Is controlled ovarian stimulation safe in patients with hormone receptor-positive breast cancer receiving neoadjuvant chemotherapy?

INTRODUCTION: Controlled ovarian stimulation (COS) for oocyte/embryo cryopreservation is the method of choice for fertility preservation (FP) in young patients diagnosed with early-stage breast cancer (eBC). Nevertheless, some challenges still question its role, particularly in the neoadjuvant setting, where concerns arise about potential delay in the onset of anticancer treatment, and in hormone receptor-positive (HR+) disease, as cancer cells may proliferate under the estrogenic peak associated with stimulation. Therefore, this review aims to examine the available evidence on the safety of COS in eBC patients eligible for neoadjuvant treatment (NAT), particularly in HR+ disease. METHODS: A comprehensive literature search was conducted to identify studies evaluating the feasibility and safety of COS in eBC and including patients referred to NAT and/or with HR+ disease. Time to NAT and survival outcomes were assessed. RESULTS: Of the three matched cohort studies assessing the impact of COS on time to start NAT, only one reported a significant small delay in the cohort undergoing COS compared with the control group, whereas the other studies found no difference. Regarding survival outcomes, overall, no increased risk of recurrence or death was found, either in patients undergoing COS in the neoadjuvant setting regardless of HR expression or in HR+ disease regardless of the timing of COS relative to surgery. However, there are no data on the safety of COS in the specific combined scenario of HR+ disease undergoing NAT. CONCLUSION: Neither the indication to NAT nor the HR positivity constitutes per se an a priori contraindication to COS. Shared decision making between clinicians and patients is essential to carefully weigh the risks and benefits in each individual case. Prospective studies designed to specifically investigate this issue are warranted.

Evolution of overall survival and receipt of new therapies by subtype among 20 446 metastatic breast cancer patients in the 2008-2017 ESME cohort.

BACKGROUND: Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. PATIENTS AND METHODS: We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2-; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). RESULTS: The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2- MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2- and TNBC cohorts, respectively, whatever YOD. CONCLUSION: OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed.

Is intra-arterial hepatic chemotherapy painful?

BACKGROUND: Liver metastases are mainly supplied by the hepatic artery, allowing the administration of intra-arterial hepatic chemotherapy (IAHC) while preserving normal parenchyma. The progression-free survival and response rate are prolonged by IAHC which can improve the rate of secondary resectability. Severe abdominal pain requiring high-dose opioids can appear during HIAC administration. This pain is related to extrahepatic infusion and gastroduodenal ulceration. However, intense abdominal pain was observed under oxaliplatin IAHC specifically without any extrahepatic infusion. METHOD: We retrospectively reviewed the charts of 68 patients who received IAHC in our center between 2011 and 2015. Patient's demographics and disease characteristics were collected. Other variables such as the type, duration, and dosage of the chemotherapy administered, as well as the usage of painkillers before, during, or after intra-arterial administration, were also registered. RESULTS: The mean age of the patients was 59 years. 61.7% were male (n = 42). The mean dose of oxaliplatin administered was 162 mg per cure over 6.7-h course. Fifty percent were diagnosed with a left colon cancer, and 85.2% had synchronous liver metastasis. While 47% of patients received IAHC as a third-line therapy, the main chemotherapeutic drug was oxaliplatin (85.2% of cases; n = 58), then OPTILIV protocol (5FU, irinotecan, oxaliplatin) (13.3%; n = 9), and mitomycin C (1.5%; n = 1). A dose reduction of 23.6% had been noted in 58.8% (n = 40) cases due to adverse effects. Among patients who received opioids during IAHC (n = 40), 20% required opioids in intercure. Before, during, and after IAHC administration, patients complained of abdominal pain in 8.8%, 58.8%, and 19.1%, and opioids were used in 10.2%, 57.3%, and 19.1%, respectively. The main onset of pain occurs during the third cycle of chemotherapy. Among our patients, 11.7% and 22% had ulcer and extrahepatic perfusion, respectively, while 7.3% of them were asymptomatic. The mean occurrence of these signs was during the fourth cycle of IAHC. 33.8% and 52.9% of patients had abdominal pain while an extended and short infusion time, respectively. CONCLUSION: Lengthening of the infusion time did not prevent the occurrence of abdominal pain significantly but was nonetheless decreased compared with patients undergoing short infusion durations. Pain was more common in patients who did not have a dose reduction and who presented with ulcer and extrahepatic perfusion. Abdominal pain occurred on average one cycle before ulcer or extrahepatic perfusion diagnosis. In current practice, pain should be an alarming indicator in patients receiving IAHC, as it may be associated with ulcer or extrahepatic perfusion and thus requiring opioids.