Enhanced axillary assessment using intradermally injected microbubbles and contrast-enhanced ultrasound (CEUS) before neoadjuvant systemic therapy (NACT) identifies axillary disease missed by conventional B-mode ultrasound that may be clinically relevant.

PURPOSE: The purpose of this study is to measure pre-treatment diagnostic yield of malignant lymph nodes (LN) using contrast-enhanced ultrasound (CEUS) in addition to B-mode axillary ultrasound and compare clinicopathological features, response to NACT and long-term outcomes of patients with malignant LN detected with B-mode ultrasound versus CEUS. METHODS: Between August 2009 and October 2016, NACT patients were identified from a prospective database. Follow-up data were collected until May 2019. RESULTS: 288 consecutive NACT patients were identified; 77 were excluded, 110 had malignant LN identified by B-mode ultrasound (Group A) and 101 patients with negative B-mode axillary ultrasound had CEUS with biopsy of sentinel lymph nodes (SLN). In two cases CEUS failed. Malignant SLN were identified in 35/99 (35%) of B-mode ultrasound-negative cases (Group B). Patients in Group A were similar to those in Group B in age, mean diagnostic tumour size, grade and oestrogen receptor status. More Group A patients had a ductal phenotype. In the breast, 34 (31%) Group A patients and 8 (23%) Group B patients achieved a pathological complete response (PCR). In the axilla, 41 (37%) and 13 (37%) Groups A and B patients, respectively, had LN PCR. The systemic relapse rate was not statistically different (5% and 16% for Groups A and B, respectively). CONCLUSIONS: Enhanced assessment with CEUS before NACT identifies patients with axillary metastases missed by conventional B-mode ultrasound. Without CEUS, 22 (63%) of cases in Group B (negative B-mode ultrasound) may have been erroneously classed as progressive disease by surgical SLN excision after NACT.

Phase 2 study of anastrozole in recurrent estrogen (ER)/progesterone (PR) positive endometrial cancer: The PARAGON trial - ANZGOG 0903.

BACKGROUND: The clinical benefit rate with aromatase inhibitors and the impact of treatment on quality of life (QOL) in endometrial cancer is unclear. We report the results of a phase 2 trial of anastrozole in endometrial cancer. METHODS: Investigator initiated single-arm, open label trial of anastrozole, 1 mg/d in patients with ER and/or PR positive hormonal therapy naive metastatic endometrial cancer. Patients were treated until progressive disease (PD) or unacceptable toxicity. The primary end-point was clinical benefit (response + stable disease) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life (QOL) and toxicity. RESULTS: Clinical benefit rate in 82 evaluable patients at 3 months was 44% (95% CI: 34-55%) with a best response by RECIST of partial response in 6 pts. (7%; 95% CI: 3-15%). The median PFS was 3.2 months (95% CI: 2.8-5.4). Median duration of clinical benefit was 5.6 months (95% CI: 3.0-13.7). Treatment was well tolerated. Patients who had clinical benefit at 3 months reported clinically significant improvements in several QOL domains compared to those with PD; this was evident by 2 months including improvements in: emotional functioning (39 vs 6%: p = 0.002), cognitive functioning (45 vs 19%: p = 0.021), fatigue (47 vs 19%: p = 0.015) and global health status (42 vs 9%: p = 0.003). CONCLUSION: Although the objective response rate to anastrozole was relatively low, clinical benefit was observed in 44% of patients with ER/PR positive metastatic endometrial cancer and associated with an improvement in QOL.

Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial.

BACKGROUND: The optimum endocrine treatment for postmenopausal women with advanced hormone-receptor-positive breast cancer that has progressed on non-steroidal aromatase inhibitors (NSAIs) is unclear. The aim of the SoFEA trial was to assess a maximum double endocrine targeting approach with the steroidal anti-oestrogen fulvestrant in combination with continued oestrogen deprivation. METHODS: In a composite, multicentre, phase 3 randomised controlled trial done in the UK and South Korea, postmenopausal women with hormone-receptor-positive breast cancer (oestrogen receptor [ER] positive, progesterone receptor [PR] positive, or both) were eligible if they had relapsed or progressed with locally advanced or metastatic disease on an NSAI (given as adjuvant for at least 12 months or as first-line treatment for at least 6 months). Additionally, patients had to have adequate organ function and a WHO performance status of 0-2. Participants were randomly assigned (1:1:1) to receive fulvestrant (500 mg intramuscular injection on day 1, followed by 250 mg doses on days 15 and 29, and then every 28 days) plus daily oral anastrozole (1 mg); fulvestrant plus anastrozole-matched placebo; or daily oral exemestane (25 mg). Randomisation was done with computer-generated permuted blocks, and stratification was by centre and previous use of an NSAI as adjuvant treatment or for locally advanced or metastatic disease. Participants and investigators were aware of assignment to fulvestrant or exemestane, but not of assignment to anastrozole or placebo. The primary endpoint was progression-free survival (PFS). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, numbers NCT00253422 (UK) and NCT00944918 (South Korea). FINDINGS: Between March 26, 2004, and Aug 6, 2010, 723 patients underwent randomisation: 243 were assigned to receive fulvestrant plus anastrozole, 231 to fulvestrant plus placebo, and 249 to exemestane. Median PFS was 4·4 months (95% CI 3·4-5·4) in patients assigned to fulvestrant plus anastrozole, 4·8 months (3·6-5·5) in those assigned to fulvestrant plus placebo, and 3·4 months (3·0-4·6) in those assigned to exemestane. No difference was recorded between the patients assigned to fulvestrant plus anastrozole and fulvestrant plus placebo (hazard ratio 1·00, 95% CI 0·83-1·21; log-rank p=0·98), or between those assigned to fulvestrant plus placebo and exemestane (0·95, 0·79-1·14; log-rank p=0·56). 87 serious adverse events were reported: 36 in patients assigned to fulvestrant plus anastrozole, 22 in those assigned to fulvestrant plus placebo, and 29 in those assigned to exemestane. Grade 3-4 adverse events were rare; the most frequent were arthralgia (three in the group assigned to fulvestrant plus anastrozole; seven in that assigned to fulvestrant plus placebo; eight in that assigned to exemestane), lethargy (three; 11; 11), and nausea or vomiting (five; two; eight). INTERPRETATION: After loss of response to NSAIs in postmenopausal women with hormone-receptor-positive advanced breast cancer, maximum double endocrine treatment with 250 mg fulvestrant combined with oestrogen deprivation is no better than either fulvestrant alone or exemestane.

A Nationwide Survey of UK Oncologists' Views on the Choice of Radiotherapy Regime for the Reconstructed Chest Wall in Breast Cancer Patients.

Aims. This paper describes a UK survey of the choice of radiotherapy regime for the reconstructed chest wall in breast cancer patients. Questions focused on which fractionation regime consultants choose, their reasons for this, whether the type of reconstruction influences their choice, and whether bolus is used in patients who have undergone immediate reconstructive surgery. Materials and Methods. Between July 2014 and July 2015 a survey was sent by email to UK consultant radiation oncologists treating breast cancer. Results. The response rate was 73%. 67% of respondents use 40 Gray (Gy) in 15 fractions, with 22% using 50 Gy in 25 fractions and 7% using other regimes. For 90% of consultants the type of reconstruction did not influence their decision regarding choice of fractionation. 83% of respondents do not usually use a bolus for chest wall radiotherapy in patients who have had immediate reconstructive surgery. Conclusions. This survey illustrates there is variation in practice in the management of patients with breast cancer who have undergone immediate reconstructive surgery in the UK. There is a need for further research to determine which fractionation regime is optimal, whether the type of surgery is relevant, and whether bolus should be added.

Technique and outcome of post-mastectomy adjuvant chest wall radiotherapy-the role of tissue-equivalent bolus in reducing risk of local recurrence.

OBJECTIVE:: Adjuvant chest wall radiotherapy is used in patients with high-risk histological features post-mastectomy to reduce the risk of locoregional recurrence. Treatment can be given with or without a tissue-equivalent bolus to increase skin surface dose. The additional benefit of using a bolus remains unclear; however, it is known to be associated with a higher incidence of skin toxicity. This study compared chest wall recurrence and skin toxicity in patients treated with and without a bolus. METHODS:: This retrospective cohort study reviewed 314 consecutive patients who received chest wall radiotherapy between 2005 and 2010. Data were collected on histological, demographic and treatment parameters and on the incidence and grade of acute skin reactions. Treatment outcomes analyzed included chest wall recurrence, disease-free survival and overall survival (OS). RESULTS:: 101 patients received treatment with a bolus; 213 patients received treatment without a bolus. A significantly higher incidence of acute skin toxicity was seen in the bolus treatment group (p = 0.002). One patient treated with a bolus developed chest wall recurrence compared with four patients treated without a bolus. No statistically significant difference could be shown between the two groups. 66 (21%) patients had metastatic relapse. Median time to relapse was 29.5 months and OS was 76% in both treatment groups. CONCLUSION:: No statistically significant difference in chest wall recurrence can be demonstrated between patients treated with and without a bolus. ADVANCES IN KNOWLEDGE:: This study is consistent with limited previous literature and invites further evaluation of the role of a bolus in post-mastectomy chest wall radiotherapy, especially considering the increased toxicity that the use of a bolus generates.

Osteonecrosis of the jaw and oral health-related quality of life after adjuvant zoledronic acid: an adjuvant zoledronic acid to reduce recurrence trial subprotocol (BIG01/04).

PURPOSE: In patients with early breast cancer, adjuvant zoledronic acid (zoledronate) may reduce recurrence and improve survival. However, zoledronate is associated with the occasional development of osteonecrosis of the jaw (ONJ). We report on the frequency of ONJ and investigate oral health-related quality of life (Oral-QoL) in a large randomized trial (Adjuvant Zoledronic Acid to Reduce Recurrence [AZURE]). PATIENTS AND METHODS: Three thousand three hundred sixty women with stage II or III breast cancer were randomly assigned to receive standard adjuvant systemic therapy alone or with zoledronate administered at a dose of 4 mg for 19 doses over 5 years. All potential occurrences of ONJ were reported as serious adverse events and centrally reviewed. Additionally, we invited 486 study participants to complete the Oral Health Impact Profile-14 (OHIP-14) to assess Oral-QoL around the time the patients completed 5 years on study. Multivariable linear regression was used to calculate mean scores and 95% CIs in addition to identifying independent prognostic factors. RESULTS: With a median follow-up time of 73.9 months (interquartile range, 60.7 to 84.2 months), 33 possible cases of ONJ were reported, all in the zoledronate-treated patients. Twenty-six cases were confirmed as being consistent with a diagnosis of ONJ, representing a cumulative incidence of 2.1% (95% CI, 0.9% to 3.3%) in the zoledronate arm. Three hundred sixty-two patients (74%) returned the OHIP-14 questionnaire. Neither the prevalence nor severity of impacts on Oral-QoL differed significantly between zoledronate patients and control patients. CONCLUSION: Adjuvant zoledronate used in the intensive schedule studied in the AZURE trial is associated with a low incidence of ONJ but does not seem to adversely affect Oral-QoL.