Quality of Life Outcomes Associated With Optimization of Treatment by Omitting Radiotherapy in Early Breast Cancer.

PURPOSE: Improved prognosis of early breast cancer (EBC) has created opportunities for treatment optimization but reducing morbidity should not inadvertently compromise quality of life (QoL). PROSPECT1 used pre-operative MRI and pathology findings to identify women suitable for radiotherapy (RT) omission following breast conserving surgery. We retrospectively explored the association between de-escalation by omission of RT and QoL in women with EBC. MATERIALS AND METHODS: Three groups were recruited: PROSPECT participants who omitted RT following preoperative MRI (A); participants who received RT following preoperative MRI (B); and women who received usual care - No MRI, received RT (C). Measures included the EORTC QLQ-C30 and BR23, BCTOS, DASS-21 and a measure of decision regret. Between group differences were assessed using ANOVA or nonparametric equivalents. Semi-structured interviews were analyzed with qualitative description (n = 44). RESULTS: Data from 400 women were analyzed (125A, 102B, 173C). Group A had fewer symptoms and better body image (breast symptoms: A-B P = .003, A-C P = <.001; arm symptoms: A-B P = .004, A-C P = .011; body image: A-C P = .041) and fewer differences between the treated and untreated breasts (cosmetic: A-B P < .001, A-C P < .001; functional: A-C P = .011; breast specific pain: A-B P < .001, A-C P < .001). Two qualitative themes were found: Treatment with the biggest impact on QoL, and Specific impact of RT on QoL. CONCLUSIONS: Omission of RT was associated with better QoL and functional and cosmetic outcomes. It was highly acceptable to patients. Clinicians should consider the potential for preserved QoL associated with treatment optimization via omission of RT in treatment planning for patients with EBC.

Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study.

BACKGROUND: Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy. METHODS: PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011). FINDINGS: Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient. INTERPRETATION: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy. FUNDING: Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation.

Is de-escalation of treatment by omission of radiotherapy associated with fear of cancer recurrence in women with early breast cancer? An exploratory study.

PURPOSE: Safe de-intensification of adjuvant radiotherapy (RT) for early breast cancer (BC) is currently under evaluation. Little is known about the patient experience of de-escalation or its association with fear of cancer recurrence (FCR), a key issue in survivorship. We conducted a cross-sectional study to explore this association. METHODS: Psychometrically validated measures including the Fear of Cancer Recurrence Inventory-Short Form were completed by three groups of women with early BC: Women in the PROSPECT clinical trial who underwent pre-surgical MRI and omitted RT (A), women who underwent pre-surgical MRI and received RT (B); and women who received usual care (no MRI, received RT; C). Between group differences were analysed with non-parametric tests. A subset from each group participated in a semi-structured interview. These data (n = 44) were analysed with directed content analysis. RESULTS: Questionnaires from 400 women were analysed. Significantly lower FCR was observed in Group A (n = 125) than in Group B (n = 102; p = .002) or Group C (n = 173; p = .001), and when participants were categorized by RT status (omitted RT vs received RT; p < .001). The proportion of women with normal FCR was significantly (p < .05) larger in Group A (62%) than in Group B (35%) or Group C (40%). Two qualitative themes emerged: 'What I had was best' and 'Coping with FCR'. CONCLUSIONS: Omitting RT in the setting of the PROSPECT trial was not associated with higher FCR than receiving RT. Positive perceptions about tailored care, lower treatment burden, and trust in clinicians appear to be protective against FCR.

Universal genetic testing for women with newly diagnosed breast cancer in the context of multidisciplinary team care.

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.

Contrast enhanced mammography in breast cancer surveillance.

PURPOSE: Mammography (MG) is the standard imaging in surveillance of women with a personal history of breast cancer or DCIS (PHBC), supplemented with ultrasound. Contrast Enhanced Mammography (CEM) has higher sensitivity than MG and US. We report the performance of CEM compared with MG ± US. METHODS: A retrospective study of patients undergoing their first surveillance CEM in an Australian hospital setting between June 2006 and October 2020. Cases where a patient was recalled for assessment were identified, recording radiology, pathology and treatment details. Blinded re-reading of recalled cases was performed to determine the contribution of contrast. Use of surveillance US across the board was assessed for the period. RESULTS: 73/1191 (6.1%) patients were recalled. 35 (48%) were true positives (TP), with 26 invasive cancers and 9 cases of DCIS, while 38 (52%) were false positive (FP) with a positive predictive value (PPV) 47.9%. 32/73 were recalled due to MG findings, while 41/73 were only recalled due to Contrast. 14/73 had 'minimal signs' with a lesion identifiable on MG with knowledge of the contrast finding, while 27/73 were visible only with contrast. 41% (17/41) recalled due to contrast were TP. Contrast-only TPs were found with low and high mammographic density (MD). Screening breast US reduced by 55% in the year after CEM was implemented. CONCLUSION: Compared to MG, CEM as a single surveillance modality for those with PHBC has higher sensitivity and comparable specificity, identifying additional malignant lesions that are clinically significant. Investigation of interval cancer and subsequent round outcomes is warranted.

Moving beyond the stage: how characteristics at diagnosis dictate treatment and treatment-related quality of life year losses for women with early stage invasive breast cancer.

Background:Although evaluations of breast cancer screening programs frequently estimate quality-adjusted life-year (QALY) losses by stage, other breast cancer characteristics influence treatment and vary by mode of detection - i.e. whether the cancer is detected through screening (screen-detected), between screening rounds (interval-detected) or outside screening (community-detected). Here, we estimate the association between early-stage invasive breast cancer (ESIBC) characteristics and treatment-related QALY losses.Methods:Using clinicopathological and treatment information from 675 women managed for ESIBC, we estimated the average five-year treatment-related QALY loss by detection group. We then used regression analysis to estimate the extent to which known cancer characteristics and the detection mode, are associated with treatment and treatment-related QALY losses.Results:Community-detected cancers had the largest QALY loss (0.76 QALYs [95% CI 0.73;0.80]), followed by interval-detected cancers (0.75 QALYs [95% CI 0.68;0.82]) and screen-detected cancers (0.69 QALYs [95%CI 0.67;0.71]). Adverse prognostic factors more common in community-detected and interval-detected breast cancers (large tumours, lymph node involvement, high grade) were largely associated with QALY losses from mastectomies and chemotherapy. Receptor-positive subtypes, more common in screen-detected cancers, were associated with QALY losses related to endocrine therapy.Conclusions:The associations between ESIBC characteristics and treatment-related QALY losses should be considered when evaluating breast cancer screening and treatment strategies.

Breast Cancer Survivor Symptoms: A Comparison of Physicians' Consultation Records and Nurse-Led Survivorship Care Plans.

BACKGROUND: Survivorship care plans (SCPs) have been used to address ongoing health problems associated with the diagnosis and treatment of early-stage breast cancer. OBJECTIVES: The aim of this article was to determine whether nurse-led consultations using SCPs, as compared with a standard medical consultation, identify more side effects and supportive care needs and lead to appropriate referral patterns. METHODS: The study audited 160 retrospective medical clinic and nursing SCP records in a sample of patients receiving treatment for early-stage breast cancer at a tertiary-level breast service in Australia. FINDINGS: Breast care nurses (BCNs) undertaking SCPs at a nurse-led consultation were significantly more likely than physicians to record symptoms related to menopausal/hormonal therapy, psychosocial/mental health, lifestyle, bone health, and sexuality. BCNs were also significantly more likely to refer patients for concerns related to psychosocial/mental health, lifestyle, and sexuality.

Treatment Intensity Differences After Early-Stage Breast Cancer (ESBC) Diagnosis Depending on Participation in a Screening Program.

BACKGROUND: While population mammographic screening identifies early-stage breast cancers (ESBCs; ductal carcinoma in situ [DCIS] and invasive disease stages 1-3A), commentaries suggest that harms from overdiagnosis and overtreatment may outweigh the benefits. Apparent benefits to patients with screen-detected cancers may be due to selection bias from exclusion of interval cancers (ICs). Treatment intensity is rarely discussed, with an assumption that all ESBCs are treated similarly. We hypothesized that women diagnosed while in a screening program would receive less-intense treatment than those never or not recently screened (NRS). METHODS: This was a retrospective analysis of all women aged 50-69 years managed for ESBC (invasive or DCIS) during the period 2007-2013 within a single service, comparing treatment according to screening status. Data on demographics, detection, pathology, and treatment were derived from hospital, cancer registry, and screening service records. RESULTS: Overall, 622 patients were active screeners (AS) at diagnosis (569 screen-detected and 53 ICs) and 169 patients were NRS. AS cancers were smaller (17 mm vs. 26 mm, p < 0.0001), less likely to involve nodes (26% vs. 48%, p < 0.0001), and lower grade. For invasive cancer, NRS patients were more likely to be recommended for mastectomies [35% vs. 16%; risk ratio(RR) 2.2, p < 0.0001], axillary dissection (43% vs. 19%; RR 2.3, p < 0.0001), adjuvant chemotherapy (65% vs. 37%; RR 1.7, p < 0.0001), and postmastectomy radiotherapy (58% vs. 39%; RR 1.5, p = 0.04). CONCLUSION: Participants in population screening diagnosed with ESBC receive substantially less-intense treatment than non-participants. Differences persist when potential overdiagnosis is taken into account; these differences should be factored into debates around mammographic screening.

Uptake of adjuvant breast cancer treatments recommended by multi-disciplinary meetings.

BACKGROUND: Adjuvant therapy for breast cancer is routinely discussed and recommended in multi-disciplinary meetings (MDMs). Current literature explores how treatments received by patients differ from national guidelines; however, it does not explore whether treatment is concordant with MDMs. This study provides an Australian perspective on the uptake of MDM recommendations and reasons for non-concordance. METHODS: A retrospective cohort study of patients with breast cancer presented at The Royal Melbourne Hospital MDM in 2010 and 2014 to investigate the concordance between MDM recommendations and treatment received. RESULTS: The study group comprised 441 patients (161 from 2010 and 280 from 2014). A total of 375 patients were included in the analyses. Overall, 82% of patients had perfect concordance between recommended and received treatment for all modes of adjuvant therapy. Concordance to endocrine therapy was higher for invasive cancers than ductal carcinoma in situ (97% versus 81%, P < 0.0001). Concordance to radiotherapy was high and did not differ according to type of cancer or surgery (ranging from 88 to 91%). Concordance to chemotherapy recommendations was high overall (92%) and did not vary with nodal status. Women aged over 65 years were least likely to be recommended for adjuvant therapy but most likely to concordant with the recommendation. CONCLUSIONS: Uptake of MDM-recommended treatments is high. There is a minority of patients in whom MDM recommendations are not followed, highlighting that there are extra steps between recommendations at an MDM and decisions with patients. More attention to this issue is appropriate, and the reasons for non-concordance warrant further study.