Surgery (RMH) - Research Publications
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ItemNo Preview AvailableUniversal genetic testing for women with newly diagnosed breast cancer in the context of multidisciplinary team care(WILEY, 2023-05-01)OBJECTIVE: To determine the feasibility of universal genetic testing of women with newly diagnosed breast cancer, to estimate the incidence of pathogenic gene variants and their impact on patient management, and to evaluate patient and clinician acceptance of universal testing. DESIGN, SETTING, PARTICIPANTS: Prospective study of women with invasive or high grade in situ breast cancer and unknown germline status discussed at the Parkville Breast Service (Melbourne) multidisciplinary team meeting. Women were recruited to the pilot (12 June 2020 - 22 March 2021) and expansion phases (17 October 2021 - 8 November 2022) of the Mutational Assessment of newly diagnosed breast cancer using Germline and tumour genomICs (MAGIC) study. MAIN OUTCOME MEASURES: Germline testing by DNA sequencing, filtered for nineteen hereditary breast and ovarian cancer genes that could be classified as actionable; only pathogenic variants were reported. Surveys before and after genetic testing assessed pilot phase participants' perceptions of genetic testing, and psychological distress and cancer-specific worry. A separate survey assessed clinicians' views on universal testing. RESULTS: Pathogenic germline variants were identified in 31 of 474 expanded study phase participants (6.5%), including 28 of 429 women with invasive breast cancer (6.5%). Eighteen of the 31 did not meet current genetic testing eligibility guidelines (probability of a germline pathogenic variant ≥ 10%, based on CanRisk, or Manchester score ≥ 15). Clinical management was changed for 24 of 31 women after identification of a pathogenic variant. Including 68 further women who underwent genetic testing outside the study, 44 of 542 women carried pathogenic variants (8.1%). Acceptance of universal testing was high among both patients (90 of 103, 87%) and clinicians; no decision regret or adverse impact on psychological distress or cancer-specific worry were reported. CONCLUSION: Universal genetic testing following the diagnosis of breast cancer detects clinically significant germline pathogenic variants that might otherwise be missed because of testing guidelines. Routine testing and reporting of pathogenic variants is feasible and acceptable for both patients and clinicians.
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ItemOutcomes of women at high familial risk for breast cancer: An 8-year single-center experience(WILEY, 2020-04)OBJECTIVES: The value of a high-risk surveillance program for mutation carriers and women at high familial breast cancer risk has not been extensively studied. A Breast and Ovarian Cancer Risk Management Clinic (BOCRMC) was established at the Royal Melbourne Hospital in 2010 to provide multimodality screening and risk management strategies for this group of women. The aims of this study were to evaluate the program and describe breast cancer diagnoses for BRCA1, BRCA2, and other germline mutation carriers as well as high-risk noncarriers attending the BOCRMC. METHODS: Clinical data from mutation carriers and noncarriers with a ≥25% lifetime risk of developing breast cancer who attended between 2010 and 2018 were extracted from clinic records and compared. The pattern and mode of detection of cancer were determined. RESULTS: A total of 206 mutation carriers and 305 noncarriers attended the BOCRMC and underwent screening on at least one occasion. Median age was 37 years. After a median follow-up of 34 months, 15 (seven invasive) breast cancers were identified in mutation carriers, with seven (six invasive) breast cancers identified in noncarriers. Of these, 20 (90.9%) were detected by annual screening, whereas two (9.1%) were detected as interval cancers (both in BRCA1 mutation carriers). Median size of the invasive breast cancers was 11 mm (range: 1.5-30 mm). The majority (76.9%) were axillary node negative. In women aged 25-49 years, the annualized cancer incidence was 1.6% in BRCA1, 1.4% in BRCA2 mutation carriers, and 0.5% in noncarriers. This compares to 0.06% annualized cancer incidence in the general Australian population. CONCLUSIONS: Screening was effective at detecting early-stage cancers. The incidence of events in young noncarriers was substantially higher than in the general population. This potentially justifies ongoing management through a specialty clinic, although further research to better personalize risk assessment in noncarriers is required.
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ItemA single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast(WILEY, 2021-06-01)To examine global changes in breast heterogeneity across different states, we determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1+/- tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes. Elucidation of the normal breast microenvironment revealed striking changes in the stroma of post-menopausal women. Single-cell profiling of 34 treatment-naive primary tumors, including estrogen receptor (ER)+ , HER2+ , and triple-negative breast cancers, revealed comparable diversity among cancer cells and a discrete subset of cycling cells. The transcriptomes of preneoplastic BRCA1+/- tissue versus tumors highlighted global changes in the immune microenvironment. Within the tumor immune landscape, proliferative CD8+ T cells characterized triple-negative and HER2+ cancers but not ER+ tumors, while all subtypes comprised cycling tumor-associated macrophages, thus invoking potentially different immunotherapy targets. Copy number analysis of paired ER+ tumors and lymph nodes indicated seeding by genetically distinct clones or mass migration of primary tumor cells into axillary lymph nodes. This large-scale integration of patient samples provides a high-resolution map of cell diversity in normal and cancerous human breast.
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ItemNo Preview AvailableMammography Adherence among High-Risk Women with Breast Cancer and Either a Non-Pathogenic Mutation Identified or Untested BRCA1/2 Genetic Status(IOS Press, 2020-11-06)Background: Little is known about the illness perceptions of women with a previous breast cancer diagnosis and either no access to a personal BRCA1/2 test or tested and a no pathogenic mutation identified result and how this might impact their mammography adherence. Objective: The aim of this study was to assess the impact of illness beliefs, specifically those relating to emotional representations and cure and control beliefs about breast cancer, and socio-economic status (SES) on mammography adherence of these women. The traditional health belief model (HBM) was compared to a modified model which allowed for the contribution of emotions in health surveillance decision-making. Method: Mailed self-report questionnaires were completed by 193 women recruited from an Australian Familial Cancer Centre. Step-wise logistic regression analyses were conducted on n=150 [aged 27-89 years (M=56.9)] for whom complete data were available. Results: The questionnaire response rate was 36%. Higher levels of emotional representations of breast cancer were associated with greater mammography adherence (OR = 1.18, 95% CI = 1.03-1.36, p =.019). Middle income was six times more likely to predict mammography adherence than lower income (OR = 6.39, 95% CI = 1.03 – 39.63, p =.047). The modified HBM was superior to the traditional HBM in predicting mammography adherence (X2 [15, N = 118] = 26.03, p =.038). Conclusions: Despite a modest response rate, our data show that emotional illness representations about breast cancer and middle income status were found to significantly predict mammography adherence. Therefore, providing surveillance services and delivering information considerate of financial status and constructed around emotional motivators may facilitate mammography adherence among women like those described in this study.
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