Measuring serum oestrogen levels in breast cancer survivors using vaginal oestrogens: a systematic review.

PURPOSE: Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum oestrogen levels as a surrogate marker of safety, but methods vary. We sought to summarise the data on serum oestrogen measurement in women with breast cancer using vaginal oestrogens to better understand the methods, levels and reliability. METHODS: We searched Medline, Embase, CENTRAL, SCOPUS and CINAHL from inception to October 2023 for clinical studies where serum oestrogen was measured in women with a history of early breast cancer using vaginal oestrogens. Studies with a reported testing methodology were included. RESULTS: Nine studies met the inclusion criteria for this systematic review. Methods used to measure oestradiol and oestriol in selected studies included mass spectrometry and immunoassays; several studies used more than one with variable concordance. Mass spectrometry detected oestradiol levels down to a lower limit between 1.0 pg/mL and 3.0 pg/mL. Immunoassays such as ELISA (enzyme-linked immunosorbent assay), ECLIA (enhanced chemiluminiscence immunoassay) and RIA (radioimmunoassay) had lower detection limits ranging between 0.8 pg/mL and 10 pg/mL. Studies were heterogeneous in testing techniques used, timing of testing, and the population including with subsequent varying results in the effect on oestrogens reported. CONCLUSIONS: Adopting consistent and standardised methods of measuring oestrogens in clinical trials involving women with early breast cancer on vaginal oestrogens is critical. Serum oestrogens are used as a surrogate marker of safety in this population, and good-quality data are necessary to enable clinicians and patients to feel confident in prescribing and taking vaginal oestrogens. Mass spectrometry, although more expensive, gives more reliable results when dealing with very low levels of oestrogens often found in women on aromatase inhibitors, compared to immunoassays.

Telehealth cognitive behaviour therapy for the management of sleep disturbance in women with early breast cancer receiving chemotherapy: a feasibility study.

PURPOSE: Sleep quality commonly deteriorates in people receiving chemotherapy for breast cancer (BC). We aimed to determine feasibility and acceptability of telehealth-delivered cognitive behaviour therapy for insomnia (CBT-I) in people with early BC receiving (neo)adjuvant chemotherapy. METHODS: Multi-centre, single arm, phase 2 feasibility trial. People with stage I-III BC received 4 sessions of telehealth CBT-I over 8 weeks, during chemotherapy. Participants completed Pittsburgh Sleep Quality Index (PSQI) and other Patient Reported Outcome Measures (PROMs) at baseline, post-program (week 9) and post-chemotherapy (week 24); and an Acceptability Questionnaire at week 9. Primary endpoint was proportion completing 4 sessions of telehealth CBT-I. RESULTS: In total, 41 participants were recruited: mean age 51 years (range 31-73). All 4 CBT-I sessions were completed by 35 (85%) participants. Acceptability of the program was high and 71% reported 'the program was useful'. There was no significant difference in the number of poor sleepers (PSQI score ≥ 5) at baseline 29/40 (73%) and week 24 17/25 (68%); or in the mean PSQI score at baseline (7.43, SD 4.06) and week 24 (7.48, SD 4.41). From baseline to week 24, 7/25 (28%) participants had a ≥ 3 point improvement in sleep quality on PSQI, and 5/25 (20%) had a ≥ 3 point deterioration. There was no significant difference in mean PROM scores. CONCLUSION: It is feasible to deliver telehealth CBT-I to people with early BC receiving chemotherapy. Contrary to literature predictions, sleep quality did not deteriorate. Telehealth CBT-I has a potential role in preventing and managing sleep disturbance during chemotherapy. Australian New Zealand Clinical Trials Registry (ANZCTR) registration number: ACTRN12620001379909 and date 22/12/2020.

Vaginal CO2 laser for the treatment of vulvovaginal atrophy in women with breast cancer: LAAVA pilot study.

PURPOSE: Vulvovaginal atrophy (VVA) is a commonly reported issue among breast cancer patients, and its aetiology is multifactorial. Treatment is difficult in these women, particularly because the use of oestrogens has traditionally been discouraged. Vaginal laser treatment has been reported to improve symptoms. We aimed to assess the impact on symptoms and sexual function of vaginal laser in women with early breast cancer (EBC). METHODS: We performed a single-arm investigator initiated pilot study of female EBC patients with symptomatic VVA. A total of 3 vaginal laser treatments were administered 4 weeks apart. Questionnaires were completed at baseline, 4, 8 and 12 weeks. Our primary endpoint was symptomatic improvement of VVA at 12 weeks on 10 cm visual analogue scales. Our secondary endpoints were improvement in sexual function using the Female Sexual Function Index (FSFI) and patient-reported improvements in symptoms, sexual function and quality of life. Statistical analysis was performed with a Wilcoxon Signed Rank test. RESULTS: 26 patients were enrolled between February 2016 and August 2017. All patients were post-menopausal, 25 of whom had received anti-oestrogen therapy for their breast cancer. Questionnaire compliance was high (98%) and all patients received the three pre-planned treatments. There was significant improvement in each of the VVA symptoms: dryness (p < 0.001), itch (p < 0.001), burning (p = 0.003), dysuria (p < 0.001) and dyspareunia (p < 0.001). Patients also reported improvement in sexual function on the FSFI (p ≤ 0.001). CONCLUSIONS: Patients receiving vaginal laser had improvement in VVA symptoms and sexual function. Further randomised sham-controlled trials are needed to further assess this treatment.

Genitourinary symptoms in women with breast cancer: what do oncology health professionals think and do about them?

OBJECTIVES: We aimed to improve understanding of health professional knowledge and management of genitourinary symptoms (GUS) in women with early breast cancer (EBC). METHODS: A survey was sent to 872 health professionals caring for women with EBC. Questions addressed most common GUS seen, experience treating GUS, and attitudes to treatment options. RESULTS: 144 surveys were completed. Respondent characteristics: median age 50 years; 76% female; 42% medical oncologists; 24% nurses; 20% breast surgeons; 8% radiation oncologists. Most (68%) reported prescribing endocrine therapies for EBC, 99% were aware endocrine therapies can cause GUS, and 55% reported "often" or "always" asking patients on endocrine therapy if they have GUS. Respondents thought vaginal dryness was the most bothersome symptom for their patients (66%), followed by dyspareunia (11%). 81% of respondents reported seeing women stop endocrine therapy prematurely due to GUS. Respondents reported receiving "none" (19%) or "a little" (46%) training or education in managing GUS and only 16% reported feeling "very confident" managing GUS. The proportions of respondents reporting "often" and "very often" recommending the following vaginal treatments were: lubricants (81%); moisturisers (68%); oestrogens (21%); and laser (3%). Vaginal oestrogens were considered "safe" or "probably safe" by 77% and 90% of respondents for women with hormone receptor positive and negative EBC, respectively. CONCLUSIONS: Despite health professionals frequently encountering GUS in women with EBC and seeing patients stop endocrine therapies prematurely, only 16% felt confident managing these symptoms. Education and training for health professionals are needed to better address this common problem.

Why pathologists and oncologists should know about tumour-infiltrating lymphocytes (TILs) in triple-negative breast cancer: an Australian experience of 139 cases.

The presence of increased tumour infiltrating lymphocytes (TILs) is established as a positive prognostic factor in triple-negative breast cancer (TNBC). The majority of studies have examined the role of TILs in predicting response to chemotherapy, but their role as a general prognostic marker in TNBC is unclear. Moreover, there is a lack of consensus in the literature regarding a suitable cut-off point by which to stratify patients into prognostic groups. Therefore, we sought to confirm the prognostic value of TILs in an independent cohort of unselected TNBCs, and to determine an appropriate cut-off point by which to stratify TIL scores into prognostically significant categories. We used the International TILs Working Group (ITWG) methodology to assess the density of stromal TILs in our cohort of 139 TNBC patients undergoing curative resection at our institution. The percentage TILs scores were categorised first into three groups: low (0-10%), intermediate (15-50%), and high (55-100%). A second binary variable was also created by separating cases into low TILs (≤50%) and high TILs (>50%) groups. Using the three-tiered system, mean disease-free survival was 156, 99 and 94 months for the high, intermediate and low TILs groups, respectively (p=0.030). However, no statistically significant improvement was observed for overall survival. Using the two-tiered system, statistically significant improvements in both overall survival (p=0.030) and disease-free survival (p=0.010) were observed. This survival benefit remained statistically significant in multivariate analyses (p=0.010, p=0.014). We conclude that TILs scored using the ITWG system and dichotomised at a cut-off score of 50%, are a powerful predictor of all-cause and disease-free survival in TNBC regardless of chemotherapy treatment.

Malignant Cardiac Tamponade from Non-Small Cell Lung Cancer: Case Series from the Era of Molecular Targeted Therapy.

Cardiac tamponade complicating malignant pericardial effusion from non-small cell lung cancer (NSCLC) is generally associated with extremely poor prognosis. With improved systemic chemotherapy and molecular targeted therapy for NSCLC in recent years, the prognosis of such patients and the value of invasive cardiothoracic surgery in this setting have not been adequately examined. We report outcomes from a contemporary case series of eight patients who presented with malignant cardiac tamponade due to NSCLC to an Australian academic medical institution over an 18 months period. Two cases of cardiac tamponade were de novo presentations of NSCLC and six cases were presentations following previous therapy for NSCLC. The median survival was 4.5 months with a range between 9 days to alive beyond 17 months. The two longest survivors are still receiving active therapy at 17 and 15 months after invasive surgical pericardial window respectively. One survivor had a histological subtype of large cell neuroendocrine carcinoma and the other received targeted therapy for epidermal growth factor receptor mutation. These results support the consideration of active surgical palliation to treating this oncological emergency complicating NSCLC, including the use of urgent drainage, surgical creation of pericardial window followed by appropriate systemic therapy in suitably fit patients.