Association of self-directed walking with toxicity moderation during chemotherapy for the treatment of early breast cancer.

BACKGROUND: In the field of exercise oncology, there is a need to quantify the potential benefits of moderate, self-directed physical activity during active treatment. In a pooled analysis of three identical single-arm intervention studies, we investigate the association of activity tracker steps with patient-reported toxicities during chemotherapy. METHODS: Women with early breast cancer who were enrolled in the intervention studies reported their symptom severity every 2-3 weeks throughout chemotherapy, and daily steps were documented through a Fitbit activity tracker. Relative risks (RR) and 95% confidence intervals (CI) were calculated using Poisson regression models with robust variance. For outcomes significant in unadjusted models, adjusted RRs were calculated controlling for race, age, and education level. Tracker step cut point (high step, low step) was determined by the means. Cumulative incidence functions of moderate, severe, and very severe (MSVS) symptoms were estimated using the Kaplan-Meier method and compared using a Cox proportional hazard model. RESULTS: In a sample of 283 women, mean age was 56 years and 76% were White. Mean tracker-documented steps/week were 29,625, with 55% walking below the mean (low step) and 45% above (high step). In multivariable analysis, high step patients had lower risk for fatigue [RR 0.83 (0.70, 0.99)] (p = 0.04), anxiety [RR 0.59 (0.42, 0.84)] (p = 0.003), nausea [RR 0.66 (0.46, 0.96)] (p = 0.03), depression [RR 0.59 (0.37, 0.03)] (p = 0.02), and ≥ 6 MSVS symptoms [RR 0.73 (0.54, 1.00)] (p = 0.05) and had 36% lower risk for dose reductions [RR 0.64 (95% CI 0.43, 0.97)] (p = 0.03). CONCLUSION: Self-directed walking at a rate of at least 30,000 steps/week may moderate the severity of treatment side effects during chemotherapy for early breast cancer. TRIAL NUMBERS: NCT02167932, NCT02328313, NCT03761706.

Behavioral cancer pain intervention dosing: results of a Sequential Multiple Assignment Randomized Trial.

ABSTRACT: Behavioral pain management interventions are efficacious for reducing pain in patients with cancer. However, optimal dosing of behavioral pain interventions for pain reduction is unknown, and this hinders routine clinical use. A Sequential Multiple Assignment Randomized Trial (SMART) was used to evaluate whether varying doses of Pain Coping Skills Training (PCST) and response-based dose adaptation can improve pain management in women with breast cancer. Participants (N = 327) had stage I-IIIC breast cancer and a worst pain score of > 5/10. Pain severity (a priori primary outcome) was assessed before initial randomization (1:1 allocation) to PCST-Full (5 sessions) or PCST-Brief (1 session) and 5 to 8 weeks later. Responders ( > 30% pain reduction) were rerandomized to a maintenance dose or no dose and nonresponders (<30% pain reduction) to an increased or maintenance dose. Pain severity was assessed again 5 to 8 weeks later (assessment 3) and 6 months later (assessment 4). As hypothesized, PCST-Full resulted in greater mean percent pain reduction than PCST-Brief (M [SD] = -28.5% [39.6%] vs M [SD]= -14.8% [71.8%]; P = 0.041). At assessment 3 after second dosing, all intervention sequences evidenced pain reduction from assessment 1 with no differences between sequences. At assessment 4, all sequences evidenced pain reduction from assessment 1 with differences between sequences ( P = 0.027). Participants initially receiving PCST-Full had greater pain reduction at assessment 4 ( P = 0.056). Varying PCST doses led to pain reduction over time. Intervention sequences demonstrating the most durable decreases in pain reduction included PCST-Full. Pain Coping Skills Training with intervention adjustment based on response can produce sustainable pain reduction.

Body mass index and patient-reported function, quality of life and treatment toxicity in women receiving adjuvant chemotherapy for breast cancer.

BACKGROUND: This study investigates whether high body mass index (BMI) in women diagnosed with early breast cancer (BC) is associated with patient-reported symptom severity during chemotherapy. METHODS: Women with Stage I-III BC completed toxicity reports for 17 side effects throughout regularly scheduled chemotherapy infusions. Toxicity reports were compared in women with obesity (BMI > = 30) versus no obesity (BMI < 30). Fisher's exact tests and 2-sample t-tests compared baseline patient characteristics. Risk ratios (RR) for women with obesity as compared to no obesity were estimated for individual symptoms that were patient-rated as moderate, severe or very severe (MSVS) severity, adjusting for marital status and race. RESULTS: In a sample of 286 patients, Black women comprised 23% of the sample. The obesity rate was 76% among Black patients and 31% among White patients (p < .0001). Women with obesity rated an average of 6.9 side effects (standard deviation, SD 4.2) as MSVS vs 5.5 side effects (SD 3.7) among women with no obesity (p = .003). In adjusted analysis, women with obesity had significantly greater risk for MSVS fatigue (RR 1.18, 95% CI 1.01-1.36), dyspnea (RR 1.71, 95% CI 1.09-2.69), arthralgia (RR 1.47, 95% CI 1.10-1.97), peripheral neuropathy (RR 1.45, 95% CI 1.01-2.08), edema of limbs (RR 1.84, 95% CI 1.18-2.88), and abdominal pain (RR 1.75, 95% CI 1.07-2.87). There were no inter-group differences in BC stage or phenotype, chemotherapy treatment modifications, or hospitalizations. CONCLUSIONS: Among women with early BC, patients with obesity reported higher chemotherapy toxicity as compared to patients without obesity; however, this did not result in differences in treatment completion.

A biomarker of aging, p16, predicts peripheral neuropathy in women receiving adjuvant taxanes for breast cancer.

Identifying patients at higher risk of chemotherapy-induced peripheral neuropathy (CIPN) is a major unmet need given its high incidence, persistence, and detrimental effect on quality of life. We determined if the expression of p16, a biomarker of aging and cellular senescence, predicts CIPN in a prospective, multi-center study of 152 participants enrolled between 2014 and 2018. Any women with newly diagnosed Stage I-III breast cancer scheduled to receive taxane-containing chemotherapy was eligible. The primary outcome was development of grade 2 or higher CIPN during chemotherapy graded by the clinician before each chemotherapy cycle (NCI-CTCAE v5 criteria). We measured p16 expression in peripheral blood T cells by qPCR before and at the end of chemotherapy. A multivariate model identified risk factors for CIPN and included taxane regimen type, p16Age Gap, a measure of discordance between chronological age and p16 expression, and p16 expression before chemotherapy. Participants with higher p16Age Gap-higher chronological age but lower p16 expression prior to chemotherapy - were at the highest risk. In addition, higher levels of p16 before treatment, regardless of patient age, conferred an increased risk of CIPN. Incidence of CIPN positively correlated with chemotherapy-induced increase in p16 expression, with the largest increase seen in participants with the lowest p16 expression before treatment. We have shown that p16 expression levels before treatment can identify patients at high risk for taxane-induced CIPN. If confirmed, p16 might help guide chemotherapy selection in early breast cancer.

Improving well-being for individuals with persistent pain after surgery for breast cancer, lobular carcinoma in situ, or ductal carcinoma in situ: A randomized clinical trial.

>276,000 Americans will be diagnosed with invasive breast cancer, lobular carcinoma in situ, or ductal carcinoma in situ this year and most will undergo breast surgery as part of their care. Although prognosis is excellent, many patients experience persistent post-surgical pain (PSP), which has no satisfactory pharmacological treatment. The causal contributions of pain-associated psychological factors (e.g., catastrophic thoughts about pain, psychological flexibility, self-efficacy) to the continuing burden of PSP have not yet been determined and may be opportune intervention targets. The randomized trial described here will compare the benefits of three manualized behavioral interventions for individuals with PSP. Participants will receive either: 1) self-guided health education (SGHE); 2) interventionist-guided health education (IGHE); or 3) interventionist-guided pain coping skills training with elements of acceptance and commitment therapy that specially target catastrophic thoughts about pain, self-efficacy, and psychological flexibility (CST-PSP). Participants will prospectively complete validated assessments of primary outcomes (PSP severity and interference) at baseline (pre-intervention) and 3-, 6-, and 12-months later. Validated measures of emotional distress and cancer-specific distress will be assessed as secondary outcomes. To test their roles as drivers of PSP, catastrophic thoughts about pain, self-efficacy, and psychological flexibility, will be assessed and statistically analyzed as mediators of hypothesized beneficial effects. The interventions' impacts on pain sensitivity and central sensitization will be investigated to test these physiological pathways as proximal drivers of PSP. To better characterize the patient experience, additional validated measures will be explored for associations with PSP, along with demographic and clinical factors. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04225585, registered January 13, 2020.

Older adult participation in cancer clinical trials: A systematic review of barriers and interventions.

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.

Patient-reported symptom severity, interference with daily activities, and adverse events in older and younger women receiving chemotherapy for early breast cancer.

BACKGROUND: To the authors' knowledge, it is unknown whether patient-reported symptom severity and symptom interference with daily activities differ between younger (aged <65 years) and older (aged ≥65 years) women receiving similar chemotherapy regimens for early breast cancer (EBC). METHODS: Study participants rated 17 side effects of chemotherapy regimens currently in use in clinical practice (2014-2019). RESULTS: Of 284 women with EBC (stage I-III), approximately 57% were aged <65 years and 43% were aged ≥65 years. For anthracycline-based regimens, a higher percentage of younger women reported moderate, severe, or very severe (MSVS) hot flashes (49% vs 18%) (P < .001). For nonanthracycline regimens, a higher percentage of younger women reported MSVS hot flashes (38% vs 19%) (P = .009) and a lower percentage reported MSVS arthralgia (28% vs 49%) (P = .005). With regard to symptom interference with daily activities, a higher percentage of younger women being treated with anthracycline-based regimens reported MSVS hot flashes (32% vs 7%) (P = .001) and myalgia (38% vs 18%) (P = .02). For nonanthracycline chemotherapy, a higher percentage of younger women reported MSVS interference for hot flashes (26% vs 9%) (P = .006) and lower percentages reported abdominal pain (13% vs 28%) (P = .02). Overall, there were no significant differences noted among younger versus older patients with regard to hospitalizations (19% vs 12%; P = .19), dose reductions (34% vs 31%; P = .50), dose delays (22% vs 25%; P = .59), or early treatment discontinuation (16% vs 16%; P = .9546). CONCLUSIONS: Older and younger women with EBC who were treated with identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events. LAY SUMMARY: In this study, women receiving chemotherapy for early breast cancer rated the severity of 17 symptoms and symptom interference with their activities of daily living. Older (aged ≥65 years) and younger (aged <65 years) women who received identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events.

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer.

BACKGROUND: The National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, collected alongside the clinician-reported Common Terminology Criteria for Adverse Events, enables comparisons of patient and clinician reports on treatment toxicity. METHODS: In a multisite study of women receiving chemotherapy for early-stage breast cancer, symptom reports were collected on the same day from patients and their clinicians for 17 symptoms; their data were not shared with each other. The proportions of moderate, severe, or very severe patient-reported symptom severity were compared with the proportions of clinician-rated grade 2, 3, or 4 toxicity. Patient-clinician agreement was assessed via κ statistics. Chi-square tests investigated whether patient characteristics were associated with patient-clinician agreement. RESULTS: Among 267 women, the median age was 58 years (range, 24-83 years), and 26% were nonwhite. There was moderate scoring agreement (κ = 0.413-0.570) for 53% of symptoms, fair agreement for 41% (κ = 0.220-0.378), and slight agreement for 6% (κ = 0.188). For example, patient-reported and clinician-rated percentages were 22% and 8% for severe or very severe fatigue, 41% and 46% for moderate fatigue, 32% and 39% for mild fatigue, and 6% and 7% for none. Clinician severity scores were lower for nonwhite patients in comparison with white patients for peripheral neuropathy, nausea, arthralgia, and dyspnea. CONCLUSIONS: Although clinician reporting of symptoms is common practice in oncology, there is suboptimal agreement with the gold standard of patient self-reporting. These data provide further evidence supporting the integration of patient-reported outcomes into oncological clinical research and clinical practice to improve monitoring of symptoms as well as timely interventions for symptoms.

The Evolving Complexity of Treating Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer: Special Considerations in Older Breast Cancer Patients-Part I: Early-Stage Disease.

The median age for breast cancer diagnosis is 62 years, but a disproportionate number of patients are over the age of 75 years and the majority of those have hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative cancers. This review provides a logical algorithm to guide providers through the many complicated issues involved in adjuvant systemic therapy decisions in older patients with hormone receptor-positive, HER2-negative breast cancer. For this subtype of breast cancer, the mainstay of treatment is surgery and adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor (AI). Adjuvant chemotherapy is added to the treatment regimen when the benefits of treatment are deemed to outweigh the risks, making the risk-benefit discussion particularly important in older women. Traditional tools for cancer risk assessment and genomic expression profiles (GEPs) are under-utilized in older patients, but yield equally useful information about cancer prognosis as they do in younger patients. Additionally, there are tools that estimate life-limiting toxicity risk from chemotherapy and life expectancy, which are both important issues in the risk-benefit discussion. For very low-risk cancers, such as non-invasive and small lymph node (LN)-negative cancers, the benefits of any adjuvant therapy is likely outweighed by the risks, but endocrine therapy might be considered to prevent future new breast cancers. For invasive tumors that are > 5 mm (T1b or larger) or involve LNs, adjuvant endocrine therapy is recommended. Generally, AIs should be included, though tamoxifen is effective and should be offered when AIs are not tolerated. Bone-preserving agents and high-dose vitamin D are options to preserve bone density or treat osteoporosis, especially in older women who are taking AIs. Where the risk-reducing benefit from adjuvant chemotherapy outweighs the toxicity risk, adjuvant chemotherapy should be considered. Adjuvant chemotherapy has similar benefits in older and younger patients and standard regimens are preferred. Several exciting clinic trials are underway and have included older patients, including those adding molecularly targeted agents, cyclin-dependent kinase (CDK) 4/6 inhibitors and everolimus, to endocrine therapy in the adjuvant setting. The high incidence of breast cancer in older women should drive us to design clinical trials for this population and emphasize their inclusion in ongoing trials as much as possible.

Breast cancer and aging: Standing on the shoulders of a giant.

With the aging of the US population, the number of individuals age 65 or older who will be diagnosed with breast cancer is expected to rise. Despite this, older adults with breast cancer remain severely under-represented in cancer clinical trials. Numerous studies have highlighted disparites in care experienced by older patients with breast cancer. Dr. Arti Hurria was one of the most influential leaders in oncology to shed light on this vunerable and growing population. By uniting the fields of geriatrics and oncology, she brought together a powerful community of like-minded individuals and, through collaborative research, pioneered the current day approach and care of older patients with cancer. In this review, we highlight Dr. Hurria's contribution in breast oncology. Specifically, we describe her work on functional and cognitive effects of breast cancer therapy, shared-decision making, toxicity risk prediction, and breast cancer therapeutics.

Decreasing incidence of upper age restriction enrollment criteria among cancer clinical trials.

BACKGROUND: Age disparities among cancer clinical trial participants are pervasive and worsening over time. Identification of factors associated with age disparities is critical to improve enrollment of older patients on trials. The incidence and impact of trial eligibility criteria that exclude patients on the basis of age remains opaque. METHODS: ClinicalTrials.gov was queried for completed oncologic randomized controlled trials (RCTs). Phase 3 RCTs assessing a therapeutic intervention among adult cancer patients were included. Trial eligibility criteria were assessed using the ClinicalTrials.gov website as well as trial publications and protocol documentation. RESULTS: Seven hundred and forty-two trials met inclusion criteria, with a total combined enrollment of 449,720 patients. Upper age restriction enrollment criteria were identified for 10.1% of RCTs; the median age cutoff for restricted trials was 72 years (interquartile range 70-80 years). Linear regression modeling revealed decreasing incidence of age restriction criteria over time, at a rate of -1.1% annually (p = .03); trials initiating enrollment in 2002-2005, for example, had a 16.1% rate of age-restrictive eligibility criteria, compared with 7.6% for trials initiating enrollment in 2010-2014. CONCLUSION: Use of eligibility criteria that explicitly exclude patients on the basis of age appears to be decreasing with time. Future efforts should aim to better characterize the relationship between eligibility criteria (such as those that exclude patients on the basis of specific organ function) and their association with age disparities among enrolled patients.

Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16INK4a.

BACKGROUND: Although chemotherapy saves lives, increasing evidence shows that chemotherapy accelerates aging. We previously demonstrated that mRNA expression of p16INK4a , a biomarker of senescence and molecular aging, increased early and dramatically after beginning adjuvant anthracycline-based regimens in early stage breast cancer patients. Here, we determined if changes in p16INK4a expression vary by chemotherapy regimen among early stage breast cancer patients. METHODS: We conducted a study of stage I-III breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. p16INK4a expression was analyzed prechemotherapy and postchemotherapy (median 6.2 months after the last chemotherapy) in peripheral blood T lymphocytes. Chemotherapy-induced change in p16INK4a expression was compared among regimens. All statistical tests were 2-sided. RESULTS: In 146 women, chemotherapy was associated with a statistically significant increase in p16INK4a expression (accelerated aging of 17 years; P < .001). Anthracycline-based regimens were associated with the largest increases (accelerated aging of 23 to 26 years; P ≤ .008). Nonanthracycline-based regimens demonstrated a much smaller increase (accelerated aging of 9 to 11 years; P ≤ .15). In addition to the type of chemotherapy regimen, baseline p16INK4a levels, but not chronologic age or race, were also associated with the magnitude of increases in p16INK4a . Patients with lower p16INK4a levels at baseline were more likely to experience larger increases. CONCLUSIONS: Our findings suggest that the aging effects of chemotherapy may be influenced by both chemotherapy type and the patient's baseline p16INK4a level. Measurement of p16INK4a expression is not currently available in the clinic, but nonanthracycline regimens offering similar efficacy as anthracycline regimens might be favored.

A behavioral cancer pain intervention: A randomized noninferiority trial comparing in-person with videoconference delivery.

OBJECTIVE: Behavioral cancer pain interventions are efficacious for improving important pain outcomes; yet, traditional in-person delivery limits patient access. This study compared videoconference-delivered mobile health pain coping skills training (mPCST) to in-person pain coping skills training (PCST-traditional). METHODS: This study was a randomized, noninferiority trial with cancer patients. Participants (N = 178) were randomly assigned to four, 45-minute sessions of mPCST or PCST-traditional. Session content focused on evidence-based cognitive and behavioral pain management skills. Assessments were completed at baseline, posttreatment, and 3-month posttreatment, and included measures of primary intervention outcomes (ie, pain severity and pain interference) and secondary intervention outcomes (ie, physical symptoms, psychological distress, physical well-being, and self-efficacy). The main study aim tested whether mPCST was more accessible (defined as feasibility, acceptability, patient burden, and engagement) than PCST-traditional. The second aim tested whether mPCST was noninferior to PCST-traditional. RESULTS: mPCST demonstrated significantly greater feasibility (ie, attrition, adherence, and time to completion) than PCST-traditional. Both groups reported similar patient burden and engagement as well as a high degree of acceptability. All intervention outcomes demonstrated noninferiority at posttreatment and, with the exception of physical symptoms, 3-month posttreatment. Concerning the primary intervention outcomes, 95% CIs for the mean differences (d) were below the noninferiority margin of 1 for pain severity (posttreatment d = 0.09, 95% CI, -0.63-0.81; 3 months d = -0.43 95% CI, -1.22-0.36) and pain interference (posttreatment d = -0.11, 95% CI, -0.99-0.76; 3 months d = -0.26 95% CI, -1.14-0.62). CONCLUSION: mPCST is highly accessible and noninferior to PCST-traditional.

Patient-reported and clinician-reported chemotherapy-induced peripheral neuropathy in patients with early breast cancer: Current clinical practice.

BACKGROUND: In the current study, the authors investigated the incidence of moderate to severe chemotherapy-induced peripheral neuropathy (CIPN) for chemotherapy regimens commonly used in current clinical practice for the treatment of patients with early breast cancer. Patient-reported and clinician-assessed CIPN severity scores were compared, and risk factors for CIPN severity were identified. METHODS: Patients completed a Patient-Reported Symptom Monitoring form and oncologists completed a Common Terminology Criteria for Adverse Events form. CIPN reports were collected prospectively during regularly scheduled infusion visits throughout the duration of chemotherapy. RESULTS: The sample included 184 women with a mean age of 55 years; approximately 73% were white. The 4 chemotherapy regimens used were doxorubicin and cyclophosphamide plus paclitaxel (60 patients); docetaxel and cyclophosphamide (50 patients); docetaxel, carboplatin, and anti-human epidermal growth factor receptor 2 (HER2) (24 patients); and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin (18 patients). All patients treated with doxorubicin and cyclophosphamide plus paclitaxel and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin received paclitaxel; all patients treated with docetaxel and cyclophosphamide and docetaxel, carboplatin, and anti-HER2 received docetaxel. The chemotherapy dose was reduced in 52 patients (28%); in 15 patients (29%), this reduction was due to CIPN. Chemotherapy was discontinued in 26 patients (14%), 8 because of CIPN. Agreement between patient-reported and clinician-assessed CIPN severity scores was minimal (weighted Cohen kappa, P = .34). Patient-reported moderate to severe CIPN was higher for paclitaxel (50%) compared with docetaxel (17.7%) (P < .001). Pretreatment arthritis and/or rheumatism (relative risk [RR], 1.58; 95% CI, 1.06-2.35 [P = .023]) and regimens containing paclitaxel (RR, 2.88; 95% CI, 1.72-4.83 [P < .0001]) were associated with higher CIPN severity. Being married (RR, 0.57; 95% CI, 0.37-0.887 [P = .01]) was found to be associated with lower CIPN severity. CONCLUSIONS: The discrepancy between patient-reported and clinician-assessed CIPN underscores the need for both patient and clinician perspectives regarding this common, dose-limiting, and potentially disabling side effect of chemotherapy.

Partner status moderates the relationships between sexual problems and self-efficacy for managing sexual problems and psychosocial quality-of-life for postmenopausal breast cancer survivors taking adjuvant endocrine therapy.

OBJECTIVE: Past studies indicate that >90% of breast cancer survivors taking adjuvant endocrine therapy (AET) experience menopausal symptoms including sexual problems (eg, vaginal dryness, dyspareunia); however, research examining the impact of these problems on quality-of-life is limited. This cross-sectional study examined (1) the impact of sexual problems and self-efficacy for coping with sexual problems (sexual self-efficacy) on quality-of-life (ie, psychosocial quality-of-life and sexual satisfaction), and (2) partner status as a moderator of these relationships. METHODS: Postmenopausal breast cancer survivors taking AET completed measures of sexual problems (Menopause-Specific Quality-of-Life [MENQOL] sexual subscale], sexual self-efficacy, psychosocial quality-of-life (MENQOL psychosocial subscale), and sexual satisfaction (Functional Assessment of Cancer Therapy-General item). RESULTS: Bivariate analyses showed that women reporting greater sexual problems and lower sexual self-efficacy had poorer quality-of-life and less sexual satisfaction (all P-values < 0.05). Partner status moderated the relationship between sexual problems and psychosocial quality-of-life (P = 0.02); at high levels of sexual problems, unpartnered women experienced poorer psychosocial quality-of-life than partnered women. Partner status also moderated the relationship between self-efficacy and psychosocial quality-of-life (P = 0.01). Self-efficacy was unrelated to psychosocial quality-of-life for partnered women; for unpartnered women, low self-efficacy was associated with poorer quality-of-life. Partner status did not moderate the relationships between sexual problems or self-efficacy with sexual satisfaction. CONCLUSIONS: Greater sexual problems and lower sexual self-efficacy were associated with poorer psychosocial quality-of-life and sexual satisfaction among postmenopausal breast cancer survivors taking AET. Interventions to address sexual problems and sexual self-efficacy, particularly among unpartnered women, may be beneficial for improving the well-being of postmenopausal breast cancer survivors on AET.

Higher symptom burden is associated with lower function in women taking adjuvant endocrine therapy for breast cancer.

OBJECTIVE: To explore the impact of symptoms on physical function in women on adjuvant endocrine therapy for breast cancer. METHODS: Eligible women were postmenopausal, had hormone receptor positive, stage I-IIIA breast cancer, completed surgery, chemotherapy, radiation, and on adjuvant endocrine therapy. At a routine follow-up visit, women (N = 107) completed standardized symptom measures: Brief Fatigue Inventory, Brief Pain Inventory, Menopause Specific Quality of Life Questionnaire, Functional Assessment of Cancer Therapy Neurotoxicity scales. Two performance measures assessed function: grip strength (Jamar dynamometer; n = 71) and timed get-up-and-go (TUG; n = 103). Analyses were performed with an overall symptom composite score. Correlations and multiple linear regression analyses were performed to test adverse effects on physical function. RESULTS: The mean age was 64 years (range 45-84), 81% white, 84% on an aromatase inhibitor, and on endocrine therapy for mean 35 months (range 1-130 months). Dominant hand grip strength was inversely correlated with symptom composite scores (r = -0.29, p = .02). Slower TUG was positively correlated with higher Charlson comorbidity level (r = 0.36, p < .001) and higher symptom composite scores (r = 0.24, p = .01). In multivariate analyses, weaker dominant and non-dominant hand grip strength were significantly associated with greater symptom composite scores (ß = -0.27, t = 2.43, p = .02 and ß = -0.36, t = 3.15, p = .003, respectively) and slower TUG was associated with higher symptom composite scores (ß = 0.18, t = 1.97, p = .05). CONCLUSIONS: Higher symptom burden is associated with worse physical function, as measured by hand grip strength and TUG. Further study to determine the impact of endocrine therapy and its side effects on function is warranted.

Patient-Reported Toxicities During Chemotherapy Regimens in Current Clinical Practice for Early Breast Cancer.

BACKGROUND: This study explores the incidence of patient-reported major toxicity-symptoms rated "moderate," "severe," or "very severe"-for chemotherapy regimens commonly used in early breast cancer. PATIENTS AND METHODS: Female patients aged 21 years or older completed a validated Patient-Reported Symptom Monitoring instrument and rated 17 symptoms throughout adjuvant or neoadjuvant chemotherapy. Fisher's exact tests compared differences in percentages in symptom ratings, and general linear regression was used to model the incidence of patient-reported major toxicity. RESULTS: In 152 patients, the mean age was 54 years (range, 24-77), and 112 (74%) were white; 51% received an anthracycline-based regimen. The proportion of patients rating fatigue, constipation, myalgia, diarrhea, nausea, peripheral neuropathy, and swelling of arms or legs as a major toxicity at any time during chemotherapy varied significantly among four chemotherapy regimens (p < .05). The mean (SD) number of symptoms rated major toxicities was 6.3 (3.6) for anthracycline-based and 4.4 (3.5) for non-anthracycline-based regimens (p = .001; possible range, 0-17 symptoms). Baseline higher body mass index (p = .03), patient-reported Karnofsky performance status ≤80 (p = .0003), and anthracycline-based regimens (p = .0003) were associated with greater total number of symptoms rated major toxicities (alternative model: chemotherapy duration, p < .0001). Twenty-six percent of dose reductions (26 of 40), 75% of hospitalizations (15 of 20), and 94% of treatment discontinuations (15 of 16) were in anthracycline-based regimens. CONCLUSION: Capturing multiple toxicity outcomes throughout chemotherapy enables oncologists and patients to understand the range of side effects as they discuss treatment efficacies. Continuous symptom monitoring may aid in the timely development of interventions that minimize toxicity and improve outcomes. IMPLICATIONS FOR PRACTICE: This study investigated patient-reported toxicities for 17 symptoms recorded prospectively during adjuvant and neoadjuvant chemotherapy regimens for early breast cancer. An analysis of four commonly used chemotherapy regimens identified significant differences among regimens in both individual symptoms and total number of symptoms rated moderate, severe, or very severe. Longer chemotherapy regimens, such as anthracycline-based regimens followed by paclitaxel, had higher proportions of symptoms rated major toxicities. The inclusion of patient perspectives on multiple toxicity outcomes at the same time at multiple time points during chemotherapy has the potential for improving patient-provider communication regarding symptom management, patient satisfaction, and long-term clinical outcomes.

Obesity and mortality after locoregional breast cancer diagnosis.

PURPOSE: Higher mortality after a breast cancer diagnosis has been observed among women who are obese. We investigated the relationships between body mass index (BMI) and all-cause or breast cancer-specific mortality after a diagnosis of locoregional breast cancer. METHODS: Women diagnosed in 2004 with AJCC Stage I, II, or III breast cancer (n = 5394) were identified from a population-based National Program of Cancer Registries (NPCR) patterns of care study (POC-BP) drawing from registries in seven U.S. states. Differences in overall and breast cancer-specific mortality were investigated using Cox proportional hazards regression models adjusting for demographic and clinical covariates, including age- and stage-based subgroup analyses. RESULTS: In women 70 or older, higher BMI was associated with lower overall mortality (HR for a 5 kg/m2 difference in BMI = 0.85, 95% CI 0.75-0.95). There was no significant association between BMI and overall mortality for women under 70. BMI was not associated with breast cancer death in the full sample, but among women with Stage I disease; those in the highest BMI category had significantly higher breast cancer mortality (HR for BMI ≥ 35 kg/m2 vs. 18.5-24.9 kg/m2 = 4.74, 95% CI 1.78-12.59). CONCLUSIONS: Contrary to our hypothesis, greater BMI was not associated with higher overall mortality. Among older women, BMI was inversely related to overall mortality, with a null association among younger women. Higher BMI was associated with breast cancer mortality among women with Stage I disease, but not among women with more advanced disease.

Risk of cancer death by comorbidity severity and use of adjuvant chemotherapy among women with locoregional breast cancer.

OBJECTIVES: To examine the associations of comorbidity and chemotherapy with breast cancer- and non-breast cancer-related death. MATERIALS AND METHODS: Included were women with invasive locoregional breast cancer diagnosed in 2004 from seven population-based cancer registries. Data were abstracted from medical records and verified with treating physicians when there were inconsistencies and missing information on cancer treatment. Comorbidity severity was quantified using the Adult Comorbidity Evaluation 27. Treatment guideline concordance was determined by comparing treatment received with the National Comprehensive Cancer Network guidelines. Kaplan-Meier method and multivariable Cox proportional hazards regressions were employed for statistical analyses. RESULTS: Of 5852 patients, 76% were under 70years old and 69% received guideline concordant adjuvant chemotherapy. Comorbidity was more prevalent in women age 70 and older (79% vs. 51%; p<0.001). After adjusting for tumor characteristics and treatment, severe comorbidity burden was associated with significantly higher cancer-related mortality in older patients (Hazard Ratio [HR]=2.38, 95% CI 1.08-5.24), but not in younger patients (HR=1.78, 95% CI 0.87-3.64). Among patients receiving guideline adjuvant chemotherapy, cancer-related mortality was significantly higher in older patients (HR=2.35, 95% CI 1.52-3.62), and those with severe comorbidity (HR=3.79, 95% CI 1.72-8.33). CONCLUSIONS: Findings suggest that, compared to women with no comorbidity, patients with breast cancer age 70 and older with severe comorbidity are at increased risk of dying from breast cancer, even after adjustment for adjuvant chemotherapy and other tumor and treatment differences. This information adds to risk-benefit discussions and emphasizes the need for further study of the role for adjuvant chemotherapy in these patient groups.