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.
•Young patients are more likely to present with high-risk disease features.•Older adults are more likely to present with indolent disease features.•Both younger and older age at diagnosis are risk factors for poor prognosis.
Background
Randomized trials have established efficacy of supervised exercise training during chemotherapy for breast cancer for numerous health outcomes. The purpose of this study was to assess ...reach, effectiveness, maintenance, and implementation of an evidence‐based exercise and healthy eating program offered within an adjuvant care setting.
Subjects, Materials, and Methods
Women receiving adjuvant chemotherapy for breast cancer were given a prescription by their oncologist to participate in the Nutrition and Exercise during Adjuvant Treatment (NExT) program. The NExT program consisted of supervised, moderate‐intensity, aerobic and resistance exercise three times a week during adjuvant therapy, followed by a step‐down in supervised sessions per week for 20 additional weeks, plus one group‐based healthy eating session. Usual moderate‐to‐vigorous physical activity (MVPA) and health‐related quality of life (HRQoL) were assessed by questionnaire at baseline, program completion, and one year later, along with measures of satisfaction and safety.
Results
Program reach encompassed referral of 53% of eligible patients, 78% uptake (n = 73 enrolled), and 78% retention for the 45.0 ± 8.3‐week program. During the program, MVPA increased (116 ± 14 to 154 ± 14 minutes per week, p = .014) and HRQoL did not change. One year later, MVPA (171 ± 24 minutes per week, p = .014) and HRQoL (44 ± 1 to 49 ± 1, p < .001) were significantly higher than baseline. Exercise adherence was 60% ± 26% to three sessions per week during treatment. No major adverse events occurred and injury prevalence did not change relative to baseline. Participants were highly satisfied.
Conclusion
This oncologist‐referred exercise and healthy eating supportive‐care program for breast cancer patients receiving chemotherapy was safe, successful in reaching oncologists and patients, and effective for improving MVPA and maintaining HRQoL.
Implications for Practice
Despite evidence that exercise is both safe and efficacious at improving physical fitness, quality of life, and treatment side effects for individuals with cancer, lifestyle programming is not offered as standard of cancer care. This study describes an oncologist‐referred, evidence‐based exercise and healthy eating program offered in collaboration with a university as supportive care to women with breast cancer receiving chemotherapy. The program was well received by oncologists and patients, safe, and relatively inexpensive to operate. Importantly, there was a significant positive impact on physical activity levels and health‐related quality of life lasting for 2 years after initiation of therapy.
The Nutrition and Exercise during Adjuvant Treatment (NExT) study was designed to assess the effectiveness of a supervised exercise and healthy eating program offered as part of supportive care in a real‐world setting for breast cancer patients receiving adjuvant chemotherapy. Reach, effectiveness, maintenance, and implementation were assessed, and the results are reported here.
Background
Previous studies demonstrated the tolerability of palbociclib plus endocrine therapy (ET). This analysis evaluated safety based on more recent cutoff dates and a longer palbociclib ...treatment exposure.
Patients and Methods
Data were pooled from three randomized studies of patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative (HR+/HER2−) advanced breast cancer (ABC), including postmenopausal women who had not received prior systemic treatment for advanced disease (PALOMA‐1/‐2) and pre‐ and postmenopausal women who had progressed on prior ET (PALOMA‐3).
Results
Updated cutoff dates were December 21, 2017 (PALOMA‐1), May 31, 2017 (PALOMA‐2), and April 13, 2018 (PALOMA‐3). Total person‐years of treatment exposure were 1,421.6 with palbociclib plus ET (n = 872) and 528.4 with ET (n = 471). Any‐grade neutropenia and infections were more frequent with palbociclib plus ET (82.1% and 59.2%, respectively) than with ET (5.1% and 39.5%). The hazard ratios were 1.6 (p = .0995) for grade 3/4 infections, 1.8 (p = .4358) for grade 3/4 viral infections, 1.4 (p = .0001) for infections, and 30.8 (p < .0001) for neutropenia. Febrile neutropenia was reported in 1.4% of patients receiving palbociclib plus ET. Cumulative incidence of all‐grade hematologic adverse events in both arms peaked during the first year of treatment and plateaued over the 5 subsequent years. Interstitial lung disease was reported in 13 patients receiving palbociclib plus ET and 3 receiving ET.
Conclusion
This 5‐year, long‐term analysis demonstrated that palbociclib plus ET has a consistent and stable safety profile and is a safe treatment for patients with HR+/HER2− ABC.
Implications for Practice
Several treatments for patients with breast cancer are associated with long‐term or latent adverse events. This long‐term, 5‐year analysis demonstrated that palbociclib plus endocrine therapy has a consistent and stable safety profile without cumulative or delayed toxicities. These results further support palbociclib plus endocrine therapy as a safe and manageable treatment in clinical practice for patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer.
This updated analysis based on data pooled from the three PALOMA studies is the largest long‐term analysis, to date, of the safety of a CDK4/6 inhibitor in combination with endocrine therapy for the treatment of advanced breast cancer.
Insulin-like growth factor-1 receptor (IGF-1R) is expressed in normal and malignant breast tissue and has been implicated in cell survival and resistance to cytotoxic therapies. We sought to assess ...the prognostic impact of IGF-1R expression among patients with early breast cancer and among breast cancer subtypes. Patients with stages I–III breast cancer with archival tumor tissue were included. Paraffin tissue blocks were used to construct a tissue microarray that was stained for ER, PR, Ki-67, HER2, EGFR, and cytokeratins 5/6 to classify the breast subgroups and for expression of IGF-1R, p27, and Bcl2 by immunohistochemistry. Kaplan–Meier plots were created by subtypes. Associations between IGF-1R and prognostic variables were examined in multivariate analysis. Among 2,871 eligible women the prognostic cut point for IGF-1R expression for breast-cancer-specific survival (BCSS) was Allred score <7 versus ≥7. IGF-1R was ≥7 in 52% (LuminalA), 57.5% (LuminalB), 44.8% (LuminalHER2), 9.7% HER2-enriched, and 22.5% (Basal-like),
P
= 1.3 × 10
−52
. IGF-1R+ was associated with age ≥50, lower histopathology grade, ER+, HER2 negativity (−), high p27 and high Bcl2 score. IGF-1R ≥7 was associated with better BCSS among LuminalB patients, hazard ratio = 0.64 (0.49–0.84);
P
= 1.2 × 10
−3,
and worse outcome in the HER2-enriched subtype, hazard ratio = 2.37 (1.21–4.64);
P
= 0.012. IGF-1R correlates with good prognostic markers among patients with early breast cancer and is differentially expressed with variable prognostic impact among breast cancer subtypes. Results may have relevance to the development of therapeutics targeting IGF-1R.
Introduction: Germ line BRCA mutations (gBRCAm) are diagnosed in approximately 5% of unselected breast cancer patients. Olaparib is a new treatment option for patients with a gBRCAm who have ...metastatic HER2-negative breast cancer.
Areas covered: Olaparib is an oral poly (ADP-ribose) polymerase inhibitor that has been shown in phase I-III clinical trials to have single-agent efficacy in breast cancer patients with gBRCAm. The recent phase III OlympiAD study demonstrated a statistically significant progression-free survival benefit compared with the chemotherapy control arm, although an overall survival benefit has not been demonstrated. The most common adverse events seen with olaparib include nausea, anemia, and vomiting. The most common grade 3 adverse events are anemia and neutropenia.
Expert commentary: The US FDA-approved olaparib tablets in January 2018 for the treatment of patients with a gBRCAm and metastatic HER2-negative breast cancer. This is a well-tolerated and effective treatment option for this patient population, particularly in patients with triple-negative breast cancer in which chemotherapy is the only alternative. More data are needed to understand the role of olaparib in combination with endocrine therapy, other targeted agents, and chemotherapy, as well as sequentially with platinum chemotherapy in the metastatic setting.
Currently, antiangiogenic strategies in metastatic breast cancer have demonstrated modest improvements in progression-free survival (PFS) but not improved quality or duration of survival, warranting ...evaluation of new agents in a placebo-controlled setting. Ramucirumab is a human immunoglobulin G1 antibody that binds vascular endothelial growth factor receptor-2 and blocks ligand-stimulated activation. The ROSE/TRIO-012 trial evaluated ramucirumab with docetaxel in unresectable, locally recurrent, or metastatic breast cancer.
In this double-blind, placebo-controlled, randomized, multinational phase III trial, 1,144 patients with human epidermal growth factor receptor 2 (HER2) -negative breast cancer who had not received cytotoxic chemotherapy in the advanced setting were randomly assigned at a two-to-one ratio to receive docetaxel 75 mg/m(2) plus ramucirumab 10 mg/kg or docetaxel 75 mg/m(2) plus placebo once every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria. Patients were stratified by previous taxane therapy, visceral metastasis, hormone receptor status, and geographic region. An independent data monitoring committee oversaw the trial. The primary end point was investigator-assessed PFS.
Median PFS in patients treated with ramucirumab plus docetaxel was 9.5 months, compared with 8.2 months in patients who received placebo plus docetaxel (hazard ratio HR, 0.88; P = .077). Median overall survival was 27.3 months in patients who received ramucirumab plus docetaxel, compared with 27.2 months in patients who received placebo plus docetaxel (HR, 1.01; P = .915). Toxicities seen at significantly higher rates in patients receiving ramucirumab included fatigue, hypertension, febrile neutropenia, palmar-plantar erythrodysesthesia syndrome, and stomatitis.
Addition of ramucirumab to docetaxel in HER2-negative advanced breast cancer did not meaningfully improve important clinical outcomes.
Most patients diagnosed with and dying from cancer in Canada are older adults, with aging contributing to the large projected growth in cancer incidence. Older adults with cancer have unique needs, ...and on a global scale increasing efforts have been made to address recognized gaps in their cancer care. However, in Canada, geriatric oncology remains a new and developing field. There is increasing recognition of the value of geriatric oncology and there is a growing number of healthcare providers interested in developing the field. While there is an increasing number of dedicated programs in geriatric oncology, they remain limited overall. Developing novel methods to delivery geriatric care in the oncology setting and improving visibility is important. Formal incorporation of a geriatric oncology curriculum into training is critical to both improve knowledge and demonstrate its value to healthcare providers. Although a robust group of dedicated researchers exist, increased collaboration is needed to capitalize on existing expertise. Dedicated funding is critical to promoting clinical programs, research, and training new clinicians and leaders in the field. By addressing challenges and capitalizing on opportunities for improvement, Canada can better meet the unique needs of its aging population with cancer and ultimately improve their outcomes.
Purpose
In rodents, a single exercise bout performed 24 h prior to a single doxorubicin treatment provides cardio-protection. This study investigated whether performing this intervention prior to ...every doxorubicin treatment for breast cancer reduced subclinical cardiotoxicity and treatment symptoms.
Methods
Twenty-four women with early stage breast cancer were randomly assigned to perform a 30-min, vigorous-intensity treadmill bout 24 h prior to each of four doxorubicin-containing chemotherapy treatments or to usual care. Established echocardiographic and circulating biomarkers of subclinical cardiotoxicity, as well as blood pressure and body weight were measured before the first and 7–14 days after the last treatment. The Rotterdam symptom checklist was used to assess patient-reported symptoms.
Results
The exercise and usual care groups did not differ in the doxorubicin-related change in longitudinal strain, twist, or cardiac troponin. However, the four total exercise bouts prevented changes in hemodynamics (increased cardiac output, resting heart rate, decreased systemic vascular resistance,
p
< 0.01) and reduced body weight gain, prevalence of depressed mood, sore muscles, and low back pain after the last treatment (
p
< 0.05) relative to the usual care group. No adverse events occurred.
Conclusions
An exercise bout performed 24 h prior to every doxorubicin treatment did not have an effect on markers of subclinical cardiotoxicity, but had a positive systemic effect on hemodynamics, musculoskeletal symptoms, mood, and body weight in women with breast cancer. A single exercise bout prior to chemotherapy treatments may be a simple clinical modality to reduce symptoms and weight gain among women with breast cancer.
Background
Palbociclib in combination with endocrine therapy is approved for treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast ...cancer. In addition to clinical trials, several real-world studies have evaluated the effectiveness of palbociclib. With increased life expectancy in the general population, breast cancer in older women is also expected to increase.
Objective
The aim was to systematically review evidence from both clinical trials and real-world studies for palbociclib treatment outcomes in older patients with HR+/HER2− advanced/metastatic breast cancer (a/mBC). Older patients are often underrepresented in clinical trials, and real-world evidence (RWE) will enrich the analysis of palbociclib outcomes in this subgroup of patients.
Design
A systematic literature search in PubMed, EMBASE, and Cochrane Library through May 4, 2023, yielded 2355 unique articles. A total of 52 articles (13 and 39 articles reporting results from seven randomized controlled trials RCTs and 37 RWE studies, respectively) were included based on study eligibility criteria.
Results
All RCTs used age cutoffs of ≥ 65 years to define older population (
n
= 722; 437 received palbociclib); all RWE studies, except one with an age cutoff of > 60 years, had age cutoffs of ≥ 65 years or higher to define older population (
n
= 9840; 7408 received palbociclib). Overall, in studies that compared efficacy (progression-free survival seven RCTs, 20 RWE studies, overall survival four RCTs, 11 RWE studies, tumor response three RWE studies, and clinical benefit rate one RCT, two RWE studies) and safety outcomes (three RCTs, three RWE studies) between older and younger patients, palbociclib showed similar benefits, regardless of age. Results from two RCTs and two RWE studies showed that global quality of life (QoL) was maintained in older patients receiving palbociclib. Overall, palbociclib dose modifications (two RWE studies), dose reductions (one RCT, seven RWE studies), and treatment discontinuation rates (three RCTs, three RWE studies) were higher in older patients compared with younger patients; however, these differences did not appear to adversely impact efficacy outcomes.
Conclusions
In this systematic review, data from RCTs showed that palbociclib was effective, well tolerated, and maintained QoL in older patients with HR+/HER2− a/mBC. Palbociclib treatment in older patients in real-world settings was associated with similar clinical benefit as in RCTs.
PROSPERO Registration
CRD42023444195.
Purpose: CPX-1 is a novel, liposome-encapsulated formulation of irinotecan and floxuridine designed to prolong in vitro optimized synergistic molar ratios of both drugs postinfusion. This open-label, ...single-arm, dose-escalating phase I study
was designed to determine the maximum tolerated dose and pharmacokinetics of CPX-1 in patients with advanced solid tumors.
Experimental Design: Patients received CPX-1 at 30, 60, 100, 150, 210, or 270 units/m 2 (1 unit = 1 mg irinotecan + 0.36 mg floxuridine) infused over 90 minutes every 14 days in 28-day cycles. Pharmacokinetic
samples were collected on days 1 and 15 of cycle 1.
Results: Thirty-three patients were enrolled, treated, and evaluated for safety; 30 patients were evaluated for response. A 1:1 plasma
irinotecan to floxuridine molar ratio was maintained for 8 to 12 hours. Grade 3/4 toxicities included diarrhea (24.2%), neutropenia
(12.1%), and hypokalemia (12.1%); 1 patient (270 units/m 2 ) died of persistent diarrhea, which led to dehydration and renal failure (grade 5). Partial response occurred in 3 (12%)
of the 25 subjects evaluated through Response Evaluation Criteria in Solid Tumors. Progression-free survival lasting >6 months
occurred in 9 patients, 6 with colorectal cancer. Among 15 colorectal cancer patients (10 with prior irinotecan), the calculated
median progression-free survival was 5.4 months; 11 patients (72.7%) achieved disease control and 2 patients (13%) had partial
response.
Conclusions: Outpatient CPX-1 was well tolerated and antitumor activity was shown in patients with advanced solid tumors. The recommended
dose for future studies is 210 units/m 2 . This is the first clinical evaluation of fixed drug ratio dosing designed to maintain synergistic molar ratios for enhanced
therapeutic benefit.
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