Purpose To make recommendations regarding the use of bisphosphonates and other bone-modifying agents as adjuvant therapy for patients with breast cancer. Methods Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature. Results Adjuvant bisphosphonates were found to reduce bone recurrence and improve survival in postmenopausal patients with nonmetastatic breast cancer. In this guideline, postmenopausal includes patients with natural menopause or that induced by ovarian suppression or ablation. Absolute benefit is greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. Most studies evaluated zoledronic acid or clodronate, and data are extremely limited for other bisphosphonates. While denosumab was found to reduce fractures, long-term survival data are still required. Recommendations It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation. Use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the scope of the guideline. Recommendations are not meant to restrict such use of bone-modifying agents in these situations. Additional information at www.asco.org/breast-cancer-adjuvant-bisphosphonates-guideline , www.asco.org/guidelineswiki , https://www.cancercareontario.ca/guidelines-advice/types-of-cancer/breast .

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Extracellular DNA production and clearance mechanisms are dysregulated in DED. Nuclease deficiency in tear fluid allows eDNA and NETs to accumulate in precorneal tear film, and results in ocular surface inflammation. These findings point to novel therapeutic interventions in severe DED based on clearance of eDNA, NETs, and other molecular components from the ocular surface.

Early alterations in textural characteristics of quantitative ultrasound spectral parametric maps, in conjunction with changes in their mean values, are demonstrated here, for the first time, to be capable of predicting ultimate clinical/pathologic responses of breast cancer patients to chemotherapy. Mechanisms of cell death, induced by chemotherapy within tumor, introduce morphological alterations in cancerous cells, resulting in measurable changes in tissue echogenicity. We have demonstrated that the development of such changes is reflected in early alterations in textural characteristics of quantitative ultrasound spectral parametric maps, followed by consequent changes in their mean values. The spectral/textural biomarkers derived on this basis have been demonstrated as non-invasive surrogates of breast cancer chemotherapy response. Particularly, spectral biomarkers sensitive to the size and concentration of acoustic scatterers could predict treatment response of patients with up to 80% of sensitivity and specificity (p=0.050), after one week within 3-4 months of chemotherapy. However, textural biomarkers characterizing heterogeneities in distribution of acoustic scatterers, could differentiate between treatment responding and non-responding patients with up to 100% sensitivity and 93% specificity (p=0.002). Such early prediction permits offering effective alternatives to standard treatment, or switching to a salvage therapy, for refractory patients.

Oncologists ranked patient- and family-related factors as the most important barriers to GOC discussions, while clinicians' self-identified difficulty estimating prognosis and uncertainty regarding treatment benefits were also considered important. Further work is required to assess patient preferences and perceptions and develop targeted interventions.

BACKGROUND.Despite the advantages from using aromatase inhibitors (AIs) compared with tamoxifen for early breast cancer, an unexpectedly greater number of grade 3 and 4 cardiovascular events (CVAE) (as defined by National Cancer Institute of Canada‐Common Toxicity Criteria [version 2.0] was demonstrated.METHODS.Phase 3 randomized clinical trials (RCTs) comparing AI with tamoxifen in early breast cancer were considered eligible for this review. The event‐based risk ratios (RRs) with 95% confidence intervals (95% CIs) were derived, and a test of heterogeneity was applied. Finally, absolute differences (ADs) in event rates and the number of patients needed to harm 1 patient (NNH) were determined.RESULTS.Seven eligible RCTs (19,818 patients) reported CVAE results. When considering all RCTs, the AD of the primary endpoint (CVAE) between the 2 arms (0.52%), tamoxifen versus AI, was statistically significant (RR, 1.31; 95% CI, 1.07–1.60; P = .007). This translated into an NNH value of 189 patients; when only third‐generation AIs were considered, the difference (0.57%) remained significant (RR, 1.34; 95% CI, 1.09–1.63; P = .0038). Thromboembolic events were significantly more frequent in the tamoxifen arm, regardless of the strategy adopted (RR, 0.53; 95% CI, 0.42–0.65; P < .0001), without significant heterogeneity (P = .21). An AD of 1.17% and an NNH value of 85 patients were observed.CONCLUSIONS.According to the results from this meta‐analysis, the risk of grade 3 and 4 CVAEs in patients who were receiving AIs was higher compared with the risk in patients who were receiving tamoxifen, and the difference reached statistical significance. However, the AD was relatively low, and from 160 to 180 patients had to be treated to produce 1 event. Cancer 2008. © 2007 American Cancer Society.

Attempted suicide is associated with significantly higher rates of maternal and perinatal morbidity, and in some cases, perinatal mortality. The best identifier for women at risk for attempting suicide is substance abuse. Care provider identification and prevention are of key importance in preventing these outcomes.

Objective To evaluate the effectiveness of remote proactive management of toxicities during chemotherapy for early stage breast cancer. Design Pragmatic, cluster randomised trial. Setting 20 cancer centres in Ontario, Canada, allocated by covariate constrained randomisation to remote management of toxicities or routine care. Participants All patients starting adjuvant or neoadjuvant chemotherapy for early stage breast cancer at each centre. 25 patients from each centre completed patient reported outcome questionnaires. Interventions Proactive, standardised, nurse led telephone management of common toxicities at two time points after each chemotherapy cycle. Main outcome measures The primary outcome, cluster level mean number of visits to the emergency department or admissions to hospital per patient during the whole course of chemotherapy treatment, was evaluated with routinely available administrative healthcare data. Secondary patient reported outcomes included toxicity, self-efficacy, and quality of life. Results Baseline characteristics of participants were similar in the intervention (n=944) and control arms (n=1214); 22% were older than 65 years. Penetration (that is, the percentage of patients who received the intervention at each centre) was 50-86%. Mean number of visits to the emergency department or admissions to hospital per patient was 0.91 (standard deviation 0.28) in the intervention arm and 0.94 (0.40) in the control arm (P=0.94); 47% (1014 of 2158 patients) had at least one visit to the emergency department or a hospital admission during chemotherapy. Among 580 participants who completed the patient reported outcome questionnaires, at least one grade 3 toxicity was reported by 48% (134 of 278 patients) in the intervention arm and by 58% (163 of 283) in the control arm. No differences in self-efficacy, anxiety, or depression were found. Compared with baseline, the functional assessment of cancer therapy trial outcome index decreased by 6.1 and 9.0 points in the intervention and control participants, respectively. Conclusions Proactive, telephone based management of toxicities during chemotherapy did not result in fewer visits to the emergency department or hospital admissions. With the rapid rise in remote care because of the covid-19 pandemic, identifying scalable strategies for remote management of patients during cancer treatment is particularly relevant. Trial registration ClinicalTrials.gov NCT02485678 .