Clinical and sociodemographic risk factors associated with the development of second primary cancers among postmenopausal breast cancer survivors.

BACKGROUND: Advancement in breast cancer (BC) diagnosis and treatment have increased the number of long-term survivors. Consequently, primary BC survivors are at a greater risk of developing second primary cancers (SPCs). The risk factors for SPCs among BC survivors including sociodemographic characteristics, cancer treatment, comorbidities, and concurrent medications have not been comprehensively examined. The purpose of this study is to assess the incidence and clinicopathologic factors associated with risk of SPCs in BC survivors. METHODS: We analyzed 171, 311 women with early-stage primary BC diagnosed between January 2000 and December 2015 from the Medicare-linked Surveillance Epidemiology and End Results (SEER-Medicare) database. SPC was defined as any diagnosis of malignancy occurring within the study period and at least 6 months after primary BC diagnosis. Univariate analyses compared baseline characteristics between those who developed a SPC and those who did not. We evaluated the cause-specific hazard of developing a SPC in the presence of death as a competing risk. RESULTS: Of the study cohort, 21,510 (13%) of BC survivors developed a SPC and BC was the most common SPC type (28%). The median time to SPC was 44 months. Women who were white, older, and with fewer comorbidities were more likely to develop a SPC. While statins [hazard ratio (HR) 1.066 (1.023-1.110)] and anti-hypertensives [HR 1.569 (1.512-1.627)] increased the hazard of developing a SPC, aromatase inhibitor therapy [HR 0.620 (0.573-0.671)] and bisphosphonates [HR 0.905 (0.857-0.956)] were associated with a decreased hazard of developing any SPC, including non-breast SPCs. CONCLUSION: Our study shows that specific clinical factors including type of cancer treatment, medications, and comorbidities are associated with increased risk of developing SPCs among older BC survivors. These results can increase patient and clinician awareness, target cancer screening among BC survivors, as well as developing risk-adapted management strategies.

Optimizing the use of adjuvant chemotherapy in non-small cell lung cancer patients with comorbidities.

Veterans with locoregional non-small cell lung cancer (NSCLC) may benefit from adjuvant chemotherapy. However, comorbidities and other factors may impact the harms and benefits of this treatment. Here, we identified the optimal indications for adjuvant chemotherapy in Veterans with NSCLC, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and/or coronary artery disease (CAD). We used data from randomized controlled trials (RCTs) and Veterans Administration (VA) databases to enhance a simulation model. Then, we conducted in-silico RCTs comparing adjuvant chemotherapy vs observation among Veterans with stage II-IIIA NSCLC. Among Veterans without COPD or CKD, adjuvant chemotherapy was the optimal strategy regardless of the presence or absence of CAD except for patients >70 years with squamous cell carcinoma. Conversely, most veterans without COPD but with CKD were optimally managed with observation. Veterans with COPD but without CKD, benefited from adjuvant chemotherapy if they were ≤70 years with stage II-IIIA adenocarcinoma or <60 years with stage II-IIIA squamous cell carcinoma. Adjuvant chemotherapy was only beneficial for Veterans with both COPD and CKD among stage II-IIIA adenocarcinoma <60 years of age. Veterans with stages II-IIIA squamous cell carcinoma, COPD, and CKD were optimally managed with observation. Many Veterans with comorbidities are optimally managed with observation post-surgical resection. However, we also identified several groups of Veterans whom the benefits of adjuvant chemotherapy outweighed the risks of early toxicity. Our findings could inform patient-provider discussions and potentially reduce physicians' uncertainty about the role of adjuvant chemotherapy in this population.

Influence of Metastatic Bone Lesion Type and Tumor Origin on Human Vertebral Bone Architecture, Matrix Quality, and Mechanical Properties.

Metastatic spine disease is incurable, causing increased vertebral fracture risk and severe patient morbidity. Here, we demonstrate that osteolytic, osteosclerotic, and mixed bone metastasis uniquely modify human vertebral bone architecture and quality, affecting vertebral strength and stiffness. Multivariable analysis showed bone metastasis type dominates vertebral strength and stiffness changes, with neither age nor gender having an independent effect. In osteolytic vertebrae, bone architecture rarefaction, lower tissue mineral content and connectivity, and accumulation of advanced glycation end-products (AGEs) affected low vertebral strength and stiffness. In osteosclerotic vertebrae, high trabecular number and thickness but low AGEs, suggesting a high degree of bone remodeling, yielded high vertebral strength. Our study found that bone metastasis from prostate and breast primary cancers differentially impacted the osteosclerotic bone microenvironment, yielding altered bone architecture and accumulation of AGEs. These findings indicate that therapeutic approaches should target the restoration of bone structural integrity. © 2022 American Society for Bone and Mineral Research (ASBMR).

The association of osteoporosis knowledge and beliefs with preventive behaviors in postmenopausal breast cancer survivors.

BACKGROUND: Postmenopausal breast cancer survivors (PBCS) are at increased risk of bone loss and fractures due to age-related decline of estrogen, and this risk is compounded by aromatase inhibitor cancer therapy. Several patient-level targetable risk factors can mitigate osteoporosis risk; however, adequate health behavior and risk perception in this population are underreported. The goal of this study was to evaluate osteoporosis knowledge and beliefs and assess their association with engagement in osteoporosis preventive behaviors among PBCS. METHODS: In this cross-sectional descriptive study, early stage I-IIIA PBCS (ages 55-86 years) completed the Facts on Osteoporosis Quiz, Osteoporosis Health Beliefs Scale, and Osteoporosis Preventive Behaviors questionnaires. Participants who were non-English speaking or declined to participate were excluded. Clinical and sociodemographic information were obtained from chart review and baseline questionnaire, respectively. Fisher's exact test, Student t-test, and Wilcoxon Mann-Whitney tests were used where appropriate to assess the association between knowledge and beliefs with engagement in osteoporosis preventive behaviors. RESULTS: The mean participant age was 66.1 years with 20% self-reporting as non-Hispanic White, 40% non-Hispanic Black, 27% Hispanic, and 13% other. Approximately 83% of the cohort had estrogen receptor positive breast cancer and received a bone density scan within the last six years. Osteoporosis knowledge (10.5 ± 3.4), seriousness (14.9 ± 3.8), and susceptibility (14.0 ± 3.5) mean scores were low among PBCS. Most PBCS (75%) were adherent to calcium and vitamin D supplements, but only 47% reported engagement in strength-training exercises. Married/partnered, higher osteoporosis knowledge and health motivation scores were associated with strength-training exercise. After adjustment for marital status and osteoporosis knowledge, only health motivation score remained significantly associated with strength-training exercise (OR 5.56, 95% CI 1.35-22.93). CONCLUSIONS: PBCS are highly motivated to keep a healthy lifestyle despite limited osteoporosis knowledge, perceived risk, and susceptibility. However, < 50% participated in strength-training exercise. Our findings suggest that oncologic care should include osteoporosis and fracture prevention strategies, directed at encouraging cancer survivors to increase their engagement in osteoporosis preventive behaviors, particularly strength-training exercises.

Assessing the association of diabetes with lung cancer risk.

BACKGROUND: Diabetes is a well-established risk factor for many cancers, but its relationship with lung cancer incidence remains unclear. In this study, we aimed to assess if diabetes is independently associated with lung cancer risk and histology subtype among participants in a screening study. METHODS: In a retrospective cohort study using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) study, we assessed the association of self-reported diabetes with lung cancer incidence using Poisson regression while adjusting for other established risk factors in the PLCOM2012, a validated lung cancer prediction model. The adjusted association of diabetes and lung cancer cell type was evaluated using nominal regression. Stratified analyses were also conducted according to sex, smoking history, and body mass index categories. RESULTS: Overall, 140,395 participants were included in our analysis. Diabetes was not significantly associated with lung cancer incidence [incidence rate ratio (IRR): 1.03, 95% confidence interval (CI): 0.91-1.17]. Similarly, stratified analyses also did not show significant associations between diabetes and lung cancer risk (all P values >0.05). We found no significant difference in the distribution of lung cancer histology in participants with vs. without diabetes (P=0.30). CONCLUSIONS: Diabetes was not an independent risk factor for lung cancer in a large cohort of PLCO participants. We did not observe differences in histology according to diabetes status. These results suggest that patients with diabetes do not need more aggressive lung cancer screening. Future research including more detailed metabolic parameters may further elucidate the relationship between metabolic disease and lung cancer risk.

The effects of metastatic lesion on the structural determinants of bone: Current clinical and experimental approaches.

Metastatic bone disease is incurable with an associated increase in skeletal-related events, particularly a 17-50% risk of pathologic fractures. Current surgical and oncological treatments are palliative, do not reduce overall mortality, and therefore optimal management of adults at risk of pathologic fractures presents an unmet medical need. Plain radiography lacks specificity and may result in unnecessary prophylactic fixation. Radionuclide imaging techniques primarily supply information on the metabolic activity of the tumor or the bone itself. Magnetic resonance imaging and computed tomography provide excellent anatomical and structural information but do not quantitatively assess bone matrix. Research has now shifted to developing unbiased data-driven tools that can predict risk of impending fractures and guide individualized treatment decisions. This review discusses the state-of-the-art in clinical and experimental approaches for prediction of pathologic fractures with bone metastases. Alterations in bone matrix quality are associated with an age-related increase in skeletal fragility but the impact of metastases on the intrinsic material properties of bone is unclear. Engineering-based analyses are non-invasive with the capability to evaluate oncological treatments and predict failure due to the progression of metastasis. The combination of these approaches may improve our understanding of the underlying deterioration in mechanical performance.