10-Year axillary recurrence in the RACS SNAC1 randomised trial of sentinel lymph node-based management versus routine axillary lymph node dissection.

BACKGROUND: Sentinel node-based management (SNBM) is the international standard of care for early breast cancer that is clinically node-negative based on randomised trials comparing it with axillary lymph node dissection (ALND) and reporting similar rates of axillary recurrence (AR) without distant disease. We report all ARs, overall survival, and breast cancer-specific survival at 10-years in SNAC1. METHODS: 1.088 women with clinically node-negative, unifocal breast cancers 3 cm or less in diameter were randomly assigned to either SNBM with ALND if the sentinel node (SN) was positive, or to SN biopsy followed by ALND regardless of SN involvement. RESULTS: First ARs were more frequent in those assigned SNBM rather than ALND (11 events, cumulative risk at 10-years 1·85%, 95% CI 0·95-3.27% versus 2 events, 0·37%, 95% CI 0·08-1·26%; HR 5·47, 95% CI 1·21-24·63; p = 0·013). Disease-free survival, breast cancer-specific survival, and overall survival were similar in those assigned SNBM versus ALND. Lymphovascular invasion was an independent predictor of AR (HR 6·6, 95% CI 2·25-19·36, p < 0·001). CONCLUSION: First ARs were more frequent with SNBM than ALND in women with small, unifocal breast cancers when all first axillary events were considered. We recommend that studies of axillary treatment should report all ARs to give an accurate indication of treatment effects. The absolute frequency of AR was low in women meeting our eligibility criteria, and SNBM should remain the treatment of choice in this group. However, for those with higher-risk breast cancers, further study is needed because the estimated risk of AR might alter their choice of axillary surgery.

Safety and efficacy of immediate autologous breast reconstruction after mastectomy in patients undergoing neoadjuvant chemoradiotherapy for locally advanced breast cancer.

PURPOSE: Immediate autologous breast reconstruction (IABR) offers fewer surgeries with better psychosocial, quality of life and aesthetic outcomes. In high-risk patients or those with locally advanced breast cancer (LABC), adjuvant postmastectomy radiotherapy decreases local recurrence and improves survival. However, it has negative effects on the reconstructed flap. Reversing the treatment protocol using neoadjuvant radiotherapy may minimise the negative effects on the reconstructed breast in women requesting IABR. We assessed the safety and efficacy of women who underwent mastectomy and IABR post-neoadjuvant chemoradiotherapy (NACRT) for LABC. METHODOLOGY: A cohort study using a retrospective and prospective analysis was performed on women with LABC who underwent mastectomy and IABR post-NACRT between 1998 and 2018. All reconstructions were performed by oncoplastic breast surgeons from a single unit. Outcome measures analysed included surgical complications, flap failure, loco-regional recurrence, overall and disease-free survival. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study was approved by the institutional review board. RESULTS: A total of 28 women with a median age of 50 (33-64) were included. 25% underwent TRAM flap and 75% underwent LD flap reconstruction. The median period of follow-up was 61 months. Post-NACRT, 35.7% achieved complete pathological response (PCR). 3/28 (10.7%) had early complications (2 implant and 1 donor site infection). 7% underwent revision surgery. There was no flap loss. 1/28 (3.5%) had loco-regional recurrence, 3.2% had distant metastasis, and 2.5% had breast cancer related mortality. CONCLUSION: In women with LABC, NACRT followed by mastectomy and IABR is safe and may not compromise oncological and cosmetic outcomes. If offers the benefits of immediate breast reconstruction and avoids delaying adjuvant therapy.

Breast cancer screening-opportunistic use of registry and linked screening data for local evaluation.

RATIONALE: Screening has been found to reduce breast cancer mortality at a population level in Australia, but these studies did not address local settings where numbers of deaths would generally have been too low for evaluation. Clinicians, administrators, and consumer groups are also interested in local service outcomes. We therefore use more common prognostic and treatment measures and survivals to gain evidence of screening effects among patients attending 4 local hospitals for treatment. AIMS AND OBJECTIVES: To compare prognostic, treatment, and survival measures by screening history to determine whether expected screening effects are occurring. METHODS: Employing routine clinical registry and linked screening data to investigate associations of screening history with these measures, using unadjusted and adjusted analyses. RESULTS: Screened women had a 10-year survival from breast cancer of 92%, compared with 78% for unscreened women; and 79% of screened surgical cases had breast conserving surgery compared with 64% in unscreened women. Unadjusted analyses indicated that recently screened cases had earlier tumor node metastasis stages, smaller diameters, less nodal involvement, better tumor differentiation, more oestrogen and progesterone receptor positive lesions, more hormone therapy, and less chemotherapy. Radiotherapy tended to be more common in screening participants. More frequent use of adjunctive radiotherapy applied when breast conserving surgery was used. CONCLUSIONS: Results confirm the screening effects expected from the scientific literature and demonstrate the value of opportunistic use of available registry and linked screening data for indicating to local health administrations, practitioners, and consumers whether local screening services are having the effects expected.

Sentinel node biopsy and large (≥3 cm) breast cancer.

BACKGROUND: Sentinel node biopsy is an accurate method for staging the axilla in early (small) breast cancers. However, data for the role of this technique for large breast cancers remain limited. METHOD: From the Royal Adelaide Hospital Sentinel Node database and the SNAC trial database, 100 subjects were identified with clinically node negative, large (≥3 cm) primary breast cancer who had undergone sentinel node biopsy and immediate axillary clearance. The pathology results from the sentinel node and axillary specimens were analysed. RESULTS: Average tumour size was 3.91 cm (range 3-10 cm) and 65 of 100 cases had metastatic disease in the axillary nodes. A sentinel node was successfully identified in 93 out of 100 cases with an average of 1.75 sentinel nodes sampled. Sixty-two per cent (58 out of 93) were sentinel node positive and 43% (43 out of 100) had a positive non-sentinel node. The false negative rate following successful sentinel node identification was 4.9% (3 out of 61). CONCLUSION: Sentinel node biopsy was an accurate tool for staging the axilla with a false negative rate comparable to that seen in small tumours. However, given the increased incidence of metastases with larger cancers, further prospective investigation is warranted.

Sentinel-lymph-node-based management or routine axillary clearance? One-year outcomes of sentinel node biopsy versus axillary clearance (SNAC): a randomized controlled surgical trial.

We sought the extent to which arm morbidity could be reduced by using sentinel-lymph-node-based management in women with clinically node-negative early breast cancer. One thousand eighty-eight women were randomly allocated to sentinel-lymph-node biopsy followed by axillary clearance if the sentinel node was positive or not detected (SNBM) or routine axillary clearance (RAC, sentinel-lymph-node biopsy followed immediately by axillary clearance). Sentinel nodes were located using blue dye, alone or with technetium-labeled antimony sulfide colloid. The primary endpoint was increase in arm volume from baseline to the average of measurements at 6 and 12 months. Secondary endpoints were the proportions of women with at least 15% increase in arm volume or early axillary morbidity, and average scores for arm symptoms, dysfunctions, and disabilities assessed at 6 and 12 months by patients with the SNAC Study-Specific Scales and other quality-of-life instruments. Sensitivity, false-negative rates, and negative predictive values for sentinel-lymph-node biopsy were estimated in the RAC group. The average increase in arm volume was 2.8% in the SNBM group and 4.2% in the RAC group (P = 0.002). Patients in the SNBM group gave lower ratings for arm swelling (P < 0.001), symptoms (P < 0.001), and dysfunctions (P = 0.02), but not disabilities (P = 0.5). Sentinel nodes were found in 95% of the SNBM group (29% positive) and 93% of the RAC group (25% positive). SNB had sensitivity 94.5%, false-negative rate 5.5%, and negative predictive value 98%. SNBM was successfully undertaken in a wide range of surgical centers and caused significantly less morbidity than RAC.

Treatment and survival from breast cancer: the experience of patients at South Australian teaching hospitals between 1977 and 2003.

RATIONALE: Treatment guidelines recommend a more conservative surgical approach than mastectomy for early stage breast cancer and a stronger emphasis on adjuvant therapy. Registry data at South Australian teaching hospitals have been used to monitor survivals and treatment in relation to these guidelines. AIMS AND OBJECTIVES: To use registry data to: (1) investigate trends in survival and treatment; and (2) compare treatment with guidelines. METHODS: Registry data from three teaching hospitals were used to analyse trends in primary courses of treatment of breast cancers during 1977-2003 (n=4671), using univariate analyses and multiple logistic regression. Disease-specific survivals were analysed using Kaplan-Meier product limit estimates and multivariable Cox proportional hazards regression. RESULTS: The 5-year survival was 79.9%, but with a secular increase, reaching 83.6% in 1997-2003. The relative risk of death (95% confidence limits) was 0.74 (0.62, 0.88) for 1997-2003, compared with previous diagnoses, after adjusting for tumour node metastasis stage, grade, age and place of residence. Treatment changes included an increase in conservative surgery (as opposed to mastectomy) from 51.7% in 1977-1990 to 76.8% in 1997-2003 for stage I (P<0.001) and from 31.1% to 52.2% across these periods for stage II (P<0.001). Adjuvant radiotherapy also became more common (P<0.001), with 20.6% of patients receiving this treatment in 1977-1990 compared with 60.7% in 1997-2003. Radiotherapy generally was more prevalent when conservative surgery was provided, although also relatively common in mastectomy patients when tumour diameters exceeded 50 mm or when there were four or more involved nodes. The proportion of patients receiving chemotherapy increased (P<0.001), from 19.6% in 1977-1990 to 36.9% in 1997-2003, and the proportion having hormone therapy also increased (P<0.001), from 34.3% to 59.4% between these periods. CONCLUSIONS: Survivals appear to be increasing and treatment trends are broadly consistent with guideline directions, and the earlier research on which these recommendations were based.

Prognostic importance of palpability as a feature of screen-detected breast cancers.

OBJECTIVES: To determine epidemiological characteristics of palpability as a feature of asymptomatic invasive breast cancers detected through screening mammography, and to determine whether palpability is predictive of case survival after adjusting for conventional prognostic indicators such as diameter, grade and nodal status. SETTING: The University of Adelaide, South Australian Department of Health, and The Cancer Council South Australia, Adelaide, South Australia. METHODS: Sociodemographic and clinical characteristics of 2108 screen-detected invasive breast cancers were compared by tumour palpability using univariate and multiple logistic regression analysis. Survival outcomes from breast cancer were compared using Kaplan-Meier product-limit estimates. Multivariable proportional hazard regression was employed to assess the association of palpability with survival after adjusting for conventional prognostic indicators. RESULTS: Palpability was associated with year of diagnosis, ductal histology type, and unfavourable prognostic indicators such as larger tumour diameter, higher grade and nodal involvement. After adjusting for these variables, no associations were found with age at diagnosis, place of residence or socioeconomic status, or with presence of multifocal disease or presence of an extensive in situ component. Palpability was predictive of death from breast cancer in an unadjusted analysis, the relative risk (95% confidence limits) being 1.75 (1.12, 2.74). After adjusting for nodal involvement and larger tumour size, the relative risk no longer was elevated, reducing to 0.99 (0.60, 1.64). DISCUSSION: Palpability is associated with unfavourable prognostic indicators, such as larger diameter, higher grade and nodal involvement, and is not an independent indicator of survival outcome for screen-detected female-breast cancers after accounting for nodal involvement and diameter.