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Cellular senescence and DNA methylation are primary aging mechanisms emerging as a potential means of monitoring human aging and evaluating interventions thought to either accelerate or slow an individual’s aging trajectory. However, it is largely unknown whether cellular senescence and signatures of methylation of the specific CpG islands that comprise various epigenetic clocks correlate in humans. We have measured the cellular senescence biomarker, p16 and the five most used epigenetic aging clocks in 251 patients with breast cancer, 49 age-matched non-cancer controls, and 48 patients undergoing cytotoxic chemotherapy treatment. Chemotherapy, a known clinically-relevant inducer of aging, increased expression of p16 but not levels of the most common epigenetic clocks (DNAm-Horvath, PhenoAge, GrimAge, mPoA), with the exception of DNAm-Hannum. Chemotherapy-induced changes in p16 were associated with increased levels of a subset of SASPs, PARC, TNFRII, ICAM1, and TNFa. Cross-sectionally, there was weak to no correlation between p16 expression and epigenetic clocks in cancer patients or non-cancer controls. GrimAge and PhenoAge were the most correlated with p16 (r

Supplementary Figures S1 - S10, Tables S1 - S2

Patients with cancer have widely divergent experiences throughout their care from screening through survivorship. Differences in care delivery and outcomes may be due to varying patient preferences, patient needs according to stage of life, access to care, and implicit or explicit bias in care according to patient age. NCCN convened a series of stakeholder meetings with patients, caregivers, and patient advocacy groups to discuss the complex challenges and robust opportunities in this space. These meetings informed the NCCN Virtual Patient Advocacy Summit: Cancer Across the Lifespan held on December 10, 2020, which featured a keynote presentation, multidisciplinary panels, and presentations from patient advocacy organizations. This article encapsulates and expounds upon the findings from the stakeholder meetings and discussions during the summit.

PURPOSE Older breast cancer survivors are at increased risk of clinical decline after adjuvant chemotherapy. This study aimed to evaluate whether inflammatory markers assessed before adjuvant chemotherapy are associated with chemotherapy-induced clinical decline in a population of fit older adults with breast cancer. METHODS In a prospective study of women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy, we measured interleukin-6 (IL-6) and C-reactive protein (CRP) prechemotherapy (T1). We assessed frailty status, using a Deficit Accumulation Index (DAI; categorized as robust, prefrail, and frail), at T1 and postchemotherapy (T2). The population of interest was robust women at T1. The primary outcome was chemotherapy-induced decline in frailty status, defined as decline in DAI from robust (T1) to prefrail or frail (T2). Multivariable logistic regression was used to examine the association between inflammatory markers and the primary outcome, adjusted for sociodemographic and clinical characteristics. RESULTS Of the 295 robust women at T1, 76 (26%) experienced chemotherapy-induced decline in frailty status, among whom 66% had high IL-6, 63% had high CRP, and 46% had high IL-6 and CRP at T1. After adjusting for sociodemographic and clinical characteristics, women with high IL-6 and CRP had a > three-fold (odds ratio, 3.52; 95% CI, 1.55 to 8.01; P = .003) odds of chemotherapy-induced decline in frailty status compared with women with low IL-6 and CRP. CONCLUSION In this cohort of older women with early breast cancer who were clinically fit before chemotherapy initiation, high IL-6 and CRP prechemotherapy were associated with chemotherapy-induced decline in frailty status independent of sociodemographic and clinical risk factors. Further research is needed to examine whether inflammatory markers can inform more personalized approaches to treating older breast cancer survivors.

In the context of cancer, whether or not to choose pregnancy termination represents a difficult and multifaceted decision. In this editorial, members of The Oncologist editorial team attempt to contextualize the potential implications of the recent Supreme Court decision in Dobbs v. Jackson Women’s Health Organizationfor patients with cancer.

Explosive growth in the use of telemedicine occurred during the COVID-19 pandemic. Telemedicine has the potential to lessen healthcare burden for older adults with frequent appointments, physical and cognitive disabilities, and reliance on caretakers. To benefit from telemedicine, patients must have the capacity to engage with technology, for which inexperience and access may pose barriers. This study aimed to better understand the perspectives of older women with non-metastatic breast cancer on telemedicine, in regards to visit convenience, completeness, and interpersonal satisfaction. In this qualitative study, semi-structured interviews were conducted in a convenience sample of women age 65+, post-primary treatment for Stage I-III breast cancer, who received in-person outpatient care at NC Cancer Hospital before transitioning to telemedicine after March 2020. Patients were interviewed about their perceptions of telemedicine (telephone, video) as compared to in-person visits. Audio files of interviews were transcribed and reviewed to identify themes established a priori in the interview protocol. 15 patients (telephone=5, video=10) were consented and interviewed (July-October 2021), mean age=74. 13/15 participants reported that they preferred a hybrid care model that included telemedicine care over in-person care alone. COVID-19, physical disability, and transportation burden were associated with telemedicine preference. Comfort with familiar patient-provider interaction and lack of physical exam were associated with in-person appointment preference. Patient-clinician conversations and clinic protocols guiding use of telemedicine should take into account newness of diagnosis, patient comfort and familiarity with the care team, travel burden, disability, and whether the physical exam is or is not essential.

Adults 65 years of age or older with metastatic cancer face complicated treatment decisions. Few studies have explored the process with oncology clinicians during clinic encounters. Our exploratory study evaluated whether symptom burden or functional status impacted treatment decision conversations between older adults, caregivers, and oncology clinicians in a single National Cancer Institute within the Mountain West region.We conducted an observational, convergent mixed methods longitudinal study between November 2019 and January 2021; participants were followed for six months. The MD Anderson Symptom Inventory (MDASI) and Katz Index of Independence in Activities of Daily Living (ADL) were administered prior to clinical encounter. Ambulatory clinic encounters were audio recorded, transcribed, and analyzed. Nineteen older adults with a metastatic cancer diagnosis or a relapsed refractory hematologic malignancy were approached to achieve a sample of fifteen participants. The main outcome of interest was the number and quality of treatment decision making conversations, defined broadly and encompassing any interaction between the participant and oncology provider that involved (a) an issue or concern (e.g., symptoms, quality of life) brought up by anyone in the room during the clinical encounter, (b) a clinician addressing the concern, or (c) the patient or caregiver making a decision that involved a discussion of their goals or treatment preferences.Nine men and six women with a mean age of 71.3 years (6.6; standard deviation [SD]) were enrolled, and four died while on study. Participants were followed from one to ten visits (mean 4.5; SD 2.8) over one to six months. Of the 67 analyzed encounters, seven encounter conversations (10%) were identified as involving any type of treatment decision discussion. The seven treatment decision conversations occurred with five participants, all male (although female participants made up 40% of the sample), and 63% of participants who reported severe symptoms on the MDASI were female. Severe symptoms or functional status did not impact treatment conversations.Our results suggest that older adults with incurable cancer and their oncology clinicians do not spontaneously engage in an assessment of costs and benefits to the patient, even in the setting of palliative treatment and significant symptom burden.

BACKGROUND AND OBJECTIVES: Novel, non-cytotoxic agents are driving a paradigm shift for treatment of older adults with acute myeloid leukemia (AML). Older patients who initially receive intensive cytotoxic induction may choose to not proceed with cytotoxic consolidation therapy. Lenalidomide is an orally-administered immunomodulatory small molecule with activity in AML and a favorable safety profile in older adults with active leukemia. We conducted a phase Ib study of lenalidomide as post-remission therapy in older adults and assessed its impact on geriatric functional domains. MATERIALS AND METHODS: Participants were patients with AML over age 60 years who had undergone induction therapy and were poor candidates for cytotoxic consolidation. Lenalidomide was administered for 28 days in three dose cohorts. A Bayesian dose-escalation method determined cohort assignment and maximum tolerated dose (MTD). Geriatric assessment (GA) was performed before and after the cycle of lenalidomide. RESULTS: Nineteen patients with median age 68 were treated with at least one 28-day course of lenalidomide. Dose-limiting toxicities were observed in three participants at 25 mg, zero participants at 35 mg, and one participant at 50 mg. MTD was 35 mg. Median relapse-free survival was 4.3 months. GA was completed before and after treatment in fifteen patients, demonstrating improved cognitive function and no changes in physical, psychological, or social function after lenalidomide. CONCLUSION: Lenalidomide can be safely administered to older adults with AML with preservation of functional domains important to older patients. Serial GA can be performed in a novel drug study as a tool to characterize treatment tolerability.

Despite the large number of patients with early breast cancer (EBC) who have been treated with capecitabine in randomised trials, no individual patient data meta-analysis has been conducted. The primary objective was to examine the effect of capecitabine on disease-free survival (DFS), and the secondary objectives were to analyse distant DFS (DDFS), overall survival (OS), pathological complete response (for neoadjuvant studies) and the interaction between capecitabine-related toxicity and treatment effect.www.gov and www.pubmed.ncbi.nlm.nih.gov were searched using the following criteria: use of capecitabine for EBC as adjuvant or neoadjuvant therapy; multicentre randomised trial with100 patients; recruitment completed, and outcomes available. Required data were available for 13 trials.Individual data from 15,993 patients were collected. Cox regression analyses of all included patients revealed that the addition of capecitabine did not alter DFS significantly compared with treatment without capecitabine (hazard ratio [HR] 0.952; 95% CI 0.895-1.012; P value = 0.115). There was also no effect on DFS in the subset of studies where capecitabine was given instead of another drug (HR 1.035; 95% CI 0.945-1.134; P = 0.455). However, capecitabine administered in addition to the standard systemic treatment improved DFS (HR 0.888; 95% CI 0.817-0.965; P = 0.005). An OS improvement was observed in the entire cohort (HR 0.892; 95% CI 0.824-0.965, P = 0.005) and in the subset of capecitabine addition (HR 0.837; 95% CI 0.751, 0.933, P = 0.001). Subgroup analyses revealed that triple-negative breast cancer (TNBC) patients benefitted from treatment with capecitabine overall and in addition to other systemic treatments in terms of DFS and OS.Capecitabine was able to improve DFS and OS in patients with TNBC and in all patients with EBC when administered in addition to systemic treatment.

Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.

The majority of new colorectal cancer diagnoses occur in adults 65 and older a rapidly growing segment of the U.S. population. Older adults are a markedly heterogeneous group, and although recent clinical trials in locally advanced colorectal cancer have incorporated limited numbers of older patients, the data can not be generalized to most older patients. In particular, patients who are not “fit”—those with poor functional reserve, major comorbidities, or who otherwise meet criteria for frailty or “prefrailty”—are poorly represented in published trials. Population-based data demonstrate that older adults are much less likely to be treated in the adjuvant or neoadjuvant settings for stage II/III colorectal cancer, but it is unclear what the basis should be for withholding potentially curative therapy. Age and Eastern Cooperative Oncology Group (ECOG) performance status (PS) are frequently used to determine eligibility for treatment, but data increasingly suggest these are inadequate; the emerging definition of a spectrum of “fit” to “frail” older patients may provide additional guidance. Available data suggest that fit older patients may benefit as much from curative-intent therapy as younger patients. For frail or vulnerable (prefrail) patients, on the other hand, the benefit must be carefully weighed against the risk of toxicity and competing risks from their comorbidities. Life expectancy and patient preferences should always be elucidated. Geriatrician comanagement may be helpful in determining priorities, providing a comprehensive assessment, and modifying competing risk factors. Even many vulnerable or frail patients can successfully complete (and derive benefit from) carefully considered treatment regimens.

Studies point to a direct association between social support and better cancer outcomes. This study examined whether baseline social support is associated with better survival and fewer chemotherapy-related adverse events in older, early-stage breast cancer patients.This study is a pre-planned secondary analysis of CALGB 49907/Alliance A171301, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in breast cancer patients 65 years of age or older. A subset reported on the extent of their social support with questionnaires that were completed 6 times over 2 years.The median age of this 331-patient cohort was 72 years (range: 65, 90); 179 (55%) were married, and 210 (65%) lived with someone. One hundred forty-five patients (46%) described a social network of 0-10 people; 110 (35%) of 11-25; and 58 (19%) of 26 or more. The Medical Outcomes Study (MOS) social support survey revealed that the median scores (range) for emotional/informational, tangible, positive social interaction, and affectionate social support were 94 (3, 100), 94 (0, 100), 96 (0, 100), and 100 (8, 100), respectively. Social support scores appeared stable over 2 years and higher (more support) than in other cancer settings. No statistically significant associations were observed between social support and survival and adverse events in multivariate analyses. However, married patients had smaller tumors, and those with arthritis reported less social support.Although social support did not predict survival and adverse events, the exploratory but plausible inverse associations with larger tumors and arthritis suggest that social support merits further study.

Health care providers have little population-based evidence about health-related quality of life (HRQOL) changes, from the pre- to postdiagnosis period, and treatment-related recovery time for women aged 65 years and older diagnosed with breast cancer.Older women with and without breast cancer completed self-reports of HRQOL at baseline and 2 years later as part of annual Medicare Health Outcomes Surveys (MHOS). MHOS was linked to Surveillance, Epidemiology, and End Results registries, which were used to categorize women with breast cancer by treatment type (breast-conserving surgery, breast-conserving surgery plus radiation, mastectomy) and time since diagnosis at follow-up. Each cancer case diagnosed in 1998 through 2007 (N = 542) was matched to 5 women without cancer (N = 2710) using propensity score matching. Analysis of covariance models examined changes in HRQOL, adjusting for demographics and initial functioning.Older women within 6 months of diagnosis had greater declines than women without cancer in SF-36 Physical (-5.8 vs -1.8) and Mental (-3.6 vs -0.7) Component Summary scores, General Health (-12.3 vs -4.6), Vitality (-11.0 vs -2.2), Bodily Pain (-8.5 vs -2.1), Social Functioning (-15.1 vs -3.3), Role-Physical (-26.5 vs -3.9), and Role-Emotional (-13.1 vs -3.1) scores (all P .05). By approximately 1 year, women with and without breast cancer had similar HRQOL. Comparable declines in Physical Component Summary and Role-Physical occurred across treatment types.Women aged 65 years and older diagnosed with breast cancer should be counseled that survivors within 6 months of diagnosis are vulnerable to HRQOL declines, compared to women without breast cancer, but that decrements generally wane after 12 months.

More than 50% of breast cancers are diagnosed in women aged 65 years or older, a quickly growing segment of the population. Healthy older women should be offered state-of-the-art screening and treatment for breast cancer, including mammography, surgery, radiation therapy, and adjuvant therapy for early stage tumors. Clinical trials focusing on the role of adjuvant treatment in older women with breast cancer are of chief importance. The optimal treatment for older women with life-threatening, comorbid conditions may be primary treatment with tamoxifen or adjuvant therapy with tamoxifen alone after definitive surgery. Outside the clinical trials setting, metastatic disease should be treated similarly in all age groups.

BACKGROUND Although patients with malignant disease frequently use dietary supplements, the effects of these agents with regard to chemotherapy are unclear. Therefore, the authors investigated the influence of vitamin B12, folate, and nutritional supplements on chemotherapy-induced toxicity. METHODS Women with breast carcinoma were asked to complete a questionnaire that recorded their use of dietary supplements. Blood samples were obtained for the assessment of serum vitamin B12 and folate levels before and after the first cycle of chemotherapy and for weekly complete blood counts. Toxicity was evaluated by measuring absolute neutrophil counts and the frequency and severity of oral mucositis. RESULTS Of the 49 women who submitted questionnaires, 35 (71%) took a combined total of 165 supplements. Compared with patients in a previous study (performed in 1990), patients in the current study had dramatically increased serum folate levels. Initial neutrophil count, but not type of chemotherapy, patient age, or serum vitamin B12 level, was predictive of nadir absolute neutropenia and the decrease from initial neutrophil count to nadir (Nfall). After adjusting for initial neutrophil count, Nfall was found to be lower for women who were taking supplements compared with women who were not taking supplements (P = 0.01) and for women who were taking multivitamins (P = 0.01) or vitamin E (P = 0.03). Women with serum folic acid levels < 20 ng/mL had a smaller decrease in neutrophil count after chemotherapy than did women with higher folate levels (P = 0.04). No significant association between oral mucositis and initial neutrophil count, nadir neutrophil count, Nfall, age, vitamin B12 level, or folate level was found. CONCLUSIONS The decrease in neutrophil count caused by chemotherapy was ameliorated by dietary supplementation with a multivitamin or vitamin E. In contrast, high serum folate levels were associated with the exacerbation of this decrease in neutrophil count. Cancer 2004. © 2004 American Cancer Society.

PURPOSE The Truquant BR radioimmunoassay (RIA) (Biomira Diagnostics Inc, Rexdale, Canada) uses the monoclonal antibody B27.29 to quantitate the MUC-1 gene product (CA 27.29 antigen) in serum. We evaluated CA 27.29 antigen in a controlled, prospective clinical trial for its ability to predict relapse in stage II and stage III breast cancer patients. PATIENTS AND METHODS Over a 2-year period, 166 patients who had completed therapy for stage II (80.1%) or III (19.9%) breast cancer and were clinically free of disease were serially tested for CA 27.29 antigen levels. The study was double-masked and cancer recurrence was documented based on clinical findings. Patients with two consecutive CA 27.29 antigen test results above the upper limit of normal were considered positive. RESULTS The Truquant BR RIA had a sensitivity of 57.7%, specificity of 97.9%, positive predictive value of 83.3%, and negative predictive value of 92.6%. The recurrence rate was 15.7%. A Cox regression analysis showed that the only variable to correlate with recurrent disease was the CA 27.29 antigen test result. Patients with a positive test result had increased odds of having a recurrence (odds ratio, 6.8; P < .00001). The test was effective in predicting recurrence in patients with both distant and locoregional disease. In a subgroup of patients with bone pain, CA 27.29 antigen level was found to identify reliably patients who would subsequently develop recurrent disease. CONCLUSION These data demonstrate that the Truquant BR RIA can be used as an aid to predict recurrent breast cancer in patients with stage II and III disease.