The Canadian Breast Cancer Symposium 2023 Meeting Report.

On 15-16 June 2023, healthcare professionals and breast cancer patients and advocates from across Canada met in Toronto, Ontario, for the 2023 Canadian Breast Cancer Symposium (CBSC.). The CBSC. is a national, multidisciplinary event that occurs every 2 years with the goal of developing a personalized approach to the management of breast cancer in Canada. Experts provided state-of-the-art information to help optimally manage breast cancer patients, including etiology, prevention, diagnosis, experimental biology, and therapy of breast cancer and premalignant breast disease. The symposium also had the objectives of increasing communication and collaboration among breast cancer healthcare providers nationwide and providing a comprehensive and real-life review of the many facets of breast cancer. The sessions covered the patient voice, the top breast cancer papers from different disciplines in 2022, artificial intelligence in breast cancer, systemic therapy updates, the management of central nervous system metastases, multidisciplinary management of ductal carcinoma in situ, special populations, optimization-based individual prognostic factors, toxicity management of novel therapeutics, survivorship, and updates in surgical oncology. The key takeaways of these sessions have been summarized in this conference report.

DUCHESS: an evaluation of the ductal carcinoma in situ score for decisions on radiotherapy in patients with low/intermediate-risk DCIS.

BACKGROUND: Identification of women with DCIS who have a very low risk of local recurrence risk (LRR) after breast-conserving surgery (BCS) is needed to de-escalate therapy. We evaluated the impact of 10-year LRR estimates after BCS, calculated by the integration of a 12-gene molecular expression assay (Oncotype Breast DCIS Score®) and clinicopathological features (CPFs), on its ability to change radiation oncologists' recommendations for RT after BCS for DCIS. METHODS: Prospective cohort study of women with DCIS treated with BCS. Eligibility criteria were as follows: age > 45 years, tumor ≤ 2.5 cm, and margins ≥ 1 mm. Radiation oncologists provided 10-year LRR estimates without RT and recommendation for RT pre- and post-assay. Primary outcome was change in RT recommendation. RESULTS: 217 patients were evaluable, with mean age = 63 years, mean tumor size = 1.1 cm, and mean DCIS Score = 32; 140 (64%) were in the low-risk (<39), 32 (15%) were in the intermediate-risk (39-54), and 45 (21%) were in the high-risk groups (≥55). The assay led to a change in treatment recommendation in 76 (35.2%) (95%CI 29.1-41.8%) patients. RT recommendations decreased from 79% pre-assay to 50% post-assay (difference = 29%; 95%CI 22-35%) due to a significant increase in the proportion of patients with a predicted low LRR (< 10%) post-assay and recommendations to omit RT for those with a low predicted risk. The assay was associated with improved patient satisfaction and reduced decisional conflict. CONCLUSION: The DCIS Score assay combined with CPFs identified more women with an estimated low (<10%) 10-yr LR risk after BCS, leading to a significant decrease in recommendations for RT compared to estimates based on CPFs alone.

The Role of Partial Breast Radiation in the Previously Radiated Breast.

OBJECTIVES: The aim of this study was to analyze breast cancer patients who previously had mantle-field or breast radiation (RT) followed by retreatment with external beam partial breast irradiation (EB PBI). MATERIALS AND METHODS: We retrospectively reviewed all women with newly diagnosed early-stage breast cancer treated with lumpectomy and partial breast irradiation between 2007 and 2017 who had undergone prior chest or breast RT. RESULTS: Of 11 patients recorded, 8 (73%) had Hodgkin lymphoma, and 3 (27%) had ipsilateral breast cancer diagnosis. Median age at initial and second diagnosis was 28 and 48 years, respectively. The lymphoma patients received a dose of 35 Gy in 16 to 20 fractions to a classic mantle-upper abdomen field. Patients with an initial diagnosis of breast cancer received whole-breast RT (2 with 50 Gy/25 fractions, 1 with 40 Gy in 16 fractions). Median time from initial to second diagnosis was 22.6 years (range, 13.5 to 32.6 y). All had early-stage (I to II) invasive ductal carcinoma and were treated with lumpectomy or repeat lumpectomy and EB PBI. Four received a dose of 45 Gy/25 fractions, 4 to 50 Gy/25 fractions, and 3 to 42.4 Gy/16 fractions. All patients received adjuvant systemic treatment. Two patients had toxicity, 1 had grade 1 induration, and the other had grade 2 fat atrophy and grade 1 fibrosis. One patient developed a contralateral breast cancer. No locoregional recurrences were reported at the median follow-up of 4.6 years (range, 0.6 to 10.5 y). CONCLUSION: EB PBI after lumpectomy seems to be a safe and effective RT treatment option for selected patients with prior RT and localized early-stage breast cancer.

A positive association between nutritional risk and the incidence of surgical site infections: A hospital-based register study.

Surgical site infections (SSI) are amongst the most common health care-associated infections and have adverse effects for patient health and for hospital resources. Although surgery guidelines recognize poor nutritional status to be a risk factor for SSI, they do not tell how to identify this condition. The screening tool Nutritional Risk Screening 2002 is commonly used at hospitals to identify patients at nutritional risk. We investigated the association between nutritional risk and the incidence of SSI among 1194 surgical patients at Haukeland University Hospital (Bergen, Norway). This current study combines data from two mandatory hospital-based registers: a) the incidence of SSI within 30 days after surgery, and b) the point-prevalence of patients at nutritional risk. Patients with more than 30 days between surgery and nutritional risk screening were excluded. Associations were assessed using logistic regression, and the adjusted odds ratio included age (continuous), gender (male/female), type of surgery (acute/elective) and score from The American Society of Anesthesiologists Physical Status Classification System. There was a significant higher incidence of SSI among patients at nutritional risk (11.8%), as compared to those who were not (7.0%) (p = 0.047). Moreover, the incidence of SSI was positively associated with the prevalence of nutritional risk in both simple (OR 1.76 (95% CI: 1.04, 2.98)) and adjusted (OR 1.81 (95% CI: 1.04, 3.16)) models. Answering "yes" to the screening questions regarding reduced dietary intake and weight loss was significantly associated with the incidence of SSI (respectively OR 2.66 (95% CI: 1.59, 4.45) and OR 2.15 (95% CI: 1.23, 3.76)). In conclusion, we demonstrate SSI to occur more often among patients at nutritional risk as compared to those who are not at nutritional risk. Future studies should investigate interventions to prevent both SSI and nutritional risk among surgical patients.

Neutrophils Kill Reactive Oxygen Species-Resistant Pseudomonas aeruginosa by Sphingosine.

BACKGROUND/AIMS: Cystic fibrosis (CF) is dominated by chronic inflammation and infection of the lung resulting in lung destruction and early death of patients. The lungs of CF patients are characterized by a massive accumulation of neutrophils. It requires definition why these massive numbers of neutrophils fail to eliminate typical CF pathogens like Staphylococcus aureus and Pseudomonas aeruginosa (P. aeruginosa) in CF lungs. METHODS: We determined ceramide, sphingosine and reactive oxygen species (ROS) in neutrophils from wildtype and CF mice and determined the effect of sphingosine and ROS alone or in combination on killing of different P. aeruginosa strains. RESULTS: We demonstrate that wildtype neutrophils are able to kill non-mucoid and mucoid clinical P. aeruginosa strains, while neutrophils from CF mice are insufficient to kill these P. aeruginosa strains, although both types of neutrophils infected with P. aeruginosa produce comparable levels of superoxide. All three analyzed P. aeruginosa strains are resistant to reactive oxygen species. The inability of CF neutrophils to kill P. aeruginosa is caused by a marked decrease of surface sphingosine levels in CF neutrophils. Wildtype neutrophils contain much higher concentrations of surface sphingosine than CF neutrophils. Further, wildtype neutrophils, but not CF neutrophils, release sphingosine, most likely as microparticles, upon infection. Sphingosine kills P. aeruginosa in vitro at low micromolar concentrations. Reconstitution of sphingosine in CF neutrophils restores their ability to kill these pathogens, demonstrating the significance of sphingosine for bacterial killing. CONCLUSION: The data provide evidence for a new paradigm explaining how neutrophils kill ROS-resistant P. aeruginosa, i.e. by sphingosine that kills P. aeruginosa at low concentrations. This mechanism is defective in CF neutrophils.

Predictors of breast radiotherapy plan modifications: quality assurance rounds in a large cancer centre.

BACKGROUND AND PURPOSE: This study describes the process and outcomes of breast radiotherapy (RT) quality assurance (QA) rounds, seeking to identify variables associated with plan modifications. MATERIALS AND METHODS: Real-time data were prospectively collected over 2 years. Descriptive statistics determined the proportion of cases requiring no (A), minor (B), or major (C) modifications, which were then subjected to univariate and multivariate analyses. RESULTS: A total of 2223 breast cancer QA cases were reviewed; 47 cases (2.1%) underwent a minor, and 52 cases (2.3%) required a major modification. Common changes included boost, volume, seroma, and bolus. On univariate analysis, regional nodal irradiation (RNI), tumour size, and axillary node dissection were significantly associated with major modifications. Upon multivariate analysis, the only independent predictor was RNI (OR 2.12, p=0.0075). For patients with no RNI, <2 cm tumours, no axillary lymph node dissection, and no boosts (n=420); the likelihood of category C was only 1.4%. CONCLUSIONS: It is feasible to conduct QA review for all breast cancer cases prior to commencing RT. Patients undergoing RNI had a higher likelihood of plan modifications; a group with low risk of modification was identified, which could direct future re-structuring of QA rounds.

Therapy adapted to molecular response in patients with chronic myelogenous leukaemia in first chronic phase: results of the Duesseldorf study.

This study evaluates response-adapted treatment of chronic myelogenous leukaemia (CML) in chronic phase using molecular response criteria. bcr-abl/G6PDH ratios were assessed by Light-Cycler quantitative real-time polymerase chain reaction (PCR( in 277 peripheral blood samples from 33 patients, before and every 3 months during therapy. Sixty-six per cent (22/33) of the patients fulfiled our molecular response criterion of > or = 1 log decrease in bcr-abl transcript after 6 or > or = 2 log decrease after 9 and every following 3 months. Dose escalation was necessary for 33% (11/33) of the patients. Of these, 54% (6/11) achieved a reduction of bcr-abl mRNA by > or = 2 log (n = 3) or > or = 3 log (n = 3) with 800 mg Imatinib. Forty-five per cent (5/11) showed insufficient molecular response with 800 mg Imatinib and received Nilotinib. In conclusion, the assessment of molecular response permits an individual patient-tailored treatment of CML in first chronic phase, resulting in the majority of patients achieving a major molecular response after 2 years of therapy.

Benefit assessment of preventive medical check-ups in patients suffering from chronic granulomatous disease (CGD).

BACKGROUND: Chronic granulomatous disease (CGD) patients are susceptible to recurrent opportunistic infections and to recurrent or chronic inflammations of presumably non-infectious origin. Both types of manifestations are often accompanied by granuloma formation. Both can remain unnoticed until they deteriorate considerably and can become life-threatening if not treated in time. OBJECTIVE: To evaluate the effectiveness of regular follow-up visits in CGD patients. METHODS: Findings of imaging (ultrasound, radiographs, computer-tomography, magnetic resonance imaging), lung function tests, histopathological and microbiological assessments of biopsies have been reviewed. RESULTS: A total of 32 CGD patients have been evaluated within 15 years. Of these eight patients have been checked regularly for more than 5 years. Early detection prior to specific clinical signs and consecutive treatment of six lung manifestations and one liver manifestation such as interstitial pneumonia with formation of small granulomas, formation of large granulomas, fibrosis, Aspergillus infections, and abscesses could presumably prevent considerable aggravation in seemingly healthy or mildly symptomatic patients. In contrast, patients without surveillance who presented with severe symptoms (seven manifestations) often had irreversible organ damage or even died. CONCLUSIONS: Regular follow-up visits can help prevent or mitigate clinical manifestations, improve life quality and expectancy and weigh indication for bone marrow transplantation in CGD patients.

Successful elimination of an invasive Aspergillus nidulans lung infection by voriconazole after failure of a combination of caspofungin and liposomal amphotericin B in a boy with chronic granulomatous disease.

Chronic granulomatous disease is an inherited defect in host defense mechanisms mainly affecting neutrophil function. Pulmonary infection with Aspergillus nidulans in a child with chronic granulomatous disease could not be eliminated by a combination of caspofungin and liposomal amphotericin B. Voriconazole was successful in clearing the infection.