemotherapy. In a subgroup with contoured surgical beds, another MVA included surgical bed-to-skin distance. RESULTS: The cohort consisted of 10,083 women treated from 2002 to 2011: 327 with 4 MV, 6006 with 6 MV, 2083 with >6 to 10 MV, and 1667 with >10 MV tangents. The median follow-up time was 11.1 years. The 10-year CILR was 3.1% (95% confidence interval [CI], 1.6-5.4) with 4 MV, 2.8% (2.4-3.3) with 6 MV, 4.2% (3.4-5.3) with >6 to 10 MV, and 2.6% (1.9-3.5) with >10 MV. On MVA of the entire cohort, LR risk was increased with positive margins, LVI, EIC, and lack of hormone therapy, but was not associated with beam energy (hazard ratio [HR], 1.01; 95% CI, 0.96-1.05; P = .8). On MVA of 3359 patients with contoured surgical beds, LR risk was not associated with surgical bed-to-skin distance (HR, 1.00; 95% CI, 0.99-1.02; P = .8). CONCLUSIONS: Use of higher breast tangent beam energies is not associated with increased risk of LR, including in cases with surgical beds that are close to the skin.

Real-World Outcomes of Oxaliplatin-Based Chemotherapy on R0 Resected Colonic Liver Metastasis.

INTRODUCTION: In resected colonic liver metastasis (CLM), randomized studies of oxaliplatin-based chemotherapy have demonstrated improvements in disease-free survival (DFS), but not overall survival (OS). Additionally, oxaliplatin regimens have not been compared to non-oxaliplatin chemotherapy. Despite limited evidence, perioperative chemotherapy is often used in the management of CLM. The primary aim of this study was to assess the impact of oxaliplatin chemotherapy regimens on OS in patients who have undergone resection of CLM in a real-world setting. PATIENTS AND METHODS: Patients who underwent resection of CLM in the provinces of Alberta and British Columbia, Canada, were identified from 1996 to 2016. Perioperative (pre- and/or post-) systemic therapy was categorized as oxaliplatin or non-oxaliplatin-based chemotherapy or no chemotherapy. The primary and secondary outcomes were OS and DFS, respectively. RESULTS: We identified 511 patients who underwent R0 resection of CLM. A significant difference in median OS was identified among the oxaliplatin, non-oxaliplatin, and no-chemotherapy groups of 100, 60, and 59 months, respectively (P = .009). In multivariate analysis, patients who received oxaliplatin regimens had a lower risk of death (hazard ratio, 0.68; 95% confidence interval, 0.51-0.92; P = .012), whereas the non-oxaliplatin chemotherapy group did not (hazard ratio, 0.88; 95% confidence interval, 0.65-1.20; P = .422) compared with no chemotherapy. CONCLUSIONS: In this multicenter, retrospective, population-based study, perioperative oxaliplatin-based chemotherapy was associated with improved OS in conjunction with R0 resection of CLM. Further studies should evaluate the optimal duration and sequencing of perioperative chemotherapy in relation to curative-intent surgical resection of CLM.

The Effect of Bolus on Local Control for Patients Treated With Mastectomy and Radiation Therapy.

PURPOSE: Bolus use during postmastectomy radiation therapy doubles the risk of grade 2 and 3 skin toxicity. Despite its unknown benefit, bolus is often prescribed during postmastectomy radiation therapy for patients without skin involvement. METHODS AND MATERIALS: For women with breast cancer receiving photon 3-dimensional conformal radiation therapy, bolus was used routinely for chest walls but was omitted for breast reconstructions by about half of radiation oncologists from 2007 to 2011. Eligible patients had newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with adjuvant or neoadjuvant radiation therapy. For the bolus and no-bolus groups, we compared the cumulative incidence of local recurrence (LR) and locoregional recurrence (LRR) with distant recurrence and death as competing risks and breast cancer mortality (BCM). Multivariable analysis of LR and BCM included stage, subtype, lymphovascular invasion, grade, margin status, beam energy, bolus use, hormone therapy, chemotherapy, and reconstruction. RESULTS: Systemic therapy was used for 98% of the 1887 patients. The bolus group had 1569 patients and the no-bolus group had 318 patients. Bolus was used in 51% (281/550) of patients treated with reconstruction and 96% (1288/1337) of patients treated without reconstruction. The 10-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: LR 1.9% (1.3-2.7) versus 0.9% (0.3-2.6), LRR 3.1% (2.3-4.0) versus 3.2% (1.6-5.5), and BCM 19.4% (17.3-21.6) versus 18.3% (13.9-23.2). On multivariable analysis, bolus use was not associated with better LR (hazard ratio = 1.4 [0.3-6.4]) or BCM (hazard ratio = 0.8 [0.5-1.2]). CONCLUSIONS: For patients treated with mastectomy, radiation therapy, and modern systemic therapy, the cumulative incidence of LR was low, with or without bolus. Because bolus use increases toxicity and does not reduce LR or BCM, it should no longer be used routinely for patients without skin involvement who receive systemic therapy.

Breast Cancer Molecular Subtype as a Predictor of Radiation Therapy Fractionation Sensitivity.

PURPOSE: The predictive benefit of breast cancer molecular subtypes for systemic therapy approaches has been well established; yet, there is a paucity of data regarding their use as a predictor of radiation therapy fractionation sensitivity. The purpose of this study was to determine whether rates of local recurrence (LR) for patients treated with hypofractionated (HF) radiation therapy, in comparison to conventional fractionation, differ across breast cancer molecular subtypes in a large, prospectively collected cohort treated with modern systemic therapy. METHODS AND MATERIALS: Patients who received a diagnosis of stage I-III breast cancer between 2005 and 2009 were identified. Molecular subtype was determined using the American Joint Committee on Cancer classification system (luminal-A, luminal-B, HER2+, triple negative [TN]). Multivariable Cox regression modeling was used to identify predictors of LR. LR-free-survival (LRFS) was determined using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 5868 cases were identified with a median follow-up of 10.8 years. Patients with luminal-A subtype composed 45% of the cohort (n = 2628), compared with 30% luminal-B (n = 1734), 15% HER2+ (n = 903), and 10% TN (n = 603). A total of 76% (n = 4429) of patients were treated with HF. The 10-year LRFS was 97.1% (95% confidence interval [CI], 96.6-97.6) for the whole cohort. The 10-year LRFS based on molecular subtypes was 98.3% (95% CI, 97.6-98.7) luminal-A, 96.6% (95% CI, 95.5-97.4) luminal-B, 97.0% (95% CI, 95.5-98.0) HER2+, and 93.5% (95% CI, 91.1-95.3) TN (P < .001). There was no difference in the 10-year LRFS between patients treated with HF versus conventional fractionation among those with luminal-A (98.2% vs 98.4%; P = .42), luminal-B (96.6% vs 96.8%; P = .90), HER2+ (97.5% vs 95.8%; P = .12), or TN (93.9% vs 92.2%; P = .47). There was no significant interaction between subtype and fractionation regimen. CONCLUSIONS: These data support the routine use of hypofractionated radiation therapy regimens across all breast cancer subtypes.

Hypofractionated Adjuvant Radiation Therapy Is Effective for Patients With Lymph Node-Positive Breast Cancer: A Population-Based Analysis.

PURPOSE: This study evaluated long-term, population-based, breast cancer-specific outcomes in patients treated with radiation therapy (RT) to the breast/chest wall plus regional nodes using hypofractionated (HF) (40-42.5 Gy/16 fractions) versus conventionally fractionated (CF) regimens (50-50.4 Gy/25-28 fractions). METHODS AND MATERIALS: A prospective provincial database was used to identify patients with lymph node-positive breast cancer treated with curative-intent breast/chest wall + regional nodal RT from 1998 to 2010. The effect of RT fractionation on locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and breast cancer-specific survival (BCSS) was assessed for the entire cohort and for high-risk subgroups: grade 3, ER-/HER2-, HER2+, and ≥4 positive nodes. Multivariable analysis and 2:1 case-match comparison of HF versus CF were also performed. RESULTS: A total of 5487 patients met the inclusion criteria (4006 HF and 1481 CF). Median age was 55 years, and median follow-up was 12.7 years. On multivariable analysis, no statistically significant differences were identified in 10-year LRRFS (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.59-1.27; P = .46), DRFS (HR 0.90; 95% CI, 0.76-1.06; P = .19), or BCSS (HR 0.92; 95% CI, 0.76-1.10; P = .36) between the HF and CF cohorts. There was no statistical difference in breast cancer-specific outcomes in the high-risk subgroups. On analysis of 2962 HF cases matched to 1481 CF controls, no statistical difference was observed in LRRFS (HR 0.98; 95% CI, 0.71-1.33; P = .87), DRFS (HR 0.97; 95% CI, 0.85-1.11; P = .68), or BCSS (HR 1.00; 95% CI, 0.87-1.16; P = .92). CONCLUSIONS: This large, population-based analysis with long-term follow-up after locoregional RT demonstrated that modest HF provides similar breast cancer-specific outcomes compared with CF. HF is an effective option for patients with stage I to III breast cancer receiving nodal RT.

PET/CT of breast cancer regional nodal recurrences: an evaluation of contouring atlases.

BACKGROUND: To validate the Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast cancer nodal clinical target volumes (CTVs) and to investigate the Radiotherapy Comparative Effectiveness Consortium (RADCOMP) Posterior Neck volume in relation to regional nodal recurrences (RNR). METHODS: From a population-based database, 69 patients were identified who developed RNR after curative treatment for breast cancer. RNRs were detected with 18-fluorodeoxyglucose-positron emission tomography-computed tomography (PET/CT). All patients were treatment-naïve for RNR when imaged. The RTOG and ESTRO nodal CTVs and RADCOMP Posterior Neck volumes were contoured onto a template patient's CT. RNRs were contoured on each PET/CT and deformed onto the template patient's CT. Each RNR was represented by a 5 mm diameter epicentre, and categorized as 'inside', 'marginal' or 'outside' the CTV boundaries. RESULTS: Sixty-nine patients with 226 nodes (median 2, range 1-11) were eligible for inclusion. Thirty patients had received adjuvant tangent and regional nodal radiotherapy, 16 tangent-only radiotherapy and 23 no adjuvant radiotherapy. For the RTOG CTVs, the RNR epicentres were 70% (158/226) inside, 4% (8/226) marginal and 27% (60/226) outside. They included the full extent of the RNR epicentres in 38% (26/69) of patients. Addition of the RADCOMP Posterior Neck volume increased complete RNR coverage to 48% (33/69) of patients. For the ESTRO CTVs, the RNR epicentres were 73% (165/226) inside, 2% (4/226) marginal and 25% (57/226) outside. They included the full extent of the RNR epicentres in 57% (39/69) of patients. Addition of the RADCOMP Posterior Neck volume increased complete RNR coverage to 70% (48/69) of patients. CONCLUSIONS: The RTOG and ESTRO breast cancer nodal CTVs do not fully cover all potential areas of RNR, but the ESTRO nodal CTVs provided full coverage of all RNR epicentres in 19% more patients than the RTOG nodal CTVs. With addition of the RADCOMP Posterior Neck volume to the ESTRO CTVs, 70% of patients had full coverage of all RNR epicentres.

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.

Do surgeons convey all the details? A provincial assessment of operative reporting for breast cancer.

INTRODUCTION: A breast cancer synoptic operative report was developed using a modified Delphi process METHODS: Data from the British Columbia Cancer Breast Cancer Outcomes Unit (BCOU) was used to analyze the association between the completion of a synoptic operative report and reporting of operative details and The American Society of Breast Surgeons quality indicators. RESULTS: 3662 patients had surgery for breast cancer by 185 surgeons. 2281 reports were narrative and 1007 synoptic. Requested surgical details were more commonly reported with synoptic reports for both posterior (96 vs 58%, p < 0.0001) and anterior margins (96 vs 5%, p < 0.0001). This was true for high and low volume surgeons. Quality Indicators were higher in those cases with an associated synoptic report for high and low volume surgeons. CONCLUSION: Communication of operative details is improved with synoptic reporting. Investment in platforms to facilitate synoptic reporting could improve patient care through improved multidisciplinary communication.

The impact of new systemic therapies on survival and time on hormonal treatment in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: A population-based study in British Columbia from 2003 to 2013.

BACKGROUND: The purpose of this study was to determine whether new systemic therapy regimens have resulted in improved survival and increased time on first- and second-line hormonal treatment for patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) over time. METHODS: Patients diagnosed with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative MBC were identified across 3 time cohorts (2003-2005, 2007-2009, and 2011-2013). Data were prospectively collected. Cases with previous, synchronous, or subsequent contralateral breast cancer were excluded. The types of first- and second-line therapies, the times on first- and second-line hormonal treatment, and the median survival times were compared across the cohorts. RESULTS: Within the time period analyzed, 9 new adjuvant systemic therapies (with or without neoadjuvant therapy) and 2 metastatic systemic therapies were approved at BC Cancer for the treatment of HR-positive, HER2-negative MBC. In the 3 time cohorts, 3953 patients diagnosed with MBC were identified. Among the 2432 patients (62%) who had HR-positive/HER2-negative disease, 2197 (90%) received at least 1 line of systemic therapy after the diagnosis of MBC, and 80% of these patients (1752 of 2197) received first- and/or second-line hormonal treatment. The median duration on hormonal treatment was 9.0 months for the first line and 6.1 months for the second line. The durations were similar across the time cohorts (range for the first line, 8.9-9.0 months; range for the second line, 6.0-6.1 months). The median survival for the entire study population was 2.0 years (95% confidence interval, 1.8-2.1 years), and there was no significant difference between the cohorts (range, 1.9-2.0 years). CONCLUSIONS: Even though more adjuvant and metastatic systemic therapies have been approved since 2003, population-level gains in survival and the time on hormonal treatment for patients with HR-positive, HER2-negative MBC have not been made over the course of a decade.

Cardiac death after breast radiotherapy and the QUANTEC cardiac guidelines.

BACKGROUND: Breast/chest wall irradiation (RT) increases risk of cardiovascular death. International Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines state for partial heart irradiation a "V25Gy <10% will be associated with a <1% probability of cardiac mortality" in long-term follow-up after RT. We assessed whether women treated with breast/chest wall RT 10-years ago who died of cardiovascular disease (CVD) violated QUANTEC guidelines. MATERIALS/METHODS: A population-based database identified all cardiovascular deaths in women with early-stage breast cancer <80 years, treated with adjuvant breast/chest wall RT from 2002 to 2006. Ten-year rate of cardiovascular death was calculated using a Kaplan-Meier method. Patients were matched on a 2:1 basis with controls that did not die of CVD. For left-sided cases, the heart and left anterior descending (LAD) artery were retrospectively delineated. Dose-volume histograms were calculated, and heart V25Gy compared to QUANTEC guidelines. RESULTS: 5249 eligible patients received breast/chest wall RT from 2002 to 2006: 76 (1.4% at 10-years) died of CVD by June 2015. Forty-two patients received left-sided RT (1.7% CVD death at 10-years), 34 right-sided RT (1.3% at 10-years). Heart V25Gy did not exceed 10% in any left-sided cases. No cardiac dosimetry parameter distinguished left-sided cases from controls. CONCLUSIONS: QUANTEC guidelines were not violated in any patient that died of CVD after left-sided RT. The risk of radiation induced cardiac death at 10-years appears to be very low if MHD is <3.3 Gy and maximum LAD dose (EQD23 Gy) is <45.4 Gy. Further studies are needed to evaluate heart and LAD constraints in the CT-planning era.

Local Relapse After Breast-Conserving Therapy Versus Mastectomy for Extensive Pure Ductal Carcinoma In Situ ≥4 cm.

PURPOSE: The optimal treatment for patients with extensive pure ductal carcinoma in situ (DCIS) ≥4 cm is controversial. This study evaluates local relapse according to type of local therapy: mastectomy, breast-conserving surgery (BCS) alone, and BCS + radiation therapy (RT). METHODS AND MATERIALS: Subjects were female patients who received diagnoses of pure DCIS ≥4 cm between 1989 and 2010 and were referred to British Columbia Cancer. Clinicopathologic and treatment characteristics were compared between treatment cohorts. Local relapse (LR) was estimated using competing risk analysis. Multivariable analysis was performed using Cox regression analysis. RESULTS: Patients had the following treatments: 490 mastectomy, 38 BCS alone, and 192 BCS + RT. The 10-year cumulative incidence of LR was 16% after BCS (95% confidence interval [CI], 6-29%), 8% after BCS + RT (95% CI, 4-12%), and 2% after mastectomy (95% CI, 1-4%). On multivariable analysis, estrogen receptor-negative disease (hazard ratio [HR], 3.32; 95% CI, 1.08-10.18; P = .04) and positive margins (HR, 3.55; 95% CI, 1.56-8.05; P = .002) were associated with increased LR. BCS alone (HR, 7.87; 95% CI, 2.82-21.92; P < .0001), BCS + RT + no boost (HR, 3.80; 95% CI, 1.56-9.28; P = .003), and BCS + RT + boost (HR, 5.76; 95% CI, 2.59-12.83; P < .0001) were all associated with a higher risk of relapse relative to mastectomy. CONCLUSIONS: Mastectomy remains a standard local treatment option for extensive DCIS, but BCS + RT may also be reasonably considered in selected patients with a careful discussion of the benefits, side effects, and patient preferences.