Ines Vaz-Luis

Outcomes by Tumor Subtype and Treatment Pattern in Women With Small, Node-Negative Breast Cancer: A Multi-Institutional Study

PURPOSE Treatment decisions for patients with T1a,bN0M0 breast cancer are challenging. We studied the time trends in use of adjuvant chemotherapy and survival outcomes among these patients. PATIENTS AND METHODS This was a prospective cohort study within the National Comprehensive Cancer Network Database that included 4,113 women with T1a,bN0M0 breast cancer treated between 2000 and 2009. Tumors were grouped by size (T1a, T1b), biologic subtype defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, and receipt of chemotherapy with or without trastuzumab. RESULTS Median follow-up time was 5.5 years. Eight percent of patients with HR-positive/HER2-negative tumors were treated with chemotherapy. Fifty-two percent of those with HER2-positive or HR-negative/HER2-negative breast cancers received chemotherapy, with an increase over the last decade. Survival outcomes diverged by subtype and size, but the 5-year distant relapse-free survival (DRFS) did not exceed 10% in any subgroup. The 5-year DRFS for patients with T1a tumors untreated with chemotherapy ranged from 93% to 98% (n = 49 to 972), and for patients with T1b tumors, it ranged from 90% to 96% (n = 17 to 2,005). Patients with HR-positive/HER2-negative disease had the best DRFS estimates, and patients with HR-negative/HER2-negative tumors had the lowest. In this observational, nonrandomized cohort study, the 5-year DRFS for treated patients with T1a tumors was 100% for all subgroups (n = 12 to 33), and for patients with T1b tumors, it ranged from 94% to 96% (n = 88 to 241). CONCLUSION Women with T1a,b tumors have an excellent prognosis without chemotherapy. Size and tumor subtype may identify patients in whom the rate of recurrence justifies consideration of chemotherapy. These patients represent an optimal group for evaluating less toxic adjuvant regimens to maintain efficacy while minimizing short- and long-term risks.

Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study

IntroductionIn gene expression experiments, hormone receptor (HR)-positive/human epidermal growth factor-2 (HER2)-positive tumors generally cluster within the luminal B subset; whereas HR-negative/HER2-positive tumors reside in the HER2-enriched subset. We investigated whether the clinical behavior of HER2-positive tumors differs by HR status.MethodsWe evaluated 3,394 patients who presented to National Comprehensive Cancer Network (NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007. Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive (HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression were used to compare groups.ResultsMedian follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total) to present with high histologic grade and higher stages (P <0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53, 95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to 2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002).As compared with patients with HR+/HER2+ disease, those with HR-/HER2+ disease had significantly increased hazard of early, but not late, death (hazard ratio of death zero to two years after diagnosis = 1.92, 95% CI: 1.28 to 2.86, P = 0.002, hazard ratio of death two to five years after diagnosis = 1.55, 95% CI: 1.19 to 2.00, P = 0.001; hazard ratio of death more than five years after diagnosis = 0.81, 95% CI: 0.55 to 1.19, P = 0.285, adjusting for age, race/ethnicity, stage at diagnosis, grade and year of diagnosis).ConclusionsPresenting features, patterns of recurrence and survival of HER2-positive breast cancer differed by HR status. These differences should be further explored and integrated in the design of clinical trials.

Duration and Toxicity of Adjuvant Trastuzumab in Older Patients With Early-Stage Breast Cancer: A Population-Based Study

PURPOSE Few data are available regarding adjuvant trastuzumab use in older women with early-stage breast cancer. We examined rates and predictors of adjuvant trastuzumab completion and cardiac events in this population. PATIENTS AND METHODS We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify patients age ≥ 66 years with stage I to III breast cancer diagnosed between 2005 and 2009 who received trastuzumab. Completion of trastuzumab was defined as receipt of more than 270 days of therapy. We used multivariable logistic regression to examine patient, clinical, and geographic characteristics associated with trastuzumab completion. We also examined rates of hospital admissions for cardiac events. RESULTS Among 2,028 women, most (71.2%) were younger than age 76 years and had a comorbidity score of 0 (66.8%); 85.2% received trastuzumab with chemotherapy. Overall, 1,656 women (81.7%) completed trastuzumab. Older patients and those with more comorbidity had lower odds of treatment completion (odds ratio [OR], 0.40 [95% CI, 0.30 to 0.55] for age ≥ 80 years v age 66 to 70 years; OR, 0.65 [95% CI, 0.49 to 0.88] for comorbidity score of 2 v 0). During treatment, 73 patients (3.6%) were hospitalized for cardiac events (2.6% of those who completed trastuzumab v 8.1% of those who did not; P < .001). CONCLUSION Most older patients who initiated adjuvant trastuzumab completed therapy. Age and comorbidity were among factors that were associated with treatment completion, and rates of significant cardiac events were higher in those who did not complete therapy. Further exploration of toxicities and optimal treatments for older women with human epidermal growth factor receptor 2-positive breast cancer are warranted.

Patient Prognostic Score and Associations With Survival Improvement Offered by Radiotherapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ: A Population-Based Longitudinal Cohort Study

PURPOSE Radiotherapy (RT) after breast-conserving surgery (BCS) is a standard treatment option for the management of ductal carcinoma in situ (DCIS). We sought to determine the survival benefit of RT after BCS on the basis of risk factors for local recurrence. PATIENTS AND METHODS A retrospective longitudinal cohort study was performed to identify patients with DCIS diagnosed between 1988 and 2007 and treated with BCS by using SEER data. Patients were divided into the following two groups: BCS+RT (RT group) and BCS alone (non-RT group). We used a patient prognostic scoring model to stratify patients on the basis of risk of local recurrence. We performed a Cox proportional hazards model with propensity score weighting to evaluate breast cancer mortality between the two groups. RESULTS We identified 32,144 eligible patients with DCIS, 20,329 (63%) in the RT group and 11,815 (37%) in the non-RT group. Overall, 304 breast cancer-specific deaths occurred over a median follow-up of 96 months, with a cumulative incidence of breast cancer mortality at 10 years in the weighted cohorts of 1.8% (RT group) and 2.1% (non-RT group; hazard ratio, 0.73; 95% CI, 0.62 to 0.88). Significant improvements in survival in the RT group compared with the non-RT group were only observed in patients with higher nuclear grade, younger age, and larger tumor size. The magnitude of the survival difference with RT was significantly correlated with prognostic score (P < .001). CONCLUSION In this population-based study, the patient prognostic score for DCIS is associated with the magnitude of improvement in survival offered by RT after BCS, suggesting that decisions for RT could be tailored on the basis of patient factors, tumor biology, and the prognostic score.

Human epidermal growth factor receptor-2-positive breast cancer: does estrogen receptor status define two distinct subtypes?

BACKGROUND Human epidermal growth factor receptor-2 (HER2) overexpression occurs in ∼20% of breast cancers and has historically been associated with decreased survival. Despite substantial improvements in clinical outcomes, particularly with the emergence of HER2-targeted therapy, a substantial minority of patients still relapses, and progression is inevitable in metastatic disease. Accumulating data indicate that HER2-positive disease is itself a heterogeneous entity. METHODS AND RESULTS In this article, we qualitatively review the data supporting the classification of HER2-positive disease as at least two separate entities, distinguished by estrogen receptor (ER) status. We summarize differences in clinical outcomes, including response to neoadjuvant therapy, timing and patterns of dissemination, efficacy of therapy in the metastatic setting and survival outcomes. CONCLUSIONS The collective data are sufficiently strong at this point to propose that ER status defines two distinct subtypes within HER2-positive breast cancer, and we highlight the implications of this knowledge in future research, including understanding of the basic biology of HER2-positive breast cancer and the design of future clinical trials.BACKGROUND Human epidermal growth factor receptor-2 (HER2) overexpression occurs in ∼20% of breast cancers and has historically been associated with decreased survival. Despite substantial improvements in clinical outcomes, particularly with the emergence of HER2-targeted therapy, a substantial minority of patients still relapses, and progression is inevitable in metastatic disease. Accumulating data indicate that HER2-positive disease is itself a heterogeneous entity. METHODS AND RESULTS In this article, we qualitatively review the data supporting the classification of HER2-positive disease as at least two separate entities, distinguished by estrogen receptor (ER) status. We summarize differences in clinical outcomes, including response to neoadjuvant therapy, timing and patterns of dissemination, efficacy of therapy in the metastatic setting and survival outcomes. CONCLUSIONS The collective data are sufficiently strong at this point to propose that ER status defines two distinct subtypes within HER2-positive breast cancer, and we highlight the implications of this knowledge in future research, including understanding of the basic biology of HER2-positive breast cancer and the design of future clinical trials.

Clinicopathological features among patients with advanced human epidermal growth factor-2-positive breast cancer with prolonged clinical benefit to first-line trastuzumab-based therapy: a retrospective cohort study.

BACKGROUND The magnitude of benefit of trastuzumab for the treatment of advanced HER2-positive breast cancer varies widely. In this retrospective study, we investigated the clinicopathological features associated with prolonged first-line trastuzumab-based treatment duration. PATIENTS AND METHODS A total of 164 patients diagnosed with advanced HER2-positive breast cancer and treated with first-line trastuzumab-based therapy from 1999 to 2009 were identified. Duration of treatment was classified according to tertiles. Different logistic regression models including age, disease-free interval, number of metastatic sites, visceral disease, hormone receptor, and adjuvant trastuzumab were fitted to investigate associations with benefit of prolonged trastuzumab-based therapies. The predictive value of each model was assessed using C-statistics. RESULTS At a median follow-up of 5.8 years (range, 0.7-22.1 years), patients in the short-, intermediate-, and long-term treatment duration groups were given first-line trastuzumab-based therapy for < 7.2 months, 7.2 to 14 months, and > 14 months, respectively. In the multivariate analysis, patients with long-term clinical benefit had a higher likelihood of having hormone receptor-positive tumors (odds ratio [OR]positive vs. negative = 2.39 [95% confidence interval (CI), 1.08-5.31]; P = .032); and a lower likelihood of having received adjuvant trastuzumab (ORadjuvant trastuzumab vs. no adjuvant trastuzumab = 0.30 [95% CI, 0.10-0.96]; P = .043]. C-statistics varied between 0.634 and 0.699. CONCLUSION Long-term benefit of trastuzumab-based therapy is associated with hormone receptor positivity and the absence of previous adjuvant trastuzumab. Nevertheless, clinicopathological features had a low predictive value for prolonged treatment duration. The validation of the current findings and the identification of molecular features associated the magnitude of trastuzumab benefit should be encouraged.

Factors Associated with Early Mortality Among Patients with De Novo Metastatic Breast Cancer: A Population‐Based Study

BACKGROUND Although improvements in survival have been achieved for patients with metastatic breast cancer, some patients experience early death after diagnosis. PATIENTS AND METHODS Using Surveillance, Epidemiology, and End Results data, we identified 26,538 patients with de novo metastatic breast cancer diagnosed between January 1, 2000 and June 30, 2011. We evaluated time trends for deaths at 1 and 6 months after diagnosis. We then restricted the cohort to patients diagnosed between 2010 and 2011 (n = 3,317), when human epidermal growth factor receptor 2 was routinely collected, and examined factors associated with early death. RESULTS In 2000, 15.9% of patients died within 1 month of diagnosis and 33.2% within 6 months. In 2011, the proportion of women dying within 1 month decreased to 13.4% and 26.3% within 6 months (p < .001). Older age and uninsured status were associated with early death (at both time points, age ≥70 [versus age <40] had >8.5 higher odds of dying, and uninsured [versus insured] patients had >2.5 higher odds of death). In addition, in some subgroups (e.g., no insurance and triple negative disease), more than half of patients died within 6 months. Region was also associated with early death. CONCLUSION Although we observed improvements in the proportion of patients experiencing early death, one quarter of patients with de novo metastatic disease diagnosed in 2011 died within 6 months of diagnosis. In addition to tumor factors and older age, geography and uninsured status were associated with early death. Our findings highlight the need for focused interventions for metastatic patients at highest risk for poor outcomes. The Oncologist 2017;22:386-393 IMPLICATIONS FOR PRACTICE: With nearly one quarter of patients in our dataset diagnosed in 2011 dying within 6 months of diagnosis, our findings highlight the persistent and critical need of further characterization and identification of patients who are risk for poor outcomes in order to optimize care, impact change, and improve outcomes for all women with metastatic breast cancer. Our data also emphasize the need for interventions among those at highest risk for early death. These interventions would likely promote immediate referral for clinical trial participation, early palliative care referrals, and additional supportive services, optimizing equitable patient access to cancer treatment and care.

Survival benefit needed to undergo chemotherapy: Patient and physician preferences

Published studies have suggested that most patients with early stage breast cancer are willing, for modest survival benefits, to receive 6 months of adjuvant cyclophosphamide, methotrexate, and 5‐fluorouracil, an older regimen that is used infrequently today. We examined preferences regarding the survival benefit needed to justify 6 months of a contemporary chemotherapy regimen.

Variation in type of adjuvant chemotherapy received among patients with stage I breast cancer: A multi‐institutional study

Among patients with stage I breast cancer, there is significant uncertainty concerning the optimal threshold at which to consider chemotherapy, and when considered, there is controversy regarding whether to consider non‐intensive versus intensive regimens. The authors examined the types and costs of adjuvant chemotherapy received among patients with stage I breast cancer.

Optimizing Adjuvant Chemotherapy and Surgery for Early- and Late-Stage Breast Cancer

Introduction The findings presented during the 2016 American Society of Clinical Oncology (ASCO) meeting will further advance our understanding of, and ability to treat, breast cancer. Anthracyclineand taxane-based chemotherapy are the current standard for adjuvant treatment in high-risk, earlystage, and locally advanced breast cancer. In 2006, the United States Oncology Research (USOR) Trial 9735 showed that treatment with docetaxel and cyclophosphamide(TC)resultedinasignificantlyhigherdisease-freesurvival rate than 4 cycles of doxorubicin and cyclophosphamide (AC).1 These data—in concert with the paradigm shift in chemotherapy use for estrogen receptor (ER)-positive breast cancer prompted by genomic signatures and the availabilityofnon-anthracyclineoptionsforhumanepidermal growth factor receptor 2 (HER2)-positive breast cancer—have precipitated a decline in the use of adjuvant anthracyclines.